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Sample records for levonorgestrel induces endothelium-independent

  1. The progestin levonorgestrel induces endothelium-independent relaxation of rabbit jugular vein via inhibition of calcium entry and protein kinase C: role of cyclic AMP

    Science.gov (United States)

    Herkert, Olaf; Kuhl, Herbert; Busse, Rudi; Schini-Kerth, Valérie B

    2000-01-01

    The progestin and oestrogen component of oral contraceptives have been involved in the development of venous thromboembolic events in women. In the present study we determined the vasoactive effects of sex steroids used in oral contraceptives in isolated preconstricted rabbit jugular veins in the presence of diclofenac and examined the underlying mechanisms.The natural hormone progesterone, the synthetic progestins levonorgestrel, 3-keto-desogestrel, gestodene and chlormadinone acetate, and the synthetic estrogen 17 α-ethinyloestradiol induced concentration-dependent relaxations of endothelium-intact veins constricted with U46619. Levonorgestrel also inhibited constrictions evoked by either a high potassium (K+) solution or phorbol myristate acetate (PMA) in the absence and presence of extracellular calcium (Ca2+). In addition, levonorgestrel depressed contractions evoked by Ca2+ and reduced 45Ca2+ influx in depolarized veins.Relaxations to levonorgestrel in U46619-constricted veins were neither affected by the presence of the endothelium nor by the inhibitor of soluble guanylyl cyclase, NS2028, but were significantly improved either by the selective cyclic AMP phosphodiesterase inhibitor rolipram or in the absence of diclofenac, and decreased by the protein kinase A inhibitor, Rp-8-CPT-cAMPS. Rolipram also potentiated relaxations to levonorgestrel in PMA-constricted veins in the presence, but not in the absence of extracellular Ca2+. Levonorgestrel increased levels of cyclic AMP and inhibited PMA-induced activation of protein kinase C in veins.These findings indicate that levonorgestrel caused endothelium-independent relaxations of jugular veins via inhibition of Ca2+ entry and of protein kinase C activation. In addition, the cyclic AMP effector pathway contributes to the levonorgestrel-induced relaxation possibly by depressing Ca2+ entry. PMID:10952682

  2. Xanthorrhizol induces endothelium-independent relaxation of rat thoracic aorta.

    Science.gov (United States)

    Campos, M G; Oropeza, M V; Villanueva, T; Aguilar, M I; Delgado, G; Ponce, H A

    2000-06-08

    Xanthorrhizol, a bisabolene isolated from the medicinal plant Iostephane heterophylla, was assayed on rat thoracic aorta rings to elucidate its effect and likely mechanism of action, by measuring changes of isometric tension. Xanthorrhizol (1, 3, 10, 30 and 100 microg/mL) significantly inhibited precontractions induced by KCI-; (60mM), noradrenaline (10(-6) M) or CaCl2 (1.0 mM). Increasing concentrations of external calcium antagonized the inhibitory effect on KCl-induced contractions. The vasorelaxing effect of xanthorrhizol was not affected by indomethacin (10 microM) or L-NAME (100 microM) in intact rat thoracic aorta rings precontracted by noradrenaline, which suggested that the effect was not mediated through either endothelium-derived prostacyclin (PGI2) or nitric oxide release from endothelial cells. Endothelium removal did not affect the relaxation induced by xanthorrhizol on rat thoracic aorta rings, discarding the participation of any substance released by the endothelium. Xanthorrhizol inhibitory effect was greater on KCI- and CaCl2-induced contractions than on those induced by noradrenaline. Xanthorrhizol inhibitory effect in rat thoracic aorta is likely explained for interference with calcium availability by inhibiting calcium influx through both voltage- and receptor-operated channels.

  3. Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries

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    Daniela Medeiros Lobo de Andrade

    2016-01-01

    Full Text Available Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE on vascular smooth muscle (VSM of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL. Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM. Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.

  4. Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries

    Science.gov (United States)

    de Andrade, Daniela Medeiros Lobo; Borges, Leonardo Luis; Torres, Ieda Maria Sapateiro; da Conceição, Edemilson Cardoso; Rocha, Matheus Lavorenti

    2016-01-01

    Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect. PMID:27533258

  5. Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries.

    Science.gov (United States)

    Andrade, Daniela Medeiros Lobo de; Borges, Leonardo Luis; Torres, Ieda Maria Sapateiro; Conceição, Edemilson Cardoso da; Rocha, Matheus Lavorenti

    2016-09-01

    Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect. Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina tamb

  6. Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility.

    Science.gov (United States)

    Je, Hyun Dong; Sohn, Uy Dong; La, Hyen-Oh

    2016-01-01

    Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.

  7. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries.

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    Tangsucharit, Panot; Takatori, Shingo; Zamami, Yoshito; Goda, Mitsuhiro; Pakdeechote, Poungrat; Kawasaki, Hiromu; Takayama, Fusako

    2016-01-01

    The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  8. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries

    Directory of Open Access Journals (Sweden)

    Panot Tangsucharit

    2016-01-01

    Full Text Available The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist or 4-DAMP (M1 and M3 antagonist plus hexamethonium (nicotinic AChR antagonist, but not methoctramine (M2 and M4 antagonist. These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation.

  9. Impaired endothelium independent vasodilation in the cutaneous microvasculature of young obese adults.

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    Patik, Jordan C; Christmas, Kevin M; Hurr, Chansol; Brothers, R Matthew

    2016-03-01

    Microvascular dysfunction contributes to the development of cardiovascular and metabolic disease. This study tested the hypothesis that young obese (BMI>30 kg m(-2)), otherwise healthy, adults (N=15) have impaired microvascular function relative to age and sex matched, lean (BMIvasodilator methacholine (MCh) and the other for the endothelium-independent vasodilator sodium nitroprusside (SNP). Local temperature at each site was clamped at 33 °C and cutaneous blood flow was indexed by laser Doppler flowmetry (LDF). LDF was recorded while 7 doses of each drug (MCh: 10(-6)-1M; SNP: 5 × 10(-8)-5 × 10(-2)M) were infused at a rate of 2 μl/min for 8 min per dose. Both sites finished with heating to 43 °C and 5 × 10(-2)M SNP to achieve site specific maximal vasodilation. Mean arterial blood pressure (MAP) was assessed in the last minute of each dose and was used for subsequent calculation of cutaneous vascular conductance (CVC; LDF/MAP) and responses were normalized to each individual site's maximal response (%CVCmax). Group four-parameter dose response curves were compared with an extra sum of squares F-test. SNP EC50 was greater in obese relative to lean (-2.931 ± 0.10 vs -3.746 ± 0.18 Log[SNP]M, P0.05). These results suggest attenuated endothelium-independent response to nitric oxide while endothelium-dependent vasodilation function is maintained.

  10. Prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERβ suppression in the amygdala.

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    Zou, Yuanlin; Lu, Qiaomei; Zheng, Dan; Chu, Zhigang; Liu, Zhaoyu; Chen, Haijia; Ruan, Qiongfang; Ge, Xiaohu; Zhang, Ziyun; Wang, Xiaoyan; Lou, Wenting; Huang, Yongjian; Wang, Yifei; Huang, Xiaodong; Liu, Zhengxiang; Xie, Weiguo; Zhou, Yikai; Yao, Paul

    2017-01-01

    Autism spectrum disorder (ASD) is characterized by impairments in social communication and restricted or repetitive behaviors or interests. ASD is now diagnosed in more than one out of 100 children and is biased towards males by a ratio of at least 4:1. Many possible explanations and potential causative factors have been reported, such as genetics, sex, and environmental factors, although the detailed mechanisms of ASD remain unclear. The dams were exposed through oral contraceptives to either vehicle control (VEH) alone, levonorgestrel (LNG) alone, ethinyl estradiol (EE) alone, or a combination of LNG/EE for 21 days during their pregnancy. The subsequent 10-week-old offspring were used for autism-like behavior testing, and the limbic tissues were isolated for analysis. In another experimental group, 8-week-old male offspring were treated by infusion of ERβ overexpression/knockdown lentivirus in the amygdala, and the offspring were analyzed after 2 weeks. We show that prenatal exposure of either LNG alone or a LNG/EE combination, but not EE alone, results in suppression of ERβ (estrogen receptor β) and its target genes in the amygdala with autism-like behavior in male offspring, while there is a much smaller effect on female offspring. However, we find that there is no effect on the hippocampus and hypothalamus. Further investigation shows that ERβ suppression is due to LNG-mediated altered methylation on the ERβ promoter and results in tissue damage with oxidative stress and the dysfunction of mitochondria and fatty acid metabolism, which subsequently triggers autism-like behavior. Overexpression of ERβ in the amygdala completely restores LNG-induced ERβ suppression and autism-like behaviors in offspring, while ERβ knockdown mimics this effect, indicating that ERβ expression in the amygdala plays an important role in autism-like behavior development. We conclude that prenatal levonorgestrel exposure induces autism-like behavior in offspring through ER

  11. Hypoadiponectinemia predicts impaired endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients: an 8-year prospective study

    Institute of Scientific and Technical Information of China (English)

    LI Hui; XIAO Yang; LIU Hui; CHEN Xiao-yan; LI Xin-ying; TANG Wei-li; LIU Shi-ping; XU Ai-min; ZHOU Zhi-guang

    2011-01-01

    Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties.The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study.Methods In the prospective study,we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years.Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia,hypertension,dyslipidaemia and obesity.We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay,endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound.At year 8,102 patients were reexamined for endothelium-dependent and -independent vasodilation.Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r=0.150,P=0.043) and at year 8 (r=0.339,P=0.001),whereas no association was found between adiponectin and endothelium-dependent vasodilation.In a stepwise multivariate linear regression model,adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P=0.001).Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention.These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.

  12. Levonorgestrel Intrauterine System

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    Levonorgestrel intrauterine system (Mirena, Skyla) is used to prevent pregnancy. The manufacturer states that Mirena brand intrauterine ... to use an intrauterine system to prevent pregnancy. Levonorgestrel is in a class of medications called hormonal ...

  13. Activation of G protein-coupled estrogen receptor induces endothelium-independent relaxation of coronary artery smooth muscle

    Science.gov (United States)

    Yu, Xuan; Ma, Handong; Barman, Scott A.; Liu, Alexander T.; Sellers, Minga; Stallone, John N.; Prossnitz, Eric R.; White, Richard E.

    2011-01-01

    Estrogens can either relax or contract arteries via rapid, nongenomic mechanisms involving classic estrogen receptors (ER). In addition to ERα and ERβ, estrogen may also stimulate G protein-coupled estrogen receptor 1 (GPER) in nonvascular tissue; however, a potential role for GPER in coronary arteries is unclear. The purpose of this study was to determine how GPER activity influenced coronary artery reactivity. In vitro isometric force recordings were performed on endothelium-denuded porcine arteries. These studies were augmented by RT-PCR and single-cell patch-clamp experiments. RT-PCR and immunoblot studies confirmed expression of GPER mRNA and protein, respectively, in smooth muscle from either porcine or human coronary arteries. G-1, a selective GPER agonist, produced a concentration-dependent relaxation of endothelium-denuded porcine coronary arteries in vitro. This response was attenuated by G15, a GPER-selective antagonist, or by inhibiting large-conductance calcium-activated potassium (BKCa) channels with iberiotoxin, but not by inhibiting NO signaling. Last, single-channel patch-clamp studies demonstrated that G-1 stimulates BKCa channel activity in intact smooth muscle cells from either porcine or human coronary arteries but had no effect on channels isolated in excised membrane patches. In summary, GPER activation relaxes coronary artery smooth muscle by increasing potassium efflux via BKCa channels and requires an intact cellular signaling mechanism. This novel action of estrogen-like compounds may help clarify some of the controversy surrounding the vascular effects of estrogens. PMID:21791623

  14. Spasmolytic effect of curcumin on goat ruminal artery is endothelium independent and by activation of sGC.

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    Dash, J R; Parija, S C

    2013-10-01

    The aim of the present work was to study the mechanism of action of curcumin in vasomotion of a physiologically important artery of ruminant i.e. ruminal artery. ACh and SNP were used to study the role of endothelium in relaxation of this artery. Vasorelaxatation by curcumin was studied in a dose dependent manner, on rings precontracted with 5-hydroxy tryptamine and noradrenalin, in presence and absence of L-NAME, 4AP, ODQ and 4AP+ODQ combination. SNP (1 ηM-100 μM) produced a significant relaxation compared to ACh (0.1-100 μM) on 5-HT (10 μM) and NA (10 μM) induced contraction in endothelium intact rings. Curcumin (10 ηM-100 μM) relaxed the vascular rings in dose dependent manner with maximal relaxation up to 20.94% and 13.81% in 5-HT and NA induced contraction, respectively which was potently blocked by ODQ (10 μM) and combination of 4AP and ODQ (10 μM) but 4AP (10 μM) and L-NAME (100 μM) alone could not block the relaxation and interestingly we observed a slight increase in the tension at higher dose of the agonist (>10 μM). Therefore in goat ruminal artery, curcumin at least in part, act via direct activation of sGC mediated cGMP pathway followed by opening of K(+) ion channel. However other mechanisms may not be ruled out.

  15. Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men: a randomized controlled trial.

    Science.gov (United States)

    Hobbs, Ditte A; Goulding, Marie G; Nguyen, Annie; Malaver, Thomas; Walker, Claire F; George, Trevor W; Methven, Lisa; Lovegrove, Julie A

    2013-09-01

    Dietary nitrate, from beetroot, has been reported to lower blood pressure (BP) by the sequential reduction of nitrate to nitrite and further to NO in the circulation. However, the impact of beetroot on microvascular vasodilation and arterial stiffness is unknown. In addition, beetroot is consumed by only 4.5% of the UK population, whereas bread is a staple component of the diet. Thus, we investigated the acute effects of beetroot bread (BB) on microvascular vasodilation, arterial stiffness, and BP in healthy participants. Twenty-three healthy men received 200 g bread containing 100 g beetroot (1.1 mmol nitrate) or 200 g control white bread (CB; 0 g beetroot, 0.01 mmol nitrate) in an acute, randomized, open-label, controlled crossover trial. The primary outcome was postprandial microvascular vasodilation measured by laser Doppler iontophoresis and the secondary outcomes were arterial stiffness measured by Pulse Wave Analysis and Velocity and ambulatory BP measured at regular intervals for a total period of 6 h. Plasma nitrate and nitrite were measured at regular intervals for a total period of 7 h. The incremental area under the curve (0-6 h after ingestion of bread) for endothelium-independent vasodilation was greater (P = 0.017) and lower for diastolic BP (DBP; P = 0.032) but not systolic (P = 0.99) BP after BB compared with CB. These effects occurred in conjunction with increases in plasma and urinary nitrate (P vasodilation and decreased DBP. Therefore, enriching bread with beetroot may be a suitable vehicle to increase intakes of cardioprotective beetroot in the diet and may provide new therapeutic perspectives in the management of hypertension.

  16. 左炔诺孕酮下调survivin基因促进人子宫肌瘤细胞凋亡%Levonorgestrel induces apoptosis through down-regulation of survivin gene expression in human uterine leiomyoma cells

    Institute of Scientific and Technical Information of China (English)

    仇黎丽; 徐青; 徐昌芬

    2012-01-01

    Objective To explore the function of Survivin in levonorgestrel ( LNG) -induced apoptosis in cultured human uterine leiomyoma cells (UtLMC) in vitro. Methods AO/EB double staining was applied to discriminate the apoptotic cells from dead ones. The changes of survivin mRNA expressions in UtLMC after LNG treatment were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Furthermore, Western blot was used to determine survivin protein expression in LNG-induced UtLMC apoptosis. Results The result of AO/EB double staining showed that there were more viable apoptotic cells in LNG-treated groups than control group and the number of non-viable apoptotic cells and dead cells increased while the concentration of LNG elevated. Survivin expression in LNG-treated cells was decreased both at mRNA and protein levels according to RT-PCR and Western blot results. Conclusions Levonorgestrel treatment may induce a substantial apoptotic response in UtLMC, which was enhanced with the raise of levonorgestrel concentration. It may be due to the marked down-regulation of survivin gene expression.%目的 探讨左炔诺孕酮(LNG)诱导人子宫肌瘤细胞(UtLMC)凋亡过程中survivin的表达变化.方法 原代培养人子宫肌瘤细胞传代后,加入不同浓度LNG,以AO/EB双染法区分早、晚期凋亡细胞和坏死细胞;RT-PCR检测抑凋亡基因survivin mRNA的表达,Western blot测定survivin蛋白的表达.结果 10 mg/L LNG作用UtLMC后早期凋亡细胞多于阴性对照组,随着LNG剂量的增加,晚期凋亡细胞也逐渐增多,核浓聚、偏位,被染成桔红色;在10 mg/L以上LNG诱导的UtLMC凋亡中,survivin mRNA表达显著下降,蛋白表达由对照组的33.82±0.02下降至10.37±0.03 (P <0.05).结论 一定浓度的左炔诺孕酮所诱导的人子宫肌瘤细胞凋亡,可能与抑制survivin抗凋亡活性相关.

  17. Chemical composition and vasorelaxant effect induced by the essential oil of Lippia alba (Mill. N.E. Brown. (Verbenaceae in rat mesenteric artery

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    Luana G Maynard

    2011-01-01

    Conclusions : The results demonstrated that EOLA induces endothelium-independent vasorelaxation, which appears to be caused, at least in part, by blocking Ca 2+ influx through voltage-operated Ca 2+ channels.

  18. Levonorgestrel

    Science.gov (United States)

    ... It works by preventing the release of an egg from the ovary or preventing fertilization of the egg by sperm (male reproductive cells). It also may ... as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant ...

  19. The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

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    Êurica Adélia Nogueira Ribeiro

    2012-01-01

    Full Text Available The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy. In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS, indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

  20. Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism

    DEFF Research Database (Denmark)

    Hornum, Mads; Clausen, Peter; Idorn, Thomas

    2011-01-01

    BACKGROUND: The aim of this study is to investigate the effect of kidney transplantation on arterial function in relation to changes in glucose metabolism. METHODS: Included were 40 kidney recipients (Tx group, age 38 ± 13 years) and 40 patients without known diabetes remaining on the waiting list...... for kidney transplantation (uraemic control group, age 47 ± 11 years). Arterial function was estimated by the pulse wave velocity (PWV) of the carotid-femoral pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and nitroglycerin-induced vasodilatation (NID) of the brachial artery performed...... before transplantation and after 12 months. PWV recorded sequentially at the carotid and femoral artery is an estimate of arterial stiffness; AIX is an integrated index of vascular and ventricular function. FMD and NID are the dilatory capacities of the brachial artery after increased flow (endothelium...

  1. Molecular effects and bioaccumulation of levonorgestrel in the non-target organism Dreissena polymorpha

    Energy Technology Data Exchange (ETDEWEB)

    Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Lorenz, Claudia, E-mail: claudia.lorenz@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Department of Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark, Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

    2011-01-15

    Bioaccumulation and effects of the contraceptive hormone levonorgestrel were examined in the non-target organism Dreissena polymorpha. Molecular biomarkers of biotransformation, elimination, antioxidant defence and protein damage were analyzed after exposure to increasing concentrations of levonorgestrel in a flow-through system. The lowest concentration (0.312 {mu}g L{sup -1}) was 100-fold bioconcentrated within four days. A decrease of the bioconcentration factor was observed within one week for the highest test concentrations (3.12 and 6.24 {mu}g L{sup -1}) suggesting enhanced excretory processes. The immediate mRNA up-regulation of pi class glutathione S-transferase proved that phase II biotransformation processes were induced. Disturbance of fundamental cell functions was assumed since the aryl hydrocarbon receptor has been permanently down-regulated. mRNA up-regulation of P-glycoprotein, superoxide dismutase and metallothioneine suggested enhanced elimination processes and ongoing oxidative stress. mRNA up-regulation of heat shock protein 70 in mussels exposed to the two highest concentrations clearly indicated impacts on protein damage. - Fundamental cell processes as biotransformation, elimination and prevention from oxidative stress are influenced by exposure of the contraceptive levonorgestrel in non-target organisms. - Research highlights: Bioaccumulation of levonorgestrel in mussels is higher than expected based on its lipophilicity. Exposure to levonorgestrel causes oxidative stress and enhanced elimination processes. Glutathione S-transferase (pi class) mRNA induction after one day hint on phase II biotransformation. mRNA induction of heat shock protein 70 after one week prove protein damage.

  2. Ectopic pregnancy following levonorgestrel emergency contraception: a case report

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    Kaymak, Oktay; Şimşek, Yavuz; Doğanay, Melike; Yıldız, Yasemin; Mollamahmutoğlu, Leyla

    2010-01-01

    Hormonal contraceptive pills containing 750 microgram levonorgestrel are the most commonly used postcoital contraceptive method because of their high efficacy and fewer side effects. Emergency contraceptive pills containing levonorgestrel present their effects by several mechanisms, including delayed tubal transport of the ovum. A delay of tubal transportation of an ovum is also one of the possible etiologic factors of tubal ectopic pregnancies. There are limited data on the risk of ectopic pregnancy following levonorgestrel treatment as an emergency contraception. Here, a case of tubal pregnancy associated with the use of levonorgestrel containing emergency contraceptive pills has been presented along with discussion of the relevant literature. PMID:24591928

  3. Evaluation of levonorgestrel intrauterine system upon presumed nonintact removal.

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    Bukowski, Josh; Rogers, Anna; Cansino, Catherine

    2014-12-01

    A 51 year old woman presented for removal of her expired levonorgestrel intrauterine device (IUD). The IUD arms appeared absent upon IUD removal. Further examination of the device revealed that the arms were concealed inside the hormonal cylinder. Recognizing abnormal presentations of the levonorgestrel IUD upon removal can avoid unnecessary procedures.

  4. Efecto del levonorgestrel como anticonceptivo oral de emergencia en la ovulación, el endometrio y los espermatozoides Effect of levonorgestrel in the ovulation, endometrium, and spermatozoa for emergency oral contraception

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    Víctor J. Suárez

    2010-06-01

    Full Text Available Existe amplia controversia acerca del mecanismo de acción del levonorgestrel como anticonceptivo oral de emergencia; numerosas organizaciones, tanto científicas como de la sociedad civil, muestran su disconformidad con su uso, debido a su posible acción como inductor de aborto. Con el objetivo de evaluar la evidencia científica disponible sobre los mecanismos de acción del levonorgestrel utilizado como anticonceptivo oral de emergencia (AOE, se realizó una revisión sistemática en las bases de datos Medline y Cochrane Library donde se encontró 444 artículos; después de revisar los resúmenes, se seleccionó 22 artículos, los cuales fueron evaluados a texto completo. Se encontró que el principal mecanismo de acción del levonorgestrel, a las dosis recomendadas como AOE, es la inhibición o retraso de la ovulación; no afecta a los espermatozoides en su capacidad de migración ni de penetración al óvulo. No se ha demostrado alteraciones morfológicas ni moleculares en el endometrio que puedan interferir con la implantación del huevo fecundado. No existe evidencia científica actual disponible que sustente que el uso de levonorgestrel como AOE sea abortivo.There is wide controversy about the mechanism of action of the levonorgestrel used for emergency oral contraception, and many organizations, both scientific as well as from the civil society, show their discrepancy with its use, due to its possible action as an abortion- inducer. In order to evaluate the scientific evidence available on the mechanisms of action of the levonorgestrel used for emergency oral contraception (EOC, a systematic revision was performed in the Medline and Cochrane library databases. We found 444 articles. After reviewing the abstracts, we selected 22 articles, whose complete texts were evaluated. We found that the main mechanism of action of the levonorgestrel, given at the doses recommended for EOC, is the inhibition or retardation of the ovulation, it

  5. Levonorgestrel, not etonogestrel, provides contraception in free-ranging koalas.

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    Hynes, E F; Handasyde, K A; Shaw, Geoff; Renfree, Marilyn B

    2010-01-01

    Management of high-density koala (Phascolarctos cinereus) populations is essential because of the browsing damage they inflict on their habitat. We have tested two types of gestagen implant, namely levonorgestrel and etonogestrel, as contraceptives for koalas. Free-ranging female koalas were given either a control, levonorgestrel (70 mg) or etonogestrel (34 or 68 mg) implant before the breeding season. Koalas were monitored every 4-12 weeks for births. Plasma progesterone was measured and a cytological smear of the urogenital sinus was taken. Fertility was high in the control group and the two etonogestrel-treated groups, with approximately 90% of females giving birth. In contrast, no levonorgestrel-treated female produced young during the study. Removal of levonorgestrel implants from six females reversed the contraceptive effect in the next breeding season, whereas the eight females in which the levonorgestrel implants were left in remained infertile for six breeding seasons. Vaginal cytology showed evidence of oestrous cycles during the breeding season in all females from all groups and there was no difference seen in the prevalence of cornified epithelial cells in the oestrous smears. This indirectly suggests that levonorgestrel does not prevent follicular development and oestrous cycling. Plasma progesterone in levonorgestrel-treated females remained low all year, but rose in controls concurrent with the onset of the breeding season. This suggests that levonorgestrel prevents pregnancy by blocking ovulation. Etonogestrel had absolutely no contraceptive effect at the two doses delivered and so is not suitable for controlling koala populations. In contrast, levonorgestrel was effective as a long-term, reversible contraceptive in wild koalas.

  6. Contracepción de emergencia con Levonorgestrel Emergency contraception with levonorgestrel

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    Fernando D. Saraví

    2007-10-01

    Full Text Available La contracepción de emergencia puede evitar el embarazo luego de un coito sin medidas contraceptivas o cuando éstas fallan. Se recomienda el levonorgestrel, un gestágeno sintético, en dosis única de 1.5 mg (alternativamente en dos dosis de 0.75 mg espaciadas 12 h. Su eficacia es moderada, pues impide aproximadamente 80% de los embarazos. La eficacia es mayor cuanto más precozmente se administre, pero puede darse hasta 5 días post-coito. La tolerancia es similar o superior a la de otros preparados empleados con igual propósito. Los efectos adversos comprenden náuseas, vómitos, cefalea, tensión mamaria y alteraciones transitorias en la siguiente menstruación. Se desconoce si el levonorgestrel aumenta la probabilidad de embarazo ectópico cuando el tratamiento fracasa. No se recomienda su empleo como contraceptivo habitual. Cuando se administra antes del pico preovulatorio de LH, el levonorgestrel generalmente bloquea o retrasa la ovulación. Puede asimismo afectar la migración de los espermatozoides en el tracto genital femenino e, indirectamente, la fertilización. Pese a haberse postulado reiteradamente, no existe evidencia de un efecto antiimplantatorio. El conocimiento del método es muy variable en diferentes sociedades, pero aun donde es bien conocido permanece subutilizado. Se ha propuesto proveer levonorgestrel por adelantado para promover su uso. En ensayos clínicos, tal provisión no afectó adversamente el comportamiento sexual ni el empleo de otros contraceptivos, pero tampoco redujo el número de embarazos o abortos. En consecuencia, el empleo de levonorgestrel debe considerarse un método de respaldo que no reemplaza el uso de contraceptivos más eficaces.Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12

  7. Levonorgestrel decreases cilia beat frequency of human fallopian tubes and rat oviducts without changing morphological structure.

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    Zhao, Weihong; Zhu, Qian; Yan, Mingxing; Li, Cheng; Yuan, Jiangjing; Qin, Guojuan; Zhang, Jian

    2015-02-01

    Levonorgestrel, a derivative of progesterone, effectively protects women against unwanted pregnancy as an emergency contraceptive. Previous studies have not been successful in determining the mechanism by which levonorgestrel acts. In the present study we analysed cilia beat action and cilia morphology following levonorgestrel exposure in vitro and in vivo using both light and electron microscopy. There was a significant decrease in the ciliary beat frequency (CBF) of human fallopian tubes between mucosal explants bathed in 5 μmol/L levonorgestrel and those bathed in medium alone (P levonorgestrel produced a similar reduction in CBF (~ 10%) compared with the saline control group (P levonorgestrel treatment in either system. Thus, levonorgestrel reduces CBF without damaging cilia morphology. Decreases in CBF may indicate a pathological role for levonorgestrel in the transportation of the ovum and zygote in the fallopian tube.

  8. Efficacy of levonorgestrel releasing intrauterine system on menorrhagia induced by anticoagulant therapy in women after cardiac valve replacement%左炔诺孕酮宫内缓释系统用于治疗心脏瓣膜置换术后抗凝药物所致月经过多的疗效观察

    Institute of Scientific and Technical Information of China (English)

    莫小亮; 蒋晓莉; 郑晓宇; 孙燕

    2013-01-01

    目的:探讨左炔诺孕酮宫内缓释系统(levonorgestrel releasing intrauterine system,LNG-IUS)用于治疗心脏换瓣术后抗凝药物所致月经过多的有效性和安全性.方法:32例月经过多妇女,曾接受换瓣术,术后口服抗凝药物.将这32例患者随机分为观察组16例,月经1 ~5d放置LNG-IUS;对照组16例,未采取任何干预措施.记录活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、国际标准化比值(INR)、纤维蛋白原、血红蛋白(Hb)、铁蛋白水平及月经改变.结果:观察组放置3个月后,月经量显著减少,子宫内膜显著变薄,Hb、铁蛋白升高(P<0.05),凝血指标两组比较差异无统计学意义(P>0.05).结论:LNG-IUS是治疗换瓣术后抗凝药物所致月经过多的有效方法.%Objective To evaluate the efficacy and safety of levonorgestrel releasing intrauterine system (LNG-IUS) on menorrhagia induced by anticoagulant therapy in women after cardiac valve replacement. Methods 32 women with menorrhagia induced by anticoagulant therapy after cardiac valve replacement were randomly divided into 2 groups: 16 patients in observation group received LNG-IUS replacement, 16 patients in control group received no intervention. APTT, PT, INR, Hb, ferritin levels and menstrual quantity in both groups were recorded. Results Menstrual blood volume was decreased, the endometrium became thinner, the levels of Hb and ferritin were increased in observation group 3 months after therapy (P < 0.05). Conclusion LNG-IUS was an effective method for menorrhagia induced by anticoagulant therapy in women after cardiac valve replacement.

  9. Ectopic pregnancy after levonorgestrel emergency contraception

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    Ahmet Karatas

    2013-08-01

    Full Text Available Levonorgestrel Emergency Contraception (LNG-EC is the safest and the most commonly used oral regimen that can be used after an unprotected intercourse. Although it is highly effective, failures can occur especially if it is used in the peri /or postovulatory period. It can not inhibit ovulation if used in these periods and the altered tubal motility together with the ciliary dysfunction can prevent the transfer of the fertilized ovum from the fallopian tube to the endometrial cavity, causing an ectopic pregnancy, which is one of the important concerns after failed LNG-EC. This risk was reported not to be higher than the risk of ectopic pregnancy observed in the general population, but the users of this medication should still warned about this risk. Here we report a case of ectopic pregnancy from Turkey after midcyclic use and failure of LNG-EC. [Int J Reprod Contracept Obstet Gynecol 2013; 2(4.000: 749-750

  10. The levonorgestrel-releasing intrauterine device potentiates stress reactivity.

    Science.gov (United States)

    Aleknaviciute, Jurate; Tulen, Joke H M; De Rijke, Yolanda B; Bouwkamp, Christian G; van der Kroeg, Mark; Timmermans, Mirjam; Wester, Vincent L; Bergink, Veerle; Hoogendijk, Witte J G; Tiemeier, Henning; van Rossum, Elisabeth F C; Kooiman, Cornelis G; Kushner, Steven A

    2017-06-01

    The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P<0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P<0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P<0.0001). Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Controlling levonorgestrel binding and release in a multi-purpose prevention technology vaginal ring device.

    Science.gov (United States)

    Murphy, Diarmaid J; Boyd, Peter; McCoy, Clare F; Kumar, Sandeep; Holt, Jonathon D S; Blanda, Wendy; Brimer, Andrew N; Malcolm, R Karl

    2016-03-28

    Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine - a lead candidate antiretroviral microbicide - for combination HIV prevention and hormonal contraception.

  12. Non-contraceptive applications of the levonorgestrel intrauterine system

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    Maria Isabel Rodriguez

    2010-04-01

    Full Text Available Maria Isabel Rodriguez, Philip D DarneyDepartment of Obstetrics, Gynecology, and Reproductive Sciences, San Francisco General Hospital and Bixby Center for Global Reproductive Health, University of California, San Francisco, CA, USAAbstract: Intrauterine progestins have many important current and potential gynecologic applications. This article describes the evidence for use of intrauterine progestin for common gynecologic conditions beyond its important role in contraception. The pharmacology of and selection criteria for use of the levonorgestrel intrauterine device is discussed, and the evidence for use of intrauterine progestin delivery for menorrhagia, endometriosis management, uterine fibroids, adenomyosis and endometrial hyperplasia is reviewed.Keywords: intrauterine progestin, levonorgestrel, contraceptive

  13. Phototoxic reaction to a combined oral contraceptive (levonorgestrel/ethinylestradiol).

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    Richarz, N A; Aguilera, J; Castillo, G; Fuente, M J; Ferrándiz, C; Carrascosa, J M

    2017-09-13

    We present the case of a phototoxic skin reaction due to the regular intake of a combined oral contraceptive (levonorgestrel/ethinylestradiol). Upon spectrophotometer testing, we demonstrated high absorption in the UV-B region of the solar spectrum of the combined product (Ovoplex®), especially for the estrogen compound (ethinylestradiol).

  14. STUDY ON A NEW LEVONORGESTREL VAGINAL CONTRACEPTIVE RING

    Institute of Scientific and Technical Information of China (English)

    ZHANGHai-Wei; ZHENGHuai-Mei

    1989-01-01

    A new contraceptive vaginal ring was jointly produced by the Shanghai Medical University and the Shanghai Rubber Products Research Institute. It has an outer silicone elastomer shell and a tilling of 35 mg levonorgestrel gel in inner core. Amount of LNG release is

  15. PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES ON VAGINALLY ADMINISTERED LEVONORGESTREL

    Institute of Scientific and Technical Information of China (English)

    HEChang-Hai; XUJian-Qiu; ZHUYue-Hua; SHIYong-En

    1989-01-01

    Comparative studies on pharmacokinetics of vaginally and orally administered levonorgestrel (LNG) tablet (Postinor) in one single dose containing 0,75mg LNG were performed. The pharmacokinetics of LNG and its effects on ovarian functions werealso studied after repeated vaginal administration.

  16. Quantitative Determination of Levonorgestrel in Fish Plasma using UPLC-MS/MS

    Science.gov (United States)

    In this study, a sensitive high-performance liquid chromatography electrospray tandem mass spectrometric method was developed for the determination of levonorgestrel in fish plasma using levonorgestrel-d6 as an internal standard (IS). In the laboratory, the fish cunner, (Tautogol...

  17. Removal of an intraabdominal levonorgestrel-releasing intrauterine device during pregnancy.

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    Peleg, David; Latta, Richard

    2013-06-01

    A woman with a viable intrauterine 12-week pregnancy and an intraabdominal levonorgestrel-releasing intrauterine device had the device successfully removed under local anesthesia. The pregnancy continued without complication. The decision to remove an intraabdominal levonorgestrel-releasing intrauterine device during pregnancy remains controversial.

  18. Quantitative Determination of Levonorgestrel in Fish Plasma using UPLC-MS/MS

    Science.gov (United States)

    In this study, a sensitive high-performance liquid chromatography electrospray tandem mass spectrometric method was developed for the determination of levonorgestrel in fish plasma using levonorgestrel-d6 as an internal standard (IS). In the laboratory, the fish cunner, (Tautogol...

  19. Adsorption properties and degradation dynamics of endocrine-disrupting chemical levonorgestrel in soils.

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    Tang, Tao; Shi, Tianyu; Li, Deguang; Xia, Jinming; Hu, Qiongbo; Cao, Yongsong

    2012-04-25

    Levonorgestrel, a synthetic progesterone used as an oral contraceptive or emergency contraceptive pill, has been shown to be an endocrine-disrupting chemical. To assess the environmental risk of levonorgestrel, batch experiments and laboratory microcosm studies were conducted to investigate the adsorption and degradation of levonorgestrel in five contrasting soils of China. Freundlich and Langmuir models were applied to sorption data to examine the affinity of levonorgestrel for soils with varying physical and chemical properties. The K(f) of levonorgestrel in the tested soils ranged from 10.79 to 60.92 mg(1-n) L(n) kg(-1) with N between 0.69 and 1.23, and the Q(m) ranged from 18.18 to 196.08 mg/kg. The multiple regression analysis was conducted between K(f) and soil properties. Results indicate that total organic carbon plays a dominant role in the adsorption process. Gibbs free energy values less than 40 kJ/mol demonstrate that levonorgestrel sorption on soils could be considered as a physical adsorption. The degradation of levonorgestrel in five soils was fitted by the first-order reaction kinetics model. The half-lives of levonorgestrel were between 4.32 and 11.55 days. The initial concentration and sterilization experiments illustrated that the degradation rate of levonorgestrel in soil was concentration-dependent and microbially mediated. The low mobility potential of levonorgestrel in soils was predicted by the groundwater ubiquity score (GUS) and retardation factor (R(f)).

  20. Serum levonorgestrel concentration and cervical mucus viscosity after six months of monoplant® implantation

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    Eka R. Gunardi

    2014-03-01

    Full Text Available Background: The use of levonorgestrel implants as a contraceptive method have undergone changes in the number of implants used, beginning from six rods in the early methods to two rods in the present method and have been proven effective. This study aims to evaluate the efficacy of single rod implant (Monoplant® by measuring serum levonorgestrel concentration and cervical mucus quality.Methods: Thirty healthy women, aged 20-40 year old, and have been proven fertile, underwent single rod implant insertion. Levonorgestrel serum levels was measured every month and cervical mucus viscosity was examined every three month, until six months.Results: Levonorgestrel serum concentration was consistently above minimum effective level (200 pg/mL, from month 3 to 6 respectively 338.9 pg/mL, 424.8 pg/mL, 320.3 pg/mL, and 337.5 pg/mL. Almost all of the acceptors (96.7% had good cervical mucus viscosity since three months following implant insertion. Conclusion: Levonorgestrel serum concentration in Monoplant® users was still above minimum contraceptive level until the sixth month. Viscosity of cervical mucus increased immediately following implant insertion. This indicates that single rod levonorgestrel implant is effective as a contraceptive method.Keywords: cervical mucus viscosity, implant monoplant®, serum levonorgestrel

  1. Role of the levonorgestrel intrauterine system in effective contraception

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    Attia AM

    2013-08-01

    Full Text Available Abdelhamid M Attia,1 Magdy M Ibrahim,1 Ahmed M Abou-Setta21Department of Obstetrics and Gynecology, Cairo University, Cairo, Egypt; 2George and Fay Yee Centre for Healthcare Innovation, University of Manitoba/Winnipeg Regional Health Authority, Winnipeg, MB, CanadaAbstract: Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS provides a long-acting, highly effective, and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200–800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenorrhea with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids.Keywords: levonorgestrel, intrauterine device, contraception, family planning, Mirena, Skyla

  2. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

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    Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

    2005-03-01

    Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

  3. Non-contraceptive benefits of intrauterine levonorgestrel administration: why not?

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    Sabbioni, Lorenzo; Petraglia, Felice; Luisi, Stefano

    2017-06-06

    Levonorgestrel intrauterine systems (LNG-IUS) represent a modern therapy for an array of preexisting gynecological conditions, though they were first marketed in Finland in 1990. However, there are countries in which their use is extremely limited by social and cultural factors. This manuscript describes the possible reasons for this misuse, taking in consideration the clinical noncontraceptive benefits of intrauterine levonorgestrel in routinary practice. Medical diseases in which LNG-IUS represent a treatment include abnormal uterine bleeding, iron-deficiency anemia, endometrial hyperplasia, uterine fibroids, adenomyosis, endometriosis, and coagulopathies. The advantage of reducing the need for more radical treatments such as surgery or hysterectomy is well demonstrated, with remarkable benefits for patients. However, in many countries, surgery is still used as a first-line treatment and there is a need to define who could benefit from a less invasive option. It seems clear that such a reduced use of LNG-IUS depends on factors that imply both patients and practitioners, and that the role of counseling is becoming a key component in the decision-making process to reach the ultimate goal of compliance.

  4. Importance of levonorgestrel dose in oral contraceptives for effects on coagulation

    NARCIS (Netherlands)

    Kluft, C.; Maat, M.P.M. de; Heinemann, L.A.J.; Spannagl, M.; Schramm, W.

    1999-01-01

    Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and

  5. STUDIES ON THE FEASIBILITY OF IUD RELEASING BOTH LEVONORGESTREL AND COPPER

    Institute of Scientific and Technical Information of China (English)

    LIUYun-Guo; WUXi-Rui

    1989-01-01

    Levonorgestrel ( LNG ) -and copper ions ( Cu++ ) are main active constituents of the medicated IUDs. In order to explore the feasibility of developing IUDs which could release both components, a comparative study of the effects of LNG-IUD,

  6. [Abdominal migration of a levonorgestrel-releasing intrauterine device. Case report and review of the literature].

    Science.gov (United States)

    Pont, M; Lantheaume, S

    2009-04-01

    We report the case of a 27-year-old woman in amenorrhea after the installation of a levonorgestrel releasing intra-uterine device, 3 years previously. In front of pelvic continuing pains, paraclinic explorations diagnosed the DIU-LNG in intra-abdominal situation. An exploratory laparoscopy was realized and allowed its ablation. The authors discuss the systemic distribution of the levonorgestrel and the impact of the DIU-LNG in intra-abdominal situation by a review of the literature.

  7. Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study.

    Science.gov (United States)

    Phillips, Sharon J; Hofler, Lisa G; Modest, Anna M; Harvey, Lara F B; Wu, Lily H; Hacker, Michele R

    2017-07-01

    Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intrauterine device, and whether women who continue using intrauterine devices differ from those who discontinue. We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ(2) tests and calculated hazard ratios using a multivariable Cox model. Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P 4 years was 0.71 (95% confidence interval, 0.55-0.93) and >5 years was 0.82 (95% confidence interval, 0.64-1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper intrauterine device vs 4.9% levonorgestrel intrauterine device, P < .01) over the study period and to become pregnant in the first year of use (1.6% copper intrauterine device vs 0.1% levonorgestrel intrauterine device, P < .01). We found a difference in continuation rates between levonorgestrel and copper intrauterine device users at 4 years but not at 5 years. Copper intrauterine device users were more likely

  8. The in vitro metabolism of ethinyloestradiol, mestranol and levonorgestrel by human jejunal mucosa.

    OpenAIRE

    Back, D J; Bates, M; Breckenridge, A M; Ellis, A.; Hall, J.M.; Maciver, M; Orme, M L; Rowe, P H

    1981-01-01

    1 Ethinyloestradiol was extensively metabolised in vitro by human jejunal mucosa to form ethinyloestradiol sulphate. 2 The amount of conjugation was directly related to the weight of biopsy tissue. 3 The degree of conjugation of mestranol and levonorgestrel was much lower than for ethinyloestradiol suggesting that the 17-position of the steroid nucleus is relatively inaccessible for conjugation. 4 No Phase I metabolism of ethinyloestradiol or levonorgestrel was apparent in the conditions used...

  9. Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.

    Science.gov (United States)

    Simone, Jean; Bogue, Elizabeth A; Bhatti, Dionnet L; Day, Laura E; Farr, Nathan A; Grossman, Anna M; Holmes, Philip V

    2015-12-01

    In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory.

  10. Exposure effects of levonorgestrel on oogenesis in the fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Frankel, Tyler; Yonkos, Lance; Frankel, Jack

    2017-07-06

    The synthetic progestin levonorgestrel is commonly utilized in human oral contraceptives. It enters the environment as a component of wastewater treatment plant effluent, and has been measured at low ng/L concentrations in surface waters. It has been shown to activate fish androgen receptors, causing the physical masculinization of females, changes in reproductive behavior, and decreases in fecundity. In the present study, the effects of levonorgestrel exposure on early-stage oogenesis in the fathead minnow (Pimephales promelas) was examined. Adult females were exposed to 0, 10, or 100 ng/L levonorgestrel for 14 d using a flow-through exposure system. The ovaries from each female were then removed via dissection and weighed for gonadosomatic index (GSI) calculations, and oocytes from one lobe preserved in Serra's fixative. Total numbers of late-stage vitellogenic oocytes exhibiting a germinal vesicle were then quantified. In a second exposure, blood plasma samples were collected from adult females and analyzed for vitellogenin concentrations using enzyme-linked immunosorbent assay. Females exposed to both concentrations of levonorgestrel developed male secondary sexual characteristics in a dose-dependent manner, and ovaries contained significantly fewer late stage oocytes. Exposure to 100 ng/L of levonorgestrel resulted in decreased GSI and blood plasma vitellogenin concentrations. The results suggest that female exposure to levonorgestrel alone may have profound effects on reproduction in progestin-contaminated environments. Environ Toxicol Chem 2017;9999:1-6. © 2017 SETAC. © 2017 SETAC.

  11. Cornual pregnancy as a complicaton of the use of a levonorgestrel intrauterine device: a case report

    Science.gov (United States)

    2009-01-01

    Introduction Complications of copper load intrauterine devices, including ectopic pregnancies are well reported. Rates of ectopic pregnancy are 0.6 to 1.1% per year. However, the levonorgestrel intrauterine device has been described as more protective against ectopic pregnancies due to the addition of the hormone levonorgestrel. The hormone released from the intrauterine device causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to foreign body reaction, are dominant. Few case reports have described ampullary ectopic pregnancies. However, we report, for the first time, a major complication of levonorgestrel intrauterine device: a cornual pregnancy. Case presentation A 36-year-old Caucasian nulliparous woman presented with complaints of progressive nausea, abdominal pain and irregular vaginal bleeding for 2 months. For 3 years, she had been using a levonorgestrel intrauterine device. A two-dimensional transvaginal sonogram noted a sac situated external to the endometrial cavity in the right cornua of the uterus with an empty uterus. She was successfully treated with chemotherapy. Conclusion Many complications have been described, including ectopic pregnancies, using copper intrauterine devices. The levonorgestrel-releasing intrauterine system is a particularly good choice for adolescents because of associated non-contraceptive benefits such as decreased menstrual bleeding, dysmenorrhea and pain associated with endometriosis [1]. Yet a cornual pregnancy following the use of a levonorgestrel intrauterine device is a complication which, to our knowledge, has not been described before. Physicians prescribing this type of intrauterine device should be aware of this rare event. PMID:19830226

  12. Capacidade reprodutiva de ratas aleitadas por mães que receberam levonorgestrel durante a lactação

    OpenAIRE

    GUERRA MARTHA DE OLIVEIRA; SOUZA EEVELISE ROCHA DE; PETERS VERA MARIA

    2002-01-01

    O levonorgestrel é um dos contraceptivos usados por mulheres durante a lactação. Estudos prévios mostraram que a administração de levonorgestrel a ratas lactando causou nas crias retardo de puberdade em machos e alterações no peso de oviduto e útero. OBJETIVO: Estudar a capacidade reprodutiva das fêmeas F1, de mães tratadas com levonorgestrel. MÉTODOS: Ratas Wistar foram tratadas com levonorgestrel (0.030 mg/1 ml de água destilada) do 7masculine ao 13masculine dia após o nascimento (dia 1 = n...

  13. Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern?

    Science.gov (United States)

    King, Olivia C; van de Merwe, Jason P; McDonald, James A; Leusch, Frederic D L

    2016-06-01

    Synthetic hormones have been widely reported in treated sewage effluents, and consequently receiving aquatic environments. Ethinylestradiol (EE2) is a potent synthetic estrogen commonly used in conjunction with levonorgestrel in oral contraceptive pills. Both EE2 and levonorgestrel have been identified in the aquatic environment, but although there is a significant amount of literature on EE2, there is much less information on levonorgestrel. Using Australian prescription data as well as excretion and predicted wastewater removal rates, the concentrations of EE2 and levonorgestrel in Australian wastewater were calculated at 0.1 ng/L to 0.5 ng/L and 0.2 ng/L to 0.6 ng/L, respectively. Both compounds were analyzed in treated wastewater and surface water grab samples from 3 Southeast Queensland, Australia sites. The predicted no-effect concentration (PNEC) for EE2 of 0.1 ng/L was exceeded at most sites, with EE2 concentrations up to 2 ng/L in treated effluent, albeit quickly diluted to 0.1 ng/L to 0.2 ng/L in the receiving environment. A provisional PNEC for levonorgestrel of 0.1 ng/L derived in the present study was slightly lower than predicted effluent concentrations of 0.2 ng/L to 0.6 ng/L, indicating a potential risk of endocrine-related effects in exposed aquatic species. The detection limit for levonorgestrel in the present study was 2.5 ng/L, and all samples were below detection limit. The present study's results suggest that improvements in analytical capabilities for levonorgestrel are warranted to more accurately quantify the risk of this compound in the receiving environment. Environ Toxicol Chem 2016;35:1378-1385. © 2015 SETAC.

  14. Repeated use of mifepristone and levonorgestrel and their effect on the ovarian function in mice.

    Science.gov (United States)

    Chen, Yuanyuan; Shi, Xiaobo

    2016-11-01

    To investigate the effects of repeated mifepristone and levonorgestrel use on estrous cycle and expression of ovarian follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in mice. Ovarian FSHR and LHR mRNA expression was measured using real-time quantitative reverse transcription-polymerase chain reaction, while the protein levels were measured using immunohistochemistry. Repeated use of mifepristone and levonorgestrel significantly lengthened the estrous cycle and decreased FSHR and LHR mRNA and protein expression in the ovaries of mice at 4, 24, and 48 days after discontinuing drug use. Repeated use of mifepristone and levonorgestrel had significant main effects on estrous cycle length and the mRNA expression and protein level of ovarian FSHR and LHR. Repeated mifepristone and levonorgestrel use and withdrawal time had a significant interaction with mouse estrous cycle (F = 16.65, P < 0.05), ovarian LHR and FSHR mRNA expression (F = 563.072, P < 0.05), and protein level (F = 6.536, P < 0.05). Repeated use of mifepristone and levonorgestrel can lead to sustained damage to ovarian function through inhibition of ovarian FSHR and LHR expression in mice. © 2016 Japan Society of Obstetrics and Gynecology.

  15. The Effectiveness of Levonorgestrel-Releasing Intrauterine System in the Treatment of Heavy Menstrual Bleeding.

    Science.gov (United States)

    Eralil, Georgy Joy

    2016-10-01

    Levonorgestrel-releasing intrauterine system (LNG-IUS) has been shown to be an effective treatment for patients with abnormal uterine bleeding (AUB) in many Western studies. The purpose of study was to examine the effectiveness of LNG-IUS in the treatment of Indian women with AUB. We conducted a retrospective observational study of 70 women diagnosed with AUB and treated with LNG-IUS insertion between February 2010 and 2014 at the Department of Gynecology of Sree Narayana Institute of Medical Sciences. Baseline endometrial biopsies were done before insertion of LNG-IUS, and outpatient follow-up with symptom diary was undertaken at 3-month intervals after insertion of LNG-IUS. Primary outcome in the two treatment groups was significantly greater among women assigned to levonorgestrel-IUS than among those assigned to usual treatment (mean difference in scores over the course of 1 year 13.4 points; 95 % confidence interval [CI] 9.9-16.9; P < 0.001). All six domains of the MMAS favored the levonorgestrel-IUS at every time point (P < 0.001) with the use of a test for trend. In conclusion, our study showed that both the levonorgestrel-IUS and usual medical treatments reduced the adverse effect of menorrhagia on women's lives over the course of 2 years, but the levonorgestrel-IUS was the more effective first choice, as assessed by the impact of bleeding on the women's quality of life.

  16. Review of the safety, efficacy and patient acceptability of the levonorgestrel-releasing intrauterine system

    Directory of Open Access Journals (Sweden)

    Chandra Kailasam

    2008-10-01

    Full Text Available Chandra Kailasam1, David Cahill21Bristol Centre for Reproductive Medicine, Southmead Hospital, Bristol, UK; 2Dept of Obstetrics and Gynaecology, University of Bristol, St Michael’s Hospital, Bristol, UKAbstract: The levonorgestrel-containing intrauterine system is an extremely effective, reversible and safe form of long-term yet reversible birth control. In view of its efficacy, it is a safer alternative to permanent contraceptive methods such as sterilization. It is especially useful in situations where use of estrogen-containing contraceptives is contraindicated. While menstrual disturbances are a common side effect, proper counseling improves compliance. In addition to its contraceptive effect, the levonorgestrel intrauterine system offers potential therapeutic benefits in other clinical contexts, including menorrhagia, symptomatic fibroids, endometriosis, and endometrial protection.Keywords: intrauterine device, levonorgestrel intrauterine device, contraception

  17. Molecular effects and bioaccumulation of levonorgestrel in the non-target organism Dreissena polymorpha

    DEFF Research Database (Denmark)

    Contardo-Jara, V.; Lorenz, Claudia; Pflugmacher, S.

    2011-01-01

    Bioaccumulation and effects of the contraceptive hormone levonorgestrel were examined in the nontarget organism Dreissena polymorpha. Molecular biomarkers of biotransformation, elimination, antioxidant defence and protein damage were analyzed after exposure to increasing concentrations of levonor......Bioaccumulation and effects of the contraceptive hormone levonorgestrel were examined in the nontarget organism Dreissena polymorpha. Molecular biomarkers of biotransformation, elimination, antioxidant defence and protein damage were analyzed after exposure to increasing concentrations...... of levonorgestrel in a flow-through system. The lowest concentration (0.312 mu g L-1) was 100-fold bioconcentrated within four days. A decrease of the bioconcentration factor was observed within one week for the highest test concentrations (3.12 and 6.24 mu g L-1) suggesting enhanced excretory processes...

  18. Cornual pregnancy as a complicaton of the use of a levonorgestrel intrauterine device: a case report

    Directory of Open Access Journals (Sweden)

    Beltman JJ

    2009-07-01

    Full Text Available Abstract Introduction Complications of copper load intrauterine devices, including ectopic pregnancies are well reported. Rates of ectopic pregnancy are 0.6 to 1.1% per year. However, the levonorgestrel intrauterine device has been described as more protective against ectopic pregnancies due to the addition of the hormone levonorgestrel. The hormone released from the intrauterine device causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to foreign body reaction, are dominant. Few case reports have described ampullary ectopic pregnancies. However, we report, for the first time, a major complication of levonorgestrel intrauterine device: a cornual pregnancy. Case presentation A 36-year-old Caucasian nulliparous woman presented with complaints of progressive nausea, abdominal pain and irregular vaginal bleeding for 2 months. For 3 years, she had been using a levonorgestrel intrauterine device. A two-dimensional transvaginal sonogram noted a sac situated external to the endometrial cavity in the right cornua of the uterus with an empty uterus. She was successfully treated with chemotherapy. Conclusion Many complications have been described, including ectopic pregnancies, using copper intrauterine devices. The levonorgestrel-releasing intrauterine system is a particularly good choice for adolescents because of associated non-contraceptive benefits such as decreased menstrual bleeding, dysmenorrhea and pain associated with endometriosis 1. Yet a cornual pregnancy following the use of a levonorgestrel intrauterine device is a complication which, to our knowledge, has not been described before. Physicians prescribing this type of intrauterine device should be aware of this rare event.

  19. Review of the safety, efficacy and patient acceptability of the levonorgestrel-releasing intrauterine system

    Science.gov (United States)

    Kailasam, Chandra; Cahill, David

    2008-01-01

    The levonorgestrel-containing intrauterine system is an extremely effective, reversible and safe form of long-term yet reversible birth control. In view of its efficacy, it is a safer alternative to permanent contraceptive methods such as sterilization. It is especially useful in situations where use of estrogen-containing contraceptives is contraindicated. While menstrual disturbances are a common side effect, proper counseling improves compliance. In addition to its contraceptive effect, the levonorgestrel intrauterine system offers potential therapeutic benefits in other clinical contexts, including menorrhagia, symptomatic fibroids, endometriosis, and endometrial protection. PMID:19920976

  20. The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine.

    Science.gov (United States)

    Neary, M; Lamorde, M; Olagunju, A; Darin, K M; Merry, C; Byakika-Kibwika, P; Back, D J; Siccardi, M; Owen, A; Scarsi, K K

    2017-09-01

    Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based antiretroviral therapy (ART), in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin . Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  1. Timing of insertion of levonorgestrel-releasing intrauterine system : a randomised controlled trial

    NARCIS (Netherlands)

    van der Heijden, Pahh; Geomini, Pmaj; Herman, M C; Veersema, S; Bongers, M Y

    OBJECTIVE: The objective was to assess whether patient-perceived pain during the insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) depends on the timing during the menstrual cycle. DESIGN: A stratified two-armed non-inferiority randomised controlled trial. SETTING: Large

  2. Uterine Perforation with the Levonorgestrel-Releasing Intrauterine Device Analysis of Reports from Four National Pharmacovigilance Centres

    NARCIS (Netherlands)

    van Grootheest, Kees; Sachs, Bernhardt; Harrison-Woolrych, Mira; Caduff-Janosa, Pia; van Puijenbroek, Eugene

    2011-01-01

    Background: Levonorgestrel-releasing intrauterine devices (LNG-IUD) are commonly used for contraception and other indications in many countries. National pharmacovigilance centres have been receiving reports from healthcare professionals and patients of uterine perforation associated with the use of

  3. Uterine Perforation with the Levonorgestrel-Releasing Intrauterine Device Analysis of Reports from Four National Pharmacovigilance Centres

    NARCIS (Netherlands)

    van Grootheest, Kees; Sachs, Bernhardt; Harrison-Woolrych, Mira; Caduff-Janosa, Pia; van Puijenbroek, Eugene

    2011-01-01

    Background: Levonorgestrel-releasing intrauterine devices (LNG-IUD) are commonly used for contraception and other indications in many countries. National pharmacovigilance centres have been receiving reports from healthcare professionals and patients of uterine perforation associated with the use of

  4. Pharmacokinetic interaction study between riociguat and the combined oral contraceptives levonorgestrel and ethinylestradiol in healthy postmenopausal women.

    Science.gov (United States)

    Frey, Reiner; Unger, Sigrun; van der Mey, Dorina; Becker, Corina; Saleh, Soundos; Wensing, Georg; Mück, Wolfgang

    2016-03-01

    Female patients requiring treatment for pulmonary arterial hypertension (PAH) are advised to avoid pregnancy because of the high associated mortality rate. Oral contraception is one of the main methods of preventing pregnancy in this context, mandating pharmacokinetic and safety studies for new agents in this setting. Riociguat is a soluble guanylate cyclase stimulator approved for treatment of PAH and inoperable and persistent or recurrent chronic thromboembolic pulmonary hypertension. This single-center, randomized, nonblinded study involving healthy postmenopausal women investigated the effect of riociguat on plasma concentrations of levonorgestrel (0.15 mg) and ethinylestradiol (0.03 mg) in a combined oral contraceptive. Treatment A was a single oral tablet of levonorgestrel-ethinylestradiol. In treatment B, subjects received 2.5 mg riociguat 3 times daily for 12 days. On the eighth day, they also received a single oral tablet of levonorgestrel-ethinylestradiol. Subjects received both regimens in a crossover design. There was no change in area under the plasma concentration-time curves of levonorgestrel or ethinylestradiol or maximum concentration in plasma (C max) of levonorgestrel during combined administration versus levonorgestrel-ethinylestradiol alone. A 20% increase in the C max of ethinylestradiol was noted during coadministration; this is not anticipated to adversely impact the contraceptive efficacy or to require any dose adjustment for ethinylestradiol. Plasma concentrations and exposures of riociguat were within the expected range and were not influenced by coadministration with levonorgestrel-ethinylestradiol. Combined treatment was safe and well tolerated. In conclusion, riociguat did not change the exposure to levonorgestrel or ethinylestradiol relative to oral contraceptive administered alone.

  5. 左炔诺孕酮宫内缓释系统在妇科疾病治疗中的作用%Effects of levonorgestrel-releasing intrauterine system in treating gynecological diseases

    Institute of Scientific and Technical Information of China (English)

    李广华; 何金良

    2011-01-01

    背景:左炔诺孕酮宫内缓释系统有很高的避孕可靠性,可对子宫内膜产生明显的抑制作用.目的:阐述左炔诺孕酮宫内缓释系统在妇科疾病治疗中的作用.方法:由第一作者检索CBM、PubMed数据库(http://www.ncbi.nlm.nih.gov/PubMed)、万方数据库(http://www.wanfangdata.com.cn)及google学术网1990/2010有关左炔诺孕酮宫内缓释系统治疗妇科疾病的文献,排除重复性研究.结果与结论:共保留17篇文献进行归纳总结.结果显示,左炔诺孕酮宫内缓释系统作为释放微量孕激素的宫内缓释系统,可安全、有效地应用于避孕,治疗月经过多、内异症、子宫腺肌病,以及激素替代治疗中对子宫内膜的保护等,对治疗子宫肌瘤引起的月经过多也有良好效果.提示左炔诺孕酮宫内缓释系统治疗妇科疾病效果显著,但还需要大样本、长期的临床研究加以验证.%BACKGROUND: Levonorgestrel-releasing intrauterine system is reliable in contraception by inhibiting endometrium.OBJECTIVE: To elucidate effects of levonorgestrel-releasing intrauterine system in treating gynecological diseases.METHODS: A computer-based online search of CBM, PubMed database (http://www.ncbi.nlm.nih.gov/PubMed), Wanfang database (http://www.wanfangdata.com.cn), and google search was performed for articles related to levonorgestrel-releasing intrauterine system in treating gynecological diseases, published between 1990 and 2010. Repetitive studies were excluded.RESULTS AND CONCLUSION: A total of 17 articles were included. As intrauterine progestogen-releasing system,levonorgestrel-releasing intrauterine system can be used as a safe and effective contraception method. In addition, it can treat menorrhagia, endometriosis, adenomyosis, protect endometrium, and ameliorate hysteromyoma-induced menorrhagia. Results revealed that levonorgestrel-releasing intrauterine system can effectively treat gynecological diseases. However, large

  6. Estimating systemic exposure to levonorgestrel from an oral contraceptive.

    Science.gov (United States)

    Basaraba, Cale N; Westhoff, Carolyn L; Pike, Malcolm C; Nandakumar, Renu; Cremers, Serge

    2017-04-01

    The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC. We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively]. Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Immediate postpartum levonorgestrel intrauterine device insertion and breast-feeding outcomes: a noninferiority randomized controlled trial.

    Science.gov (United States)

    Turok, David K; Leeman, Lawrence; Sanders, Jessica N; Thaxton, Lauren; Eggebroten, Jennifer L; Yonke, Nicole; Bullock, Holly; Singh, Rameet; Gawron, Lori M; Espey, Eve

    2017-08-23

    Immediate postpartum levonorgestrel intrauterine device insertion is increasing in frequency in the United States, but few studies have investigated the effect of early placement on breast-feeding outcomes. This study examined the effect of immediate vs delayed postpartum levonorgestrel intrauterine device insertion on breast-feeding outcomes. We conducted this noninferiority randomized controlled trial at the University of Utah and the University of New Mexico Health Sciences Centers from February 2014 through March 2016. Eligible women were pregnant and planned to breast-feed, spoke English or Spanish, were aged 18-40 years, and desired a levonorgestrel intrauterine device. Enrolled women were randomized 1:1 to immediate postpartum insertion or delayed insertion at 4-12 weeks' postpartum. Prespecified exclusion criteria included delivery <37.0 weeks' gestational age, chorioamnionitis, postpartum hemorrhage, contraindications to levonorgestrel intrauterine device insertion, and medical complications of pregnancy that could affect breast-feeding. We conducted per-protocol analysis as the primary approach, as it is considered the standard for noninferiority studies; we also report the alternative intent-to-treat analysis. We powered the study for the primary outcome, breast-feeding continuation at 8 weeks, to detect a 15% noninferiority margin between groups, requiring 132 participants in each arm. The secondary study outcome, time to lactogenesis, used a validated measure, and was analyzed by survival analysis and log rank test. We followed up participants for ongoing data collection for 6 months. Only the data analysis team was blinded to the intervention. We met the enrollment target with 319 participants, but lost 34 prior to randomization and excluded an additional 26 for medical complications prior to delivery. The final analytic sample included 132 in the immediate group and 127 in the delayed group. Report of any breast-feeding at 8 weeks in the immediate

  8. Levonorgestrel-releasing intrauterine systems for long-acting contraception: current perspectives, safety, and patient counseling

    Directory of Open Access Journals (Sweden)

    Costescu DJ

    2016-10-01

    Full Text Available Dustin J Costescu Department of Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada Abstract: Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS; however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception. Keywords: LNG IUS, long-acting contraception, intrauterine contraception, levonorgestrel, contraception, family planning

  9. Ultrasound Location of Misplaced Levonorgestrel Releasing Intrauterine System (LNG-IUS) – is it easy?

    Science.gov (United States)

    Gowri, Vaidyanathan; Mathew, Mariam

    2009-01-01

    The Levonorgestrel intrauterine device (LNG-IUD) is a hormone-containing device licensed for treatment of menorrhagia and contraception. Though complications such as perforation have been reported similar to other non-hormonal intrauterine devices, the diagnosis of such complications is difficult with this device because the LNG-IUD has a different ultrasound appearance compared to copper devices and these case reports are intended to emphasize this point. PMID:22303513

  10. Successful Treatment of Early Endometrial Carcinoma by Local Delivery of Levonorgestrel: A Case Report

    Directory of Open Access Journals (Sweden)

    D. Wildemeersch

    2010-01-01

    Full Text Available We describe a case of a 67-year-old Caucasian woman with an early, moderately-differentiated adenocarcinoma of the endometrium. A levonorgestrel-releasing intrauterine system was inserted, which she tolerated well. A full D&C, following removal of the device, was performed after 9 months, confirming absence of tumoral tissue. Examination after 24 months showed a very thin endometrium, indicating complete remission.

  11. Clinical efficacy of levonorgestrel and norethisterone for the treatment of chronic abnormal uterine bleeding.

    Science.gov (United States)

    Ashraf, Muhammad Nadeem; Habib-Ur-Rehman, Agha; Shehzad, Zahid; AlSharari, Shakir DakheelAllah; Murtaza, Ghulam

    2017-09-01

    To compare the clinical efficacy of levonorgestrel intrauterine system with oral norethisterone for the treatment of idiopathic chronic abnormal uterine bleeding. This cross-sectional study was conducted at Bahawal Victoria Hospital, Jubilee Female Hospital, Civil Hospital and private clinics of consultant gynaecologists in Bahawalpur, Pakistan, from March to August 2014, and comprised patients presenting with abnormal uterine bleeding. The patients were equally and randomly divided into two groups, i.e. intrauterine levonorgestrel administered (group A) and norethisterone administered (group B). Mean age, duration of the disease and parity were determined using a predesigned questionnaire. The primary outcomes of the treatments, i.e. reduction in menstrual blood loss assessed by the pictorial blood assessment chart score, were recorded before the initiation of therapy, at 3 months and at 6months of the study. SPSS 16 was used for data analysis. There were 76 subjects; 38(50%) in each group. In group A, the mean age and mean duration of the disease was 34.16±6.327 years and 6.18±2.415 years compared to 34.21±3.595 years and 6.21±2.418 years in group B. The reduction in menstrual blood loss did not differ significantly between the groups after 3 months (p= 0.321). However, levonorgestrel intrauterine system was found more effective in reducing menstrual blood loss in 36(94.73%) patients, compared to norethisterone-treated patients 28(73.68%) after 6 months of the treatment (p=0.041). The response of both the treatments was found independent of patient's age, parity and chronicity of the disease. The levonorgestrel intrauterine system was better than norethisterone with marked clinical benefit of profound reduction in menstrual blood loss.

  12. Ultrasound Location of Misplaced Levonorgestrel Releasing Intrauterine System (LNG-IUS) - is it easy?

    Science.gov (United States)

    Gowri, Vaidyanathan; Mathew, Mariam

    2009-01-01

    The Levonorgestrel intrauterine device (LNG-IUD) is a hormone-containing device licensed for treatment of menorrhagia and contraception. Though complications such as perforation have been reported similar to other non-hormonal intrauterine devices, the diagnosis of such complications is difficult with this device because the LNG-IUD has a different ultrasound appearance compared to copper devices and these case reports are intended to emphasize this point.

  13. Continuation of a Levonorgestrel Intrauterine Device During Hematopoietic Stem Cell Transplant: A Case Report.

    Science.gov (United States)

    Brady, Paula C; Soiffer, Robert J; Ginsburg, Elizabeth S

    2017-04-01

    During treatment of hematologic malignancies in premenopausal women, both menstrual suppression and contraception are crucial. Continuation of hormonal intrauterine devices (IUDs) - widely used and highly effective contraceptives that also decrease menstrual flow - is controversial during hematopoietic stem cell transplants (SCTs) due to infectious and vaginal bleeding concerns. A 23-year-old nulligravid female was diagnosed with acute myeloid leukemia (AML, positive for FLT3-ITD, DNMT3A and RUNX1, with normal cytogenetics). She elected to retain her existing levonorgestrel-containing IUD during chemotherapy and SCT. During and following treatment, she remained amenorrheic without infection, despite severe neutropenia and thrombocytopenia. Eight months later, she remains in remission without IUD-related complications. This is the first report of levonorgestrel IUD retention during hematopoietic SCT. Despite severe neutropenia and thrombocytopenia, the patient developed neither pelvic infection by retaining her IUD nor significant vaginal bleeding. Future studies are needed to confirm the safety of levonorgestrel IUDs in women undergoing SCT. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/ zidovudine, and ethinyloestradiol/ levonorgestrel in healthy volunteers

    Science.gov (United States)

    Abel, Samantha; Russell, Deborah; Whitlock, Lyndsey A; Ridgway, Caroline E; Muirhead, Gary J

    2008-01-01

    Aims To assess the effect of maraviroc on the pharmacokinetics of midazolam, a sensitive probe CYP3A4 substrate; lamivudine/zidovudine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs); and ethinyloestradiol/levonorgestrel, a combination oral contraceptive. Methods Three randomized, double-blind, placebo-controlled studies were conducted in healthy subjects to assess the effect of maraviroc on pharmacokinetics of other drugs. Two, two-period crossover studies were conducted to assess (i) the effect of steady-state maraviroc (300 mg b.i.d.) on pharmacokinetics of midazolam; and (ii) the effect of steady-state maraviroc (300 mg b.i.d.) on the pharmacokinetics of lamivudine/zidovudine. A third two-way crossover study was conducted to evaluate the effect of steady-state maraviroc (100 mg b.i.d.) on the pharmacokinetics of 30 μg ethinyloestradiol/150 μg levonorgestrel (Microgynon®). Results The geometric mean ratios for Cmax and AUC for each of the compounds tested in the presence and absence of maraviroc were between 92% and 121%. There were no notable differences in Tmax, t1/2 or CLR (where measured) for any of the compounds. Conclusions Maraviroc had no clinically relevant effects on the pharmacokinetics of the CYP3A4 substrate midazolam, the NRTIs zidovudine/lamivudine, or the oral contraceptive steroids ethinyloestradiol and levonorgestrel. PMID:18333862

  15. Levonorgestrel-releasing intrauterine system use in premenopausal women with symptomatic uterine leiomyoma: a systematic review.

    Science.gov (United States)

    Jiang, Wenxiao; Shen, Qi; Chen, Miaomiao; Wang, Ying; Zhou, Qingfeng; Zhu, Xuejie; Zhu, Xueqiong

    2014-08-01

    A systematic review is done to determine the efficacy and safety of levonorgestrel-releasing intrauterine systems as a treatment using in premenopausal women with symptomatic uterine leiomyoma. We searched the Medline, Central and ICTRP databases for all articles published from inception through July 2013 that examined the following outcomes: uterine volume, uterine leiomyoma volume, endometrial thickness, then menstrual blood loss, blood haemoglobin, ferritin and hematocrit levels, treatment failure rate, device expulsion rate, hysterectomy rate and side effects. From 645 studies, a total of 11 studies met our inclusion criteria with sample sizes ranging from 10 to 104. Evidence suggested that levonorgestrel-releasing intrauterine systems could decrease uterine volume and endometrial thickness, significantly reduce menstrual blood loss, and increase blood haemoglobin, ferritin and hematocrit levels. There was no evidence for decreasing uterine leiomyoma volume. There were no adverse effects on the ovarian function except for ovarian cysts. Device expulsion rates were low, which associated with leiomyoma size (larger than 3cm) but not with leiomyoma location. Irregular bleeding/spotting was observed at the beginning of the follow-up period and then decreased progressively. Results of this systematic review indicate that levonorgestrel-releasing intrauterine systems may be effective and safe treatment for symptomatic uterine leiomyoma in premenopausal women.

  16. A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

    Science.gov (United States)

    Borgatta, Lynn; Buhling, Kai J; Rybowski, Sarah; Roth, Katrin; Rosen, Kimberly

    2016-10-01

    To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

  17. The Cost-Effectiveness of Emergency Hormonal Contraception with Ulipristal Acetate versus Levonorgestrel for Minors in France.

    Directory of Open Access Journals (Sweden)

    Ramona Schmid

    Full Text Available To evaluate the cost-effectiveness of ulipristal acetate and levonorgestrel in minors in France, and analyze whether it is worthwhile to provide ulipristal acetate to minors free of charge.The cost-effectiveness of two emergency contraceptive methods was compared based on a decision-analytical model. Pregnancy rates, outcomes of unintended pregnancies, and resource utilization were derived from the literature. Resources and their costs were considered until termination or a few days after delivery. Deterministic and probabilistic sensitivity analyses were performed.The cost of an unintended pregnancy in a French minor is estimated to be 1,630 € (range 1,330 € - 1,803 €. Almost 4 million € (3.1 € - 13.7 € million in unintended pregnancy spending in 2010 could have been saved by the use of ulipristal acetate instead of levonorgestrel. The incremental cost of ulipristal acetate compared to levonorgestrel is 3.30 € per intake, or 418 € per pregnancy avoided (intake within 72 hours. In the intake within 24 hours subgroup, ulipristal acetate was found to be more efficacious at a lower cost compared to levonorgestrel.Ulipristal acetate dominates levonorgestrel when taken within 24 hours after unprotected intercourse, i.e., it is more effective at a lower cost. When taken within 72 hours, ulipristal acetate is a cost- effective alternative to levonorgestrel, given that the cost of avoiding an additional pregnancy with ulipristal acetate is less than the average cost of these pregnancies. In the light of these findings, it is worthwhile to provide free access to minors.

  18. Comparison of human papillomavirus infection and cervical cytology in women using copper-containing and levonorgestrel-containing intrauterine devices.

    Science.gov (United States)

    Lekovich, Jovana P; Amrane, Selma; Pangasa, Misha; Pereira, Nigel; Frey, Melissa K; Varrey, Aneesha; Holcomb, Kevin

    2015-05-01

    To investigate whether there is a difference in cervical cytology and high-risk human papillomavirus (HPV) infection clearance between levonorgestrel- and copper-containing intrauterine device (IUD) users. The electronic medical record system was searched by the appropriate procedural code for IUD insertion for all patients undergoing IUD placement during the study period (January 31, 2005 to January 31, 2012). Patients who received treatment for cervical dysplasia, had their IUDs removed, or conceived during the study period were excluded. High-risk HPV and cervical cytology results immediately preceding and after IUD placement were obtained. One hundred fifty patients had a copper-containing and 152 patients a levonorgestrel-containing IUD placed. The groups were comparable in terms of age, body mass index, duration of follow-up, and percentage of smokers. Sixty-six patients were high-risk HPV-positive before IUD insertion (30 in copper compared with 36 in the levonorgestrel IUD group, P=.4), and the groups had similar follow-up times (364.1±26.3 compared with 357.2±29.7 days, respectively, between the IUD placement and a repeat Pap test with high-risk HPV cotesting, P=.2). Of those, 21 (70%; 95% confidence interval [CI] 53.6-86.4%) cleared the infection after copper-containing IUD placement compared with 15 (42%; 95% CI 25.6-57.8%) in the levonorgestrel group (P=.04). There were only two (1.7%) new high-risk HPV infections in the copper compared with eight (6.9%) in the levonorgestrel group (P=.056). Our data suggest that levonorgestrel-containing IUD could be associated with decreased high-risk HPV infection clearance and possibly increased acquisition compared with the copper-containing IUD. II.

  19. Endometrial cancer treated with levonorgestrel-releasing intrauterine device for almost three years in an elderly woman with comorbidity

    DEFF Research Database (Denmark)

    Andreasen, Lisbeth Anita; Antonsen, Sofie Leisby; Settnes, Annette

    2016-01-01

    In this case report we describe the treatment of a 95-year-old woman with endometrioid adenocarcinoma. She suffered from cardiovascular comorbidity and did not want surgical treatment. Instead a levonorgestrel-releasing intrauterine device (Mirena) was inserted. She had progression of the tumor...... but with a minimum of symptoms and side effects. At the final examination there were no signs of extra uterine disease. The levonorgestrel-releasing intrauterine device may be an acceptable alternative to surgery in severely comorbid patients, or if the patient refuses surgical treatment. © 2016, Springer...

  20. The synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of Xenopus laevis tadpoles.

    Science.gov (United States)

    Lorenz, Claudia; Opitz, Robert; Trubiroha, Achim; Lutz, Ilka; Zikova, Andrea; Kloas, Werner

    2016-08-01

    The synthetic gestagen levonorgestrel (LNG) was previously shown to perturb thyroid hormone-dependent metamorphosis in Xenopus laevis. However, so far the mechanisms underlying the anti-metamorphic effects of LNG remained unknown. Therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of LNG action along the pituitary-thyroid axis of X. laevis tadpoles. Prometamorphic tadpoles were treated in vivo with LNG (0.01-10nM) for 72h and brain-pituitary and thyroid tissue was analyzed for marker gene expression. While no treatment-related changes were observed in brain-pituitary tissue, LNG treatment readily affected thyroidal gene expression in tadpoles including decreased slc5a5 and iyd mRNA expression and a strong induction of dio2 and dio3 expression. When using an ex vivo organ explant culture approach, direct effects of LNG on both pituitary and thyroid gland gene expression were detecTable Specifically, treatment of pituitary explants with 10nM LNG strongly stimulated dio2 expression and concurrently suppressed tshb expression. In thyroid glands, ex vivo LNG treatment induced dio2 and dio3 mRNA expression in a thyrotropin-independent manner. When thyroid explants were cultured in thyrotropin-containing media, LNG caused similar gene expression changes as seen after 72h in vivo treatment including a very strong repression of thyrotropin-induced slc5a5 expression. Concerning the anti-thyroidal activity of LNG as seen under in vivo conditions, our ex vivo data provide clear evidence that LNG directly affects expression of genes important for thyroidal iodide handling as well as genes involved in negative feedback regulation of pituitary tshb expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

    Science.gov (United States)

    Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

    2013-01-01

    This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit - 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease.

  2. The Effect of Levonorgestrel on Fibrinolytic Factors in Human Endometrial Endothelial Cells.

    Science.gov (United States)

    Pakrashi, Tarita; Taylor, Joelle E; Nelson, Ashley; Archer, David F; Jacot, Terry

    2016-11-01

    The levonorgestrel-releasing intrauterine system is considered a highly effective treatment of heavy menstrual bleeding (HMB). While LNG has established effects on the stromal and glandular compartments of the endometrial tissue, its effect on the endometrial endothelial cells has not been investigated. We examined whether LNG regulates fibrinolytic factors, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) secreted by human endometrial endothelial cells (HEECs) and determined the steroid receptor through which LNG exerts its effect on the endothelium. The HEECs were treated with LNG or progesterone and levels of tPA and plasminogen activator inhibitor 1 (PAI-1) measured. The HEECs were specifically examined for the presence of androgen receptors through Western blot. Levonorgestrel ± flutamide were added to HEECs and the levels of tPA and uPA were examined. An enzyme-linked immunosorbent assay performed on culture media confirmed a statistically significant decrease in tPA levels in cells treated with LNG (77.80% ± 8.0% of control; n = 5, P < .05 vs control) but not progesterone. The androgen receptor (110 kDa) was detected in HEEC lysates. The decrease in tPA was blocked by the addition of flutamide (101.3% ± 16% of control), a classic nonsteroidal androgen receptor blocker. There was no change in uPA or PAI-1 levels in cells treated with LNG. Levonorgestrel decreases tPA levels through the androgen receptor in HEECs. Thus, LNG inhibits tPA secretion by the endometrial endothelial cell. This response suggests reduction in HMB with LNG-IUS could reflect an LNG-mediated promotion of hemostasis. © The Author(s) 2016.

  3. From single chemicals to mixtures--reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow.

    Science.gov (United States)

    Runnalls, Tamsin J; Beresford, Nicola; Kugathas, Subramaniam; Margiotta-Casaluci, Luigi; Scholze, Martin; Scott, Alexander P; Sumpter, John P

    2015-12-01

    The aquatic environment is polluted with thousands of chemicals. It is currently unclear which of these pose a significant threat to aquatic biota. The typical exposure scenario is now represented by a widespread blanket of contamination composed of myriads of individual pollutants-each typically present at a low concentration. The synthetic steroids, 17α-ethinylestradiol and levonorgestrel, have been widely reported to be present in the aquatic environment in the low ng to sub-ng/l range. They are widely used in contraceptive formulations, both individually and in combination. Our research employed the fathead minnow (Pimephales promelas) 21 day 'pair-breeding' assay to assess reproductive output when pairs of fish were exposed to the single chemicals at low environmentally relevant concentrations, and then to a binary mixture of them. A variety of endpoints were assessed, including egg production, which was inhibited in a concentration-dependent manner by both the individual chemicals and the mixture. Significant, sex specific effects were also seen with both chemicals, at differing levels of biological organisation. Plasma concentrations of EE2 and levonorgestrel were predicted and in the case of levonorgestrel measured, and compared with the human therapeutic plasma concentrations (Read-Across approach) to support the interpretation of the results. A novel quantitative method was developed for the data analysis, which ensured a suitable endpoint for the comparative mixture assessment. This approach compares the reproductive performance from individual pairs of fish during chemical exposure to its pre-treatment performance. The responses from the empirical mixture study were compared to predictions derived from the single substance data. We hypothesised combined responses which were best described by the concept of concentration addition, and found no clear indications against this additivity expectation. However, the effect profiles support the current

  4. MECANISMO DE ACCIÓN DEL LEVONORGESTREL EN LA ANTICONCEPCIÓN DE EMERGENCIA

    OpenAIRE

    Croxatto A,Horacio; Ortiz S,María Elena

    2004-01-01

    En esta revisión se actualiza el mecanismo de acción del levonorgestrel (LNG) usado en anticoncepción de emergencia. El análisis crítico de la estimación de la eficacia anticonceptiva del LNG indica que su tasa de falla es más alta que la publicada. El LNG aumenta la viscosidad del moco cervical impidiendo que los espermatozoides del reservorio cervical vayan a renovar la población espermática en el sitio de fecundación. Diversos autores han documentado que LNG suprime el pico preovulatorio d...

  5. Chronic vulvovaginal candidiasis in patients using a levonorgestrel-containing intrauterine device.

    Science.gov (United States)

    Nguyen, Yvonne; Fischer, Gayle

    2016-12-13

    Chronic vulvovaginal candidiasis is usually responsive to therapy with oral antifungals. We present a case series of 13 patients with this condition who were also using a levonorgestrel intrauterine system (LNG-IUS). All cases responded to ongoing oral fluconazole therapy while the LNG-IUS was in situ. The LNG-IUS was removed in six patients and of these, two experienced clinical improvement with lower fluconazole dosage requirements and three experienced complete resolution of symptoms. One remains on fluconazole 100 mg daily. © 2016 The Australasian College of Dermatologists.

  6. Levonorgestrel-releasing intrauterine systems for long-acting contraception: current perspectives, safety, and patient counseling.

    Science.gov (United States)

    Costescu, Dustin J

    2016-01-01

    Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS); however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception.

  7. A 1-year study to compare the hemostatic effects of oral contraceptive containing 20 microg of ethinylestradiol and 100 microg of levonorgestrel with 30 microg of ethinylestradiol and 100 microg of levonorgestrel

    DEFF Research Database (Denmark)

    Jespersen, Jørgen; Endrikat, Jan; Düsterberg, Bernd

    2005-01-01

    OBJECTIVES: To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol (EE) and 100 microg of levonorgestrel (LNG...

  8. Use of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients: a case series.

    Science.gov (United States)

    Huguelet, P S; Sheehan, C; Spitzer, R F; Scott, S

    2017-04-01

    This case series reports on the safety and efficacy of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients. All patients used the device for contraception, with no documented cases of disseminated pelvic infection or unplanned pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding : a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Herman, Malou C.; van den Brink, Marian; Geomini, Peggy M.; van Meurs, Hannah S.; Huirne, Judith A.; Eising, Heleen P.; Timmermans, Anne; Pijnenborg, Johanna M. A.; Klinkert, Ellen R.; Coppus, Sjors F.; Nieboer, Theodoor E.; Catshoek, Ruby; van der Voet, Lucet F.; van Eijndhoven, Hugo W. F.; Graziosi, Giuseppe C. M.; Veersema, Sebastiaan; van Kesteren, Paul J.; Langenveld, Josje; Smeets, Nicol A. C.; van Vliet, Huib A. A. M.; van der Steeg, Jan Willem; Lisman-van Leeuwen, Yvonne; Dekker, Janny H.; Mol, Ben W.; Berger, Marjolein Y.; Bongers, Marlies Y.

    2013-01-01

    Background: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As

  10. Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Herman, M.C.; Brink, M.J. van den; Geomini, P.M.; Meurs, H.S. van; Huirne, J.A.; Eising, H.P.; Timmermans, A.; Pijnenborg, J.; Klinkert, E.R.; Coppus, S.F.P.J.; Nieboer, T.; Catshoek, R.; Voet, L.F. van der; Eijndhoven, H.W. van; Graziosi, G.; Veersema, B.S.; Kesteren, P.J.M. van; Langenveld, J.; Smeets, Nathalie; Vliet, H.A. Van; Steeg, J.W. van der; Leeuwen, Y.L.; Dekker, J.H.; Mol, B.W.; Berger, M.Y.; Bongers, M.Y.

    2013-01-01

    BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As

  11. Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding : a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Herman, Malou C.; van den Brink, Marian; Geomini, Peggy M.; van Meurs, Hannah S.; Huirne, Judith A.; Eising, Heleen P.; Timmermans, Anne; Pijnenborg, Johanna M. A.; Klinkert, Ellen R.; Coppus, Sjors F.; Nieboer, Theodoor E.; Catshoek, Ruby; van der Voet, Lucet F.; van Eijndhoven, Hugo W. F.; Graziosi, Giuseppe C. M.; Veersema, Sebastiaan; van Kesteren, Paul J.; Langenveld, Josje; Smeets, Nicol A. C.; van Vliet, Huib A. A. M.; van der Steeg, Jan Willem; Lisman-van Leeuwen, Yvonne; Dekker, Janny H.; Mol, Ben W.; Berger, Marjolein Y.; Bongers, Marlies Y.

    2013-01-01

    Background: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As

  12. Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Herman, M.C.; Brink, M.J. van den; Geomini, P.M.; Meurs, H.S. van; Huirne, J.A.; Eising, H.P.; Timmermans, A.; Pijnenborg, J.; Klinkert, E.R.; Coppus, S.F.P.J.; Nieboer, T.; Catshoek, R.; Voet, L.F. van der; Eijndhoven, H.W. van; Graziosi, G.; Veersema, B.S.; Kesteren, P.J.M. van; Langenveld, J.; Smeets, Nathalie; Vliet, H.A. Van; Steeg, J.W. van der; Leeuwen, Y.L.; Dekker, J.H.; Mol, B.W.; Berger, M.Y.; Bongers, M.Y.

    2013-01-01

    BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As

  13. Immunologic evaluation of the endometrium with a levonorgestrel intrauterine device in solid organ transplant women and healthy controls.

    Science.gov (United States)

    Kim, Caron R; Martinez-Maza, Otoniel; Magpantay, Larry; Magyar, Clara; Gornbein, Jeffrey; Rible, Radhika; Sullivan, Peggy

    2016-11-01

    The objective was to describe the endometrial milieu of stable transplant patients and healthy women before and after levonorgestrel intrauterine system (LNG-IUS) insertion. Women between 18 and 45 years of age desiring LNG-IUS insertion were enrolled with a 2:1 ratio of healthy to stable solid organ transplant patients. The first visit entailed a blood draw, uterine lavage and endometrial biopsy followed by LNG-IUS insertion. Follow-up visit involved a repeat serum draw, uterine lavage and endometrial biopsy. Cytokine levels were measured in the uterine lavage and serum by quantifying inflammatory biomarkers. Immunohistochemistry staining was performed on the endometrial tissue to measure macrophage levels. Statistical analysis included a nonparametric analysis that compared medians of the marker levels before and after intrauterine device (IUD) insertion within the group and between the two groups. Sixteen participants completed the study: 5 solid organ transplant patients and 11 healthy patients. For the serum, there were no marked changes in the cytokines or soluble receptor levels in either group after IUD insertion. However, in the uterine lavage, there was an increase in cytokine levels post-IUD insertion for both healthy and transplant women. For the endometrial tissue, there was evidence of macrophage activity in both groups after device insertion. This pilot study investigated the uterine environment of the transplant patient population. Findings have pointed to the strong local inflammatory response following LNG-IUS insertion for the transplant recipients. In addition, these preliminary findings will help power a larger study that can investigate the safety and effectiveness of the IUD in this patient population. Findings from this pilot study suggest that the IUD is inducing a local inflammatory reaction in the uterus of the transplant patient as in the healthy control. A larger study can build on these preliminary results to pursue the efficacy and

  14. Cómo y cuando el levonorgestrel previene el embarazo cuando se administra como anticonceptivo de emergencia

    Directory of Open Access Journals (Sweden)

    Ortiz, Maria Elena

    2007-01-01

    Full Text Available La anticoncepción hormonal de emergencia (AHE es uno de los pocos recursos que la mujer puede usar para prevenir un embarazo no deseado después de haber tenido una relación sexual en la que no usó método anticonceptivo o el que usó presentó una falla. Actualmente, el método preferido para la AHE es la píldora que contiene solamente levonorgestrel (LNG. Según la OMS, puede prevenir embarazos si se usa hasta 120 horas después del acto sexual, pero su eficacia disminuye drásticamente desde 85% a 31% mientras más se posterga su administración. La introducción de la AHE ha generado controversia en muchos países latinoamericanos por la percepción errónea de que induce aborto y la oposición de los sectores más conservadores de la sociedad que temen que favorezca la promiscuidad. Con el propósito de dar a conocer la evidencia científica producida por las investigaciones diseñadas para dilucidar como el LNG previene el embarazo cuando se administra como AHE, y su correcta interpretación, este artículo analiza críticamente dichos estudios y explica además en que circunstancias este método no logra prevenir el embarazo. El conjunto de la evidencia indica que LNG previene el embarazo solamente cuando impide la fecundación y descarta que el prevenga el embarazo interfiriendo con la implantación del embrión, por lo que la creencia de que es abortivo no tiene sustento científico.

  15. The levonorgestrel-releasing intrauterine system: Safety, efficacy, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Megan N Beatty

    2009-07-01

    Full Text Available Megan N Beatty, Paul D BlumenthalDepartment of Obstetrics and Gynecology, Stanford University, Stanford, CA, USAAbstract: The levonorgestrel-releasing intrauterine system (LNG-IUS is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women’s health issues.Keywords: Mirena®, levonorgestrel-releasing, intrauterine system, intrauterine contraceptive device

  16. An overview of four studies of a continuous oral contraceptive (levonorgestrel 90 mcg/ethinyl estradiol 20 mcg) on premenstrual dysphoric disorder and premenstrual syndrome

    DEFF Research Database (Denmark)

    Freeman, Ellen W; Halbreich, Uriel; Grubb, Gary S

    2012-01-01

    This article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).......This article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS)....

  17. Mixture effects of levonorgestrel and ethinylestradiol: estrogenic biomarkers and hormone receptor mRNA expression during sexual programming.

    Science.gov (United States)

    Säfholm, Moa; Jansson, Erika; Fick, Jerker; Berg, Cecilia

    2015-04-01

    Synthetic progesterone (progestins) and estrogens are widely used pharmaceuticals. Given that their simultaneous unintentional exposure occurs in wildlife and also in human infants, data on mixture effects of combined exposures to these hormones during development is needed. Using the Xenopus (Silurana) tropicalis test system we investigated mixture effects of levonorgestrel (LNG) and ethinylestradiol (EE2) on hormone sensitive endpoints. After larval exposure to LNG (0.1nM), or EE2 (0.1nM) singly, or in combination with LNG (0.01, 0.1, 1.0nM), the gonadal sex ratio was determined histologically and hepatic mRNA levels of genes encoding vitellogenin (vtg beta1) and the estrogen (esr1, esr2), progesterone (ipgr) and androgen (ar) receptors were quantified using quantitative PCR. All EE2-exposed groups showed female-biased sex ratios and increased vtg beta1 mRNA levels compared with the controls. Compared with the EE2-alone group (positive control) there were no significant alterations in vtg beta1 levels or in sex ratios in the co-exposure groups. Exposure to LNG-alone caused an increase in ar mRNA levels in females, but not in males, compared to the controls and the co-exposed groups, indicating that co-exposure to EE2 counteracted the LNG-induced ar levels. No treatment related impacts on the mRNA expression of esr1, esr2, and ipgr in female tadpoles were found, suggesting that these endpoints are insensitive to long-term exposure to estrogen or progestin. Due to the EE2-induced female-biased sex ratios, the mRNA expression data for the low number of males in the EE2-exposed groups were not statistically analyzed. In conclusion, our results suggest that induced vtg expression is a robust biomarker for estrogenic activity in exposure scenarios involving both estrogens and progestins. Developmental exposure to LNG caused an induction of hepatic ar mRNA expression that was antagonized by combined exposure to EE2 and LNG. To our knowledge this is the first study to

  18. The effects of levonorgestrel on FSH-stimulated primary rat granulosa cell cultures through gene expression profiling are associated to hormone and folliculogenesis processes.

    Science.gov (United States)

    Lira-Albarrán, Saúl; Larrea-Schiavon, Marco F; González, Leticia; Durand, Marta; Rangel, Claudia; Larrea, Fernando

    2017-01-05

    Levonorgestrel (LNG), a synthetic progestin, is used in emergency contraception (EC). The mechanism is preventing or delaying ovulation at the level of the hypothalamic pituitary unit; however, little knowledge exists on LNG effects at the ovary. The aim of this study was to identify the effects of LNG on FSH-induced 17β-estradiol (E2) production, including LNG-mediated changes on global gene expression in rat granulosa cells (GC). Isolated GC from female Wistar rats were incubated in vitro in the presence or absence of human FSH and progestins. At the end of incubations, culture media and cells were collected for E2 and mRNA quantitation. The results showed the ability of LNG to inhibit both hFSH-induced E2 production and aromatase gene expression. Microarray analysis revealed that LNG treatment affects GC functionality particularly that related to folliculogenesis and steroid metabolism. These results may offer additional evidence for the mechanisms of action of LNG as EC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Abnormal uterine bleeding in midlife: The role of levonorgestrel intrauterine system

    Directory of Open Access Journals (Sweden)

    Osama Shawki

    2013-01-01

    Full Text Available Abnormal uterine bleeding is a common gynecological complaint affecting 10-30% of women in midlife and constitute about one-third of all outpatient gynecological visits. It adversely affects the quality of woman′s life and can lead to psychological, social, medical, and sexual problems and thus necessitating appropriate and adequate management. Different treatment modalities for such problems are available, yet the levonorgestrel intrauterine system (LNG-IUS has recently provided a good treatment option effective in treating such complaints and at the same time, having a reliable contraceptive effect which is desired by such age group. For women in their reproductive years, the LNG-IUS has become one of the most acceptable medical treatments for menorrhagia, reducing referrals to specialists, and decreasing the recourse to operative treatments. It is easy to insert, has a sustained effect, cost-effective, and well tolerated besides providing reliable contraception.

  20. Levonorgestrel intrauterine system: Current role in management of heavy menstrual bleeding

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2013-01-01

    Full Text Available A review of literature was conducted to report on the effectiveness of levonorgestrel intrauterine system (LNG-IUS in women with heavy menstrual bleeding (HMB. The relevant data were obtained by computerized searches of PubMed up to December 2012 and other references available with the authors. Information was obtained from references listed. Studies and case reports were excluded if they did not specifically provide information about LNG-IUS usage in women with HMB. After perusal, each relevant publication was summarized and appraised in terms of whether it contained information relevant to the stated objective. Available data shows that LNG-IUS therapy is effective and safe, providing significant reduction of menstrual bleeding in patients with HMB. LNG-IUS is a good strategy to reduce the number of hysterectomies in women with HMB.

  1. Osteoporosis in a young woman after 6 years of levonorgestrel administration from intrauterine devices?

    Science.gov (United States)

    Greiner, Christine Ursula; Brune, Kay; Haen, Ekkehard

    2009-01-01

    This report describes a young woman who developed dysmenorrhoea at the age of 12. She received a levonorgestrel (LNg)-releasing intrauterine device at the age of 21, and this was replaced twice within 8 years. At the age of 28, she started to have multiple bone and joint pain (predominantly low back pain), which, after intensive diagnostic of blood parameters and bone CT, turned out to result – from a manifest (mild) osteoporosis. Since the woman developed very low (postmenopausal) oestradiol levels during the presence of the gestagen-releasing device and encountered normalisation of oestradiol production after removal, suppression of the hypophysial–ovarian axis is proposed as the cause of both lack of oestradiol and osteoporosis. This poses the question of whether long-term use of such devices in young women may result in reduced bone density in the early phases of life, paving the way to serious osteoporosis at menopause. PMID:21686786

  2. Levonorgestrel Intrauterine Device Placement in a Premenopausal Breast Cancer Patient with a Bicornuate Uterus.

    Science.gov (United States)

    Eskew, Ashley M; Crane, Erin K

    2016-01-01

    Young women with breast cancer face contraceptive challenges. Data are limited and conflicting on the use of the levonorgestrel intrauterine device (LNG-IUD) in this patient population. A 32-year-old nulligravid woman with a history of breast cancer on tamoxifen presented with new-onset vaginal bleeding. Further workup revealed a previously undiagnosed bicornuate uterus. She underwent hysteroscopy, dilation and curettage, and LNG-IUD placement in each uterine horn. Postoperative follow-up confirmed retention and proper placement of both IUDs. Pathology from the dilation and curettage was benign, and the abnormal uterine bleeding abated. LNG-IUD placement in a young patient with a personal history of breast cancer on tamoxifen and a bicornuate uterus is a safe and feasible alternative for contraception.

  3. Levonorgestrel-releasing intrauterine systems for long-acting contraception: current perspectives, safety, and patient counseling

    Science.gov (United States)

    Costescu, Dustin J

    2016-01-01

    Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS); however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception. PMID:27785107

  4. Perbedaan Profil Lipid pada Akseptor Depo Medroksi Progesteron Asetat dengan Implant Levonorgestrel di Wilayah Kerja Puskesmas Air Tawar Padang Tahun 2014

    Directory of Open Access Journals (Sweden)

    Rafika Oktova

    2015-01-01

    Full Text Available AbstrakDepo Medroksiprogesteron Asetat dan Implant Levonorgestrel merupakan kontrasepsi hormonal progestin sintetik yang memiliki efek samping yaitu peningkatan berat badan dan mempengaruhi metabolisme lipid. Tujuan penelitian ini adalah untuk mengetahui perbedaan profil lipid pada akseptor Depo Medroksiprogesteron Asetat dengan Implant Levonorgestrel. Ini adalah studi observasional dengan desain cross sectional comparative. Penelitian dilakukan di laboratorium Bagian Biokimia Fakultas Universitas Andalas dari Maret sampai Mei 2014. Subjek penelitian terdiri dari dua kelompok, masing-masing 20 subjek. Pemeriksaan dengan metode enzimatis kolorimetri yaitu GPO-PAP untuk trigliserida, dan CHOD-PAP untuk kolesterol total, HDL dan LDL. Data dianalisis menggunakan uji t dengan nilai p<0.05 dianggap bermakna secara statistik. Rerata kadar LDL pada Depo Medroksiprogesteron Asetat lebih tinggi (95,51 ± 20,47 mg/dl daripada Implant Levonorgestrel (79,35 ± 12,55 mg/dl dengan nilai p<0,05 artinya terdapat perbedaan yang bermakna sedangkan kadar trigliserida, kolesterol total dan HDL tidak bermakna. Kesimpulan penelitian in adalah terdapat perbedaan yang bermakna rerata kadar LDL pada Depo MedroksiprogesteronAsetat dan Implant Levonorgestrel, sedangkan kadar trigliserida, kolesterol total dan HDL tidak bermakna. Secara klinis profil lipid pada kedua kelompok dalam keadaan normal.Kata kunci: profil lipid, depo medroksiprogesteron asetat, implant levonorgestrelAbstractDepo Medroxyprogesterone Acetate and Levonorgestrel Implants are synthetic progestine hormonal contraceptives that have side effect in body weight and lipid metabolism. The objective of this study was to determine the differences of lipid profile between acceptors Depo Medroxyprogesterone Acetate and Levonorgestrel Implants. This was a comparative cross sectional study. The study was done at laboratory of Biochemistry Departement in Medical Faculty of Andalas University from March until May

  5. Immediate versus delayed postpartum use of levonorgestrel contraceptive implants: a randomized controlled trial in Uganda.

    Science.gov (United States)

    Averbach, Sarah; Kakaire, Othman; Kayiga, Herbert; Lester, Felicia; Sokoloff, Abby; Byamugisha, Josaphat; Dehlendorf, Christine; Steinauer, Jody

    2017-06-10

    Use of long-acting, highly effective contraception has the potential to improve women's ability to avoid short interpregnancy intervals, which are associated with an increased risk of maternal morbidity and mortality, and preterm delivery. In Uganda, contraceptive implants are not routinely available during the immediate postpartum period. The purpose of this study was to compare the proportion of women using levonorgestrel contraceptive implants at 6 months after delivery in women randomized to immediate or delayed insertion. This was a randomized controlled trial among women in Kampala, Uganda. Women who desired contraceptive implants were randomly assigned to insertion of a 2-rod contraceptive implant system containing 75 mg of levonorgestrel immediately following delivery (within 5 days of delivery and before discharge from the hospital) or delayed insertion (6 weeks postpartum). The primary outcome was implant utilization at 6 months postpartum. From June to October 2015, 205 women were randomized, 103 to the immediate group and 102 to the delayed group. Ninety-three percent completed the 6 month follow-up visit. At 6 months, implant use was higher in the immediate group compared with the delayed group (97% vs 68%; P < .001), as was the use of any highly effective contraceptive (98% vs 81%; P = .001). Women in the immediate group were more satisfied with the timing of implant placement. If given the choice, 81% of women in the immediate group and 63% of women in the delayed group would choose the same timing of placement again (P = .01). There were no serious adverse events in either group. Offering women the option of initiating contraceptive implants in the immediate postpartum period has the potential to increase contraceptive utilization, decrease unwanted pregnancies, prevent short interpregnancy intervals, and help women achieve their reproductive goals. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks.

    Science.gov (United States)

    Scarsi, Kimberly K; Darin, Kristin M; Nakalema, Shadia; Back, David J; Byakika-Kibwika, Pauline; Else, Laura J; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E; Merry, Concepta; Lamorde, Mohammed

    2016-03-15

    Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. NCT01789879. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. Levonorgestrel Intrauterine Device as an Endometrial Cancer Prevention Strategy in Obese Women: A Cost-Effectiveness Analysis.

    Science.gov (United States)

    Dottino, Joseph A; Hasselblad, Vic; Secord, Angeles Alvarez; Myers, Evan R; Chino, Junzo; Havrilesky, Laura J

    2016-10-01

    To estimate the cost-effectiveness of the levonorgestrel intrauterine device (IUD) as an endometrial cancer prevention strategy in obese women. A modified Markov model was used to compare IUD placement at age 50 with usual care among women with a body mass index (BMI, kg/m) 40 or greater or BMI 30 or greater. The effects of obesity on incidence and survival were incorporated. The IUD was assumed to confer a 50% reduction in cancer incidence over 5 years. Costs of IUD and cancer care were included. Clinical outcomes were cancer diagnosis and deaths from cancer. Incremental cost-effectiveness ratios were calculated in 2015 U.S. dollars per year of life saved. One-way and two-way sensitivity analyses and Monte Carlo probabilistic analyses were performed. For a 50 year old with BMI 40 or greater, the IUD strategy is costlier and more effective than usual care with an incremental cost-effectiveness ratio of $74,707 per year of life saved. If the protective effect of the levonorgestrel IUD is assumed to be 10 years, the incremental cost-effectiveness ratio decreases to $37,858 per year of life saved. In sensitivity analysis, a levonorgestrel IUD that reduces cancer incidence by at least 68% in women with BMIs of 40 or greater or costs less than $500 is potentially cost-effective. For BMI 30 or greater, the incremental cost-effectiveness ratio of IUD strategy is $137,223 per year of life saved compared with usual care. In Monte Carlo analysis, IUD placement for BMI 40 or greater is cost-effective in 50% of simulations at a willingness-to-pay threshold of $100,000 per year of life saved. The levonorgestrel IUD is a potentially cost-effective strategy for prevention of deaths from endometrial cancer in obese women.

  8. Partial and complete expulsion of the Multiload 375 IUD and the levonorgestrel-releasing IUD after correct insertion

    OpenAIRE

    Merki-Feld, G.S.; Schwarz, D.; Imthurn, B.; Keller, P. J.

    2008-01-01

    OBJECTIVE: The contraceptive efficacy of intrauterine devices (IUD) is thought to relate to the position of the IUD in the uterine cavity. Several trials examined the number of copper IUD expulsions, but none evaluated the partial and complete expulsion rate of the levonorgestrel-releasing device (LNG-IUD). STUDY DESIGN: This retrospective cohort study compares the dislocation rate of the Multiload 375 IUD (ML 375) and the LNG-IUD in 214 women (107 subjects with each IUD). Transvaginal ultras...

  9. Levonorgestrel-releasing IUD versus copper IUD in control of dysmenorrhea, satisfaction and quality of life in women using IUD

    OpenAIRE

    Seyed Javad Purafzali Firuzabadi; Toktam Tavakolianfar; Mamak Shariat; Fatemeh Ramazanzadeh; Fedieh Hagholahi

    2012-01-01

    Background: The levonorgestrel-releasing IUD can help the treatment of dysmenorrhea by reducing the synthesis of endometrial prostaglandins as a conventional treatment. Objective: This study was performed to assess the frequency of dysmenorrhea, satisfaction and quality of life in women using Mirena IUDs as compared to those using copper IUDs. Materials and Methods: This double-blind randomized clinical trial was performed between 2006 and 2007 on 160 women aged between 20 to 35 years who att...

  10. Analysis and Evaluation of Adverse Drug Reactions of Levonorgestrel Emergency Contraception at Home and Abroad%国内外关于左炔诺孕酮紧急避孕药不良反应的数据分析与评价

    Institute of Scientific and Technical Information of China (English)

    朱向珺; 李瑛

    2011-01-01

    OBJECTIVE: To provide reference for safe use and evaluation of levonorgestrel emergency contraception in China.METHODS: By the means of literature retrieval and analysis, the reports of adverse drug reactions induced by levonorgestrel emergency contraception from MedWatch (FDA Medical Products Reporting Program), National Center for ADR Monitoring, WHO and State Contraceptives Adverse Reaction Surveillance Center were analyzed to find out the differences of types and data of adverse drug reactions induced levonorgestrel emergency contraception and analyze the reasons. RESULTS: There were large type and data differences of adverse drug reactions induced by levonorgestrel emergency contraception at home and aboard. CONCLUSION:The public education, professional training of issue personnel and the cognition of doctors and immediate processing are key to reduce and prevent the adverse drug reaction induced by emergency contraception.%目的:为我国左炔诺孕酮紧急避孕药安全使用与评价提供参考.方法:对美国食品与药品管理局医药产品不良事件报告体系、我国国家药品不良反应监测中心、世界卫生组织和我国国家人口计生委计划生育药具不良反应监测中心所收集到的左炔诺孕酮紧急避孕药不良反应报告进行分析,并对左炔诺孕酮紧急避孕药的不良反应进行文献检索与分析,找出国内、外关于左炔诺孕酮紧急避孕药不良反应发生类型与报告数据的差距并分析原因.结果:国内、外关于左炔诺孕酮紧急避孕药不良反应的发生类型、种类和报告数据方面均存在较大差距.结论:左炔诺孕酮紧急避孕药不良反应的公众教育、发放人员的专业培训及医师对紧急避孕药不良反应的认知与及时处理是减少与预防紧急避孕药不良反应发生的关键.

  11. An ethinyl estradiol-levonorgestrel containing oral contraceptive does not alter cytochrome P4502C9 in vivo activity.

    Science.gov (United States)

    Cherala, Ganesh; Pearson, Jacob; Maslen, Cheryl; Edelman, Alison

    2014-03-01

    Oral contraceptives have been in wide use for more than 50 years. Levonorgestrel, a commonly employed progestin component of combined oral contraceptives, was implicated in drug-drug interactions mediated via CYP2C9. Although in vitro studies refuted this interaction, there are no confirmatory in vivo studies. In the current study, we examined the phenotypic status of CYP2C9 using low-dose (125 mg) tolbutamide before and after oral contraceptive use in reproductive age women. Blood was collected 24 hours after the tolbutamide oral dose was administered, plasma was isolated, and tolbutamide concentration (C24) was measured using liquid chromatography-mass spectrometry. The natural logarithm of tolbutamide C24, a metric for CYP2C9 phenotype, was found to be equivalent (within 80%-125% equivalency boundaries) before and after oral contraceptive use. In conclusion, levonorgestrel-containing oral contraceptives, the most commonly used form of oral contraception, do not affect the status of the CYP2C9 enzyme. This suggests that it is safe to co-administer levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs.

  12. Correlation between uterine artery Doppler indices and menstrual irregularities among levonorgestrel releasing intrauterine system and depot medroxyprogesterone acetate users: a prospective observational study.

    Science.gov (United States)

    Rezk, Mohamed; Al-Halaby, Alaa; Emarh, Mohamed; Shawky, Mohamed

    2017-08-01

    To ascertain whether menstrual irregularities among users of levonorgestrel releasing intrauterine system (LNG-IUS) and depot medroxyprogesterone acetate (DMPA), were associated with changes in uterine artery Doppler indices or not. This three-year prospective observational study included 102 women using LNG-IUS and 104 women using DMPA for contraception. Participants were followed at regular intervals over three years with performance of transvaginal ultrasound to measure uterine artery pulsatility index (PI) and resistance index (RI) before starting the method and at six months, 12 months, two and three years thereafter. Data was collected and tabulated. Significant changes in uterine artery PI and RI were detected. PI indices were reduced after six months of use in both groups and elevated significantly at 12 months in both groups compared to initial values (p < .001) while RI significantly reduced after six months in both groups and elevated significantly at 12 months, two and three years in both groups compared to initial values (p < .001). Both PI and RI significantly reduced in women suffered abnormal uterine bleeding and significantly elevated in women experienced amenorrhea irrespective of the method used (p < .001). LNG-IUS and DMPA induce hemodynamic changes in the uterine arteries denoting positive correlation with menstrual irregularities. Larger multicentre studies are warranted to potentiate our findings.

  13. Capacidade reprodutiva de ratas aleitadas por mães que receberam levonorgestrel durante a lactação

    Directory of Open Access Journals (Sweden)

    GUERRA MARTHA DE OLIVEIRA

    2002-01-01

    Full Text Available O levonorgestrel é um dos contraceptivos usados por mulheres durante a lactação. Estudos prévios mostraram que a administração de levonorgestrel a ratas lactando causou nas crias retardo de puberdade em machos e alterações no peso de oviduto e útero. OBJETIVO: Estudar a capacidade reprodutiva das fêmeas F1, de mães tratadas com levonorgestrel. MÉTODOS: Ratas Wistar foram tratadas com levonorgestrel (0.030 mg/1 ml de água destilada do 7masculine ao 13masculine dia após o nascimento (dia 1 = nascimento. Aos 90 dias, as fêmeas F1 foram acasaladas com machos férteis e a inseminação comprovada pela presença de espermatozóides no esfregaço vaginal (primeiro dia de prenhez. As fêmeas inseminadas foram distribuídas em três lotes de 20 animais (10 F1 Controles e 10 F1 Tratadas. Os animais foram sacrificados no 2masculine, 4masculine e 5masculine dias após a inseminação, por excesso de inalação com éter, e os ovários, ovidutos e cornos uterinos foram removidos. Os ovários foram pesados e os corpos lúteos contados. Ovidutos e cornos uterinos foram lavados com solução fisiológica e os pré-embriões obtidos foram contados e examinados em cada um dos segmentos. RESULTADOS: O peso de ovários, número de corpos lúteos, número e fase de desenvolvimento de pré-embriões foram semelhantes nos dois grupos. CONCLUSÃO: No modelo experimental usado, o aleitamento de crias de ratas por mães tratadas com levonorgestrel não interfere com a capacidade reprodutiva de fêmeas F1.

  14. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

    Directory of Open Access Journals (Sweden)

    Giuseppe Benagiano

    2009-04-01

    Full Text Available Giuseppe Benagiano, Sabina Carrara, Valentina FilippiDepartment of Gynaecology and Obstetrics, Sapienza University, Rome, ItalyAbstract: The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic and peripheral (cervical mucus and endometrium levels. Levonorgestrel (LNG, alone or in combination with ethinyl estradiol (EE, is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years

  15. LEVONORGESTREL-RELEASING INTRAUTERINE SYSTEM AS AN ALTERNATIVE THERAPY IN ABNORMAL UTERINE BLEEDING

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    Kunjamma Roy

    2017-05-01

    Full Text Available BACKGROUND Abnormal uterine bleeding is one of the most frequent reasons for gynaecological consultation, occurring in approximately 30% of women of reproductive age. Menorrhagia by definition implies a menstrual blood loss equal to or greater than 80 mL. Many women seek consultation for bleeding episodes of less than this amount because of the stress associated with it. Most frequently used medications are combinations of prostaglandin synthetase inhibitors and antifibrinolytic drugs, nonsteroidal antiinflammatory drugs, oral progesterone like Norethisterone or medroxyprogesterone acetate and combined oral contraceptives. The usual treatment for women with menorrhagia not desiring further pregnancies and those not responding to medical managements is either hysterectomy or endometrial ablation. Endometrial ablation less commonly performed due to low success rate. Levonorgestrel intrauterine system (LNG-IUS is a new modality in the treatment of AUB. The objective of this study is to evaluate the use of Levonorgestrel intrauterine system as a treatment for women with menorrhagia. MATERIALS AND METHODS This is a prospective interventional comparative study conducted on women with abnormal uterine bleeding. The duration of study was from March 2012 to October 2013. The respondents include those outpatients attending Gynaecology Department of Government Medical College, Kottayam with menorrhagia. The samples size was 50 of which 25 were in experimental groups and remaining 25 in control group. Experimental group were given LNG IUS for menorrhagia and the remaining 25 patients were given oral progestins for heavy menstrual bleeding. In order to make a comparison of the impact of the two different kinds of interventions, the Hb level as well as the amount of blood loss were systematically estimated at frequent intervals. Accordingly, these measurements were carried for the said both groups at the commencement of research study and thereafter at an

  16. Failure of the emergency contraceptive levonorgestrel and the risk of adverse effects in pregnancy and on fetal development: an observational cohort study.

    Science.gov (United States)

    De Santis, Marco; Cavaliere, Anna Franca; Straface, Gianluca; Carducci, Brigida; Caruso, Alessandro

    2005-08-01

    To determine pregnancy and neonatal outcome after the failure of levonorgestrel as an emergency contraceptive. A retrospective observational cohort study. Telephone consultations concerning reproductive risk factors conducted by Telefono Rosso-Teratology Information Service, Catholic University of Sacred Heart, Rome, Italy. Women exposed to levonorgestrel (36 cases) compared with a control group (80 cases). Teratological counseling. The rate of congenital anomalies, the prepartum or peripartum complications, and the pregnancy outcomes. Twenty-five exposed newborns with length and weight identical to that of the control group were shown to be without increased risk of congenital malformation. No statistical differences were observed in terms of spontaneous or legal abortion and pregnancy and neonatal complications, and there was no ectopic pregnancy in either group. Although the sample size was small, in our experience, the failure of levonorgestrel as an emergency contraceptive was not associated with an increased risk of major congenital malformations, prepartum or peripartum complications, or an adverse pregnancy outcome.

  17. Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

    Science.gov (United States)

    Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

    2016-01-01

    LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions.

  18. Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B, and Efavirenz

    Directory of Open Access Journals (Sweden)

    Monica L. Carten

    2012-01-01

    Full Text Available Objectives. Compare the Plan B levonorgestrel (LNG area under the concentration- time curve (AUC12 prior to and with efavirenz (EFV. Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62% from 42.9 to 17.8 ng*hr/mL, and maximum concentration (Cmax⁡ was reduced 41% (95% CI: 33%, 50% from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV.

  19. Uterine flushings from women treated with levonorgestrel affect sperm functionality in vitro.

    Science.gov (United States)

    Chirinos, Mayel; Durand, Marta; González-González, María Elena; Hernández-Silva, Gabriela; Maldonado-Rosas, Israel; Lopez, Pablo; Larrea, Fernando

    2017-09-08

    Levonorgestrel (LNG), a synthetic 19 nor-testosterone derivative, is widely used for emergency contraception. It is well known that LNG prevents ovulation only when given prior to the surge of serum luteinizing hormone (LH) during the periovulatory phase of the menstrual cycle. This observation suggests that LNG, given its contraceptive efficacy, has additional effects other than those affecting ovulation. In this study, we have evaluated the effects on human sperm functionality of uterine flushings (UF) obtained from women at day LH+1 of a control cycle (CTR-LH+1) and after receiving LNG (LNG-LH+1) two days before the surge of LH. Human sperm from normozoospermic donors were incubated with UF and protein tyrosine phosphorylation, sperm motility, acrosome reaction as well as zona pellucida (ZP) binding capacity were assessed. A significant decrease in total motility and tyrosine phosphorylation accompanied by an increase on spontaneous acrosome reaction was observed when sperm were incubated in the presence of LNG-LH+1. None of these effects were mimicked by purified glycodelin A (GdA). Moreover, the addition of UF obtained during the periovulatory phase from LNG-treated women or the presence of purified GdA significantly decreased sperm-ZP binding. The data were compatible with changes affecting sperm capacitation, motility and interaction with the ZP. These results may offer evidence on additional mechanisms of action of LNG as an emergency contraceptive.

  20. Pregnant with a perforated levonorgestrel intrauterine system and visible threads at the cervical os.

    Science.gov (United States)

    Howard, David L; Beasley, Lauren M

    2017-05-22

    We present a case in which a patient presented with a pregnancy of unknown location and normally rising human chorionic gonadotropin (hCG) levels but with a levonorgestrel intrauterine device (LNG-IUD) present. The LNG-IUD had been placed 4.5 years ago. Although unintended, this pregnancy was desired. Strings were clearly visible and initial 2D ultrasound suggested intrauterine location of the LNG-IUD. The LNG-IUD could not be removed however. The patient was managed expectantly with close follow-up, serial beta-hCGs and serial ultrasounds until definitive diagnosis of the location of the pregnancy. The patient was diagnosed with an ectopic pregnancy and during laparoscopy the body of the IUD was noted in the posterior cul-de-sac. When patients present with multiple competing clinical problems it is important to look at the patient as a whole, taking into account their desires, in order to construct a cohesive management plan. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Evaluating the Efficacy of Levonorgestrel Intrauterine System and Danazol for Relief of Postoperative Pain in Endometriosis.

    Science.gov (United States)

    Taneja, Ashima; Kaur, Satinder; Soni, R K; Bhanupriya; Kaur, Jaspreet; Singla, Laveen

    2017-07-01

    Endometriosis is an oestrogen-dependent disorder, manifests during reproductive years and is associated with pain and infertility. There is considerable debate about the effectiveness of various interventions for pain relief. To evaluate the efficacy of Levonorgestrel Intrauterine System (LNG-IUS) and Danazol in postoperative pain relief for patients with endometriosis. Hundred patients with diagnosis of endometriosis, who were treated laparoscopically, entered the study to receive either danazol (600 mg once daily) or LNG-IUS (inserted during immediate post operative period) postsurgery, for pain relief. Patients were analysed for pain relief according to VAS score and recurrence of disease using ultrasonography at third and sixth months of follow up. There were 50% patients in stage IV of endometriosis. Majority of them presented with complaint of infertility (49%) and pelvic pain (43%). It was observed that LNG-IUS was significantly more effective in relieving pain compared to danazol (65.2% vs 38.0%, p<0.05). Recurrence rate was significantly lower in LNG-IUS users compared to other group. LNG-IUS was found to be more effective in relieving pain compared to danazol.

  2. The effects of the levonorgestrel intrauterine system (Mirena coil) on endometrial morphology

    Science.gov (United States)

    Phillips, V; Graham, C T; Manek, S; McCluggage, W G

    2003-01-01

    Aims: The Mirena coil is a levonorgestrel releasing intrauterine device that is in widespread use. This study aims to document the endometrial morphology associated with this device. Methods: Endometrial specimens from 75 women with the Mirena coil were reviewed and the histological features detailed. Results: Morphological features found in most of the endometria were decidualisation of stroma (72 of 75 cases), atrophy of endometrial glands (65 of 75 cases), a surface papillary pattern (38 of 75 cases), and a stromal inflammatory cell infiltrate (59 of 75 cases). Additional common histological features were the presence of foci of stromal myxoid change (29 of 75 cases) and stromal haemosiderin pigment (24 of 75 cases). Reactive atypia of surface glands, glandular metaplastic changes, stromal necrosis, and stromal calcifications were found in small numbers of cases. Conclusion: The endometrial features are characteristic and relatively constant and are in keeping with the effects of both a progestogenic compound and a mechanical device. Pathologists should be aware of these histological features because the Mirena coil is in widespread use. PMID:12663645

  3. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology

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    Stefano Lello

    2014-01-01

    Full Text Available Estroprogestins (EPs are combinations of estrogen and progestin with several actions on women’s health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100. This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100. Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group. Cycle control was effective and body weight/body composition did not vary among treated and untreated groups in most studies. The EE20/LNG100 combination shows mild or no effect on lipid and glucose metabolism. Lastly, EE20/LNG100 is associated with a low risk of venous thromboembolism (VTE. In conclusion, in the process of decision making for the individualization of EPs choice, EE20/LNG100 should be considered for its favorable clinical profile.

  4. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia.

    Science.gov (United States)

    Ewies, Ayman A A; Alfhaily, Fadi

    2012-11-01

    Endometrial hyperplasia is a commonly seen gynecological condition that affects women of all age groups. Whereas hysterectomy is the most preferred treatment option for complex endometrial hyperplasia with atypia, there is no consensus regarding the first-line management of women with hyperplasia without cytological atypia. Oral progestogen therapy was used with some success. Nonetheless, it may be plausible to argue that women with endometrial hyperplasia need continuous treatment and high level of compliance to ensure complete regression, which may not be guaranteed with oral therapy. Observational studies suggested that levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used to treat endometrial hyperplasia without cytological atypia and selected cases of atypical endometrial hyperplasia. Furthermore, there is strong evidence from randomized controlled trials that LNG-IUS prevents the development of endometrial hyperplasia in exogenous estrogen users; however, its protective role and safety in tamoxifen-treated breast cancer survivors remain uncertain. This article evaluates the current evidence for the use of LNG-IUS, releasing 20 μg of LNG per day, in the prevention and treatment of endometrial hyperplasia.

  5. Emerging indications for the levonorgestrel-releasing intrauterine system (LNG-IUS).

    Science.gov (United States)

    Heikinheimo, Oskari; Gemzell-Danielsson, Kristina

    2012-01-01

    The levonorgestrel intrauterine system (LNG-IUS), originally designed for long-term contraceptive use, has been on the Scandinavian market for approximately 20 years. Novel clinical indications for the LNG-IUS, derived mainly from investigator-initiated studies, are emerging. These include heavy menstrual bleeding associated with uterine fibroids, endometriosis, adenomyosis, as well as endometrial hyperplasia. In both cohort and randomized studies, the LNG-IUS is effective in decreasing heavy menstrual bleeding, also in women diagnosed with uterine fibroids. In randomized studies the LNG-IUS has shown comparable clinical efficacy to GnRH analogues or progestins for the symptomatic treatment of endometriosis. Experience with LNG-IUS in adenomyosis is based on prospective cohort studies. Dysmenorrhea has been reported to decrease in all women, and uterine volume was seen to diminish in some of these studies. In the treatment of endometrial hyperplasias, including atypical hyperplasia, the LNG-IUS is equal or superior to treatment with systemic progestins. Further studies are needed to examine the full potential of the LNG-IUS in such common clinical situations.

  6. The levonorgestrel-releasing intrauterine system for endometrial protection during estrogen replacement therapy: a clinical review.

    Science.gov (United States)

    Depypere, H; Inki, P

    2015-01-01

    Estrogen replacement therapy (ERT) is a well-established method of managing climacteric symptoms in women approaching the menopause, but it is associated with a significant risk of endometrial hyperplasia if unopposed by concomitant progestogen administration. The levonorgestrel-releasing intrauterine system (LNG-IUS) offers a highly effective method of minimizing this risk and has additional benefits beyond endometrial protection. The LNG-IUS provides excellent contraception, which may still be necessary in perimenopausal women, and is suitable for women with underlying conditions that may preclude their use of estrogen-containing contraceptive methods. It can effectively manage bleeding problems through the transition from perimenopause into menopause, with many women developing amenorrhea. The LNG-IUS is well tolerated with a favorable safety profile, which generally mirrors that of women of reproductive age using it for contraception only. Moreover, the LNG-IUS plus ERT combination does not appear to be associated with clinically relevant effects on plasma lipids or other markers of cardiovascular risk. Women using the LNG-IUS plus ERT also experience improvements in quality of life, and adherence and continuation rates are high. This review will summarize the clinical evidence for the use of the LNG-IUS plus ERT in peri- and postmenopausal women and present the key attributes of this combined therapy.

  7. Treatment with liraglutide--a once-daily GLP-1 analog--does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug.

    Science.gov (United States)

    Jacobsen, Lisbeth V; Vouis, Jan; Hindsberger, Charlotte; Zdravkovic, Milan

    2011-12-01

    Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.

  8. Cómo y cuando el levonorgestrel previene el embarazo cuando se administra como anticonceptivo de emergencia

    OpenAIRE

    Ortiz, Maria Elena; Croxatto, Horacio

    2007-01-01

    La anticoncepción hormonal de emergencia (AHE) es uno de los pocos recursos que la mujer puede usar para prevenir un embarazo no deseado después de haber tenido una relación sexual en la que no usó método anticonceptivo o el que usó presentó una falla. Actualmente, el método preferido para la AHE es la píldora que contiene solamente levonorgestrel (LNG). Según la OMS, puede prevenir embarazos si se usa hasta 120 horas después del acto sexual, pero su eficacia disminuye drást...

  9. Oral toxicity of isotretinoin, misoprostol, methotrexate, mifepristone and levonorgestrel as pregnancy category X medications in female mice

    OpenAIRE

    KIM, SEONG-KWAN; Shin, Soo-Jeong; YOO, YOHAN; KIM, NA-HYUN; KIM, DONG-SOON; Zhang, Dan; PARK, JIN-A; Yi, Hee; Kim, Jin-Suk; Shin, Ho-Chul

    2015-01-01

    An oral toxicity study of several pregnancy category X drugs was performed in female ICR mice. The drugs were administered orally once daily for 3 days at doses of 1, 10 and 100 ?g/kg for isotretinoin; 6.7, 67 and 670 ?g/kg for misoprostol; 83, 830 and 8,300 ?g/kg for methotrexate; 3.3, 33 and 330 ?g/kg for mifepristone; and 25, 250 and 2,500 ?g/kg for levonorgestrel. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry and necropsy findings were exam...

  10. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

    Science.gov (United States)

    Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina

    2009-01-01

    The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84

  11. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience.

    Science.gov (United States)

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman D; Hasskamp, Thomas; Jackers, Geert

    2017-01-01

    The concept of using a frameless intrauterine device (IUD) instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs) are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant(®)) when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in

  12. Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel.

    Science.gov (United States)

    Boyd, Peter; Fetherston, Susan M; McCoy, Clare F; Major, Ian; Murphy, Diarmaid J; Kumar, Sandeep; Holt, Jonathon; Brimer, Andrew; Blanda, Wendy; Devlin, Brid; Malcolm, R Karl

    2016-09-10

    A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. In vitro assessment of some sperm function following exposure to levonorgestrel in human fallopian tubes

    Directory of Open Access Journals (Sweden)

    Hermanny Alexia

    2012-01-01

    Full Text Available Abstract Background The mechanism of action of levonorgestrel (LNG as emergency contraception (EC remains a subject of debate and its effect on sperm function has been only partially explained. The aim of this study was to assess whether LNG at a similar dose to those found in serum following oral intake for EC could affect spermatozoa when exposed to human fallopian tubes in vitro. Methods Fifteen mini-laparotomies were performed, the side on which ovulation occurred was recorded, and both tubes were removed and perfused with a suspension containing 1 × 10(6 motile spermatozoa, with or without LNG. Following 4-hour incubation, the tubes were sectioned to separate the isthmus and the ampulla. Each segment was flushed and the material was evaluated to quantify the number of motile sperm, the number of spermatozoa adhering to the oviductal epithelium and the acrosome reaction (AR rate. Results The addition of LNG did not significantly alter the number of recovered motile spermatozoa either at the isthmus or at the ampulla, nor did it have any effect on the number of recovered spermatozoa adhered to the human tubal epithelium. Furthermore, LNG did not affect the AR rate. No significant differences were found even when the side on which ovulation occurred was taken into account. Conclusions In a similar dose to that observed in serum following oral intake for EC, LNG had no effect on the number of motile spermatozoa recovered from the human fallopian tubes in vitro, on their adhesion to the tubal epithelium, distribution or AR rate. The possible effect of LNG as EC on sperm function remains poorly understood.

  14. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding.

    Science.gov (United States)

    Shaw, Valentina; Vandal, Alain C; Coomarasamy, Christin; Ekeroma, Alec J

    2016-12-01

    To evaluate the effectiveness of the levonorgestrel intrauterine system (LNG-IUS) in obese women with heavy menstrual bleeding in Counties Manukau Auckland area, New Zealand. Prospective observational study in a tertiary teaching hospital. Twenty women with heavy menstrual bleeding (HMB) who agreed to treatment with the LNG-IUS and had a body mass index (BMI) of >30 kg/m(2) were recruited between May and December 2014. The women completed two validated tools (Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart) at recruitment, 6 and 12 months follow-up. Demographic, medical and laboratory variables were obtained from the relevant CMH databases. Data on side effects and satisfaction were obtained from the women at 12 months. The median age (range) and BMI of the 20 women were 40.5 years (27-52 years) and 40.6 kg/m(2) (30-68), respectively. Three LNG-IUS were removed due to infection and pain and these women were subsequently booked for a hysterectomy. The reduction in menstrual loss was estimated at 19.7% per month (95% CI (12.5%, 26.2%); P < 0.001), which translates to 73.2% per period of 6 months (95% CI (55.3%, 83.9%)) and 92.8% per period of 12 months (95% CI (80.0%, 97.4%)). The six items in the quality of life measure improved significantly in 14 women but only 12 women were satisfied with the treatment. The LNG-IUS was an effective treatment for 67% of obese women with heavy menstrual bleeding over a 12-month period, as assessed by the reduction in menstrual bleeding and the improvement in the quality of life measures. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  15. Association of baseline bleeding pattern on amenorrhea with levonorgestrel intrauterine system use.

    Science.gov (United States)

    Mejia, Manuela; McNicholas, Colleen; Madden, Tessa; Peipert, Jeffrey F

    2016-11-01

    This study aims to evaluate the effect of baseline bleeding patterns on rates of amenorrhea reported at 12 months in levonorgestrel (LNG) 52 mg intrauterine system (IUS) users. We also assessed the effect of baseline bleeding patterns at 3 and 6 months postinsertion. In this secondary analysis of the Contraceptive CHOICE Project, we included participants who had an LNG-IUS inserted within 1 month of enrollment and continued use for 12 months. Using 12-month telephone survey data, we defined amenorrhea at 12 months of use as no bleeding or spotting during the previous 6 months. We used chi-square and multivariable logistic regression to assess the association of baseline bleeding pattern with amenorrhea while controlling for confounding variables. Of 1802 continuous 12-month LNG-IUS users, amenorrhea was reported by 4.9%, 14.8% and 15.4% of participants at 3, 6 and 12 months, receptively. Participants with light baseline bleeding or short duration of flow reported higher rates of amenorrhea at 3 and 6 months postinsertion (p<.03), while LNG-IUS users with heavy or prolonged flow were less likely to report amenorrhea at 3 and 6 months (p<.03). In a multivariable analysis, participants with self-reported heavy bleeding at baseline were less likely to report amenorrhea at 12 months than those who reported moderate bleeding (ORadj, 0.36; 95% CI, 0.16-0.69). Women with heavier menstrual bleeding are less likely than women with moderate flow to report amenorrhea following 12 months of LNG-IUS use. Baseline heavy menstrual flow reduces the likelihood of amenorrhea with LNG-IUS use, information that could impact contraceptive counseling. Anticipatory counseling can improve method satisfaction and continuation, an important strategy to continue to reduce unintended pregnancy and abortion rates. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Relationship between user satisfaction with the levonorgestrel-releasing intrauterine system and bleeding patterns.

    Science.gov (United States)

    Carvalho, Nelsilene M; Chou, Victoria; Modesto, Waleska; Margatho, Deborah; Garcia, Elaine A L; Bahamondes, Luis

    2017-08-17

    Satisfaction with a contraceptive method constitutes an important factor in its acceptance and long-term use. The objective of this study was to assess the relationship between user satisfaction with the 20-μg/day levonorgestrel-releasing intrauterine system (LNG-IUS) and the bleeding patterns reported at two different time-points during follow-up. A total of 251 LNG-IUS users aged 18-45 years were invited to answer a questionnaire on their return to the clinic for a routine follow-up visit and again 1 year later. Data were collected face-to-face. Twenty women discontinued prematurely; therefore, the analysis was performed on 231 women. Most users were either highly satisfied (66.6% and 66.2% at the first and second interviews, respectively) or satisfied (26.4% and 26.4% at the first and second interviews, respectively) with the LNG-IUS. Satisfaction was related to amenorrhea (P < 0.001) and duration of use (P < 0.001). Prolonged bleeding and spotting were the main causes of dissatisfaction with the device. Most LNG-IUS users in this sample were satisfied with the device. The only two factors associated with satisfaction were amenorrhea and duration of use, while prolonged bleeding and spotting were the main causes of dissatisfaction. These findings could be useful for health-care professionals and policy-makers when developing information material for women. The study provides insight into the profile of satisfied LNG-IUS users; however, this information is not suitable for counseling women who are considering using an LNG-IUS. © 2017 Japan Society of Obstetrics and Gynecology.

  17. Trends in Levonorgestrel Emergency Contraception Use, Births, and Abortions: The Utah Experience

    Science.gov (United States)

    Turok, David K.; Simonsen, Sara E.; Marshall, Nicole

    2009-01-01

    Context Published reports to date have failed to demonstrate a decrease in abortion rates with increased dispersal of levonorgestrel emergency contraception (LNG EC). Objective To evaluate whether there is an association between statewide increases in LNG EC use and birth, fertility, and abortion rates. Design Ecological study. The number of LNG EC doses dispensed at all Planned Parenthood Association of Utah (PPAU) sites (n = 6) were obtained for 2000–2006. For this time period, birth and abortion data were obtained from the Utah Department of Health. Setting State of Utah. Patients Women of childbearing age. Main Outcome Measures Birth rates were calculated as the number of live births per 1000 population; general fertility rates, abortion rates, and LNG EC rates were calculated per 1000 women of childbearing age (15–44 years). Results Between 2000 and 2006, yearly distribution of LNG EC increased from 11,263 to 52,083 doses. Over this period, the rate of Plan B use per 1000 women age 15–44 years increased from 21.30 doses/1000 to 87.82 doses/1000, an increase of 312%. During the same period, there were corresponding changes in the statewide birth rate (−2.94%), general fertility rate (0.73%), and abortion rate (−6.36%). Pearson correlation coefficients were statistically significant for the association between the LNG EC rate and the birth rate (−0.9053; P = .0050) and the abortion rate (−0.8749; P < .001), but not between the Plan B rate and the general fertility rate (0.2446; P = .5970). Conclusion This ecological study represents, to the authors' knowledge, the first statistically significant association between increasing rates of LNG EC distribution and decreasing abortion rates. PMID:19295951

  18. Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia().

    Science.gov (United States)

    Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

    2017-04-01

    Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m(2) vs. 31 kg/m(2); p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

  19. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Science.gov (United States)

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman D; Hasskamp, Thomas; Jackers, Geert

    2017-01-01

    The concept of using a frameless intrauterine device (IUD) instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs) are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant®) when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing

  20. Effect of Guizhifuling capsule combined with levonorgestrel releasing intrauterine system on adenomyosis

    Institute of Scientific and Technical Information of China (English)

    Dong-Tao Shi; Rui Bai

    2016-01-01

    Objective:To explore the clinical efficacy of Guizhifuling capsule combined with levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM). Methods: A total of 80 patients with AM who were admitted in our hospital from February, 2015 to February, 2016 were included in the study and randomized into the study group and the control group. LNG-IUS was placed in patients in the two groups 7 d after menstruation. The patients in the study group were given additional Guizhifuling capsule, 3 capsules/time, 3 times/d, and the drug was withdrawn in the menstrual period. Six-month treatment was regarded as one course. PBAC was used to evaluate the menstrual blood volume before and after treatment. The chronic pain grading questionnaire method was used for dysmenorrhea degree rating. The vaginal B ultrasound 3 d after menstruation was performed to detect the uterine volume. E2, FSH, LH, and serum CA125 level before and after treatment were detected.Results: The menstrual blood volume, dysmenorrhea degree, and uterine volume after treatment in the two groups were significantly reduced when compared with before treatment (P0.05). After treatment, CA125 level in the two groups was significantly reduced when compared with before treatment (P<0.05), and the reduced degree in the study group was significantly superior to that in the control group (P<0.05).Conclusions:Guizhifuling capsule combined with LNG-IUS in the treatment of AM can significantly improve the clinical symptoms, effectively reduce CA125 level, and has no significant effect on the sex hormone levels with a satisfactory clinical efficacy; therefore, it deserves to be widely recommended in the clinic.

  1. The progestin levonorgestrel affects sex differentiation in zebrafish at environmentally relevant concentrations.

    Science.gov (United States)

    Hua, Jianghuan; Han, Jian; Guo, Yongyong; Zhou, Bingsheng

    2015-09-01

    Synthetic progestins have become widespread environmental contaminants and may cause adverse effects on fish. In the present study, we investigated the effects of levonorgestrel (LNG) on sex differentiation in zebrafish (Danio rerio). Embryos were exposed to LNG at environmentally relevant concentrations (0, 1, 10, 33, and 100ng/L) and allowed to develop until sexual maturity. Histological examination at 63 days post fertilization (dpf) caused complete sex reversal and 100% males were observed in the 10, 33 and 100ng/L treatments; gross morphological and histological examination of gonads at 142dpf further confirmed 100% males at these exposure concentrations. The results indicate androgenic activity of LNG, and masculinization during zebrafish gonadal differentiation. The mRNA expression levels of genes involved in fish sex differentiation and gonadal development were examined at 28 and 42dpf. Down-regulation of the mRNA expression of aromatase (e.g., cyp19a1a, cyp19a1b), the forkhead transcription factor gene L2 (foxl2) and the Fushi tarazu factor-1d (nr5a1b) were observed. In contrast, transcription of the doublesex and mab-3-related transcription factor 1 (dmrt1) gene was up-regulated. Androgen receptor (ar) mRNA expression was significantly down-regulated at 28 and 42dpf. Co-exposure to flutamide (an androgen antagonist) and LNG, led to a decrease in the sex inversion potency of LNG. Our study has demonstrated that environmentally relevant concentrations of LNG could alter sex differentiation and gonadal development in zebrafish. Our results also suggest a potentially high ecological risk of LNG to fish populations in LNG-contaminated aquatic environments.

  2. Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women.

    Science.gov (United States)

    Baker, William D; Pierce, Stuart R; Mills, Anne M; Gehrig, Paola A; Duska, Linda R

    2017-07-01

    To assess the endometrial response rates to treatment with the levonorgestrel intrauterine device in post-menopausal women with atypical hyperplasia/endometrial intraepithelial neoplasia and grade 1 endometrioid (AH/EC) endometrial carcinoma who are not surgical candidates. Chart review was undertaken of patients with AH/EC who underwent levonorgestrel intrauterine device insertion by a gynecologic oncologist within two academic health systems between 2002 and 2013. When available, tissue blocks were evaluated with immunohistochemical staining for progesterone receptor expression. A total of 41 patients received treatment for AH/EC with the levonorgestrel intrauterine device. Follow up sufficient to assess response occurred in 36 women (88%). Complete response was documented in 18 of 36 women (50%), no response in 8 patients (22%), partial response in 3 women (8%) and progression of disease in 7 patients (19%). Four of 18 patients with complete response (22%) later experienced relapse of hyperplasia or cancer. Four patients (10%) died during the study period: none had evidence of metastatic disease and 1 of the 4 woman died of perioperative complications following hysterectomy for stage I disease. Patients responding to treatment had significantly lower progesterone receptor expression on post-treatment biopsies. Intrauterine levonorgestrel is a viable treatment option for post-menopausal women with AH/EC who are poor candidates for standard surgical management. The response rate in this series is similar to published reports in premenopausal patients and includes cases of disease recurrence following conversion to benign endometrium. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A multicenter randomized clinical trial of one-rod etonogestrel and two-rod levonorgestrel contraceptive implants with nonrandomized copper-IUD controls: methodology and insertion data.

    Science.gov (United States)

    Meirik, Olav; Brache, Vivian; Orawan, Kiriwat; Habib, Ndema Abu; Schmidt, Johannes; Ortayli, Nuriye; Culwell, Kelly; Jackson, Emily; Ali, Moazzam

    2013-01-01

    Comparative data on etonogestrel and two-rod levonorgestrel contraceptive implants are lacking. A multicenter, open, parallel-group trial with random allocation of implants was performed. For every second implant user, an age-matched woman choosing an intrauterine device (IUD) (TCu380A) was admitted. Methods and data on implant/IUD insertion and 6-week follow-up are reported. A total of 2008 women were randomized to an implant, and 974 women were enrolled in the IUD group. Results from 997 etonogestrel implant users, 997 levonorgestrel implant users and 971 IUD users were analyzed. In the etonogestrel and levonorgestrel groups, respectively, mean insertion durations were 51 (SD 50.2) s and 88 (SD 60.8) s; complication rates at insertion were 0.8% and 0.2%; and at follow-up, 27.2% and 26.7% of women, respectively, had signs or symptoms at the insertion site. At follow-up within 6 weeks after insertion, all implants were in situ, while 2.1% of IUDs were expelled. Performance of etonogestrel and levonorgestrel implants at insertion and within the first 6 weeks is similar. Short-term (6 weeks) continuation rates appear higher for implants than TCu380A. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Aqueous exposure to the progestin, levonorgestrel, alters anal fin development and reproductive behavior in the eastern mosquitofish (Gambusia holbrooki).

    Science.gov (United States)

    Frankel, Tyler E; Meyer, Michael T; Orlando, Edward F

    2016-08-01

    Endogenous progestogens are important regulators of vertebrate reproduction. Synthetic progestins are components of human contraceptive and hormone replacement pharmaceuticals. Both progestogens and progestins enter the environment through a number of sources, and have been shown to cause profound effects on reproductive health in various aquatic vertebrates. Progestins are designed to bind human progesterone receptors, but they also have been shown to strongly activate androgen receptors in fish. Levonorgestrel (LNG) activates fish androgen receptors and induces development of male secondary sex characteristics in females of other species. Although behavior has been postulated to be a sensitive early indicator of exposure to certain environmental contaminants, no such research on the reproductive behavior of gestagen-exposed fish has been conducted to date. The goal of our study was to examine the exposure effects of a human contraceptive progestin, LNG, on the reproductive development and behavior of the viviparous eastern mosquitofish (Gambusia holbrooki). Internal fertilization is a requisite characteristic of viviparous species, and is enabled by an androgen driven elongation of the anal fin into the male gonopodium (i.e., phallus). In this study, we exposed adult mosquitofish to ethanol (EtOH control), 10ng/L, and 100ng/L LNG for 8d using a static replacement exposure design. After 8d, a subset of males and females from each treatment were examined for differences in the 4:6 anal fin ratio. In addition, paired social interaction trials were performed using individual control males and control females or females treated 10ng/L or 100ng/L LNG. Female mosquitofish exposed to LNG were masculinized as evidenced by the elongation of the anal fin rays, a feature normal to males and abnormal to females. LNG caused significant increases in the 4:6 anal fin ratios of female mosquitofish in both the 10ng/L and 100ng/L treatments, although these differences were not

  5. High-sensitivity simultaneous liquid chromatography–tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma

    Directory of Open Access Journals (Sweden)

    Abhishek Gandhi

    2015-10-01

    Full Text Available A sensitive and simultaneous liquid chromatography–tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C18 (50 mm×4.6 mm, 2.6 µm column with a mobile phase of 0.1% (v/v formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100–20.0 ng/mL for levonorgestrel and 4.00–500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.

  6. Effect of Efavirenz on Endogenous Progesterone Concentrations and Contraceptive Outcomes among Ugandan HIV Infected Women Coadministering Ethinylestradiol/Levonorgestrel.

    Science.gov (United States)

    Munkwase, Grant; Bisaso, Kuteesa R; Kakaire, Othman; Nanzigu, Sarah

    2017-01-01

    This study assessed the effect of efavirenz mid-dose plasma concentrations on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among 49 HIV infected women coadministering ethinylestradiol/levonorgestrel, including 34 HIV positive women on Highly Active Antiretroviral Therapy (HAART) and 15 HAART naïve HIV infected women, purposively selected from Mulago Hospital, Uganda. A blood sample was collected once between days 20 and 22 of each woman's menstrual cycle for measuring endogenous progesterone and efavirenz concentrations by electrochemiluminescence technology and High Performance Liquid Chromatography (HPLC), respectively. Descriptive statistical analysis and correlation and logistic regression analysis were done using SPSS v.21 and R3.1. Efavirenz showed a weak positive linear relationship with endogenous progesterone at efavirenz concentrations below 12 μg/ml. Based on serum endogenous progesterone, the observed hormonal contraceptives failure rate (24.5%) was higher than expected (maximum 8%). A higher proportion of HIV positive women on efavirenz based HAART (26.5%) was at risk of contraceptive failure than their HIV infected HAART naïve counterparts (20%) though it was not statistically significant (p = 0.63). Efavirenz mid-dose plasma concentrations seem to have no significant effect on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among HIV infected Ugandan women coadministering ethinylestradiol/levonorgestrel oral pills.

  7. Effect of Efavirenz on Endogenous Progesterone Concentrations and Contraceptive Outcomes among Ugandan HIV Infected Women Coadministering Ethinylestradiol/Levonorgestrel

    Directory of Open Access Journals (Sweden)

    Grant Munkwase

    2017-01-01

    Full Text Available This study assessed the effect of efavirenz mid-dose plasma concentrations on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among 49 HIV infected women coadministering ethinylestradiol/levonorgestrel, including 34 HIV positive women on Highly Active Antiretroviral Therapy (HAART and 15 HAART naïve HIV infected women, purposively selected from Mulago Hospital, Uganda. A blood sample was collected once between days 20 and 22 of each woman’s menstrual cycle for measuring endogenous progesterone and efavirenz concentrations by electrochemiluminescence technology and High Performance Liquid Chromatography (HPLC, respectively. Descriptive statistical analysis and correlation and logistic regression analysis were done using SPSS v.21 and R3.1. Efavirenz showed a weak positive linear relationship with endogenous progesterone at efavirenz concentrations below 12 μg/ml. Based on serum endogenous progesterone, the observed hormonal contraceptives failure rate (24.5% was higher than expected (maximum 8%. A higher proportion of HIV positive women on efavirenz based HAART (26.5% was at risk of contraceptive failure than their HIV infected HAART naïve counterparts (20% though it was not statistically significant (p=0.63. Efavirenz mid-dose plasma concentrations seem to have no significant effect on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among HIV infected Ugandan women coadministering ethinylestradiol/levonorgestrel oral pills.

  8. Sol-Gel Entrapped Levonorgestrel Antibodies: Activity and Structural Changes as a Function of Different Polymer Formats

    Directory of Open Access Journals (Sweden)

    Moran Shalev

    2011-02-01

    Full Text Available The paper describes development of a sol-gel based immunoaffinity method for the steroid hormone levonorgestrel (LNG and the effects of changes in the sol-gel matrix format on the activity of the entrapped antibodies (Abs and on matrix structure. The best sol-gel format for Ab entrapment was found to be a tetramethoxysilane (TMOS based matrix at a TMOS:water ratio of 1:8, containing 10% polyethylene glycol (PEG of MW 0.4 kDa. Addition of higher percentages of PEG or a higher MW PEG did not improve activity. No activity was obtained with a TMOS:water ratio of 1:12, most likely because of the very dense polymer that resulted from these polymerization conditions. Only minor differences in the non-specific binding were obtained with the various formats. TMOS was found to be more effective than tetrakis (2-hydroxyethylorthosilicate (THEOS for entrapment of anti-levonorgestrel (LNG Abs. However, aging the THEOS-based sol-gel for a few weeks at 4 °C stabilized the entrapped Abs and increased its binding capacity. Confocal fluorescent microscopy with fluorescein isothiocyanate (FITC labeled immunoglobulines (IgGs entrapped in the sol-gel matrix showed that the entrapped Abs were distributed homogenously within the gel. Scanning electron microscopy (SEM images have shown the diverse structures of the various sol-gel formats and precursors.

  9. High-sensitivity simultaneous liquid chromatography-tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma

    Institute of Scientific and Technical Information of China (English)

    Abhishek Gandhi; Swati Guttikar; Priti Trivedi

    2015-01-01

    A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C18 (50 mm × 4.6 mm, 2.6μm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.

  10. Barriers to Single-Dose Levonorgestrel-Only Emergency Contraception Access in Retail Pharmacies.

    Science.gov (United States)

    Chau, Van Mimi; Stamm, Carol A; Borgelt, Laura; Gaffaney, Michelle; Moore, Alia; Blumhagen, Rachel Z; Rupp, Leanne; Topp, Daniel; Gilroy, Christine

    In February 2014, the Food and Drug Administration updated its regulations to make all single-dose levonorgestrel-only emergency contraception (LNG-EC) available over the counter. This study examines the availability and access to LNG-EC shortly after this policy change, and any additional barriers to obtaining LNG-EC in Colorado retail pharmacies. From June to July 2014, three female interviewers posing as women seeking LNG-EC conducted a telephone survey of all 633 Colorado retail pharmacies listed in The Little Blue Book (2014) phone directory. Completely accessible was defined as LNG-EC available on store shelves for purchase without presentation of an ID or prescription on the day of the call. Of 633 pharmacies analyzed, 85.0% (538/633) were in urban settings and 85.3% (540/633) were chain stores. Eighteen of 64 (28.1%) counties in Colorado did not have a pharmacy listed in the phone directory. Overall, 86.9% of pharmacies (550/633) had EC in stock on the day of contact but only 23.2% (147/633) of these had EC completely accessible. Of pharmacies with EC in stock, 41.6% (229/550) kept it behind the counter and 56.0% (308/550) required additional documentation to purchase. In stock and completely accessible rates were not different across rural, urban, and frontier geographic regions within the state (p = .066 and p = .905, respectively), but were significantly different across independent, chain, and 24-hour type stores (p < .001 and p = .008, respectively). In stock rates were 57.5% (42/73), 90.4% (488/540), and 100% (20/20) for independent, chain, and 24-hour stores respectively. Rates of completely accessible LNG-EC are low in Colorado despite high rates of availability. Behind-the-counter status and proof-of-age requirements are identified as the main sources of access restriction in Colorado. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  11. Levonorgestrel release rates over 5 years with the Liletta® 52-mg intrauterine system.

    Science.gov (United States)

    Creinin, Mitchell D; Jansen, Rolf; Starr, Robert M; Gobburu, Joga; Gopalakrishnan, Mathangi; Olariu, Andrea

    2016-10-01

    To understand the potential duration of action for Liletta®, we conducted this study to estimate levonorgestrel (LNG) release rates over approximately 5½years of product use. Clinical sites in the U.S. Phase 3 study of Liletta collected the LNG intrauterine systems (IUSs) from women who discontinued the study. We randomly selected samples within 90-day intervals after discontinuation of IUS use through 900days (approximately 2.5years) and 180-day intervals for the remaining duration through 5.4years (1980days) to evaluate residual LNG content. We also performed an initial LNG content analysis using 10 randomly selected samples from a single lot. We calculated the average ex vivo release rate using the residual LNG content over the duration of the analysis. We analyzed 64 samples within 90-day intervals (range 6-10 samples per interval) through 900days and 36 samples within 180-day intervals (6 samples per interval) for the remaining duration. The initial content analysis averaged 52.0±1.8mg. We calculated an average initial release rate of 19.5mcg/day that decreased to 17.0, 14.8, 12.9, 11.3 and 9.8mcg/day after 1, 2, 3, 4 and 5years, respectively. The 5-year average release rate is 14.7mcg/day. The estimated initial LNG release rate and gradual decay of the estimated release rate are consistent with the target design and function of the product. The calculated LNG content and release rate curves support the continued evaluation of Liletta as a contraceptive for 5 or more years of use. Liletta LNG content and release rates are comparable to published data for another LNG 52-mg IUS. The release rate at 5years is more than double the published release rate at 3years with an LNG 13.5-mg IUS, suggesting continued efficacy of Liletta beyond 5years. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use.

    Science.gov (United States)

    Gemzell-Danielsson, Kristina; Apter, Dan; Dermout, Sylvia; Faustmann, Thomas; Rosen, Kimberly; Schmelter, Thomas; Merz, Martin; Nelson, Anita

    2017-03-01

    To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years. Copyright

  13. Levonorgestrel-Releasing Intrauterine System (52 mg) for Idiopathic Heavy Menstrual Bleeding: A Health Technology Assessment.

    Science.gov (United States)

    2016-01-01

    Heavy menstrual bleeding affects as many as one in three women and has negative physical, economic, and psychosocial impacts including activity limitations and reduced quality of life. The goal of treatment is to make menstruation manageable, and options include medical therapy or surgery such as endometrial ablation or hysterectomy. This review examined the evidence of effectiveness and cost-effectiveness of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) as a treatment alternative for idiopathic heavy menstrual bleeding. We conducted a systematic review of the clinical and economic evidence comparing LNG-IUS with usual medical therapy, endometrial ablation, or hysterectomy. Medline, EMBASE, Cochrane, and the Centres for Reviews and Dissemination were searched from inception to August 2015. The quality of the evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also completed an economic evaluation to determine the cost-effectiveness and budget impact of the LNG-IUS compared with endometrial ablation and with hysterectomy. The economic evaluation was conducted from the perspective the Ontario Ministry of Health and Long-Term Care. Relevant systematic reviews (n = 18) returned from the literature search were used to identify eligible randomized controlled trials, and 16 trials were included. The LNG-IUS improved quality of life and reduced menstrual blood loss better than usual medical therapy. There was no evidence of a significant difference in these outcomes compared with the improvements offered by endometrial ablation or hysterectomy. Mild hormonal side effects were the most commonly reported. The quality of the evidence varied from very low to moderate across outcomes. Results from the economic evaluation showed the LNG-IUS was less costly (incremental saving of $372 per person) and more effective providing higher quality-adjusted life years (incremental

  14. Timing of insertion of levonorgestrel-releasing intrauterine system: a randomised controlled trial.

    Science.gov (United States)

    van der Heijden, Pahh; Geomini, Pmaj; Herman, M C; Veersema, S; Bongers, M Y

    2017-01-01

    The objective was to assess whether patient-perceived pain during the insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) depends on the timing during the menstrual cycle. A stratified two-armed non-inferiority randomised controlled trial. Large teaching hospital in Veldhoven, the Netherlands. From October 2013 to May 2014, 60 nulliparous and 60 multiparous women were randomised. Eight women withdrew after randomisation and before insertion took place: therefore, data from 112 women were collected and analysed. Women were randomised to the groups 'during menstruation' (i.e. days 1-7 of menstruation) or 'outside menstruation' (i.e. any day of the cycle after menstruation without the presence of vaginal blood loss) in a ratio of 1 : 1. The primary outcome was pain during insertion, measured by the visual analogue scale (VAS, 0-100 mm). Second, we analysed ease of insertion, bleeding pattern, satisfaction, pregnancy, and expulsion rate. The follow-up time was 3 months. The mean VAS score for nulliparous women was 74 mm (95% confidence interval, 95% CI 67-81) in the 'during menstruation' group, compared with 66 mm (95% CI 59-74) in the 'outside menstruation' group (P = 0.14). The mean VAS score for multiparous women was 30 mm (95% CI 20-40) in the 'during menstruation group', compared with 43 mm (95% CI 32-53) in the 'outside menstruation' group (P = 0.08). There was no difference between the stratified 'during menstruation' group and the 'outside menstruation' group with regards to ease of insertion, satisfaction, bleeding pattern, and median spotting and bleeding days for the use of the LNG-IUS 3 months after insertion. As we did not find that the level of pain perceived during insertion was higher during menstruation, compared with outside menstruation, we conclude that the LNG-IUS can be inserted at any time during the menstrual cycle, especially in the case of nulliparous women. We conducted an RCT on time of insertion of

  15. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2017-01-01

    Full Text Available Dirk Wildemeersch,1 Amaury Andrade,2 Norman D Goldstuck,3 Thomas Hasskamp,4 Geert Jackers5 1Gynecological Outpatient Clinic and IUD Training Center, Ghent, Belgium; 2Centro de Biologia da Reprodução, Universidade Federal Juiz de Fora, Juiz de Fora, Brazil; 3Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Western Cape, South Africa; 4Klinik für Operativen Gynäkologie, GynMünster, Münster, Germany; 5Applied Controlled Release, Technology Park, Ghent (Zwijnaarde, Belgium Abstract: The concept of using a frameless intrauterine device (IUD instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the

  16. Levonorgestrel-Releasing Intrauterine System (52 mg) for Idiopathic Heavy Menstrual Bleeding: A Health Technology Assessment

    Science.gov (United States)

    Schaink, Alexis; Chan, Brian; Higgins, Caroline

    2016-01-01

    Background Heavy menstrual bleeding affects as many as one in three women and has negative physical, economic, and psychosocial impacts including activity limitations and reduced quality of life. The goal of treatment is to make menstruation manageable, and options include medical therapy or surgery such as endometrial ablation or hysterectomy. This review examined the evidence of effectiveness and cost-effectiveness of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) as a treatment alternative for idiopathic heavy menstrual bleeding. Methods We conducted a systematic review of the clinical and economic evidence comparing LNG-IUS with usual medical therapy, endometrial ablation, or hysterectomy. Medline, EMBASE, Cochrane, and the Centres for Reviews and Dissemination were searched from inception to August 2015. The quality of the evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also completed an economic evaluation to determine the cost-effectiveness and budget impact of the LNG-IUS compared with endometrial ablation and with hysterectomy. The economic evaluation was conducted from the perspective the Ontario Ministry of Health and Long-Term Care. Results Relevant systematic reviews (n = 18) returned from the literature search were used to identify eligible randomized controlled trials, and 16 trials were included. The LNG-IUS improved quality of life and reduced menstrual blood loss better than usual medical therapy. There was no evidence of a significant difference in these outcomes compared with the improvements offered by endometrial ablation or hysterectomy. Mild hormonal side effects were the most commonly reported. The quality of the evidence varied from very low to moderate across outcomes. Results from the economic evaluation showed the LNG-IUS was less costly (incremental saving of $372 per person) and more effective providing higher quality

  17. Levonorgestrel-releasing intrauterine system (LNG-IUS 12) for prevention of pregnancy for up to five years.

    Science.gov (United States)

    Nelson, Anita L

    2017-08-01

    A new five-year low dose, smaller-framed, levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 12) has been introduced to complement the currently available systems. Areas Covered: This article will provide an overview of this new intrauterine system - its composition and its mechanisms of action as well as the results of the Phase II and III clinical trials of its efficacy, safety and tolerability. Expert Commentary: This new LNG-IUS 12 provides five-year contraceptive protection a pregnancy rate (less than 1%) in first year of use, which puts it into the top tier with the existing LNG-IUS 20 products; however, the LNG-IUS 12 does not have the high rates of amenorrhea often seen with the higher dose devices. On the other hand, this new IUD shares the smaller frame and narrower insertion tube with the lower dose LNG-IUS 8, but offers longer effective life.

  18. The comparative study of side effect of the two kinds of LD combined oral contraceptive pills containing Norgestimate and Levonorgestrel

    Directory of Open Access Journals (Sweden)

    Ghazizade Sh

    1998-05-01

    Full Text Available In order to compare the new generation of oral contraceptive pills containing Norgestimate (NGM with currently available pills containing levonorgestrel (LNG a clinical trial was conducted. 413 women (age 18-35 years with no contrainindication to pill use entered the study and randomly received one type of pills. Premenstrual syndrome and depression were significantly decreased in NGM group (P=0.00016, P=0.005, on the other hand, breast tenderness, mood changes and hair loss were significantly increased in LNG group (P=0.001, P=0.042, P=0.011. Comparing two groups with each other, following variables were significantly lower in NGM group: headache (P<0.05, vertigo (P<0.05, cloasma (P<0.05, acne (P<0.04, depression (P<0.05, appetite change (P<0.03. Overall patient satisfaction was similar in two groups.

  19. Prosprective study of the forearrm bone mineral density of long-term users of levonorgestrel - releasing intrauterine syustem

    OpenAIRE

    Maria Valeria Bahamondes Makuch

    2009-01-01

    Resumo: Introdução: A osteoporose é uma doença sistêmica que afeta principalmente as mulheres. Alguns dos fatores que aceleram a aparição desta doença são a idade e o uso, por longa data, de métodos anticoncepcionais com somente progestágenos. O sistema intrauterino liberador de levonorgestrel (SIU-LNG) é um método difundido para a contracepção e o tratamento de diversas patologias ginecológicas. Na literatura não foram identificados estudos longitudinais prospectivos, com usuárias de longa d...

  20. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction.

    Science.gov (United States)

    Chang, Jennifer; Fedinec, Alexander L; Kuntamallappanavar, Guruprasad; Leffler, Charles W; Bukiya, Anna N; Dopico, Alex M

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  1. Sino-implant (II) - a levonorgestrel-releasing two-rod implant: systematic review of the randomized controlled trials

    Science.gov (United States)

    Steiner, Markus J.; Lopez, Laureen M.; Grimes, David A.; Cheng, Linan; Shelton, Jim; Trussell, James; Farley, Timothy M.M.; Dorflinger, Laneta

    2013-01-01

    Background Sino-implant (II) is a subdermal contraceptive implant manufactured in China. This two-rod levonorgestrel-releasing implant has the same amount of active ingredient (150 mg levonorgestrel) and mechanism of action as the widely available contraceptive implant Jadelle. We examined randomized controlled trials of Sino-implant (II) for effectiveness and side effects. Study design We searched electronic databases for studies of Sino-implant (II), and then restricted our review to randomized controlled trials. The primary outcome of this review was pregnancy. Results Four randomized trials with a total of 15,943 women assigned to Sino-implant (II) had first-year probabilities of pregnancy ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the four years of the product's approved duration of use were 0.9% and 1.06% in the two trials that presented date for four-year use. Five-year cumulative probabilities of pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may be why the implant is approved for four years of use in China. Five-year cumulative probabilities of discontinuation due to menstrual problems ranged from 12.5% to 15.5% for Sino-implant (II). Conclusions Sino-implant (II) is one of the most effective contraceptives available today. These available clinical data, combined with independent laboratory testing, and the knowledge that 7 million women have used this method since 1994, support the safety and effectiveness of Sino-implant (II). The lower cost of Sino-implant (II) compared with other subdermal implants could improve access to implants in resource-constrained settings. PMID:20159174

  2. Conservative management in ureteric hydronephrosis due to deep endometriosis: Could the levonorgestrel-intrauterine device be an option?

    Science.gov (United States)

    Simón, Elisa; Tejerizo, Álvaro; Muñoz, José Luis; Álvarez, Carmen; Marqueta, Laura; Jiménez, Jesús S

    2017-07-01

    Endometriosis can affect up to 10% of women of reproductive age, in a wide range of clinical presentations that vary from mild to severe or deep endometriosis. Deep endometriosis can affect the urinary tract in 1-5% to 15-25% cases. Even though deep endometriosis' surgeries are usually complex with higher rate of complications, conservative management is not always considered as an option because of its high failure rates. This paper describes two cases of deep endometriosis with ureteric involvement (hydronephrosis) treated conservatively with a double-pigtail stent plus a Levonorgestrel intrauterine device, after conservative surgery, who remained symptom free with no evidence of recurrence at 3 years follow-up, avoiding radical high-risk surgery. Impact statement Several treatments have been described for endometriosis. From a symptomatic perspective, conservative medical management has been proposed with a variable response. Concerning deep endometriosis (affecting the urinary or digestive tract), the definitive treatment has always been thought to be radical surgery. However, this can lead to several complications. To illustrate a possible more conservative approach this paper describes two cases of deep infiltrating endometriosis affecting the ureter, treated conservatively with a temporary pigtail ureter stent plus a Levonorgestrel intrauterine device. The management demonstrates that, in a selected population, conservative treatment solves the urinary disease avoiding the surgical complications and, what is more, improving patients' symptoms in a permanent way. Further prospective studies are needed to confirm whether the introduction of this management in clinical practice would reduce the need for surgery thereby, avoiding high-risk surgery and improving the success rate of conservative management.

  3. Oral toxicity of isotretinoin, misoprostol, methotrexate, mifepristone and levonorgestrel as pregnancy category X medications in female mice.

    Science.gov (United States)

    Kim, Seong-Kwan; Shin, Soo-Jeong; Yoo, Yohan; Kim, Na-Hyun; Kim, Dong-Soon; Zhang, Dan; Park, Jin-A; Yi, Hee; Kim, Jin-Suk; Shin, Ho-Chul

    2015-03-01

    An oral toxicity study of several pregnancy category X drugs was performed in female ICR mice. The drugs were administered orally once daily for 3 days at doses of 1, 10 and 100 μg/kg for isotretinoin; 6.7, 67 and 670 μg/kg for misoprostol; 83, 830 and 8,300 μg/kg for methotrexate; 3.3, 33 and 330 μg/kg for mifepristone; and 25, 250 and 2,500 μg/kg for levonorgestrel. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry and necropsy findings were examined. Following administration of methotrexate at 8,300 μg/kg, a number of animals exhibited decreased spontaneous activity, and one animal died. In the hematological analysis, compared with those treated with the control, the animals treated with the drugs exhibited similar significant decreases in the number of granulocytes and granulocyte differentiation, and increases in lymphocyte differentiation. In the serum biochemical analysis, animals receiving high doses of the five drugs demonstrated significant changes in uric acid, glucose, alkaline phosphatase, total bilirubin, lipase, total cholesterol and calcium. At necropsy, intestinal redness was frequently observed in animals that received the high dose of methotrexate. Uterus enlargement and ovary dropsy were also detected in the groups receiving mifepristone and levonorgestrel. Despite the short-term exposure, these drugs exhibited significant side effects, including white blood cell toxicity, in the mouse model. Category X drugs can be traded illegally via the internet for the purpose of early pregnancy termination. Thus, illegal abuse of the drugs should be further discouraged to protect mothers.

  4. A randomized trial of levonorgestrel intrauterine system insertion 6 to 48 h compared to 6 weeks after vaginal delivery; lessons learned.

    Science.gov (United States)

    Stuart, Gretchen S; Lesko, Catherine R; Stuebe, Alison M; Bryant, Amy G; Levi, Erika E; Danvers, Antoinette I

    2015-04-01

    The objective of this randomized trial was to compare breastfeeding among women who received a levonorgestrel-releasing intrauterine system within 6-48 h (early) or 4-6 weeks (standard) after an uncomplicated vaginal birth. Analysis groups of 86 women in each arm were needed to demonstrate a 20% difference in any breastfeeding. Thirty-five women were randomized to the early (N=17) and standard (N=18) arms. The combination of unsuccessful placement (2/17; 12%), expulsions (7/17; 41%) and removals (3/17; 18%) reached 71% (12/17) in the early arm, so the study was stopped. In our small study cohort, levonorgestrel-releasing intrauterine system insertion between 6 and 48 h after vaginal birth was associated with a high rate of expulsion or removal soon after insertion.

  5. Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

    Directory of Open Access Journals (Sweden)

    Bruna P. V. Dantas

    2014-07-01

    Full Text Available It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4–(hydroxyimino-2-(3-methylbut-2-enylnaphtalen-1(4H-one (Oxime S1 derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10, 15, 20 and 30 mg/Kg, i.v. produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10−8 M to 10−4 M. In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO pathway. Additionally, Oxime S1 (30 and 100 µM significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting a role for potassium channels, more precisely Kir, Kv and KATP channels. We observed the involvement of BKCa channels in Oxime S1-induced relaxation in mesenteric artery rings. In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC and K+ channels.

  6. Comparison of the levonorgestrel-releasing intrauterine system, hysterectomy, and endometrial ablation for heavy menstrual bleeding in a decision analysis model.

    Science.gov (United States)

    Louie, Michelle; Spencer, Jennifer; Wheeler, Stephanie; Ellis, Victoria; Toubia, Tarek; Schiff, Lauren D; Siedhoff, Matthew T; Moulder, Janelle K

    2017-08-10

    A better understanding of the relative risks and benefits of common treatment options for abnormal uterine bleeding (AUB) can help providers and patients to make balanced, evidence-based decisions. To provide comparative estimates of clinical outcomes after placement of levonorgestrel-releasing intrauterine system (LNG-IUS), ablation, or hysterectomy for AUB. A PubMED search was done using combinations of search terms related to abnormal uterine bleeding, LNG-IUS, hysterectomy, endometrial ablation, cost-benefit analysis, cost-effectiveness, and quality-adjusted life years. Full articles published in 2006-2016 available in English comparing at least two treatment modalities of interest among women of reproductive age with AUB were included. A decision tree was generated to compare clinical outcomes in a hypothetical cohort of 100 000 premenopausal women with nonmalignant AUB. We evaluated complications, mortality, and treatment outcomes over a 5-year period, calculated cumulative quality-adjusted life years (QALYs), and conducted probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system had the highest number of QALYs (406 920), followed by hysterectomy (403 466), non-resectoscopic ablation (399 244), and resectoscopic ablation (395 827). Ablation had more treatment failures and complications than LNG-IUS and hysterectomy. Findings were robust in probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system and hysterectomy outperformed endometrial ablation for treatment of AUB. © 2017 International Federation of Gynecology and Obstetrics.

  7. Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas.

    Science.gov (United States)

    Wang, Hui-Ping; Lu, Jian-Feng; Zhang, Guo-Lin; Li, Xu-Yun; Peng, Hong-Yun; Lu, Yuan; Zhao, Liang; Ye, Zhi-Guo; Bruce, Iain C; Xia, Qiang; Qian, Ling-Bo

    2014-09-01

    Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper contaminated soil in China, which has been reported to benefit cardiovascular systems as folk medicine. However, few direct evidences have been found to clarify the vasorelaxation effect of total flavonoids of ES (TFES). The vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFES (5-200mg/L) caused a concentration-dependent vasorelaxation in endothelium-intact rings, which was not abolished but significantly reduced by the removal of endothelium. The nitric oxide synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (100μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (30μM) significantly blocked the endothelium-dependent vasorelaxation of TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration-dependently elevated by TFES. However, indomethacin (10μM) did not affect TFES-induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was significantly attenuated by KATP channel blocker glibenclamide. The accumulative Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or phenylephrine was markedly weakened by TFES. These results revealed that the NOS/NO/cGMP pathway is likely involved in the endothelium-dependent vasorelaxation induced by TFES, while activating KATP channel, inhibiting intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+) influx into vascular smooth muscle cells might contribute to the endothelium-independent vasorelaxation conferred by TFES.

  8. Definitive Hematopoiesis in the Yolk Sac Emerges from Wnt-Responsive Hemogenic Endothelium Independently of Circulation and Arterial Identity.

    Science.gov (United States)

    Frame, Jenna M; Fegan, Katherine H; Conway, Simon J; McGrath, Kathleen E; Palis, James

    2016-02-01

    Adult-repopulating hematopoietic stem cells (HSCs) emerge in low numbers in the midgestation mouse embryo from a subset of arterial endothelium, through an endothelial-to-hematopoietic transition. HSC-producing arterial hemogenic endothelium relies on the establishment of embryonic blood flow and arterial identity, and requires β-catenin signaling. Specified prior to and during the formation of these initial HSCs are thousands of yolk sac-derived erythro-myeloid progenitors (EMPs). EMPs ensure embryonic survival prior to the establishment of a permanent hematopoietic system, and provide subsets of long-lived tissue macrophages. While an endothelial origin for these HSC-independent definitive progenitors is also accepted, the spatial location and temporal output of yolk sac hemogenic endothelium over developmental time remain undefined. We performed a spatiotemporal analysis of EMP emergence, and document the morphological steps of the endothelial-to-hematopoietic transition. Emergence of rounded EMPs from polygonal clusters of Kit(+) cells initiates prior to the establishment of arborized arterial and venous vasculature in the yolk sac. Interestingly, Kit(+) polygonal clusters are detected in both arterial and venous vessels after remodeling. To determine whether there are similar mechanisms regulating the specification of EMPs with other angiogenic signals regulating adult-repopulating HSCs, we investigated the role of embryonic blood flow and Wnt/β-catenin signaling during EMP emergence. In embryos lacking a functional circulation, rounded Kit(+) EMPs still fully emerge from unremodeled yolk sac vasculature. In contrast, canonical Wnt signaling appears to be a common mechanism regulating hematopoietic emergence from hemogenic endothelium. These data illustrate the heterogeneity in hematopoietic output and spatiotemporal regulation of primary embryonic hemogenic endothelium.

  9. [Levonorgestrel-releasing intrauterine device (Mirena) and breast cancer: what do we learn from literature for clinical practice?].

    Science.gov (United States)

    Boutet, G

    2006-11-01

    Annual occurrence of breast cancer is constantly increasing in France. In 2000, the number of breast cancer cases for women of 30-49 years was estimated at 9,918, which represents 23.7% of all breast cancer cases diagnosed that year. The levonorgestrel-releasing intrauterine device (IUD LNG) is one of the most frequently used coils in France. Because contraception is an important matter for women whose ovarian function survived cancer treatments, the question of whether to use such device on a woman with breast cancer has become a frequent and controversial gynaecological issue. With the review of available literature as a basis, we have tried to answer the following questions. First, whether the use of IUD LNG increases the risk of breast cancer: there is at the moment no "A" level answer available. According to the only study published, which may be considered "C" level, there is no such increase. Second, whether the use of IUD LNG counterbalances the endometrial effects of Tamoxifene: based on a limited level of evidence via a single randomised controlled trial on a small number of patients for one year only, this device appears to be able to prevent benign endometrial modifications. However, there is no conclusive study regarding its effectiveness on the prevention of endometrium adenocarcinoma caused by Tamoxifene. In addition, there are numerous uncertainties as to whether levonorgestrel presence in the plasma would have a systemic prejudicial impact. Third, whether a woman with a personal antecedent of breast cancer can safely use DIU LNG: it is necessary to remove it promptly upon suspicion or diagnosis, to dissuade its use in case of current cancer, and, in the event of cancer remission for more than 5 years, to generally avoid this contraceptive method except on a case by case basis and with a regular medical follow-up. In the latter situation, the use of IUD LNG can be considered only after a multidisciplinary collective formal decision and after the

  10. Experience and levels of satisfaction with the levonorgestrel-releasing intrauterine system in China: a prospective multicenter survey

    Directory of Open Access Journals (Sweden)

    Zhao S

    2014-10-01

    Full Text Available Shuping Zhao,1 Jihong Deng,2 Yan Wang,3 Shiliang Bi,4 Xiaoye Wang,5 Wen Qin,6 Zirong Huang,7 Li Li,8 Xin Mi,9 Liping Han,10 Qing Chang,11 Jian Li12 1The Affiliated Hospital of the Medical College Qingdao University, Qingdao, 2Kunming Maternal and Child Health Hospital, Kunming, 3Hubei Maternity and Child Health Hospital, Wuhan, 4West China Second University Hospital, Sichuan University, Chengdu, 5Peking University Third Hospital, Beijing, 6Changzhou Maternity and Child Health Hospital, Affiliated to Nanjing Medical University, Jiangsu, 7The Affiliated Women’s Hospital of Fudan University, Shanghai, 8Guangzhou Women and Children’s Medical Center, Guangzhou, 9Maternity and Child Health Care Hospital, Shunyi District, Beijing, 10The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, 11Southwest Hospital, Chongqing City, Chongqing, 12Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Although surveys conducted in Western countries have shown that the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena® is well accepted by European women, its acceptance by Chinese women is not yet clearly known. The purpose of this study was to analyze the experiences and levels of satisfaction with Mirena among Chinese women living in 12 different cities. Methods: In total, 1,021 women who attended 21 medical centers for insertion of Mirena were invited to complete a questionnaire regarding their contraceptive decision at baseline (preinsertion, and two further questionnaires on their experience and satisfaction with Mirena at 3–6 months and 1 year after insertion. Results: At baseline, 36% of women self-reported heavy or very heavy menstrual bleeding, while 41% reported normal bleeding. The majority of women (98% were satisfied with the preinsertion counseling, during which contraceptive reliability was identified as the most important reason for

  11. Levonorgestrel-releasing IUD versus copper IUD in control of dysmenorrhea, satisfaction and quality of life in women using IUD

    Directory of Open Access Journals (Sweden)

    Seyed Javad Purafzali Firuzabadi

    2012-01-01

    Full Text Available Background: The levonorgestrel-releasing IUD can help the treatment of dysmenorrhea by reducing the synthesis of endometrial prostaglandins as a conventional treatment. Objective: This study was performed to assess the frequency of dysmenorrhea, satisfaction and quality of life in women using Mirena IUDs as compared to those using copper IUDs.Materials and Methods: This double-blind randomized clinical trial was performed between 2006 and 2007 on 160 women aged between 20 to 35 years who attended Shahid Ayat Health Center of Tehran, and they were clients using IUDs for contraception. 80 individuals in group A received Mirena IUD and 80 individuals in group B received copper (380-A IUD. Demographic data, assessment of dysmenorrhea, and follow-up 1, 3 and 6 months after IUD replacement were recorded in questionnaires designed for this purpose. To assess the quality of life, SF36 questionnaire was answered by the attending groups, and to assess satisfaction, a test with 3 questions was answered by clients. Results: Dysmenorrhea significantly was decreased in both groups six months after IUD insertion as compared to the first month (p<0.001. However, statistically, Mirena reduced dysmenorrhea faster and earlier compared to cupper IUD (p<0.003. There isn’t any significant difference between these two groups in satisfaction and quality of life outcomes. Conclusion: There is no difference between these two groups in terms of the satisfaction and quality of life, therefor the usage of Mirena IUD is not a preferred contraception method.

  12. New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.

    Science.gov (United States)

    Nelson, Anita

    2010-08-09

    To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.

  13. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection.

    Science.gov (United States)

    Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L

    2016-11-01

    Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.

  14. Treatment of Women With an Endometrial Polyp and Heavy Menstrual Bleeding: A Levonorgestrel-Releasing Intrauterine Device or Hysteroscopic Polypectomy?

    Science.gov (United States)

    van Dijk, Myrthe M; van Hanegem, Nehalennia; de Lange, Maria E; Timmermans, Anne

    2015-01-01

    We performed a literature review of reports comparing a levonorgestrel-releasing intrauterine device (LNG-IUD) with transcervical polyp resection (TCRP) as a treatment for heavy menstrual bleeding (HMB). Our second objective was to investigate the effectiveness of LNG-IUD and TCRP in reducing menstrual bleeding and the patient satisfaction with each technique. No previously reported studies have compared TCRP and LNG-IUD as treatment for HMB in premenopausal women with an endometrial polyp. Likewise, no studies are available on LNG-IUD as a treatment for HMB in the presence of an endometrial polyp. Several studies have found the LNG-IUD to be an effective treatment option for HMB, with high patient satisfaction rates. Evidence of the effectiveness of TCRP as treatment of HMB is scarce. Patient satisfaction is reported relatively good, although persistent or recurrent symptoms appear to be frequent. We conclude that no evidence is available on LNG-IUD as treatment for HMB in women with an endometrial polyp. We hypothesize that LNG-IUD could be a good alternative to TCRP for treating HMB in premenopausal women with a polyp; however, further evidence is needed, and a randomized controlled trial should be performed.

  15. Physical and mental development of children after levonorgestrel emergency contraception exposure: a follow-up prospective cohort study.

    Science.gov (United States)

    Zhang, Lin; Ye, Weiping; Yu, Wen; Cheng, Linan; Shen, Lixiao; Yang, Zujing

    2014-07-01

    Levonorgestrel (LNG), a dedicated emergency contraception (EC) product, has been available over-the-counter in China for more than 14 yr. Although LNG-EC is considered to have no effects on the developing fetus if the contraceptive fails and pregnancy occurs, there have been a few studies specifically examining this issue. The purpose of this study was to compare the physical and mental development of children born after LNG-EC failure with that of a cohort of children born to mothers with no history of exposure to LNG or any teratogenic substances. A group of 195 children who were exposed to LNG-EC during their mothers' conception cycle (study group) were matched to a group of 214 children without exposure to LNG (control group). The physical and mental development of the children were evaluated and compared over a 2-yr period. There were four congenital malformations in the study group and three in the control group (2.1% vs. 1.4%, respectively, P > 0.05). Over the 2-yr follow-up period, there were no statistically significant differences between the two groups with respect to children's weight, height, head circumference, and intelligence scores, and the values of all parameters of both groups were similar to those of the national standards. In summary, LNG-EC has no effect on the physical growth, mental development, or occurrence of birth defects in children born from pregnancies in which EC failed.

  16. Responses to various exposure durations of levonorgestrel during early-life stages of fathead minnows (Pimephales promelas).

    Science.gov (United States)

    Overturf, Matthew D; Huggett, Duane B

    2015-04-01

    Pharmaceuticals are routinely detected in the environment; and several of these compounds have been extensively researched due to their potential impacts to the endocrine system of aquatic organisms. The negative reproductive consequences of synthetic progestins in teleost species have only recently been investigated. The current study examined different exposure periods that may be most sensitive for levonorgestrel (LNG) in early-life stages of fathead minnow larvae. Larvae were exposed to a single concentration of LNG (125ng/L) for different durations from fertilized egg through 28 days post hatch (dph) with growth and mRNA expression of FSH, 3β-HSD, 20β-HSD, and CYP19a1 measured. Regardless of the duration of exposure, LNG significantly decreased growth in the fathead minnow larvae at day 28. For both 20β-HSD and CYP19a1, mRNA expression was decreased following LNG exposure durations ≥7 days. 3β-HSD and FSH showed similar trends after exposure to LNG with later stages of development exhibiting decreased expression. 20β-HSD and 3β-HSD were the only transcripts to remain down regulated once larvae were moved to clean water after the 7-14dph LNG exposure. This study is the first to investigate the effects of exposure time to a synthetic progestin on developing fish. Future research is needed to understand what impacts these changes have on adult stages of development.

  17. The incidence of actinomyces-like organisms in Papanicolaou-stained smears of copper- and levonorgestrel-releasing intrauterine devices.

    Science.gov (United States)

    Merki-Feld, G S; Lebeda, E; Hogg, B; Keller, P J

    2000-06-01

    Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD). The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic actinomycosis is a severe disease that may require hysterectomy and salpingo-oophorectomy. In a retrospective study we compared the incidence of ALOs positive PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG-IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104). All IUDs had been inserted from 1996-1998. Women with a follow-up period of more than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n = 65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are discussed controversially. The low incidence in the LNG-IUD users probably leads to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

  18. Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Folkmann, Janne K; Jacobsen, Nicklas R

    2009-01-01

    (apoE-/-) with different degree of atherosclerosis. RESULTS: The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal...... injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium...... nitroprusside-induced vasorelaxation response in young apoE-/- mice. CONCLUSION: Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene...

  19. [Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women].

    Science.gov (United States)

    Jóźwik, Maciej; Jóźwik, Marcin; Modzelewska, Beata; Niewińska, Marta; Jóźwik, Michał

    2015-04-01

    The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

  20. Semaglutide, a Once-Weekly Human GLP-1 Analog, Does Not Reduce the Bioavailability of the Combined Oral Contraceptive, Ethinylestradiol/Levonorgestrel

    OpenAIRE

    Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

    2015-01-01

    The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0....

  1. Femilis(®) 60 Levonorgestrel-Releasing Intrauterine System-A Review of 10 Years of Clinical Experience.

    Science.gov (United States)

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman

    2016-01-01

    The aim of this study was to update the clinical experience with the Femilis® 60 levonorgestrel-releasing intrauterine system (LNG-IUS), now up to 10 years in parous and nulliparous women, particularly with regard to ease and safety of insertion, contraceptive performance, retention, acceptability, continuation of use, impact on menstrual blood loss (MBL), and duration of action. Using the Femilis® 60 LNG-IUS releasing 20 µg of levonorgestrel/day, the following studies were conducted: an open, prospective noncomparative contraceptive study, an MBL study, a perimenopausal study, a study for the treatment of endometrial hyperplasia, and early cancer of the uterus, a residue study. A total of 599 Femilis LNG-IUS were inserted in various clinical trials, the majority for contraceptive purposes. The total exposure in the first and second contraceptive studies, covering 558 parous and nulliparous women, was 32,717 woman-months. Femilis has high contraceptive effectiveness as only one pregnancy occurred. Expulsion of the LNG-IUS was rare with only two total and no partial expulsions (stem protruding through the cervical canal) occurred. Femilis was well tolerated, with continuation rates remaining high. Several MBL studies were conducted, totaling 80 heavy and normal menstrual bleeders, using the pictorial bleeding assessment chart method or the quantitative alkaline hematin technique. Virtually all women responded well with strongly reduced menstrual bleeding. Amenorrhea rates were high, up to 80% after three months, and ferritin levels simultaneously increased significantly. The Femilis LNG-IUS was tested in 104 symptomatic perimenopausal women for seamless transition to and through menopause, adding estrogen therapy when required. Patient tolerability appeared high as >80% requested a second and a third LNG-IUS. Twenty women presenting with nonatypical and atypical hyperplasia and one woman presenting with early endometrial carcinoma were treated with Femilis LNG

  2. Femilis® 60 Levonorgestrel-Releasing Intrauterine System—A Review of 10 Years of Clinical Experience

    Science.gov (United States)

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman

    2016-01-01

    OBJECTIVE The aim of this study was to update the clinical experience with the Femilis® 60 levonorgestrel-releasing intrauterine system (LNG-IUS), now up to 10 years in parous and nulliparous women, particularly with regard to ease and safety of insertion, contraceptive performance, retention, acceptability, continuation of use, impact on menstrual blood loss (MBL), and duration of action. STUDY DESIGN Using the Femilis® 60 LNG-IUS releasing 20 µg of levonorgestrel/day, the following studies were conducted: an open, prospective noncomparative contraceptive study, an MBL study, a perimenopausal study, a study for the treatment of endometrial hyperplasia, and early cancer of the uterus, a residue study. RESULTS A total of 599 Femilis LNG-IUS were inserted in various clinical trials, the majority for contraceptive purposes. The total exposure in the first and second contraceptive studies, covering 558 parous and nulliparous women, was 32,717 woman-months. Femilis has high contraceptive effectiveness as only one pregnancy occurred. Expulsion of the LNG-IUS was rare with only two total and no partial expulsions (stem protruding through the cervical canal) occurred. Femilis was well tolerated, with continuation rates remaining high. Several MBL studies were conducted, totaling 80 heavy and normal menstrual bleeders, using the pictorial bleeding assessment chart method or the quantitative alkaline hematin technique. Virtually all women responded well with strongly reduced menstrual bleeding. Amenorrhea rates were high, up to 80% after three months, and ferritin levels simultaneously increased significantly. The Femilis LNG-IUS was tested in 104 symptomatic perimenopausal women for seamless transition to and through menopause, adding estrogen therapy when required. Patient tolerability appeared high as >80% requested a second and a third LNG-IUS. Twenty women presenting with nonatypical and atypical hyperplasia and one woman presenting with early endometrial carcinoma

  3. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems.

    Science.gov (United States)

    Janagam, Dileep R; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R; Lowe, Tao L

    2016-09-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r² ≥ 0.98) well with that under real-time conditions at four months.

  4. Cardiovascular risk markers among obese women using the levonorgestrel-releasing intrauterine system: A randomised controlled trial.

    Science.gov (United States)

    Zueff, Lucimara Facio Nobre; Melo, Anderson Sanches de; Vieira, Carolina S; Martins, Wellington P; Ferriani, Rui A

    2017-07-07

    According to international guidelines, women with obesity without other comorbidities can safely use any hormonal contraceptive (HC). However, limited information is available about contraceptive safety for women with obesity since obesity is an exclusion criterion of most contraceptive clinical trials. As such little is known about the possible risks of HC exposure for women with obesity without comorbidities. One way to assess possible long-term risks in this population, even prior to the development of any clinical disease, is to measure alterations in subclinical atherosclerosis markers. We evaluated the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on subclinical markers of cardiovascular risk in women with obesity. This is a randomised clinical trial in which 106 women with obesity [body mass index (BMI)≥30kg/m(2)] were randomised to the LNG-IUS (n=53) or to non-hormonal methods (n=53) and followed for 12 months. We evaluated waist circumference (WC), blood pressure, blood glucose, insulin, lipid profile, and endothelial function markers (carotid intima-media thickness, brachial artery flow-mediated dilation, and carotid arterial stiffness). At 12 months, BMI (p=0.005), WC (p=0.045), and glucose levels (p=0.015) were significantly lower in the LNG-IUS group than in the control group. We did not find any clinically relevant changes in subclinical markers of cardiovascular risk among with obesity women at 12 months after LNG-IUS placement compared to users of non-hormonal contraceptive methods. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  5. Determination of ethinylestradiol and levonorgestrel in oral contraceptives with HPLC methods with UV detection and UV/fluorescence detection

    Directory of Open Access Journals (Sweden)

    Zorica Arsova-Sarafinovska

    2006-06-01

    Full Text Available Oral contraceptives are pharmaceutical formulations containing an estrogen in a small amount and a synthetic progestin in 5-30 times bigger amount. A sensitive, accurate and rapid method for determination of active compounds is required. We have developed HPLC methods for determination of ethinylestradiol (EED and levonorgestrel (LNG in commercially available tablets. Chromatographic separation was performed on a Purospher® STAR RP-18e reversed-phase column (150 X 4.0 mm I.D.; particle size 5 µm in an isocratic mode with a mobile phase constituted of 47% acetonitrile: 53% water (V/V for both methods. The elution was carried out at a flow rate of 1.50 ml /min. All analyses were performed at room temperature (24 +/- 2°C. In the HPLC method with UV detection (internal standard method both compounds were detected at 215 nm. Drospirenone was used as an internal standard. In HPLC method with UV/fluorescence detection (external standard method LNG was monitored at 242 nm, while EED was detected with fluorescence detector at 310 nm (excitation 285 nm. The methods’ performances were fully validated by a determination of linearity, reproducibility, accuracy and sensitivity. Both methods were applied for determination of Uniformity of Dosage Units. The results obtained with both methods were highly comparable. However, the HPLC method with UV/ fluorescence detection has showed superior sensitivity for EED indicated by 83 times lower detection limit. HPLC method with UV/ fluorescence detection could be recommended as a method of choice for determination of ethinylestradiol, present at a very low dosage level in low-dose oral contraceptives, that also contain bigger amount of synthetic progestin.

  6. Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: an economic evaluation alongside a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Sabina Sanghera

    Full Text Available OBJECTIVE: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS' and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. METHODS: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY estimated using both EQ-5D and SF-6D. RESULTS: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100 and generated 0.002 more QALYs. CONCLUSION: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most cost-effective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial.

  7. Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow?

    Directory of Open Access Journals (Sweden)

    Carlo Bastianelli

    2014-01-01

    Full Text Available Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I, amenorrheic women (Group II, and women with prolonged bleedings (Group III. Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI and resistance index (RI in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates.

  8. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    Directory of Open Access Journals (Sweden)

    Dileep R. Janagam

    2016-09-01

    Full Text Available Biodegradable polymer-based injectable in situ forming depot (ISD systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term conditions (PBS, pH 7.4, 37 °C and four accelerated (short-term conditions: (A PBS, pH 7.4, 50 °C; (B 25% ethanol in PBS, pH 7.4, 50 °C; (C 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98 well with that under real-time conditions at four months.

  9. Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

    Science.gov (United States)

    Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

    2017-05-01

    Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

  10. Usage of the levonorgestrel-releasing intrauterine system (LNG-IUS) in adolescence: what is the evidence so far?

    Science.gov (United States)

    Patseadou, Magdalini; Michala, Lina

    2017-03-01

    The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective method of contraception, while also providing various non-contraceptive benefits. Although targeted primarily to adults, there is increasing experience in its use in adolescence. The aim of this review is to assess the available information on LNG-IUS usage in adolescence. We conducted an online search on MEDLINE and SCOPUS from inception to May 24, 2015. All studies that examined LNG-IUS use in teen populations were eligible for inclusion. Primary outcome measures included description of indications for LNG-IUS usage and relevant efficacy. Secondary outcomes included complications, such as device-related problems (perforation and expulsion) and other adverse events (pelvic inflammatory disease, PID). Acceptability of the LNG-IUS was also estimated through evaluation of continuation rate and reasons for removal were assessed. Twenty-one studies met our inclusion criteria. We identified only one randomized controlled trial (RCT). All other twenty studies were observational. Pregnancy rates ranged from 0 to 2.7%. Management of heavy or/and painful periods was successful in 92-100%. Menstrual manipulation in patients with developmental delay was achieved in over 93% of cases. Expulsion rates ranged from 0 to 13% and pelvic infection/cervicitis between 0 and 2.7%. There were no reported uterine perforations. Usage of the LNG-IUS in teen populations appears to be safe and efficacious both in terms of contraception and menstrual management. However, more robust evidence is needed so as to provide firm confirmation on benefits and potential side effects.

  11. One-year continuation of copper or levonorgestrel intrauterine devices initiated at the time of emergency contraception.

    Science.gov (United States)

    Sanders, J N; Turok, D K; Royer, P A; Thompson, I S; Gawron, L M; Storck, K E

    2017-08-01

    This study compares 1-year intrauterine device (IUD) continuation among women presenting for emergency contraception (EC) and initiating the copper (Cu T380A) IUD or the levonorgestrel (LNG) 52 mg IUD plus 1.5 mg oral LNG. This cohort study enrolled 188 women who presented at a single family planning clinic in Utah between June 2013 and September 2014 and selected either the Cu T380A IUD or LNG 52 mg IUD plus oral LNG for EC. Trained personnel followed participants by phone, text or e-mail for 12 months or until discontinuation occurred. We assessed reasons for discontinuation and used Cox proportional hazard models, Kaplan-Meier estimates and log-rank tests to assess differences in continuation rates between IUDs. One hundred seventy-six women received IUDs; 66 (37%) chose the Cu T380A IUD and 110 (63%) chose the LNG 52 mg IUD plus oral LNG. At 1 year, we accounted for 147 (84%) participants, 33 (22%) had requested removals, 13 (9%) had an expulsion and declined reinsertion, 3 (2%) had a pregnancy with their IUD in place and 98 (67%) were still using their device. Continuation rates did not differ by IUD type; 60% of Cu T380A IUD users and 70% of LNG 52 mg IUD plus oral LNG users were still using their device at 12 months (adjusted hazard ratio 0.72, 95% confidence interval 0.40-1.3). Two-thirds of women who chose IUD placement at the EC clinical encounter continued use at 1 year. Women initiating Cu T380A IUD and LNG 52 mg IUD had similar 1-year continuation rates. These findings support same-day insertion of IUDs for women who are seeking EC and would like to use a highly effective reversible method going forward. Providing IUD options for EC users presents an opportunity to increase availability of highly effective contraception. Copyright © 2017. Published by Elsevier Inc.

  12. Impact of levonorgestrel-releasing intrauterine system use on the cancer risk of the ovary and fallopian tube.

    Science.gov (United States)

    Soini, Tuuli; Hurskainen, Ritva; Grénman, Seija; Mäenpää, Johanna; Paavonen, Jorma; Pukkala, Eero

    2016-11-01

    Levonorgestrel-releasing intrauterine system (LNG-IUS) is used for contraception and heavy menstrual bleeding. A long-term hormone therapy can modify the risk of gynecologic cancers. Little is known about the impact of LNG-IUS use on the risk for invasive and borderline ovarian tumor subtypes or for primary fallopian tube carcinoma. We examined the associations of LNG-IUS use with these tumors. We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 years who had used LNG-IUS for menorrhagia in 1994-2007, and from the Finnish Cancer Registry ovarian cancers and primary fallopian tube carcinomas diagnosed before the age of 55 and by the end of 2013. A total of 77 invasive ovarian cancers and seven primary fallopian tube carcinoma cases were diagnosed in a cohort of 93 843 LNG-IUS users during the follow-up of 1 083 126 women-years. The LNG-IUS users had decreased risk for both invasive ovarian cancer [standardized incidence ratio (SIR) 0.59, 95% confidence interval (CI) 0.47-0.73] and for borderline ovarian tumors (SIR 0.76, 95% CI 0.57-0.99) as compared to the background population. The risk of primary fallopian tube carcinoma was not increased (SIR 1.22, 95% CI 0.49-2.50). Decreased risks for mucinous (SIR 0.49, 95% CI 0.24-0.87), endometrioid (SIR 0.55, 95% CI 0.28-0.98), and serous ovarian carcinomas (SIR 0.75, 95% CI 0.55-0.99) were seen in LNG-IUS users. LNG-IUS use associated with decreased risk for both invasive and borderline ovarian tumors. The incidence of primary fallopian tube carcinoma did not significantly differ between LNG-IUS users and the background population.

  13. Fast-track vs. delayed insertion of the levonorgestrel-releasing intrauterine system after early medical abortion - a randomized trial.

    Science.gov (United States)

    Korjamo, Riina; Mentula, Maarit; Heikinheimo, Oskari

    2017-08-05

    To compare levonorgestrel (LNG) 52-mg intrauterine system (IUS) expulsion rates with fast-track (≤3 days) or delayed (2-4 weeks) insertion following mifepristone and misoprostol medical abortion. In this pilot trial, we randomized 108 women at ≤63 days' gestation to fast-track (n=55) or delayed (n=53) insertion. Follow-up visits occurred at 2-4 weeks, 3 months and 1 year. We assessed total and partial expulsion at 3 months and 1 year, adverse effects and bleeding profiles. We had follow-up data at 3 months and 1 year for 41 (74.5%) and 37 (69.8%) women in the fast-track group and 31 (56.4%) and 28 (52.8%) women in the delayed group. By 3 months, expulsion occurred in six (12.5%) women after fast-track and one (2.3%) woman after delayed insertion [risk ratio (RR) 5.50, 95% confidence interval (CI) 0.69-43.90]; most (n=5) of these were partial expulsions in the fast-track group. By 1 year, expulsion had occurred in seven (14.6%) and five (11.5%) women in the fast-track and delayed groups, respectively (RR 1.28, 95% CI 0.44-3.75). We found no differences in rates of vacuum aspiration, residual tissue, infection and bleeding or bleeding patterns within 3 months of insertion. Fast-track insertion of the LNG 52-mg IUS after medical abortion is feasible but may result in higher expulsion rates compared to delayed insertion. Due to lack of statistical power and high lost-to-follow-up rates, we were unable to fully address this question. Fast-tract initiation of LNG 52-mg IUS contraception after medical abortion is feasible. It results in higher expulsion rates than delayed insertion but may improve postabortal intrauterine contraception uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control

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    Anita Nelson

    2010-05-01

    Full Text Available Anita NelsonHarbor-UCLA Hospital, Los Angeles Biomedical Research Institute, Los Angeles, CA, USAAim: To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills.Methods: This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation.Results: The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation.Conclusion: The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis, fewer scheduled bleeding episodes (to meet women’s desires for fewer and shorter menses and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding. Hopefully, this unique formation will motivate women to be more successful contraceptors.Keywords: extended-cycle oral contraceptives, low-dose extended-cycle pills, Lo Seasonique

  15. Hormonal contraception in Chinese men:variations in suppression of spermatogenesis with injectable testosterone undecanoate and levonorgestrel implants

    Institute of Scientific and Technical Information of China (English)

    Si-TianLiu; You-LunOui; Cui-HongLin; Chang-HalHe

    2004-01-01

    Aim:To explore the causes of the difference in spermatogenic suppression between responders and non-responders in Chinese men treated with levonorgestrel (LNG) implants plus testosterone undecanoate (TU) injectable.Methods:The 16 Chinese volunteers treated were divided into two groups in regard to the sperm count during the treatment period,7 men in the responder group (Group R),including 6 azoospermia and one severe oligozoospermia,and the remaining 9 in the non-responder group (Group N),including 4 oligozoospermia and 5 with sperm counts greater than 20×106/mL.The differences in serum profiles of FSH,LH,T,LNG and T/LH ratio were compared between the two groups and the correlation between the seminal fluid parameters and serum reproductive hormones was analyzed.Results:The serum FSH level was lower in Group R than that in Group N (P<0.05),while the serum LH and LNG levels were higher in Group R than those in Group N (P<0.05).The sperm density (P<0.01,r=0.235),motility (P<0.01,r=0.326) and vitality (P<0.01,r=0.219) showed significantly positive correlation with the serum FSH level.Conclusion:The blood LNG and T levels,the degree of FSH inhibition and/or the sensitivity of the pituitary-testis axis to exogenous steroids,as well as the individual spermatogenetic potential and the functional status of the Leydig cells may be factors bringing about individual differences in spermatogenic suppression in Chinese men treated with LNG and TU.(Asian J Androl 2004 Mar;6:41-46)

  16. Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis.

    Science.gov (United States)

    Yuk, Jin-Sung; Song, Jae Yen; Lee, Jung Hun; Park, Won I; Ahn, Hyeong Sik; Kim, Hyun Jung

    2017-05-01

    This study aimed to compare the levonorgestrel-releasing intrauterine system (LNG-IUS) with oral cyclic medroxyprogesterone acetate (MPA) in endometrial hyperplasia therapy using randomized controlled trials (RCTs). The study searched MEDLINE, EMBASE, CENTRAL, and other databases. All regression outcomes were calculated for dichotomous outcomes in terms of relative risk (RR) and 95% confidence intervals (CIs) using a Mantel-Haenszel random effects model. The search found 543 articles but selected 342 articles after the removal of duplicates. A meta-analysis found five RCTs (377 patients). The study did not analyze RR for total outcome because of high heterogeneity (I (2) = 87%). In a subgroup analysis of studies with non-obese women, the LNG-IUS treatment appeared to have a higher regression rate than oral MPA (RR 1.41; 95% CI 1.23-1.62; 4 trials, 265 patients; I (2) = 0%). In a subgroup analysis of studies with obese women, LNG-IUS appeared to have a regression rate similar to that of oral MPA (RR 1.03; 95% CI 0.94-1.13; 1 trial, 60 patients). In a subgroup analysis according to histology in the non-obese group, the LNG-IUS treatment appeared to have a higher regression rate than oral cyclic MPA in a meta-analysis of women with non-atypical endometrial hyperplasia (RR 1.36; 95% CI 1.07-1.73; 2 trials, 92 patients; I (2) = 6%) and mixed endometrial hyperplasia (atypical and non-atypical) (RR 1.44; 95% CI 1.21-1.71; 2 trials, 173 patients; I (2) = 0%). The LNG-IUS treatment has a higher regression rate than cyclic MPA in non-atypical endometrial hyperplasia and mixed endometrial hyperplasia therapy for non-obese women but has a similar regression rate, albeit limited, for obese women.

  17. Levonorgestrel-releasing intrauterine system (Mirena in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia

    Directory of Open Access Journals (Sweden)

    Fariba Behnamfar

    2014-01-01

    Full Text Available Background: This study was designed to evaluate the comparison of insertion of levonorgestrel (LNG-releasing intrauterine system versus oral medroxyprogesterone acetate on endometrial hyperplasia in a randomized controlled trial. Materials and Methods: A total of 60 women with the initial histopathological diagnosis of endometrial hyperplasia in two groups received LNG or medroxyprogesterone (10 mg/d orally for 12 days a month for 3 months. Endometrial biopsy was obtained for all patients after 3 months of treatment. Response to treatment was defined based on the histopathology of the post treatment pipelle endometrial specimens in three categories of resolution, persistence and progression. Results: Treatment response rate in patients in the LNG group was 89.3% (25 of 28 patients, versus 70.4% (19 of 27 patients in patients in the medroxyprogesterone group. The rate of persistence was 10.7% (3 of 28 patients and 22.2% (6 of 27 patients in LNG and medroxyprogesterone groups respectively. No progression of endometrial hyperplasia observed in any of the patients in LNG group, but progression of endometrial hyperplasia was observed in 7.4% (2 of 27 patients in the medroxyprogesterone group. There was no statistically significant difference between groups regarding the response to treatment (P = 0.15. Side effects such as bloating, weight gain, fatigue and hair loss were comparable between the groups (P > 0.05. Hirsutism was significantly more in the medroxyprogesterone group than LNG group (P = 0.013. Conclusion: Results showed that the use of LNG for treating endometrial hyperplasia for 3 months was associated with high-treatment response rate and the low proportion of patients with progression compared to the use of medroxyprogesterone.

  18. Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome.

    Science.gov (United States)

    Brooks, J Paul; Edwards, David J; Blithe, Diana L; Fettweis, Jennifer M; Serrano, Myrna G; Sheth, Nihar U; Strauss, Jerome F; Buck, Gregory A; Jefferson, Kimberly K

    2017-04-01

    Prior studies suggest that the composition of the vaginal microbiome may positively or negatively affect susceptibility to sexually transmitted infections (STIs) and bacterial vaginosis (BV). Some female hormonal contraceptive methods also appear to positively or negatively influence STI transmission and BV. Therefore, changes in the vaginal microbiome that are associated with different contraceptive methods may explain, in part, effects on STI transmission and BV. We performed a retrospective study of 16S rRNA gene survey data of vaginal samples from a subset of participants from the Human Vaginal Microbiome Project at Virginia Commonwealth University. The subset included 682 women who reported using a single form of birth control that was condoms, combined oral contraceptives (COCs), depot medroxyprogesterone acetate (DMPA) or the levonorgestrel-releasing intrauterine system (LNG-IUS). Women using COCs [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.13-0.64] and DMPA (aOR 0.34, 95% CI 0.13-0.89), but not LNG-IUS (aOR 1.55, 95% CI 0.72-3.35), were less likely to be colonized by BV-associated bacteria relative to women who used condoms. Women using COCs (aOR 1.94, 95% CI 1.25-3.02) were more likely to be colonized by beneficial H2O2-producing Lactobacillus species compared with women using condoms, while women using DMPA (aOR 1.09, 95% CI 0.63-1.86) and LNG-IUS (aOR 0.74, 95% CI 0.48-1.15) were not. Use of COCs is significantly associated with increased vaginal colonization by healthy lactobacilli and reduced BV-associated taxa. COC use may positively influence gynecologic health through an increase in healthy lactobacilli and a decrease in BV-associated bacterial taxa. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Combined Oral Medroxyprogesterone/Levonorgestrel-Intrauterine System Treatment for Women With Grade 2 Stage IA Endometrial Cancer.

    Science.gov (United States)

    Hwang, Ji Young; Kim, Da Hee; Bae, Hyo Sook; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju; Shin, Eunah; Kim, Mi Kyoung

    2017-05-01

    The aim of this study was to evaluate the oncologic and pregnancy outcomes of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment in young women with grade 2-differentiated stage IA endometrial adenocarcinoma who wish to preserve fertility. We retrospectively reviewed the medical records of patients with grade 2 stage IA endometrial adenocarcinoma who had received fertility-sparing treatment at CHA Gangnam Medical Center between 2011 and 2015. All of the patients were treated with combined oral MPA (500 mg/d)/LNG-IUS, and follow-up dilatation and curettage were performed every 3 months. A total of 5 patients were included in the study. The mean age was 30.4 ± 5.3 years (range, 25-39 years). After a mean treatment duration of 11.0 ± 6.2 months (range, 6-18 months), complete response (CR) was shown in 3 of the 5 patients, with partial response (PR) in the other 2 patients. One case of recurrence was reported 14 months after achieving CR. This patient was treated again with combined oral MPA/LNG-IUS and achieved CR by 6 months. The average follow-up period was 44.4 ± 26.2 months (range, 12-71 months). There were no cases of progressive disease. No treatment-related complications arose. Combined oral MPA/LNG-IUS treatment is considered to be a reasonably effective fertility-sparing treatment of grade 2 stage IA endometrial cancer. Although our results are encouraging, it is preliminary and should be considered with experienced oncologists in well-defined protocol and with close follow-up.

  20. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    Science.gov (United States)

    Janagam, Dileep R.; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R.; Lowe, Tao L.

    2016-01-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months. PMID:27598191

  1. A randomized clinical trial to compare levonorgestrel-releasing intrauterine system (Mirena vs trans-cervical endometrial resection for treatment of menorrhagia

    Directory of Open Access Journals (Sweden)

    Ghazizadeh S

    2011-07-01

    Full Text Available Shirin Ghazizadeh1, Fatemeh Bakhtiari1, Haleh Rahmanpour2, Fatemeh Davari-Tanha1, Fatemeh Ramezanzadeh11Valie-Asr Reproductive Health Research Center, Valie-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Obstetrics and Gynecology, Ayatollah Mousavi Hospital, Zanjan, IranObjective: To compare the acceptability, efficacy, adverse effects, and user satisfaction of the levonorgestrel intrauterine system (LNG-IUS and trans-cervical resection of the endometrium (TCRE for the treatment of menorrhagia.Method: 104 women with menorrhagia were divided into 2 groups: 52 women had the LNG-IUS inserted and 52 underwent TCRE. Menstrual pattern, pictorial blood loss assessment chart score, adverse effects, and rates of acceptability and satisfaction, were recorded at 6 and 12 months after the procedure.Results: After a year there were reductions of 93.9% and 88.4% in menstrual blood loss in the TCRE and LNG-IUS groups, respectively. Amenorrhea was more common in the TCRE group and spotting and systemic effects in the LNG-IUS group. Satisfaction rates of the TCRE group were higher than the LNG-IUS group (80.8% vs 69.2%, but the difference was not statistically significant.Conclusion: Although both treatments were found to be equally effective, LNG-IUS was less invasive and can be advised for younger women with a desire to preserve fertility.Keywords: menorrhagia, trans-cervical endometrial resection, levonorgestrel-releasing intrauterine system

  2. An evaluation of the simultaneous use of the levonorgestrel-releasing intrauterine device (LNG-IUS, Mirena®) combined with endometrial ablation in the management of menorrhagia.

    LENUS (Irish Health Repository)

    Vaughan, D

    2012-05-01

    The objective of our study was to document the efficacy and possible complications in women who were treated for menorrhagia with the simultaneous use of endometrial ablation and the levonorgestrel-releasing intrauterine device. Women were offered this combined treatment if they complained of menorrhagia and needed contraception. A structured questionnaire was mailed to 150 women who had undergone this combined treatment; 105 (70%) returned a completed questionnaire. The mean duration of follow-up was 25 months (range 6-54 months). Following treatment, 53 women (50.5%) described their periods as being lighter than normal and 49 (46%) had become amenorrhoeic. Overall, 101 (96%) stated that they were satisfied with the treatment. Of the women, 95 (90.5%) said that the treatment had been a \\'complete success\\'; eight (7.6%) \\'partly successful\\' and two women (1.9%) said the treatment had been a \\'failure\\'. One woman subsequently required a hysterectomy. This observational study supports the hypothesis that combined endometrial ablation and insertion of a levonorgestrel-releasing intrauterine device is an effective treatment for menorrhagia and has some advantages when compared with the individual use of these treatments.

  3. Influencia de polimorfismos genéticos de CYP3A4/5 en la farmacocinética de levonorgestrel: estudio piloto

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    Iván Moreno

    2012-12-01

    Full Text Available Introducción. El levonorgestrel, un progestágeno sintético usado para endometriosis, dismenorrea y anticoncepción de emergencia, es rápida y completamente absorbido en el tubo digestivo. Su metabolismo es principalmente hepático, mediante las enzimas CYP3A4 y CYP3A5. Objetivo. El presente estudio tuvo como objetivo evaluar la asociación entre la farmacocinética de levonorgestrel y las variantes alélicas de CYP3A4*1B y CYP3A5*3. Materiales y métodos. En un grupo de 17 mujeres adultas sanas, que firmaron un consentimiento informado, se practicó genotipificación para CYP3A4*1B y CYP3A5*3 mediante PCR. Posteriormente, las voluntarias fueron sometidas a un estudio farmacocinético donde, luego de 12 horas de ayuno, recibieron una dosis de 0,75 mg de levonorgestrel. Se extrajeron muestras sanguíneas seriadas (0 a 24 horas y se determinaron las concentraciones de levonorgestrel mediante un método validado de UPLC-ms/ms, para luego obtener los parámetros farmacocinéticos. Todos los procedimientos consideraron los aspectos éticos de la Declaración de Helsinki y las buenas prácticas clínicas. Resultados. Las frecuencias genotípicas observadas para el grupo de estudio fueron 11,8 % para*1B/*1B; 5,8 % para *1/*1B, y 82,4 % para *1/*1 de CYP3A4*1B. Para CYP3A5*3, las frecuencias genotípicas fueron 70,5 % para *3/*3; 23,5 % para *1/*3, y 6,5 % para *1/*1. Se observa una interesante variabilidad entre las voluntarias que sugiere una relación con las variantes genéticas CYP3A, pero que no permite establecer una asociación estadísticamente significativa, presumiblemente debido albajo número de individuos homocigotos mutados de CYP3A4 y silvestres de CYP3A5. Conclusiones. Los polimorfismos genéticos podrían ser factores relevantes en la determinación de la variabilidad entre pacientes en las concentraciones plasmáticas de levonorgestrel, lo cual, sin embargo, no pudo ser establecido estadísticamente en este estudio. Por lo tanto

  4. Uterine Length in Adolescents with Developmental Disability: Are Ultrasound Examinations Necessary before Insertion of the Levonorgestrel Intrauterine System?

    Science.gov (United States)

    Whyte, Helena; Pecchioli, Yael; Oyewumi, Lamide; Kives, Sari; Allen, Lisa M; Kirkham, Yolanda A

    2016-12-01

    (1) To determine if there are any differences in uterine length between adolescents with developmental disability (DD) compared with their normally developing (ND) peers that might necessitate ultrasonography before insertion of levonorgestrel intrauterine system (LNG-IUS) in patients with DD; and (2) to characterize the LNG-IUS insertion procedure in adolescents with disabilities. This was a retrospective cohort study of 223 female adolescents with or without DDs. Seventy-five adolescents had DD; 33 underwent intrauterine system insertion in the operating room and 42 did not. A comparative cohort of 148 ND adolescents who had pelvic ultrasound examinations for abnormal uterine bleeding were included. The study period was between January 2006 and July 2013 at the Hospital for Sick Children, Toronto, Canada. Cases were identified from surgical databases and medical records. Mean uterine length on pelvic ultrasound, demographic characteristics (age, age at menarche, time from menarche to ultrasound, weight), and descriptive statistics on intrauterine system insertion. There was a statistically significant difference (P = .03) in uterine length between adolescents with and without DD (6.7 vs 7.1 cm). However, this was not a clinically significant difference because insertion of the LNG-IUS in patients with DD was successful in patients with uteri more than 5 cm long. There was no difference (P = .97) in uterine length of adolescents with DD whether they had LNG-IUS insertion or not (6.7 cm). Adolescents with DD were younger than adolescents without DD at time of ultrasound examination (P = .01). However, among patients with DD, those who underwent intrauterine system insertion were older (P = .001). Incidence of uterine anomaly in patients with DD is low (2.7%) and was the same as in ND adolescents. Rates of complications and expulsions were low and there were no failures of LNG-IUS insertion in adolescents with DD. Routine pelvic ultrasound examinations

  5. Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

    Science.gov (United States)

    Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

    2017-08-01

    To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  6. Does levonorgestrel-releasing intrauterine system increase breast cancer risk in peri-menopausal women? An HMO perspective.

    Science.gov (United States)

    Siegelmann-Danieli, Nava; Katzir, Itzhak; Landes, Janet Vesterman; Segal, Yaakov; Bachar, Rachel; Rabinovich, Hadas Rotem; Bialik, Martin; Azuri, Joseph; Porath, Avi; Lomnicky, Yossef

    2017-09-14

    To evaluate the association between levonorgestrel-releasing intrauterine system (LNG-IUS) use and breast cancer (BC) risk. A cohort of all Maccabi Healthcare Services (MHS) female members aged 40-50 years between 1/2003 and 12/2013 was used to identify LNG-IUS users as "cases," and 2 age-matched non-users as "controls." Exclusion criteria included: prior BC diagnosis, prior (5 years pre-study) and subsequent treatment with other female hormones or prophylactic tamoxifen. Invasive tumors were characterized by treatments received (chemotherapy, hormonal therapy, trastuzumab, or combination thereof). The analysis included 13,354 LNG-IUS users and 27,324 controls (mean age: 44.1 ± 2.6 vs. 44.9 ± 2.8 years; p < 0.0001). No significant differences in 5-year Kaplan-Meier (KM) estimates for overall BC risk or ductal carcinoma in situ occurrence were observed between groups. There was a trend towards higher risk for invasive BC in LNG-IUS users (5-year KM-estimate: 1.06% vs. 0.93%; p = 0.051). This difference stemmed primarily from the younger women (40-45 years; 0.88% vs. 0.69%, p = 0.014), whereas in older women (46-50 years), it was non-significant (1.44% vs. 1.21%; p = 0.26). Characterization of invasive BC by treatment demonstrated that LNG-IUS users had similar proportions of tumors treated with hormonal therapy, less tumors treated with trastuzumab, (7.5% vs. 14.5%) and more tumors treated with chemotherapy alone (25.8% vs. 14.9%; p = 0.041). In peri-menopausal women, LNG-IUS was not associated with an increased total risk of BC, although in the subgroup of women in their early 40's, it was associated with a slightly increased risk for invasive tumors.

  7. Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index.

    Science.gov (United States)

    Praditpan, Piyapa; Hamouie, Angie; Basaraba, Cale N; Nandakumar, Renu; Cremers, Serge; Davis, Anne R; Westhoff, Carolyn L

    2017-05-01

    This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-h admissions. Study staff collected 14 blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 48h). We evaluated serum concentrations of LNG and UPA using liquid chromatography-tandem mass spectroscopy and estimated the PK parameters of both drugs using noncompartmental analysis. The main outcome of this study was a comparison of between-group differences in AUC0-24. Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants, the mean BMIs were 22.0 (range 18.8-24.6) and 34.3 (range 30.6-39.9), respectively. After LNG-EC, mean AUC0-24 and maximum concentration (Cmax) were 50% lower among obese-BMI women than among normal-BMI women (AUC0-24 100.8 vs. 208.5ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0-24 362.5 vs. 293.5ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3ng/mL, p=.70). After a single dose of EC, obese-BMI women are exposed to lower concentrations of LNG and similar concentrations of UPA, when compared to normal-BMI women. Differences in LNG-EC PK by BMI group may underlie and account for the lower LNG-EC efficacy reported among obese-BMI women, but modest differences in UPA-EC PK by BMI group provide less support for variable efficacy. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and

  8. Warming modulates the effects of the endocrine disruptor progestin levonorgestrel on the zebrafish fitness, ovary maturation kinetics and reproduction success.

    Science.gov (United States)

    Cardoso, P G; Rodrigues, D; Madureira, T V; Oliveira, N; Rocha, M J; Rocha, E

    2017-10-01

    Interactive effects between multiple stressors, namely climate drivers (e.g., temperature) and chemical pollution (e.g., endocrine disruptors) are poorly studied. Here, it was for the first time evaluated the combinatory effects of temperature and a synthetic progestin, levonorgestrel (LNG), on the fitness and reproductive-related endpoints of zebrafish (Danio rerio). A multi-factorial design was implemented by manipulating both temperature [setting as baseline an ambient temperature of 27 °C, against warming (+3 °C)] and LNG levels (10 ngL(-1) and 1000 ngL(-1)). Groups of males and females were exposed sub-acutely, for 21-days. Increased temperature caused an overall decrease in the females' gonadosomatic index (GSI), during the pre-reproduction phase, LNG did not affect GSI. In addition, fecundity (number of ovulated eggs) was negatively affected by both temperature and LNG, being the effect of the latter more intense. Fish exposed to the highest LNG concentration (at both temperatures) did not reproduce, but also in those exposed to the lowest dose of progestin at a higher temperature, a complete reproductive failure occurred. These results reflect what was observed in the stereological analysis of the ovary maturation stages prior to reproduction. Accordingly, the higher the LNG concentration, the lower the degree of maturation of the ovary. This was exacerbated by the higher temperature. As to embryonated eggs, they hatched significantly faster at higher temperatures, but exposure to 10 ngL(-1) of LNG (at 27 °C) reduced significantly the hatching rate, comparing to control. Further, the recrudescence of the ovary 48 h after spawning seems to be not affected by both stressors. Our data suggest that in a future scenario of global warming and synthetic hormones exposure, the reproduction of fish species, such as the zebrafish, can be endangered, which can put at risk their success, and consequently affect the structure and functioning of associated

  9. Choice of the levonorgestrel intrauterine device, etonogestrel implant or depot medroxyprogesterone acetate for contraception after aspiration abortion.

    Science.gov (United States)

    Steinauer, Jody E; Upadhyay, Ushma D; Sokoloff, Abby; Harper, Cynthia C; Diedrich, Justin T; Drey, Eleanor A

    2015-12-01

    Women who have abortions are at high risk of contraception discontinuation and subsequent unintended pregnancy. The objective of this analysis was to identify factors associated with choice of highly effective, long-acting, progestin-only contraceptive methods after abortion. Women presenting for surgical abortion who selected the levonorgestrel intrauterine device (IUD), the progestin implant or the progestin injection (depot medroxyprogesterone acetate or DMPA) as their postabortion contraceptives were recruited to participate in a 1-year prospective cohort study. We used multivariable multinomial logistic regression to identify factors associated with choosing long-acting reversible contraceptives (IUD or implant) compared to DMPA. A total of 260 women, aged 18-45 years, enrolled in the study, 100 of whom chose the IUD, 63 the implant and 97 the DMPA. The women were 24.9 years old on average; 36% were black, and 29% were Latina. Fifty-nine percent had had a previous abortion, 66% a prior birth, and 55% were undergoing a second-trimester abortion. In multivariable analyses, compared with DMPA users, women who chose the IUD or the implant were less likely to be currently experiencing intimate partner violence (IPV); reported higher stress levels; weighed more; and were more likely to have finished high school, to have used the pill before and to report that counselors or doctors were helpful in making the decision (all significant at p<.05, see text for relative risk ratios and confidence intervals.) In addition, women who chose the IUD were less likely to be black (p<.01), and women who chose the implant were more likely to report that they would be unhappy to become pregnant within 6 months (p<.05) than DMPA users. A variety of factors including race/ethnicity, past contraceptive use, feelings towards pregnancy, stress and weight were different between LARC and DMPA users. Notably, current IPV was associated with choice of DMPA over the IUD or implant, implying

  10. Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel.

    Science.gov (United States)

    Prasad, R N; Koh, S C; Viegas, O A; Ratnam, S S

    1999-01-01

    We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera) or second generation levonorgestrel (Microgynon 30) combination of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were apparent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. Enhanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Willebrand factor (vWF) were seen in long-term OC use except that beta-thromboglobulin (beta-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage

  11. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel.

    Science.gov (United States)

    Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

    2015-05-01

    The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady-state and semaglutide-free periods was within prespecified limits (0.80-1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0-24 h ) for semaglutide steady-state/semaglutide-free; 1.11 (1.06-1.15). AUC0-24 h was 20% higher for levonorgestrel at semaglutide steady-state vs. semaglutide-free (1.20 [1.15-1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (-1.1 ± 0.6%) and weight (-4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once-weekly dosing; the semaglutide dose and dose-escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow-up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel.

  12. Comparison of Different Extraction Methods on Pretreatment of Levonorgestrel Containing Water%左炔诺孕酮不同萃取剂萃取能力比较

    Institute of Scientific and Technical Information of China (English)

    翟俊; 荣婧; 占宏; 宁可佳; 阮雨

    2011-01-01

    比较了液液萃取和固相萃取两种方法对左炔诺孕酮的萃取效果,为含左炔诺孕酮水样分析预处理提供参考.运用高效液相色谱法检测了二氯甲烷、三氯甲烷、正己烷、乙酸乙酯4种有机溶剂和StrataTM-X(60 mg,3mL)固相萃取柱对左炔诺孕酮的萃取回收率;萃取回收率分别为:乙酸乙酯(97.22%)>二氯甲烷(91.89%)>正己烷(91.67%)>三氯甲烷( 91.33%)>StrataTM-X柱(87.11%),对应的相对标准差分别为1.05%、3.29%、2.75%、3.48%、0.97%.试验结果表明:液液萃取法整体萃取回收率要高于周相萃取法,其中乙酸乙酯的萃取回收率为最优.相对标准差值的比较表明固相萃取法的稳定性高于液液萃取.%Extraction efficiencies of levonorgestrel were compared when using liquid-liquid phase extraction and solid -phase extraction, which provided references for levonorgestrel sample pre-treatment. The recovery rates of levonorgestrel extracted with four different liquid organic solvents including dichloromethane, chloroform, hexane, ethyl, and one solid-phase extraction column, StrataTM-X (60 mg,3 mL) were analyzed with the quantity detection of high performance liquid chromatography method. The recovery rates were listed in an order of ethyl (97.22%)>dichloromethane (91.89%)> hexane (91.67%)>chloromethane (91.33%)>StrataTM-Xcolumn (87.11%), with relative standard deviations 1.05%,3.29%, 2.75% ,3.48% ,0.97% respectively. Experiment results indicated that liquid-liquid phase extraction method had a higher recovery rate than solid-phase extraction method. The results of relative standard deviation showed that solid-phase extraction is more stable than liquid-liquid phase extraction.

  13. Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats.

    Science.gov (United States)

    Sogawa, Kenji; Nagaoka, Taiji; Izumi, Naohiro; Nakabayashi, Seigo; Yoshida, Akitoshi

    2010-05-01

    To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

  14. Comparative effectiveness and impact on health-related quality of life of hysterectomy vs. levonorgestrel intra-uterine system for abnormal uterine bleeding.

    Science.gov (United States)

    Cozza, G; Pinto, A; Giovanale, V; Bianchi, P; Guarino, A; Marziani, R; Frega, A; Caserta, D

    2017-05-01

    To compare hysterectomy and levonorgestrel intra-uterine system (LNG-IUS) for the treatment of abnormal uterine bleeding (AUB) and iron deficiency anemia. Retrospective study evaluating quality of life, sexual function, satisfaction and blood hemoglobin concentration improvement in 60 pre-menopausal women treated with hysterectomy or LNG-IUS. All analysis was performed with statistical software SPSS 21.0 (SPSS Inc., Chicago, IL, USA). Despite superior control of bleeding and dysmenorrhea observed after hysterectomy, LNG-IUS showed similar impact on blood hemoglobin levels, quality of life, satisfaction and sexual function resulting more cost-effective. In the absence of contraindications, LNG-IUS should always be the first therapeutic choice for chronic AUB. Surgical treatment must be considered as an "extrema ratio".

  15. Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

    Science.gov (United States)

    McNicholas, Colleen; Swor, Erin; Wan, Leping; Peipert, Jeffrey F

    2017-06-01

    The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the current Food and Drug Administration-approved duration. We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel intrauterine device for a minimum of 3 and 5 years, respectively (started intrauterine device in ≥2007 or implant in ≥2009). Demographic and reproductive health histories, as well as objective body mass index, were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rate, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using χ(2) test and Fisher exact test, and compared serum etonogestrel levels stratified by body mass index using the Kruskal-Wallis test. Implant users (n = 291) have contributed 444.0 woman-years of follow-up. There have been no documented pregnancies in implant users during the 2 years of postexpiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (1-sided 97.5% confidence interval, 0-1.48) per 100 woman-years at 4 years and 0 (1-sided 97.5% confidence interval, 0-2.65) per 100 woman-years at 5 years. Among 496 levonorgestrel intrauterine device users, 696.9 woman-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the

  16. Effects of Levonorgestrel on Development of Embryo or Fetal%左炔诺孕酮对胚胎胎儿发育的影响

    Institute of Scientific and Technical Information of China (English)

    陈亚楠; 王娜

    2016-01-01

    目的::研究紧急避孕药左炔诺孕酮对胚胎胎儿发育的影响。方法:选取2010年7月至2015年1月来我院妇产科门诊咨询的服用左炔诺孕酮避孕失败并要求继续妊娠者78例作为研究组,选取同期在我院门诊确定早孕并继续妊娠者与研究组对象按1:1配对作为对照组,分别对两组孕妇的自然流产率、胎儿畸形率、新生儿出生情况进行分析比较。结果:研究组的自然流产率高于对照组,且有统计学意义( P0.05);两组中超声筛查胎儿畸形发生率均无明显差异,均不具有统计学意义( P>0.05);两组新生儿阿氏评分均无明显差异,均不具有统计学意义( P>0.05)。结论:口服左炔诺孕酮能够增加早期自然流产的几率;但其服用史并不增加21-三体,18-三体及开放性神经管畸形的发生率、胎儿的畸形率以及新生儿窒息的发生率。%Objective: To study the effects of levonorgestrel on the development of embryo or fetal, Methods:From July 2010 to January 2015, 78 cases of pregnancy taken levonorgestrel contraceptive failure and want to continue pregnancy were selected to be the study group, and at the same time, 78 cases of early pregnancy that want to continue pregnancy were selected as control group according to 1:1 matched. Analyze and compare the spontaneous abortion rate, the rate of fetal malformation and neonatal born. Results: Study group of spontaneous abortion rate was higher than that of the control group and had statistical significance ( P 0.05);two groups of ultrasound screening for fe-tal malformation incidence had no significant difference, and were not statistically significant (P > 0.05);neonatal Apgar scores of the two groups had no significant difference, and had no the statistical significance ( P > 0.05) . Conclusion:The levonorgestrel could increase the chance of early spontaneous abortion;but the history of taking levonorgestrel did not increase

  17. LNG对大鼠下丘脑内NPY神经元的影响%Effect of levonorgestrel (LNG) on NPY positive neurons in hypothalamus of rats

    Institute of Scientific and Technical Information of China (English)

    刘晓云; 崔慧先; 刘力斗; 康林

    2006-01-01

    左旋18-甲基炔诺酮(Levonorgestrel LNG)是第二代全合成孕激素类口服避孕药,反馈性调节下丘脑-垂体轴是基作用机制之一。在下丘脑-垂体-性腺轴中,多种神经递质参与了下丘脑促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)的分泌调节,其中神经多肽Y(ncuropeptide Y,NPY)是重要的因子之一。

  18. 复方左炔诺孕酮片溶出度测定方法研究%Research on Determination Method for Dissolution of Compound Levonorgestrel Tablets

    Institute of Scientific and Technical Information of China (English)

    胡楚楚; 郑国钢

    2016-01-01

    ABSTRACTObjective:To develop a method for determination of the dissolution of compound levonorgestrel tablets.Methods:The 0.1 mol/L hydrochloric acid solution containing 0.1% sodium dodecyl sulfate was used as a solvent, and the paddle was rotated at a rate of 75 r/min for 30 min, afterwards samples were taken and determined by HPLC using C18 colume(4.6 mm×250 mm, 5μm)as a stationary phase and acetonitrile-water (60∶40)as a mobile phase. The flow rate was 1.0 mL/min. An ultraviolet spectrophotometer set at a wavelength of 247 nm was used for levonorgestrel analysis, and a spectrofluorometric detector was used for ethinylestradiol analysis at an excitation wavelength of 285 nm and an emission wavelength of 310 nm.Results:The linear ranges of levonorgestrel and ethinylestradiol concentrations were 0.059 88~0.359 3 and 0.012 19 ~0.073 15μg/mL, while the average recovery rates were 99.2% and 99.0%, respectively.Conclusion:A novel method for determination of dissolution of compound levonorgestrel tablets was developed, which was reproducible, stable and reliable, and might be used for quality control of drugs.%目的:建立复方左炔诺孕酮片的溶出度测定方法。方法:采用桨法,以0.1%SDS的0.1 mol/L HCl溶液500 mL为溶剂,转速为75 r/min,30 min时取样。采用高效液相色谱法测定,C18柱(4.6 mm×250 mm,5μm)为固定相,以乙腈-水(60∶40)为流动相,流速为1.0 mL/min。左炔诺孕酮采用紫外检测器检测,波长为247 nm;炔雌醇采用荧光检测器检测,激发波长为285 nm,发射波长为310 nm。结果:左炔诺孕酮在0.05988~0.3593μg/mL浓度范围内,线性关系良好;炔雌醇在0.01219~0.07315μg/mL浓度范围内,线性关系良好。左炔诺孕酮平均回收率为99.2%,炔雌醇平均回收率为99.0%。结论:建立了测定复方左炔诺孕酮片溶出度的新方法,此法方法重复性好,所得结果稳定可靠,可有效控制药品的质量。

  19. Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis.

    Science.gov (United States)

    Hennessy, S; Berlin, J A; Kinman, J L; Margolis, D J; Marcus, S M; Strom, B L

    2001-08-01

    Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.

  20. The study of effect of levonorgestrel intrauterine system on the expres-sions of insulin-like growth factor-1 with endometrial polyps%子宫内膜息肉术后放置左炔诺孕酮宫内释放系统对IGF-1的影响研究

    Institute of Scientific and Technical Information of China (English)

    陶跃平; 吴晓杰

    2015-01-01

    目的:研究左炔诺孕酮宫内释放系统对子宫内膜息肉患者子宫内膜组织胰岛素样生长因子-1(IGF-1)表达的影响。方法选取2010年1月~2011年12月期间行宫腔镜下子宫内膜息肉切除术182例患者为研究对象,将其随机分为对照组(常规治疗组)94例和研究组(宫内放置左炔诺孕酮宫内释放系统)88例。后通过免疫组化法将术中内膜组织及术后6个月子宫内膜活检IGF-1的表达情况进行对比,且追踪随访2年,观察患者子宫内膜息肉复发情况。结果研究组内膜组织IGF-1表达研究组术后明显低于术中,差异有统计学意义,对照组IGF-1的表达变化无差异性。随访2年对照组87例患者中7例子宫内膜息肉复发,复发率为8.05%,而研究组无一例复发,差异有统计学意义。结论左炔诺孕酮宫内释放系统可能通过抑制子宫内膜的IGF-1来降低子宫内膜息肉复发。%Objective To study levonorgestrel intrauterine system on insulin-like growth factor-1 (IGF-1) in endometri-um tissue for patients with endometrial polyps. Methods All 182 patients with endometrial polyps in our hospital from January 2010 to December 2011 were selected as research object, and randomly divided into control group(routine treatment group)94 cases and observation group(levonorgestrel intrauterine system in uterus group)88 cases. The IGF-1 expression of endometrial biopsy specimens during intraoperative and rechected after 6 months were measurd by im-munohistochemistry. Patients were followed up for 2 years to analyse endometrial polyp recurrence. Results The ex-pressions of IGF-1 decreased significant in endometrium tissue of observation group with operation. But there were no significant differences in control group. Followed up for 2 years, the endometrial polyp recurrence was 8.05% in control group and without recurrence in study group. Conclusion Levonorgestrel intrauterine system may be involved in

  1. Aplicação de dispositivo intra-uterino liberador de levonorgestrel, previamente a ciclos de fertilização in vitro, nas portadoras de adenomiose Application of a levonorgestrel-releasing intrauterine device prior to in vitro fertilization cycles in women with adenomyosis

    Directory of Open Access Journals (Sweden)

    Nilson Donadio

    2006-08-01

    Full Text Available OBJETIVO: verificar os efeitos do dispositivo intra-uterino (DIU de levonorgestrel em portadoras de adenomiose, com falhas de implantação em ciclos de fertilização in vitro (FIV. MÉTODOS: foram selecionadas 80 mulheres inférteis, com até 38 anos, com diagnóstico de adenomiose pela ultra-sonografia e ressonância magnética pélvica. Todas apresentavam tentativas anteriores de FIV sem sucesso. No grupo Diu, de 40 mulheres, foi colocado DIU liberador de 20 µg de levonorgestrel/dia por seis meses, previamente a um novo ciclo de FIV. No grupo Fiv, de 40 mulheres, estas foram submetidas diretamente a novo ciclo, sem o prévio tratamento. No Grupo Diu, avaliaram-se o volume uterino, a espessura e os focos de hipersinal da zona juncional, pré e pós-tratamento, assim como as taxas de gravidez em novo ciclo de FIV comparadas com as obtidas no grupo Fiv. As análises estatísticas foram realizadas adotando-se o nível de significância de 5% (pPURPOSE: to verify the effects of intrauterine levonorgestrel device (IUD in women with adenomyosis, with implantation failure in previous in vitro fertilization (IVF cycles. METHODS: eighty infertile women with ages up to 38 years, who had adenomyosis diagnosed by ultrasonography and MRI were selected. All the women presented antecedents of one or more tormer IVF attempts without success due to implantation failure. The women were subdivided into IUD Group, composed of 40 women with an IUD that released 20 µg of levonorgestrel/day during six months, preceding a new IVF cycle, and IVF Group, also composed of 40 women, who were directly submitted to a new IVF cycle without previous adenomyosis treatment. In the IUD Group the uterine volume, thickness and hypersignal foci of the junctional zone were assessed before and after treatment, as well as the pregnancy rates in the new IVF cycle, compared to the data obtained with the IVF Group. Statistical analyses were performed adopting the significance level of

  2. Observation on the clinical efficacy of levonorgestrel -intrauterine releasing system%左炔诺孕酮宫内缓释系统临床效果观察

    Institute of Scientific and Technical Information of China (English)

    李俊英; 郝增平

    2011-01-01

    Objective; To explore the clinical efficacy of levonorgestrel - intrauterine releasing system ( LNG - IUS) for contraception, adenomyosis, hysteromyoma and dysfunctional uterine bleeding. Methods: LNG -IUS was placed in 94 patients with induced abortion , adenomyosis, hysteromyoma and dysfunctional uterine bleeding in the hospital from December 2003 to March 2007. The factors such as contraceptive effectiveness, menstruation, hemoglobin and blood CA125 levels were observed at 1, 3, 6 and 12 months after placement of LNG - IUS. Results; Among 30 cases with induced abortion, LNG - IUS of one case dropped after 20 days and she got pregnancy at five months; among the other 29 cases, 20.00% of the cases had abdominal pain, then the pain was relieved after 3 months; 70.00% of the cases were found with irregular vaginal bleeding, then they recovered after 6 months. Among 64 cases with adenomyosis, hysteromyoma and dysfunctional uterine bleeding, LNG - IUS of one case moved down after 1 month. Dysmenorrhea of all the cases relieved after 3 months. At 12 months, the amount of menstruation reduced by 89. 26% , the menstruation shortened by 3. 58 days, the menstrual cycle prolonged by 6. 51 days, the incidence of amenorrhea was 57. 81% , the level of hemoglobin increased by 2.91 g/L, and the level of CA125 decreased by 40. 10%, the volumes of uteri and fibroids decreased significantly. No uterine cavity infection and pregnancy with IUD occurred. Conclusion; LNG - IUS has good contraceptive effect, and it is also effective for adenomyosis, hysteromyoma and dysfunctional u-terine bleeding.%目的:探讨左炔诺孕酮宫内缓释系统(LNG-IUS)对避孕、子宫腺肌病、子宫肌瘤及功能失调性子宫出血的临床疗效。方法:选择2003年12月~2007年3月北京友谊医院妇产科早孕人工流产、子宫腺肌病、子宫肌瘤及功能失调性子宫出血患者94例,放置LNG-IUS,观察放置后1、3、6、12个月的避孕效果、

  3. 左炔诺孕酮宫内缓释系统治疗子宫腺肌病研究进展%Research of Levonorgestrel-releasing Intrauterine System Treatment for Adenomyosis

    Institute of Scientific and Technical Information of China (English)

    隋孟松

    2011-01-01

    Levonorgestrel-releasing intrauterine system is a new hormonal intrauterine contraceptive system. The system have the long-term effective in releasing levonorgestrel. In recent yeats,it found that in addition to long-term contraceptive effects, the system also can treat some gynecological diseases, especially in the treatment of adenomyosis, with efficacy, long term effective and low side effects, etc. The mechanism of levonorgestrel and the progress in the clinical application in recent years were reviewed in this paper.%左炔诺孕酮宫内缓释系统作为一种新型激素宫内避孕系统,长期有效释放左炔诺孕酮发挥作用.近年来发现其除了具有长期避孕作用外,对一些妇科疾病具有治疗作用,尤其在子宫腺肌病的治疗中,具有疗效明显、作用时间长及不良反应小等优点.现就近年来左炔诺孕酮的作用机制及在临床上的应用进展进行综述.

  4. Analysis of the Effect of Levonorgestrel Releasing Intrauterine System in the Treatment of Uterine Gland Myopathy%左炔诺孕酮宫内缓释系统治疗子宫腺肌症效果分析

    Institute of Scientific and Technical Information of China (English)

    陶俐辛

    2015-01-01

    目的:探究子宫腺肌症采用左炔诺孕酮宫内缓释系统治疗的临床疗效。方法选取42例子宫腺肌症患者,均采用左炔诺孕酮宫内缓释系统治疗,分析临床疗效。结果治疗后患者痛经评分、月经量、子宫体积、Hb(血红蛋白浓度)以及CA125(糖类抗原125)等均优于治疗前(P <0.05)。结论子宫腺肌症采用左炔诺孕酮宫内缓释系统治疗效果显著。%Objective The clinical curative effect of adenomyosis treated with levonorgestrel releasing intrauterine system.Methods Select 42 cases of patients with uterine gland muscle disease,al the levonorgestrel releasing intrauterine system in the treatment,to observe and compare the clinical indexes of patients before and after treatment.ResultsAfter treatment, dysmenorrhea score, menstrual volume, uterine volume, Hb (hemoglobin concentration) and CA125 (carbohydrate antigen 125) were superior to those of the treatment (P < 0.05). ConclusionAdenomyosis of levonorgestrel releasing intrauterine system in the treatment effect is significant.

  5. Single-walled carbon nanotubes (SWCNTs) induce vasodilation in isolated rat aortic rings.

    Science.gov (United States)

    Gutiérrez-Hernández, J M; Ramirez-Lee, M A; Rosas-Hernandez, H; Salazar-García, S; Maldonado-Ortega, D A; González, F J; Gonzalez, C

    2015-06-01

    Single-walled carbon nanotubes (SWCNTs) are used in biological systems with impact in biomedicine in order to improve diagnostics and treatment of diseases. However, their effects upon the vascular system, are not fully understood. Endothelium and smooth muscle cells (SMC) communicate through release of vasoactive factors as nitric oxide (NO) to maintain vascular tone. The aim of this study was to evaluate the effect of SWCNTs on vascular tone using isolated rat aortic rings, which were exposed to SWCNTs (0.1, 1 and 10 μg/mL) in presence and absence of endothelium. SWCNTs induced vasodilation in both conditions, indicating that this effect was independent on endothelium; moreover that vasodilation was NO-independent, since its blockage with L-NAME did not modify the observed effect. Together, these results indicate that SWCNTs induce vasodilation in the macrovasculature, may be through a direct interaction with SMC rather than endothelium independent of NO production. Further investigation is required to fully understand the mechanisms of action and mediators involved in the signaling pathway induced by SWCNTs on the vascular system.

  6. The novel ortho-chloro derivate propafenone induced relaxation in isolated rat aorta

    Directory of Open Access Journals (Sweden)

    Ivković Branka

    2013-01-01

    Full Text Available The information on the inhibitory effect of propafenone in vascular smooth muscle is sparse. Propafenone acts through blockage of voltage-dependent cardiac Na+ channels, L-type Ca2+ channels, voltage-sensitive K+ (Kv channels, as well as β-adrenergic receptors in the heart. The introduction of different chemical groups in the benzyl moiety of propafenone influences pharmacological properties of newly developed derivate of propafenone. Here we investigated the effect of new ortho-chloro derivate of propafenone (5OCl on the vascular tone of precontracted rat aorta. 5OCl produced endothelium-independent relaxation of rat aorta. In order to test the involvement of different ion channels in 5OCl mechanism of action, antagonist of Na+, lidocaine, KV channels, 4-aminopyiridine (4-AP and L-type Ca2+ channels, nifedipine were used. All tested antagonists of ion channels did not influence the relaxation of rat aorta induced by high a concentration of 5OCl (≥10 μM, but antagonized the relaxation induced by low concentrations of this propafenone derivate. Thus, 5OCl derivate has comparable potency and efficacy as propafenone. According to its interaction with lidocaine, 4-AP and nifedipine it seems that 5OCl partly shares the mechanism of action with propafenone. The mechanism of vasodilatation induced by high micromolar concentration of 5OCl is not defined and further investigations are necessary.

  7. (-)Epicatechin induces and modulates endothelium-dependent relaxation in isolated rat mesenteric artery rings

    Institute of Scientific and Technical Information of China (English)

    YAO Xiao-Qiang; CHAN Franky Leung; LAU Chi-Wai; HUANG Yu

    2002-01-01

    AIM: The present study was aimed to examine the role of endothelial nitric oxide in the relaxant response to green tea (-)epicatechin and its modulation of endothelium-mediated relaxation in the isolated rat mesenteric artery rings.METHODS: Changes in the isometric tension were measured with Grass force-displacement transducers. RESULTS:The (-)epicatechin-induced relaxation was largely dependent on the presence of intact endothelium and was reversed by NG-nitro-L-arginine methyl ester 10 μmol/L or methylene blue 10 μmol/L, the inhibitors of nitric oxidemediated relaxation. L-Arginine at 1 mmol/L antagonized the effect of L-NAME or methylene blue. Pretreatment of endothelium-intact rings with (-)epicatechin 10 μmol/L enhanced the relaxation induced by endothelium-dependent vasodilator, acetylcholine, while this concentration did not influence the endothelium-independent relaxation induced by sodium nitroprusside in the endothelium-denuded artery rings. CONCLUSION: The results indicate that the endothelium-dependent vasodilation by (-)epicatechin is mainly mediated through nitric oxide and low concentration of (-)epicatechin augments endothelium-dependent vasorelaxation in the rat mesenteric arteries.

  8. Endothelium-dependent contraction of rat thoracic aorta induced by gallic acid.

    Science.gov (United States)

    Sanae, Fujiko; Miyaichi, Yukinori; Hayashi, Hisao

    2003-02-01

    The vascular effect of a component of hydrolysable tannins, gallic acid, was examined in isolated rat thoracic aorta. Gallic acid exerted a contractile effect on the phenylephrine- or prostaglandin F(2/alpha)-precontracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to-gallic acid was absent. Pretreatment with N(G)-nitro-L-arginine methyl ester (30 microM) abolished the gallic acid-induced contraction. Pretreatment with indomethacin (10 microM) or BQ610 (100 nM) had no observed effect. Pretreatment with gallic acid (1-10 microM) significantly attenuated the relaxation induced by acetylcholine, and that with 10 microM gallic acid also reduced the potency of sodium nitroprusside in the relaxation, without a reduction in efficacy, in endothelium-denuded arteries. These findings indicate that gallic acid induced endothelium-dependent contraction and strongly inhibited the endothelium-dependent relaxation rather than the endothelium-independent relaxation, probably through inhibition of endothelial nitric oxide (NO) production. Since NO plays an important role in vasodilative regulation and inflammatory disorders, these findings may also indicate that gallic acid interferes with the inflammatory responses.

  9. Cardiotrophin-1 attenuates endotoxin-induced acute lung injury.

    Science.gov (United States)

    Pulido, E J; Shames, B D; Pennica, D; O'leary, R M; Bensard, D D; Cain, B S; McIntyre, R C

    1999-06-15

    Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following alpha-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6. 3 +/- 0.3 units MPO/gwl in the ETX group (P 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 +/- 0.039 vs 4.747 +/- 0.039 in the ETX group (P 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury. Copyright 1999 Academic Press.

  10. A novel mechanism of vascular relaxation induced by sodium nitroprusside in the isolated rat aorta.

    Science.gov (United States)

    Bonaventura, Daniella; Lunardi, Claure N; Rodrigues, Gerson J; Neto, Mário A; Bendhack, Lusiane M

    2008-06-01

    Sodium nitroprusside (SNP) is an endothelium-independent relaxant agent and its effect is attributed to its direct action on the vascular smooth muscle (VSM). Endothelium modulates the vascular tone through the release of vasoactive agents, such as NO. The aim of this study was to investigate the contribution of the endothelium on SNP vasorelaxation, NO release and Ca2+ mobilization. Vascular reactivity experiments showed that endothelium potentiates the SNP-relaxation in rat aortic rings and this effect was abolished by l-NAME. SNP-relaxation in intact endothelium aorta was inhibited by NOS inhibitors for the constitutive isoforms (cNOS). Furthermore, endogenous NO is involved on the SNP-effect and this endogenous NO is released by cNOS. Moreover, Ca2+ mobilization study shows that l-NAME inhibited the reduction of Ca2+-concentration in VSM cells and reduced the increase in Ca2+-concentration in endothelial cells induced by SNP. This enhancement in Ca2+-concentration in the endothelial cells is due to a voltage-dependent Ca2+ channels activation. The present findings indicate that the relaxation and [Ca2+]i decrease induced by SNP in VSM cells is potentiated by endothelial production of NO by cNOS-activation in rat aorta.

  11. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B

    1993-01-01

    Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood...

  12. Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection.

    Science.gov (United States)

    Quispe Calla, Nirk E; Vicetti Miguel, Rodolfo D; Mei, Ao; Fan, Shumin; Gilmore, Jocelyn R; Cherpes, Thomas L

    2016-11-28

    The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems for long-acting reversible contraception provides strong impetus to define immunomodulatory properties of this exogenous progestin. In initial in vitro studies herein, we found LNG significantly impaired activation of human dendritic cell (DCs) and their capacity to promote allogeneic T cell proliferation. In follow-up studies in a murine model of intranasal Chlamydia trachomatis infection, we analogously found that LNG treatment prior to infection dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at 2 days post infection (dpi). At 12 dpi, we also detected significantly fewer CD4(+) and CD8(+) T cells in the lungs of LNG-treated mice. This inhibition of DC activation and T cell expansion in LNG-treated mice also delayed chlamydial clearance and the resolution of pulmonary inflammation. Conversely, administering agonist anti-CD40 monoclonal antibody to LNG-treated mice at 1 dpi restored lung T cell numbers and chlamydial burden at 12 dpi to levels seen in infected controls. Together, these studies reveal that LNG suppresses DC activation and function, and inhibits formation of pathogen-specific T cell immunity. They also highlight the need for studies that define in vivo effects of LNG use on human host response to microbial pathogens.

  13. A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants

    Directory of Open Access Journals (Sweden)

    Monteiro Ilza

    2007-11-01

    Full Text Available Abstract Background The aim of this study was to evaluate bone mineral density (BMD at baseline and at 18 and 36 months of use of etonogestrel (ENG-and levonorgestrel (LNG-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use. Methods A total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry. Results There was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius. Conclusion Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.

  14. Evaluation of quality of life and cost-effectiveness of definitive surgery and the levonorgestrel intrauterine system as treatment options for heavy menstrual bleeding.

    Science.gov (United States)

    Adigüzel, Cevdet; Seyfettinoğlu, Sevtap; Aka Satar, Deniz; Arlier, Sefa; Eskimez, Eda; Kaya, Fatma; Nazik, Hakan

    2017-06-12

    This study aimed to compare the levonorgestrel intrauterine system (LNG-IUS) with abdominal hysterectomy (TAH) and total laparoscopic hysterectomy (TLH) as first-line treatments for heavy menstrual bleeding (HMB). Ninety-eight patients aged 20-55 years who complained of regular heavy menstrual bleeding were enrolled in the study. The TAH group included 29 patients, the LNG-IUS group included 34, and the TLH group included 35. These groups were compared in terms of quality of life and the cost-effectiveness of the selected methods. Quality of life was assessed using the 36-Item Short Form (SF-36), and cost-effectiveness was assessed according to the current cost of each approach. The quality of life parameters, with the exception of mental health, improved significantly in the LNG-IUS, TAH, and TLH groups. The mean costs of the LNG-IUS, TAH, and TLH procedures were $99.15 ± 4.90, $538.82 ± 193.00 and $1617.05 ± 258.44, respectively (P < 0.05). Overall, LNG-IUS was the most cost-effective treatment option. The outcome measures of the SF-36 revealed that after 6 months, these treatments were equal in terms of quality of life, except for mental health. LNG-IUS was the most cost-effective approach.

  15. The efficacy of long-term maintenance therapy with a levonorgestrel-releasing intrauterine system for prevention of ovarian endometrioma recurrence.

    Science.gov (United States)

    Kim, Mi-La; Cho, Yeon Jean; Kim, Mi Kyoung; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju

    2016-09-01

    To evaluate the cumulative recurrence rates of ovarian endometrioma among patients using a levonorgestrel-releasing intrauterine system (LNG-IUS) after conservative laparoscopic surgery. A retrospective review was conducted of premenopausal women who underwent conservative laparoscopic surgery for ovarian endometrioma and subsequent treatment with LNG-IUS at two gynecologic surgery centers in South Korea between January 1, 2007, and September 30, 2014. Eligible patients had no residual ovarian lesions before LNG-IUS insertion, underwent insertion within 12 months of primary surgery, and were followed up for at least 6 months afterwards. Recurrence was defined as a cystic mass (≥2 cm in diameter) detected by transvaginal ultrasonography. Overall, 61 patients were included. The mean duration of follow-up was 42.9 ± 22.0 months (range 8-98). Recurrence of ovarian endometrioma was detected among 7 (11%) of the patients. On Kaplan-Meier analysis, the cumulative recurrence rates were 4.0%, 6.3%, and 25.5% at 24, 36, and 60 months after surgery, respectively. In multivariate analysis, nulliparity at surgery was the only risk factor for recurrence (hazard ratio 5.892, 95% confidence interval 1.139-30.484; P=0.034). Long-term maintenance therapy with LNG-IUS after conservative surgery might be a treatment option to consider to prevent ovarian endometrioma recurrence among premenopausal women. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Postoperative Levonorgestrel-Releasing Intrauterine System Insertion After Gonadotropin-Releasing Hormone Agonist Treatment for Preventing Endometriotic Cyst Recurrence: A Prospective Observational Study.

    Science.gov (United States)

    Kim, Min Kyoung; Chon, Seung Joo; Lee, Jae Hoon; Yun, Bo Hyon; Cho, SiHyun; Choi, Young Sik; Lee, Byung Seok; Seo, Seok Kyo

    2017-01-01

    The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women. Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive.

  17. LNG-IUS 12: a 19.5 levonorgestrel-releasing intrauterine system for prevention of pregnancy for up to five years.

    Science.gov (United States)

    Nelson, Anita L

    2017-09-01

    Globally, intrauterine devices (IUDs) are the second most commonly used form of reversible contraception because of their high efficacy, safety, convenience and cost effectiveness. The levonorgestrel releasing intrauterine system with daily average release of 20 mcg (LNG-IUS 20) is the popular choice because of its favorable bleeding patterns and many noncontraceptive benefits. A three year (LNG-IUS 8) became available three years ago. More recently, the LNG-IUS 12 was added. This new IUD shares a smaller frame, narrow inserter and lower rate of amenorrhea with the LNG-IUS 8, but it offers the five years of contraceptive protection of the LNG-IUS 20. Areas covered: This article provides information on the contraceptive efficacy, safety and tolerability of this new IUS based on approximately 60,000 cycles of use. Where available, the impacts of subject age, parity and body mass index (BMI) on study outcomes are reported. Expert opinion: This new LNG-IUS 12 with mid-dose hormone levels, smaller frame and longer effective life fills a niche that may better meet the needs of women who might appreciate the narrow insertion tube and/or the lower rates of amenorrhea. Cost will ultimately help determine success.

  18. Levonorgestrel butanoate intramuscular injection does not reliably suppress ovulation for 90 days in obese and normal-BMI women: a pilot study.

    Science.gov (United States)

    Edelman, Alison B; Cherala, Ganesh; Li, Hong; Pau, Francis; Blithe, Diana L; Jensen, Jeffrey T

    2017-01-01

    We performed a pilot evaluation of a new formulation of levonorgestrel butanoate (LB) designed to be a long-acting injectable (6 months) contraceptive to determine pharmacodynamic end points in normal-body mass index (BMI) and obese women. Obese (BMI ≥30 kg/m(2)) and normal-BMI, otherwise healthy, women received a single intramuscular injection of LB after ovulation was confirmed in a baseline cycle. The primary outcome was return of ovulation in days. A total of 14 women enrolled and completed the study [normal BMI n=9, median BMI 22.7kg/m(2) (range 19.4-25.8); obese n=5, median BMI 35.7kg/m(2) (30.1-39.2)]. The first 6 subjects (normal BMI=4/9, obese BMI=2/5) received 40 mg of LB, and the remaining 8 received 20 mg. All women except one returned to ovulation prior to 6 months. Return to ovulation occurred earlier in the obese group; 3/5 obese and 0/9 normal BMI subjects returned to ovulation within 90 days (p=.03). No serious adverse events were reported during the study. Return to ovulation was earlier than 6 months in both BMI groups but more so in the obese BMI group. Since return of ovulation was earlier than expected for this LB injectable formulation, additional steps are needed to develop a preparation suitable as a longer-lasting product. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The use of long acting subcutaneous levonorgestrel (LNG) gel depot as an effective contraceptive option for cotton-top tamarins (Saguinus oedipus).

    Science.gov (United States)

    Wheaton, C J; Savage, A; Shukla, A; Neiffer, D; Qu, W; Sun, Y; Lasley, B L

    2011-01-01

    Cotton-top tamarins (Saguinus oedipus) are a critically endangered species that have been bred successfully in captivity for many years. For two decades, the Cotton-top Tamarin SSP(©) has been challenged with a high rate of reproduction combined with a history of contraceptive failures and nonrecommended births using the current Depo Provera(®) (medroxyprogesterone acetate) injection followed by MGA (melengestrol acetate) implant contraception combination. To address these issues we have developed and tested the use of levonorgestrel (LNG) as an effective contraception option for cotton-top tamarins. LNG was delivered in an injectable, gel matrix consisting of polylactic-co-glycolic acid, triethyl citrate and N-methylpyrrolidone. This gel matrix forms a biodegradable depot at the subcutaneous injection site providing slow release of the active ingredient. Gel matrix composition and LNG concentration were adjusted in four gel formulations to maximize the duration of contraceptive efficacy while minimizing immediate post-injection increases in fecal LNG concentration. LNG treatment (68.44 ± 8.61 mg/kg) successfully eliminated ovarian cycles (fecal pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1) C)) for 198.8 ± 70.3 days (formulation four; range 19-50 weeks). It was demonstrated that subcutaneous LNG depot injection was an effective, reversible contraceptive option for the management of cotton-top tamarins in captivity.

  20. Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women.

    Science.gov (United States)

    Morelli, Michele; Di Cello, Annalisa; Venturella, Roberta; Mocciaro, Rita; D'Alessandro, Pietro; Zullo, Fulvio

    2013-02-01

    The aim of this retrospective study was to evaluate the efficacy of levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic postmenopausal overweight/obese women. A total of 34 overweight/obese postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified from registry data. Endometrial histology at LNG-IUS insertion showed simple EH in 20 cases (58.8%), complex EH in 14 cases (41.2%). At 36 months, 91% of patients showed no recurrence of AUB and a significant reduction in the mean endometrial thickness (from 8.2 ± 2.2 to 3.2 ± 1.5 mm, p LNG-IUS represents an effective treatment option to manage postmenopausal obese women affected by AUB and EH. The device seems to be able to prevent the onset of AH and EC in women at high risk. Further prospective controlled studies in a well selected group of women are needed.

  1. High performance liquid chromatography/ion-trap mass spectrometry for separation and simultaneous determination of ethynylestradiol, gestodene, levonorgestrel, cyproterone acetate and desogestrel.

    Science.gov (United States)

    Matejícek, David; Kubán, Vlastimil

    2007-04-11

    A fast and highly sensitive high performance liquid chromatographic/ion-trap mass spectrometric method (LC/MS) has been developed for simultaneous determination of ethynylestradiol (EE2), gestodene (GES), levonorgestrel (LNG), cyproterone acetate (CPA) and desogestrel (DES). Among three types of sorbents tested (C8, C18 and phenyl) from two suppliers, the best separation was achieved on reverse phase Zorbax SB-Phenyl column using aqueous methanol as a mobile phase. A linear gradient profile from 70 up to 100% (v/v) in 7th min, kept constant at 100% up to 10th min and followed by a negative gradient to 70% of methanol up to 12th min was used for elution. Applicability of electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) and influence of the mobile phase composition, its flow rate, capillary/vaporizer temperature of API source and in-source fragmentor voltage ionization are discussed. The on-column limits of quantification (10S/N) were 300 pg of EE2, 14 pg of GES and LNG, 4 pg of CPA and 960 pg of DES per injection (1 microL) using APCI with data collection in selected ion monitoring (SIM) mode. The analytical performance of the method was evaluated using the determination of EE2, GES, LNG, CPA and DES in contraceptives and river water samples.

  2. Study on Differences in Spermatogenic Suppression between Azoospermic and Oligozoospermic Responders Treated with Levonorgestrel Implant Plus Testosterone Undecanoate Injectable in Chinese Men

    Institute of Scientific and Technical Information of China (English)

    Si-tian LIU; You-lun GUI; W.J. Bremner; Er-sheng GAO; Chang-hai HE

    2003-01-01

    Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate(TU) injectable Methods Totally 21 Chinese male volunteers were given treatment with LNG implants (four rods, 75 mg/rod) and intramuscular injection of TU (500 mg, bimonthly for 3 times). According to the effects of treatment, they were divided into two groups, namely, azoospermia group (group A) and oligozoospermia group (group 0). Then seminal FSH, LH, T and estradiol (E2)were determined by immunoenzymetric assay, while seminal and serum dihydrotachysterol (DHT)and serum sex hormone binding globulin (SHBG) were by radioimmunoassay, and seminal transferrin (Tf) by scatter turbidimetry assay.Results Seminal FSH, LH and serum DHT, SHBG, FTI (T/SHBG × 100) levels were significantly lower in group A than in group O, while higher seminal concentrations of E2 were observed in azoospermia group.Conclusion The differences in the spermatogenic suppression in Chinese men might be attributed to different rate of peripheral androgen metabolism, variations in serum SHBG levels,5a-reductase activity and individual aromatase activity during LNG plus TU administration. In addition, seminal sex hormones might be more sensitive indexes to assess the extent of feedback inhibition on hypothalamus-pituitary-testis with exogenous testosterone plus progestogen in the efficacy hormone male contraceptive trials.

  3. Development and validation of sensitive LC/MS/MS method for quantitative bioanalysis of levonorgestrel in rat plasma and application to pharmacokinetics study.

    Science.gov (United States)

    Ananthula, Suryatheja; Janagam, Dileep R; Jamalapuram, Seshulatha; Johnson, James R; Mandrell, Timothy D; Lowe, Tao L

    2015-10-15

    Rapid, sensitive, selective and accurate LC/MS/MS method was developed for quantitative determination of levonorgestrel (LNG) in rat plasma and further validated for specificity, linearity, accuracy, precision, sensitivity, matrix effect, recovery efficiency and stability. Liquid-liquid extraction procedure using hexane:ethyl acetate mixture at 80:20 v:v ratio was employed to efficiently extract LNG from rat plasma. Reversed phase Luna column C18(2) (50×2.0mm i.d., 3μM) installed on a AB SCIEX Triple Quad™ 4500 LC/MS/MS system was used to perform chromatographic separation. LNG was identified within 2min with high specificity. Linear calibration curve was drawn within 0.5-50ng·mL(-1) concentration range. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency at three quality control (QC) concentrations 0.5 (low), 5 (medium) and 50 (high) ng·mL(-1) was found to be >90%. Stability of LNG at various stages of experiment including storage, extraction and analysis was evaluated using QC samples, and the results showed that LNG was stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of LNG in rats after SubQ injection, providing its applicability in relevant preclinical studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Appliable Study on Levonorgestrel Intrauterine System%左炔诺孕酮宫内缓释系统应用研究

    Institute of Scientific and Technical Information of China (English)

    林农; 曹小明

    2003-01-01

    宫内节育器(IUD)是育龄妇女的主要避孕工具,其发展与完善大大提高了育龄妇女对IUD的接受性,拓宽了IUD应用范围。而释放左旋18-甲基炔诺酮(LNG)的宫内节育器(LNG-IUD),近年来称之为LNG宫内缓释系统,即LNG-IUS(Levonorgestrel Intrauterine System),是当前国内外公认的性能优良的宫内抗生育系统,具有IUD使用的长效性及口服避孕药的高效性,又减少IUD的副作用,同时还具有治疗多种妇科疾病及绝经后激素替代治疗的辅助作用。

  5. Non -contraceptive therapeutic uses of Levonorgestrel releasing -intrauterine systems%左炔诺孕酮宫内缓释系统的非避孕应用

    Institute of Scientific and Technical Information of China (English)

    尚思慧; 林琬君

    2011-01-01

    左炔诺孕酮宫内缓释系统(delayed levonorgestrel -releasing intrauterine system,LNG - IUS)是90年代上市的新型避孕系统(商品名:曼月乐),其通过每天释放20μg的左炔诺孕酮至宫腔,使子宫内膜腺体萎缩、间质蜕膜样变、黏膜变薄,实现孕激素的非全身给药,应用于月经过多、子宫内膜异位症和子宫腺肌病、子宫肌瘤、激素替代治疗期间的子宫内膜保护及子宫内膜增生和早期的子宫内膜癌等,从而开辟了在非避孕领域的许多新的应用.

  6. Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

    Science.gov (United States)

    Quispe Calla, Nirk E.; Vicetti Miguel, Rodolfo D.; Mei, Ao; Fan, Shumin; Gilmore, Jocelyn R.; Cherpes, Thomas L.

    2016-01-01

    The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems for long-acting reversible contraception provides strong impetus to define immunomodulatory properties of this exogenous progestin. In initial in vitro studies herein, we found LNG significantly impaired activation of human dendritic cell (DCs) and their capacity to promote allogeneic T cell proliferation. In follow-up studies in a murine model of intranasal Chlamydia trachomatis infection, we analogously found that LNG treatment prior to infection dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at 2 days post infection (dpi). At 12 dpi, we also detected significantly fewer CD4+ and CD8+ T cells in the lungs of LNG-treated mice. This inhibition of DC activation and T cell expansion in LNG-treated mice also delayed chlamydial clearance and the resolution of pulmonary inflammation. Conversely, administering agonist anti-CD40 monoclonal antibody to LNG-treated mice at 1 dpi restored lung T cell numbers and chlamydial burden at 12 dpi to levels seen in infected controls. Together, these studies reveal that LNG suppresses DC activation and function, and inhibits formation of pathogen-specific T cell immunity. They also highlight the need for studies that define in vivo effects of LNG use on human host response to microbial pathogens. PMID:27892938

  7. Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique(®)): A Review of Its Use as an Oral Contraceptive.

    Science.gov (United States)

    Burness, Celeste B

    2015-06-01

    A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30 µg for 84 days and ethinylestradiol 10 µg for 7 days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conventional 28-day regimens. Seasonique(®) was effective in preventing pregnancy in a large (n = 1006), noncomparative trial of healthy, sexually active women. In this trial, the overall Pearl index (pregnancies per 100 woman-years of use) in women aged 18-35 years (n = 621) was 0.76 and the Pearl index for method-failure (compliant use) was 0.26. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with a mean of 2 days of bleeding and 1 day of spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting was highest during the first few cycles of use and decreased thereafter. Seasonique(®) was generally well tolerated, with a tolerability profile in line with that expected for OCs. Seasonique(®) extends the contraceptive options currently available to women, particularly in those who desire fewer withdrawal bleeding episodes.

  8. [Emergency contraception: efficacy difference between levonorgestrel and ulipristal acetate depending on the follicular size at the time of an unprotected sexual intercourse].

    Science.gov (United States)

    Jamin, C

    2015-03-01

    The most used treatment in the world for emergency contraception is the levonorgestrel (LNG) pill. However, its efficacy decreases if it is administered 3 days after unprotected sexual intercourse, whereas the ulipristal acetate (UPA) pill is effective up until 5 days afterwards. Pooled clinical data show that UPA is more effective than LNG when taken very shortly after intercourse (within 24h) or, conversely, between 72 and 120 h after intercourse. UPA is also more effective than LNG in inhibiting follicular rupture when administered near the time of ovulation. We show here why overall UPA is more effective than LNG in reducing the rate of unwanted pregnancies by demonstrating the effect of each product depending on the follicular size at the time of an unprotected sexual intercourse We also explain the difference between UPA and LNG in the maximum time to administration simply by the shift in ovulation and the fact that UPA has an effect on larger follicles than LNG does (18 mm vs. 14 mm), without postulating a hypothetical endometrial effect. We also explain why UPA and LNG remain emergency contraceptives and should not be used for daily contraception.

  9. Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery

    Directory of Open Access Journals (Sweden)

    Liciane dos Santos MENEZES

    Full Text Available Abstract Introduction Levobupivacaine (LEVO can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM, a non-selective K+ channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode’s solution (KCl 80 mM, LEVO-induced vasodilatation was not significantly different from that observed in the rings pre-contracted with phenylephrine. Moreover, it did not show a significant additional vasodilator effect compared to the maximal vasodilator effect of nifedipine. Conclusion This study demonstrated that LEVO produces a vasodilator effect in the rat superior mesenteric artery in an endothelium-independent manner. This effect seems to be mediated via Ca2+ channel blockade in the vascular smooth muscle cells.

  10. Fatty acid-induced changes in vascular reactivity in healthy adult rats.

    Science.gov (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène

    2005-12-01

    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

  11. The Contraceptive ResultAnalyze aftertheAbortion byYasmin and Levonorgestrel%屈螺酮炔雌醇与左炔诺孕酮用于人工流产后避孕效果分析

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective:To approach contraceptive effect,restore endometrial,reduce uterine cavity adhesion after the abortion by yasmin and levonorgestrel.Methods:To analyze 200 cases clinical data after the abortion by yasmin and levonorgestrel,which was to be divided into yasmin group 100 cases and levonorgestrel group 100 cases.Results:The endometrial thickness,vaginal bleeding time,menstrual recovery time of abortion patients of yasmin group were better than levonorgestrel group,P<0.05,results of the study differences were statistical significance.Conclusion:The Immediately after abortion with yasmin is safe and effective,Not only can make vaginal bleeding volume significantly reduced,shorten the time of vaginal bleeding,Also can promote the menstruation after tide and endometrial repair,which was to be used.%  目的:探讨屈螺酮炔雌醇(优思明)与左炔诺孕酮用于人工流产后避孕效果、恢复子宫内膜、减少宫腔粘连情况的效果。方法:分析人工流产患者200例临床资料,依据避孕药物的不同进行分组,优思明组100例和左炔诺孕酮组100例。结果:优思明组人工流产患者子宫内膜厚度、阴道流血时间、月经恢复时间明显优于左炔诺孕酮组,同时阴道流血量和宫腔粘连发生率均优于左炔诺孕酮组,P<0.05,研究结果差异有统计学意义。结论:人工流产后即时用优思明是安全有效的,不仅能使阴道流血量明显减少,缩短阴道流血时间,还能促进月经复潮和子宫内膜修复,值得临床应用。

  12. A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement.

    Science.gov (United States)

    Turok, David K; Eisenberg, David L; Teal, Stephanie B; Keder, Lisa M; Creinin, Mitchell D

    2016-11-01

    Misperceptions persist that intrauterine device placement is related to pelvic infections and Chlamydia and gonorrhea testing results are needed prior to placement. We sought to evaluate the relationship of Chlamydia and gonorrhea screening to pelvic infection for up to 2 years following placement of the levonorgestrel 52-mg intrauterine system. A total of 1751 nulliparous and multiparous females 16 to 45 years old enrolled in a multicenter trial designed to evaluate the efficacy and safety of a new levonorgestrel intrauterine system for up to 7 years. Participants had Chlamydia screening at study entry and yearly if they were age ≤25 years. Women also had baseline gonorrhea screening if testing had not been performed since starting their current sexual relationship. Those who changed sexual partners during the trial had repeated Chlamydia and gonorrhea testing. Intrauterine system insertion could occur on the same day as screening. Participants did not receive prophylactic antibiotics for intrauterine system placement. Investigators performed pelvic examinations after 12 and 24 months and when clinically indicated during visits at 3, 6, and 18 months after placement and unscheduled visits. Pelvic infection included any clinical diagnosis of pelvic inflammatory disease or endometritis. Most participants (n = 1364, 79.6%) did not have sexually transmitted infection test results available prior to intrauterine system placement. In all, 29 (1.7%) participants had positive baseline testing for a sexually transmitted infection (Chlamydia, n = 25; gonorrhea, n = 3; both, n = 1); 6 of these participants had known results (all with Chlamydia infection) prior to intrauterine system placement and received treatment before enrollment. The 23 participants whose results were not known at the time of intrauterine system placement received treatment without intrauterine system removal and none developed pelvic infection. The incidence of positive Chlamydia testing was

  13. Estimated disability-adjusted life years averted by free-of-charge provision of the levonorgestrel-releasing intrauterine system over a 9-year period in Brazil.

    Science.gov (United States)

    Ferreira, Jessica M; Monteiro, Ilza; Fernandes, Arlete; Bahamondes, Maria V; Pitoli, Ana; Bahamondes, Luis

    2017-07-01

    The objective was to analyse the contribution of the provision at no cost to users of the 20 µg/day levonorgestrel-releasing intrauterine system (LNG-IUS) towards disability-adjusted life years (DALY) averted over a 9-year period. We analysed data from 15 030 new users of the LNG-IUS who had the device inserted at 26 Brazilian teaching hospitals between January 2007 and December 2015. The devices came from the International Contraceptive Access Foundation (ICA), a not-for-profit foundation that donates the devices to developing countries for use by low-income women who desire long-term contraception and who freely choose to use this device. Estimation of the DALY averted included live births averted, maternal morbidity and mortality, child mortality and unsafe abortions averted. A total of 15 030 women chose the LNG-IUS as a contraceptive method during the study period. Over the 9 years of evaluation, the estimated cumulative contribution of the Brazilian program in terms of DALY averted consisted of 486 live births, 14 cases of combined maternal mortality and morbidity, 143 cases of child mortality and 410 unsafe abortions. Provision of the LNG-IUS at no cost to low-income Brazilian women reduced unwanted pregnancies and probably averted maternal mortality and morbidity, child mortality and unsafe abortions. Family planning programs, policymakers and stakeholders based in low-resource settings could take advantage of the information that the provision of this contraceptive at no cost, or at affordable cost to a publicly-insured population, is an effective policy to help promote women's health. © Faculty of Sexual and Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Additive effects of levonorgestrel and ethinylestradiol on brain aromatase (cyp19a1b) in zebrafish specific in vitro and in vivo bioassays.

    Science.gov (United States)

    Hinfray, N; Tebby, C; Garoche, C; Piccini, B; Bourgine, G; Aït-Aïssa, S; Kah, O; Pakdel, F; Brion, F

    2016-09-15

    Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding

    Science.gov (United States)

    Warner, P.; Guttinger, A.; Glasier, A.F.; Lee, R.J.; Nickerson, S.; Brenner, R.M.; Critchley, H.O.D.

    2010-01-01

    BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS. METHODS CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19–49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%). RESULTS Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (−11% points, 95% CI −19 to −2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1–18). CONCLUSIONS The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. PMID:19897857

  16. Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care.

    Science.gov (United States)

    Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

    2016-12-01

    Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. In total, 571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. © British Journal of General Practice 2016.

  17. Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

    Science.gov (United States)

    Kim, Da Hee; Seong, Seok Ju; Kim, Mi Kyoung; Bae, Hyo Sook; Kim, Mi La; Yun, Bo Seong; Jung, Yong Wook; Shim, Jeong Yun

    2017-01-01

    To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

  18. Absence of Effect of Intravaginal Miconazole, Clindamycin, Nonoxynol-9, and Tampons on the Pharmacokinetics of an Anastrozole/Levonorgestrel Intravaginal Ring.

    Science.gov (United States)

    Nave, Rüdiger; Klein, Stefan; Müller, André; Chang, Xinying; Höchel, Joachim

    2017-08-07

    A study was performed to investigate the effect of an intravaginally administered antimycotic, an antibiotic, and a spermicide plus the co-usage of tampons on the pharmacokinetics (PK) of levonorgestrel (LNG) and anastrozole (ATZ) administered as an intravaginal ring (IVR) releasing 1050 μg ATZ per day and 40 μg LNG per day. In this parallel-group, randomized, open-label study, healthy premenopausal women received an IVR as the main treatment. Comedications were administered on 3 consecutive evenings during treatment with IVR on days 9-11 (group A, 400 mg miconazole; group B, 100 mg clindamycin; group C, 75 mg nonoxynol-9); tampon co-usage (group D) was performed on days 20-23. The primary PK parameter was the average plasma concentration (Cav,ss ) of ATZ and LNG at defined intervals, mainly prior to, during, and up to 7 days after the start of comedication. Fifty-two subjects were included, and at least 11 subjects per group completed the treatments. Overall, the medications and comedications were safe and well tolerated. Very similar ATZ and LNG plasma levels were observed across all groups. The calculated ratios of Cav,ss confirmed the absence of PK interactions because all relevant point estimates and 90% confidence intervals were within the range of 0.800-1.250, which is typically used in bioequivalence studies. These results demonstrate the absence of PK interactions between ATZ/LNG released from IVR and the tested antibiotic, antimycotic, spermicide, and tampons. Therefore, no restrictions for the use of the IVR are needed to continue the clinical program intended to treat endometriosis symptoms. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  19. Immediate versus delayed initiation of the levonorgestrel-releasing intrauterine system following medical termination of pregnancy - 1 year continuation rates: a randomised controlled trial.

    Science.gov (United States)

    Korjamo, R; Mentula, M; Heikinheimo, O

    2017-06-26

    To assess the 1-year continuation rates and new pregnancies following immediate versus delayed insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) after medical termination of pregnancy (MTOP) up to 20 weeks of gestation. A randomised controlled trial. Helsinki University Hospital, Finland, January 2013 to December 2014. A total of 267 women requesting MTOP and planning LNG-IUS for post-MTOP contraception. Insertion of LNG-IUS occurred immediately (0-3 days) or after a delay (2-4 weeks) following MTOP. Follow-up visits were at 3 months and 1 year after MTOP. LNG-IUS use at 1 year after MTOP. Women were randomised to immediate (n = 134) or delayed (n = 133) insertion of the LNG-IUS, and 133 and 131 were analysed; 127 (95.5%) women received immediate insertion and 111 (84.7%) women had delayed insertion of the LNG-IUS (risk ratio [RR] 1.13, 95% CI 1.04-1.22). The verified numbers of women continuing the LNG-IUS use at 1 year were 83 (62.4%) and 52 (39.7%) (RR 1.57, 95% CI 1.23-2.02). The numbers of new pregnancies were 6 (4.5%) and 16 (12.2%) (RR 0.37, 95% CI 0.15-0.91), and numbers of subsequent TOPs were 4 (3.0%) and 5 (3.8%) (RR 0.79, 95% CI 0.22-2.87). Immediate insertion of the LNG-IUS following MTOP resulted in higher 1-year continuation rates compared with delayed insertion. In addition, those receiving immediate insertion demonstrated a decreased new pregnancy rate, but no difference in the numbers of another TOP. Immediate LNG-IUS insertion after MTOP results in a higher 1-year continuation compared with delayed insertion. © 2017 Royal College of Obstetricians and Gynaecologists.

  20. Assessment of the quality of cervical mucus among users of the levonorgestrel-releasing intrauterine system at different times of use.

    Science.gov (United States)

    Moraes, Leticia G; Marchi, Nadia M; Pitoli, Ana C; Hidalgo, Maria M; Silveira, Carolina; Modesto, Waleska; Bahamondes, Luis

    2016-08-01

    The quality of cervical mucus (CM) among the levonorgestrel-releasing intrauterine system (LNG-IUS) users is controversial. The objectives were to assess CM compared to the levels of oestradiol (E2) and the frequency of cycles with luteal activity among users of the LNG-IUS. In total, 224 LNG-IUS users for between two months and five years were recruited at a Brazilian family planning clinic. For the cross-sectional part of the study, we enrolled 175 LNG-IUS users at 2, 6 12, 24, 36, 48, and 60 months after insertion (25 women in each group), and we performed one evaluation. For the prospective part of the study, we enrolled 49 LNG-IUS users at the same lengths of use after insertion (7 women in each group), and we evaluated these women once a week for five consecutive weeks. . Mean (± SEM) CM scores of all evaluations among women with single and weekly evaluations were between 3.3 ± 0.9 and 8.5 ± 0.3, respectively independently of the length of use of the LNG-IUS. Mean E2 values ranged from 45.5 ± 6.8 to 472.5 ± 34.7 pg/ml and the maximum ovarian follicle diameter on the days of evaluation varied from 14.0 ± 1.3 to 31.2 ± 0.4 mm. The mean CM score of all evaluations, independent of the length of use of the LNG-IUS and normal levels of serum E2, was below 10 was according to the WHO is inadequate for sperm penetration.

  1. Weight variation in users of depot-medroxyprogesterone acetate, the levonorgestrel-releasing intrauterine system and a copper intrauterine device for up to ten years of use.

    Science.gov (United States)

    Modesto, Waleska; de Nazaré Silva dos Santos, Priscila; Correia, Vinicius Machado; Borges, Luiza; Bahamondes, Luis

    2015-02-01

    Data on record regarding weight variation in depot-medroxyprogesterone acetate (DMPA) and levonorgestrel-releasing intrauterine system (LNG-IUS) users are controversial. To date, no studies have yet evaluated weight variation in DMPA and LNG-IUS users in up to ten years of use compared to non-hormonal contraceptive users. A retrospective study analysed weight variations in 2138 women using uninterruptedly DMPA (150 mg intramuscularly, three-monthly; n = 714), the LNG-IUS (n = 701) or a copper-intrauterine device (Cu-IUD; n = 723). At the end of the first year of use, there was a mean weight increase of 1.3 kg, 0.7 kg and 0.2 kg among the DMPA-, LNG-IUS- and Cu-IUD users, respectively, compared to weight at baseline (p < 0.0001). After ten years of use, the mean weight had risen by 6.6 kg, 4.0 and 4.9 kg among the DMPA-, LNG-IUS- and Cu-IUD users, respectively. DMPA-users had gained more weight than LNG-IUS- (p = 0.0197) and than Cu-IUD users (p = 0.0294), with the latter two groups not differing significantly from each other in this respect (p = 0.5532). Users of hormonal and non-hormonal contraceptive methods gained a significant amount of weight over the years. DMPA users gained more weight over the treatment period of up to ten years than women fitted with either a LNG-IUS or a Cu-IUD.

  2. Molecular and histological endpoints for developmental reproductive toxicity in Xenopus tropicalis: Levonorgestrel perturbs anti-Müllerian hormone and progesterone receptor expression.

    Science.gov (United States)

    Säfholm, Moa; Jansson, Erika; Fick, Jerker; Berg, Cecilia

    2016-01-01

    There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Müllerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Müllerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Müllerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Müllerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.

  3. No clinically meaningful pharmacokinetic interaction between the hepatitis C virus inhibitors elbasvir and grazoprevir and the oral contraceptives ethinyl estradiol and levonorgestrel.

    Science.gov (United States)

    Marshall, William L; Feng, Hwa-Ping; Caro, Luzelena; Talaty, Jennifer; Guo, Zifang; Huang, Xiaobi; Panebianco, Deborah; Ma, Joanne; Mangin, Eric; O'Reilly, Terry E; Butterton, Joan R; Yeh, Wendy W

    2017-05-01

    Oral contraceptive pills (OCPs) are an important element of hepatitis C virus (HCV) treatment in women of childbearing potential. These studies evaluated the safety and pharmacokinetic interactions between elbasvir (EBR) and grazoprevir (GZR) and ethinyl estradiol/levonorgestrel (EE/LNG). Both studies were open-label, single-site, two-period, fixed-sequence, one-way interaction studies. In period 1, subjects received one tablet of EE/LNG (0.03 mg/0.15 mg). In period 2, subjects received EBR (50 mg once daily) for 13 days or GZR (200 mg once daily) for 10 days, with one tablet of EE/LNG on day 7 (GZR group) or 10 (EBR group). Each study enrolled 20 healthy, nonsmoking adult females. There was no clinically meaningful effect of multiple doses of EBR or GZR on the pharmacokinetics of EE or LNG. Geometric mean ratios (GMRs) for AUC0-∞ and Cmax in the presence and absence of EBR were 1.01 and 1.10 for EE and 1.14 and 1.02 for LNG, with 90% confidence intervals (CIs) that were contained in the interval [0.80, 1.25]. Similarly, the AUC0-∞ and Cmax GMRs in the presence and absence of GZR were 1.10 and 1.05 for EE and 1.23 and 0.93 for LNG, respectively. The 90% CIs for EE AUC0-∞ and for EE and LNG Cmax were contained in the interval [0.80, 1.25]; however, the 90% CI for the LNG AUC0-∞ [1.15, 1.32] slightly exceeded the upper bound. These results suggest that EBR/GZR can be co-administered to female patients with HCV of childbearing potential who are on OCPs to prevent pregnancy.

  4. Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

    Science.gov (United States)

    Papadakis, Efstathios P; El-Nashar, Sherif A; Laughlin-Tommaso, Shannon K; Shazly, Sherif A M; Hopkins, Matthew R; Breitkopf, Daniel M; Famuyide, Abimbola O

    2015-01-01

    To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. Cohort study (Canadian Task Force II-2). An academic institution in the upper Midwest. All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. Radiofrequency EA, thermal balloon ablation, and LNG-IUS. The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  5. Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

    Science.gov (United States)

    2017-01-01

    Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

  6. Postmenopausal hormone therapy-also use of estradiol plus levonorgestrel-intrauterine system is associated with an increased risk of primary fallopian tube carcinoma.

    Science.gov (United States)

    Koskela-Niska, Virpi; Pukkala, Eero; Lyytinen, Heli; Ylikorkala, Olavi; Dyba, Tadeusz

    2015-10-15

    Data on the possible impact of postmenopausal hormone therapy (HT) on the incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore, we conducted a nationwide case-control study analyzing the association between the use of different HTs and PFTC. All women aged 50 years or older with an incident PFTC (n = 360) during 1995-2007 were identified from the Finnish Cancer Registry. For each case of PFTC, ten age- and place of residence-matched controls were selected from the Finnish National Population Register, which also provided information on parity. Data on HT purchases were received from the Prescription Register, and data on hysterectomies and sterilizations from the National Care Register. Controls with a salpingectomy before the PFTC diagnosis of the respective case were excluded. The PFTC risk in relation to different HTs was estimated with a conditional logistic regression model, adjusted for parity, age at last delivery, hysterectomy and sterilization. The use for five years or more of estradiol combined with levonorgestrel-releasing-intrauterine system (odds ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not statistically significantly increased. The OR for the use of tibolone for one year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk of PFTC, particularly when a progestin component is intrauterine or systemic progestin is given in sequential manner.

  7. Role of levonorgestrel releasing intra-uterine system in the treatment of menorrhagia due to dysfunctional uterine bleeding and fibroid uterus

    Directory of Open Access Journals (Sweden)

    Reena Gupta

    2014-06-01

    Full Text Available Background: This study was carried out to assess the clinical effectiveness of levonorgestrel releasing intrauterine device (LNG-IUS in the treatment of menorrhagia due to either Dysfunctional Uterine Bleeding (DUB or fibroid in Indian patients, and to assess patient satisfaction with this treatment modality. Methods: Sixty women with menorrhagia, 30 due to fibroid and 30 due to DUB, meeting inclusion criteria, received LNG-IUS and were prospectively followed up for 9 months with periodic clinical assessments and transvaginal ultrasounds. Patient satisfaction was assessed on a five-point scale. Results: One patient in DUB group was lost to follow-up. In DUB patients, the treatment failure rate was only 3.4% (1 out of 29 patients. The median PBAC score reduced by 95% at 9 months. Fibroid patients also had an equally impressive 97.7% reduction of PBAC score at 9 months, although the failure rate was higher (23.3%; 7 out of 30. Majority of patients were either and lsquo;very satisfied' or and lsquo;satisfied' with the treatment, although this percentage was more in DUB (82.8% than in the fibroid group (66.7%. Haemoglobin and serum ferritin levels significantly increased in both groups. No major side effect was noted. Conclusions: LNG-IUS is an excellent treatment modality for patients of DUB, with good patient satisfaction. It is also a useful treatment option in non-submucosal small fibroids for the symptoms of menorrhagia, can reduce uterine volume and can help avoid hysterectomy, but there is no effect on fibroid volume. Majority of patients are satisfied, although satisfaction rates are less than in DUB patients. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 671-677

  8. Effect of the hepatitis C virus protease inhibitor faldaprevir on the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers.

    Science.gov (United States)

    Sabo, John P; Lang, Benjamin; Elgadi, Mabrouk; Huang, Fenglei

    2015-01-01

    Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240 mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In period 1, subjects received EE/LNG once daily (QD) for 14 days. Blood samples were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG on day 21. A total of 15/16 subjects completed the study. Overall, EE and LNG exposure (assessed by the area under the curve) was approximately 1.4-fold higher when EE and LNG were coadministered with faldaprevir than when administered alone. Median t1/2 (terminal half-life in plasma at steady state) values were prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were coadministered with faldaprevir. The mean oral clearance and apparent volume of distribution of both EE and LNG were lower (∼ 30%) when EE and LNG were coadministered with faldaprevir. Coadministration of faldaprevir and an oral contraceptive resulted in a moderate increase in exposure to both EE and LNG. However, this increase was not considered clinically meaningful, and no dose adjustment of oral contraceptives was deemed necessary. (This study has been registered at ClinicalTrials.gov under registration number NCT01570244.).

  9. Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care

    Science.gov (United States)

    Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

    2016-01-01

    Background Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. PMID:27884916

  10. Pharmacokinetics of continuous once-a-week combination 17β-Estradiol/Low- or high-dose levonorgestrel transdermal delivery systems in postmenopausal women.

    Science.gov (United States)

    Karara, Adel H; Harrison, Lester I; Melikian, Armen P; Poola, Nagaraju; Morrison, Dennis; Bourg, Dale; Bourg, Linda; Zurth, Christian

    2014-05-01

    Two open-label, randomized, two-period, crossover studies were performed to determine the safety, delivery rates, and pharmacokinetic properties of a combination estradiol (E2)/levonorgestrel (LNG) transdermal delivery system (TDS). Study 1 enrolled 24 postmenopausal women who received a single TDS containing 4.4 mg E2 and 1.39 mg of LNG (E2/LNG Low) or E2 0.050 mg/24 hours TDS and 0.090 mg LNG oral tablet. Study 2 enrolled 44 postmenopausal women who received either E2/LNG Low or TDS containing 4.4 mg E2 and 2.75 mg LNG (E2/LNG High) weekly for a period of 4 weeks. E2, estrone (E1), LNG, and sex hormone-binding globulin (SHBG) serum concentrations were determined. Overall, both E2/LNG TDS were well tolerated and had excellent adhesion properties. The average daily delivery for E2/LNG Low was 0.045 mg for E2 and 0.0132 mg for LNG. Following weekly delivery of E2/LNG Low or High for 4 weeks, the combination of E2 with two different strengths of LNG did not alter the pharmacokinetic profile of E2. SHBG, total cholesterol, and triglycerides concentrations significantly decreased compared to baseline. Both E2/LNG Low and High TDSs were well tolerated and provided continuous drug delivery over 7 days supporting the benefits of the transdermal route of administration in optimally delivering hormonal therapy.

  11. The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 µg/levonorgestrel 100 µg + ethinyl estradiol 10 µg

    Directory of Open Access Journals (Sweden)

    Sheila Krishnan

    2010-08-01

    Full Text Available Sheila Krishnan, Jessica KileyDepartment of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, USAAbstract: Extended-cycle oral contraceptives (OCs are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE and levonorgestrel (LNG + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 µg and ethinyl estradiol 20 µg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 µg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.Keywords: continuous regimen, ethinyl estradiol, extended cycle, oral contraceptive

  12. Effect of the levonorgestrel intrauterine slow-releasing system on cytokines of uterine fluid after endometrial polyps resection by hysteroscopy%子宫内膜息肉术后放置左炔诺孕酮宫内缓释系统对宫腔灌洗液中细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    蔡惠兰; 丁香翠; 钱蓉蓉; 虞如芬; 孙利敏; 李强

    2012-01-01

    目的:研究子宫内膜息肉术后放置左炔诺孕酮宫内缓释系统(the levonorgestrel intrauterine system,LNGIUS)后宫腔灌洗液中细胞因子含量的改变.方法:22例子宫内膜息肉手术患者,术后采用LNG--IUS预防息肉复发,收集手术前及随访1年后宫腔灌洗液,采用ELISA法检测IL-1β、IL-6、IFN-γ、TGF-β1等细胞因子的变化情况.结果:子宫内膜息肉患者宫腔镜手术后采用LNG-IUS治疗1年后,其宫腔灌洗液中IL- 1β、IFN-γ含量较术前明显降低,其差异具有统计学意义(P<0.01);术前22例标本灌洗液中均未检出TGF-β1,术后IL-6、TGF-β1含量明显增高,其差异具有统计学意义(IL-6,P<0.05; TGF-β1,P<0.01).结论:LNG-IUS可诱导子宫内膜蜕膜样改变且局部炎症反应较轻,可能是预防子宫内膜息肉术后复发的原因之一.%OBJECTIVE To detect the changes of cytokines levels of uterine fluid after endometrial polyps resection by hyst-eroscopy LNG-IUS placement. METHODS 22 patients with LNG-IUS placement after endometrial polyps resection by hyste-roscopy was recruited,the uterine fluid collected before endometrial polyps resection by hysteroscopy and follow-up 1 years, detected the IL-1β, IL-6, IFN-γ, TGF-β1 levels detected by ELISA. RESULTS Follow-up 1 years, IL-11β, IFN-γ levels of the uterine lavage fluid were significantly lower than the preoperative levels, the difference was statistically significant (P<0. 01) ; the TGF-β1 was not detected before endometrial polyps resection by hysteroscopy, IL-6, TGF-fil were significantly increased follow-up 1 years , the difference was statistically significant (IL-6, P<0. 05; TGF-β11, P<0. 01). CONCLUSION Levonorgestrel intrauterine slow-releasing system can induce endometrial decidual-like changes and mild local inflammatory reaction, it may be reason to prevent recurrence of endometrial polyps.

  13. Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa

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    Hisa Hui Ling Tseng

    2016-01-01

    Full Text Available Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration-dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium-dependent vasodilation, but not the endothelium-independent vasodilation, was blocked by BKCa inhibitor iberiotoxin (IbTX. Using human umbilical vein endothelial cells (HUVECs as a model, we showed calycosin and formononetin induced dose-dependent outwardly rectifying K+ currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl, charybdotoxin (ChTX, or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO production and upregulated the activities and expressions of endothelial NOS (eNOS and neuronal NOS (nNOS. These results suggested that calycosin and formononetin act as endothelial BKCa activators for mediating endothelium-dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BKCa plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation.

  14. Improvement of Acetylcholine-Induced Vasodilation by Acute Exercise in Ovariectomized Hypertensive Rats.

    Science.gov (United States)

    Cheng, Tsung-Lin; Lin, Yi-Yuan; Su, Chia-Ting; Hu, Chun-Che; Yang, Ai-Lun

    2016-06-30

    Postmenopause is associated with the development of cardiovascular disease, such as hypertension. However, limited information is available regarding effects of exercise on cardiovascular responses and its underlying mechanisms in the simultaneous postmenopausal and hypertensive status. We aimed to investigate whether acute exercise could enhance vasodilation mediated by acetylcholine (ACh) and sodium nitroprusside (SNP) in ovariectomized hypertensive rats. The fifteen-week-old female spontaneously hypertensive rats (SHR) were bilaterally ovariectomized, at the age of twenty-four weeks, and randomly divided into sedentary (SHR-O) and acute exercise (SHR-OE) groups. Age-matched WKY rats were used as the normotensive control group. The SHR-OE group ran on a motor-driven treadmill at a speed of 24 m/min for one hour in a moderate-intensity program. Following a single bout of exercise, rat aortas were isolated for the evaluation of the endothelium-dependent (ACh-induced) and endothelium-independent (SNP-induced) vasodilation by the organ bath system. Also, the serum levels of oxidative stress and antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase, were measured after acute exercise among the three groups. We found that acute exercise significantly enhanced the ACh-induced vasodilation, but not the SNP-induced vasodilation, in ovariectomized hypertensive rats. This increased vasodilation was eliminated after the inhibition of nitric oxide synthase (NOS). Also, the activities of SOD and catalase were significantly increased after acute exercise, whereas the level of MDA was comparable among the three groups. These results indicated that acute exercise improved the endothelium-dependent vasodilating response to ACh through the NOS-related pathway in ovariectomized hypertensive rats, which might be associated with increased serum antioxidant activities.

  15. Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gebhard, Catherine; Staehli, Barbara E. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Shi, Yi; Camici, Giovanni G.; Akhmedov, Alexander; Hoegger, Lisa; Lohmann, Christine [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Matter, Christian M. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Hassa, Paul O.; Hottiger, Michael O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Malinski, Tadeusz [Department of Chemistry and Biochemistry, Ohio University, Athens, OH (United States); Luescher, Thomas F. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); and others

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer The nuclear enzyme PARP-1 is a downstream effector of oxidative stress. Black-Right-Pointing-Pointer PARP-1 protects from oxidative stress induced endothelial dysfunction. Black-Right-Pointing-Pointer This effect is mediated through inhibition of vasoconstrictor prostanoid production. Black-Right-Pointing-Pointer Thus, PARP-1 may play a protective role as antioxidant defense mechanism. -- Abstract: Background: Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress. Methods: PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings were suspended in organ chambers for isometric tension recording to analyze vascular function. Results: PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p < 0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, L-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3-fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p < 0.001 vs. PQ treated PARP-1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p < 0.05 vs. PQ treated PARP-1(+/+). Conclusion: PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids.

  16. Calcium antagonism and the vasorelaxation of the rat aorta induced by rotundifolone

    Directory of Open Access Journals (Sweden)

    Guedes D.N.

    2004-01-01

    Full Text Available The vasorelaxing activity of rotundifolone (ROT, a major constituent (63.5% of the essential oil of Mentha x villosa, was tested in male Wistar rats (300-350 g. In isolated rat aortic rings, increasing ROT concentrations (0.3, 1, 10, 100, 300, and 500 µg/ml inhibited the contractile effects of 1 µM phenylephrine and of 80 or 30 mM KCl (IC50 values, reported as means ± SEM = 184 ± 6, 185 ± 3 and 188 ± 19 µg/ml, N = 6, respectively. In aortic rings pre-contracted with 1 µM phenylephrine, the smooth muscle-relaxant activity of ROT was inhibited by removal of the vascular endothelium (IC50 value = 235 ± 7 µg/ml, N = 6. Furthermore, ROT inhibited (pD2 = 6.04, N = 6 the CaCl2-induced contraction in depolarizing medium in a concentration-dependent manner. In Ca2+-free solution, ROT inhibited 1 µM phenylephrine-induced contraction in a concentration-dependent manner and did not modify the phasic contractile response evoked by caffeine (20 mM. In conclusion, in the present study we have shown that ROT produces an endothelium-independent vasorelaxing effect in the rat aorta. The results further indicated that in the rat aorta ROT is able to induce vasorelaxation, at least in part, by inhibiting both: a voltage-dependent Ca² channels, and b intracellular Ca2+ release selectively due to inositol 1,4,5-triphosphate activation. Additional studies are required to elucidate the mechanisms underlying ROT-induced relaxation.

  17. Expanding Access to a New, More Affordable Levonorgestrel Intrauterine System in Kenya: Service Delivery Costs Compared With Other Contraceptive Methods and Perspectives of Key Opinion Leaders.

    Science.gov (United States)

    Rademacher, Kate H; Solomon, Marsden; Brett, Tracey; Bratt, John H; Pascual, Claire; Njunguru, Jesse; Steiner, Markus J

    2016-08-11

    The levonorgestrel intrauterine system (LNG IUS) is one of the most effective forms of contraception and offers important non-contraceptive health benefits. However, it is not widely available in developing countries, largely due to the high price of existing products. Medicines360 plans to introduce its new, more affordable LNG IUS in Kenya. The public-sector transfer price will vary by volume between US$12 to US$16 per unit; for an order of 100,000 units, the public-sector transfer price will be approximately US$15 per unit. We calculated the direct service delivery cost per couple-years of protection (CYP) of various family planning methods. The model includes the costs of contraceptive commodities, consumable supplies, instruments per client visit, and direct labor for counseling, insertion, removal, and resupply, if required. The model does not include costs of demand creation or training. We conducted interviews with key opinion leaders in Kenya to identify considerations for scale-up of a new LNG IUS, including strategies to overcome barriers that have contributed to low uptake of the copper intrauterine device. The direct service delivery cost of Medicines360's LNG IUS per CYP compares favorably with other contraceptive methods commonly procured for public-sector distribution in Kenya. The cost is slightly lower than that of the 3-month contraceptive injectable, which is currently the most popular method in Kenya. Almost all key opinion leaders agreed that introducing a more affordable LNG IUS could increase demand and uptake of the method. They thought that women seeking the product's non-contraceptive health benefits would be a key market segment, and most agreed that the reduced menstrual bleeding associated with the method would likely be viewed as an advantage. The key opinion leaders indicated that myths and misconceptions among providers and clients about IUDs must be addressed, and that demand creation and provider training should be prioritized

  18. Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant

    Directory of Open Access Journals (Sweden)

    Kimberly Scarsi

    2014-11-01

    Full Text Available Introduction: Sub-dermal hormone implants, such as levonorgestrel (LNG, are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART may be compromised given the potential for a cytochrome P450 3A-mediated drug–drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP- or efavirenz (EFV-based ART. Material and Methods: This non-randomized, parallel group study compared LNG pharmacokinetics between HIV-positive Ugandan women not yet eligible for ART (control group, n=18 and those on stable NVP- (n=20 or EFV- (n=20 based ART. The two-rod (75 mg/rod LNG sub-dermal implant was inserted at study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS method, with an assay calibration range of 50–1500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit. Results: At enrolment, participants had a mean age of 31 years; CD4+ cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p=0.09; all women in the NVP and EFV groups had an undetectable HIV-RNA. Women in the control group had a higher baseline body weight (73 kg compared to those in the NVP (63 kg; p=0.03 or EFV groups (60 kg; p<0.01. By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight=5 pg/mL decrease in LNG, p=0.03. LNG concentrations are reported in the table. Conclusions: Over a 24-week period, LNG concentrations were 40–54% lower in women on EFV-based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP-based ART, LNG concentrations were 32–39% higher than those observed in the control group, a difference partially

  19. Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women.

    Science.gov (United States)

    Trezza, Christine; Ford, Susan L; Gould, Elizabeth; Lou, Yu; Huang, Chuyun; Ritter, James M; Buchanan, Ann M; Spreen, William; Patel, Parul

    2017-07-01

    This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)-containing oral contraceptive (OC) in healthy women. In this open-label, fixed-sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1-10 alone and with oral CAB 30 mg once daily Days 11-21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations. Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07-1.18) and 1.05 (0.96-1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97-1.08) and 0.92 (0.83-1.03), respectively. Steady-state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed. Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice. © 2017 ViiV Healthcare. British Journal of Clinical Pharmacology published by John

  20. Expanding Access to a New, More Affordable Levonorgestrel Intrauterine System in Kenya: Service Delivery Costs Compared With Other Contraceptive Methods and Perspectives of Key Opinion Leaders

    Science.gov (United States)

    Rademacher, Kate H; Solomon, Marsden; Brett, Tracey; Bratt, John H; Pascual, Claire; Njunguru, Jesse; Steiner, Markus J

    2016-01-01

    ABSTRACT Background: The levonorgestrel intrauterine system (LNG IUS) is one of the most effective forms of contraception and offers important non-contraceptive health benefits. However, it is not widely available in developing countries, largely due to the high price of existing products. Medicines360 plans to introduce its new, more affordable LNG IUS in Kenya. The public‐sector transfer price will vary by volume between US$12 to US$16 per unit; for an order of 100,000 units, the public-sector transfer price will be approximately US$15 per unit. Methods: We calculated the direct service delivery cost per couple-years of protection (CYP) of various family planning methods. The model includes the costs of contraceptive commodities, consumable supplies, instruments per client visit, and direct labor for counseling, insertion, removal, and resupply, if required. The model does not include costs of demand creation or training. We conducted interviews with key opinion leaders in Kenya to identify considerations for scale-up of a new LNG IUS, including strategies to overcome barriers that have contributed to low uptake of the copper intrauterine device. Results: The direct service delivery cost of Medicines360’s LNG IUS per CYP compares favorably with other contraceptive methods commonly procured for public-sector distribution in Kenya. The cost is slightly lower than that of the 3-month contraceptive injectable, which is currently the most popular method in Kenya. Almost all key opinion leaders agreed that introducing a more affordable LNG IUS could increase demand and uptake of the method. They thought that women seeking the product’s non-contraceptive health benefits would be a key market segment, and most agreed that the reduced menstrual bleeding associated with the method would likely be viewed as an advantage. The key opinion leaders indicated that myths and misconceptions among providers and clients about IUDs must be addressed, and that demand creation

  1. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials.

    Science.gov (United States)

    Abu Hashim, Hatem; Ghayaty, Essam; El Rakhawy, Mohamed

    2015-10-01

    We sought to evaluate the therapeutic efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) with oral progestins for treatment of non-atypical endometrial hyperplasia (EH). Searches were conducted on PubMed, SCOPUS, and CENTRAL databases to August 2014, and reference lists of relevant articles were screened. The search was limited to articles conducted on human beings and females. The PRISMA Statement was followed. Seven randomized controlled trials (n = 766 women) were included. Main outcome measures were the therapeutic effect rate (histological response) after 3, 6, 12, and 24 months of treatment; rate of irregular vaginal bleeding; and the hysterectomy rate per woman randomized. The Cochrane Collaboration risk of bias tool was used for quality assessment. Metaanalysis was performed with fixed effects model. LNG-IUS achieved a highly significant therapeutic response rate compared with oral progestins after 3 months of treatment (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.39-3.82; P = .001, 5 trials, I(2) = 0%, n = 376), after 6 months of treatment (OR, 3.16; 95% CI, 1.84-5.45; P < .00001, 4 trials, I(2) = 0%, n = 397), after 12 months of treatment (OR, 5.73; 95% CI, 2.67-12.33; P < .00001, 2 trials, I(2) = 0%, n = 224), and after 24 months of treatment (OR, 7.46; 95% CI, 2.55-21.78; P = .0002, 1 trial, n = 104). Subgroup analysis showed evidence of highly significant therapeutic response following LNG-IUS compared with oral progestins for non-atypical simple as well as complex EH (OR, 2.51; 95% CI, 1.14-5.53; P = .02, 6 trials, I(2) = 0%, n = 290; and OR, 3.31; 95% CI, 1.62-6.74; P = .001, 4 trials, I(2) = 0%, n = 216, respectively). Compared with oral progestins, LNG-IUS achieved significantly fewer hysterectomies (OR, 0.26; 95% CI, 0.15-0.45; P < .00001, 3 trials, n = 362, I² = 42%). No difference was observed in the rate of irregular vaginal bleeding between both groups (OR, 1.12; 95% CI, 0.54-2.32; P = .76, 2 trials, n = 207, I

  2. Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

    Science.gov (United States)

    Zhou, Huimei; Cao, Dongyan; Yang, Jiaxin; Shen, Keng; Lang, Jinghe

    2017-07-01

    The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is

  3. 左炔诺孕酮片在健康中国女性志愿者体内药动学及生物等效性研究%Pharmacokinetics and bioequivalence of levonorgestrel tablet in healthy female volunteers

    Institute of Scientific and Technical Information of China (English)

    徐平声; 戴智勇; 秦群; 雷鹏; 许利敏; 李新中

    2009-01-01

    目的:评价左炔诺孕酮片在健康人体内的药动学与生物等效性.方法:20名健康中国女性志愿者随机交叉单剂量口服左炔诺孕酮片后,取血,采用LC-MS/MS法测定血浆中药物浓度.结果:单次口服左炔诺孕酮片参比制剂和试验制剂1.5 mg后的C_(max)分别为(24.58±10.48)和(24.09±10.15)ng·mL~(-1);T_(max)分别为(1.8±0.2)和(1.7±0.2)h;AUC_(0-72 h)分别为(241.9±99.8)和(244.9±105.8)ng·h·mL~(-1).试验制剂相对于参比制剂的生物利用度F分别为(102.6±24.8)%.结论:试验制剂左炔诺孕酮分散片与参比制剂左炔诺孕酮片具有生物等效性.%Objective:To evaluate the bioequivalence of levonorgestrel tablet. Methods:According to the cross-over design, each volunteer was given a single oral dose of levonorgestrel tablet and then the plasma sample was obtained and determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS) method. Results: The main pharmacokinetic parameters of single dose of the products were as follows: C_(max) ( 24.58±10.48) and (24.09±10.15)ng·mL~(-1), T_(max)(1.8±0.2)and(1.7±0.2)h,AUC_(0-72h)(241.9±99.8) and(244.9±105.8) ng ·h·mL~(-1) for reference and test respectively. The relative bioavailability was (102.6±24.8) %. Conclusion: The levonorgestrel tablets were bioequivalent.

  4. 子宫内放置曼月乐节育环治疗子宫腺肌症的临床观察%Clinical observation of levonorgestrel intrauterine system in uterus treat-ing adenomyosis

    Institute of Scientific and Technical Information of China (English)

    朱少萍; 罗小茶; 黄慧文; 林小凤; 梁金兴

    2015-01-01

    Objective To investigate the clinical efficacy of levonorgestrel intrauterine system in uterus treating adeno-myosis. Methods 84 patients with adenomyosis treated in our hospital from February 2010 to October 2014 were se-lected as research objects,and they were randomly divided into control group and study group,with 42 cases in each group.control group was treated with medicine,study group was treated with levonorgestrel intrauterine system.dysmenor-rhea improvement,uterine volume,serum CA125,hemoglobin and clinical efficacy before and after treatment were com-pared between two groups. Results The total marked rate in study group was 88.1%,while in control group,it was 69.0%with statistical difference (P<0.05),symptoms of dysmenorrheal,decreased serum CA125 in study group was better than that in control group (P<0.05). Conclusion Levonorgestrel intrauterine system placed in the uterus adenomyosis treat-ment is effective and safe,which has a high clinical value.%目的:探讨子宫内放置曼月乐节育环治疗子宫腺肌症的临床效果。方法选取本院2010年2月~2014年10月收治的84例子宫腺肌症患者作为研究对象,随机分为对照组和研究组,每组42例。对照组采用药物治疗,研究组采用曼月乐节育环进行治疗,比较两组治疗前后痛经改善情况、子宫体积、血清CA125、血红蛋白及临床疗效。结果研究组的治疗总有效率为88.1%,而对照组仅为69.0%,两组差异有统计学意义(P<0.05),且研究组的痛经症状、血清CA125改善情况优于对照组(P<0.05)。结论曼月乐节育环置于子宫内治疗子宫腺肌症的效果确切、安全性高,具有较高的临床推广价值。

  5. High Efficiency Liquid Chromatography in Detecting the Dissolution Rate of Levonorgestrel Tabelts%高效液相色谱法测定左炔诺孕酮片的溶出度

    Institute of Scientific and Technical Information of China (English)

    孙秋; 商丽丽; 孙晶晶

    2016-01-01

    Objective To establish the method of high efficiency liquid chromatography in detecting the dissolution rate of levonorgestrel tabelts. Methods 0.8% lauryl sodium sulfate solution (SDS) were used as the dissolution medium with 75r/min revolving speed and 45min sampling time according to the third law in the four dissolution spectrophotometry in Chi-nese pharmacopoeia in 2015, and the dissolution amount was detected by the high efficiency liquid chromatography with the Agilent ZORBAX 300-SCX C18 chromatographic column, acetonitrile-water (60:40) mobile phase and 240nm detection wavelength. Results The linear correlation of levonorgestrel between 0.375-2.625μg was good, r2= 1.0, the average recycle rate was 99.53% and RSD was 0.85%, (n=9), the dissolution rates of three batches of samples within 45min were in turn 100.6%, 100.2% and 100.5%. Conclusion The method meets the establishment principle of the dissolution method, and it can control the inner quality of levonorgestrel tabelts.%目的:建立高效液相色谱法测定左炔诺孕酮片的溶出度方法。方法采用《中国药典》2015年版四部溶出度测定法第三法,以0.8%十二烷基硫酸钠(SDS)溶液250 mL为溶出介质,转速为75 r/min,取样时间为45 min。采用以Agilent ZORBAX 300-SCX C18为色谱柱,以乙腈-水(60:40)为流动相,检测波长为240 nm的高效液相色谱法检测溶出量。结果左炔诺孕酮在0.375~2.625μg,范围内线性关系良好(r2=1.0);平均回收率为99.53%,RSD为0.85%(n=9);3批样品45 min内的溶出度依次为:100.6%、100.2%和100.5%。结论该方法符合溶出度方法的建立原则,可控制左炔诺孕酮片的内在质量。

  6. Effects of gomisin A on vascular contraction in rat aortic rings

    OpenAIRE

    Seok, Young Mi; Choi, Young Whan; Kim, Gyung-Duck; Kim, Hye-young; Takuwa, Yoh; Kim, In Kyeom

    2011-01-01

    Gomisin A (GA) is an active ingredient of the fruits of Schisandra chinensis which has been widely used as a tonic in traditional Korean medicine. GA induces not only endothelium-dependent but also endothelium-independent relaxation in an isolated rat's thoracic aorta. This study was aimed to investigate the molecular mechanism by which GA induces endothelium-independent vasorelaxation. Rat aortic rings were denuded of endothelium, mounted in organ baths, and subjected to contraction or relax...

  7. PKA and Epac activation mediates cAMP-induced vasorelaxation by increasing endothelial NO production.

    Science.gov (United States)

    García-Morales, Verónica; Cuíñas, Andrea; Elíes, Jacobo; Campos-Toimil, Manuel

    2014-03-01

    Vascular relaxation induced by 3',5'-cyclic adenosine monophosphate (cAMP) is both endothelium-dependent and endothelium-independent, although the underlying signaling pathways are not fully understood. Aiming to uncover potential mechanisms, we performed contraction-relaxation experiments on endothelium-denuded and intact rat aorta rings and measured NO levels in isolated human endothelial cells using single cell fluorescence imaging. The vasorelaxant effect of forskolin, an adenylyl cyclase activator, was decreased after selective inhibitor of protein kinase A (PKA), a cAMP-activated kinase, or L-NAME, an endothelial nitric oxide synthase (eNOS) inhibitor, only in intact aortic rings. Both selective activation of PKA with 6-Bnz-cAMP and exchange protein directly activated by cAMP (Epac) with 8-pCPT-2'-O-Me-cAMP significantly relaxed phenylephrine-induced contractions. The vasorelaxant effect of the Epac activator, but not that of the PKA activator, was reduced by endothelium removal. Forskolin, dibutyryl cAMP (a cAMP analogue), 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP increased NO levels in endothelial cells and the forskolin effect was significantly inhibited by inactivation of both Epac and PKA, and eNOS inhibition. Our results indicate that the endothelium-dependent component of forskolin/cAMP-induced vasorelaxation is partially mediated by an increase in endothelial NO release due to an enhanced eNOS activity through PKA and Epac activation in endothelial cells.

  8. Characterization of the polymorphonuclear leukocyte-induced vasoconstriction in isolated human umbilical veins.

    Science.gov (United States)

    Kerr, S W; Yu, R; Stearns, C D; Haynes, N A; Winquist, R J

    1998-11-01

    We investigated the contractile effects of both activated and unactivated polymorphonuclear leukocytes (PMNs) on human vascular tissue to characterize the influence of human PMNs on vascular tone. PMNs were added either unactivated or after f-met-leu-phe (fMLP) activation (10(-8) M), into tissue chambers containing human umbilical vein segments under either control or cytokine-treated conditions. The activation state of different PMN preparations was measured by immunofluorescence staining of the adhesion glycoproteins Mac-1 and L-selectin. Both unactivated and activated PMNs induced a cell number-dependent (1.5 x 10(5) to 2 x 10(6) cells/ml) vasoconstriction in human umbilical vein segments. This PMN-induced response was not inhibited by treatment with indomethacin (10(-5) M), superoxide dismutase (2 x 10(-7) M) or L-nitro-monomethyl arginine (10(-4) M). However, treatment of PMNs with the leukotriene biosynthesis inhibitor BIRM-270 partially inhibited (-61 +/- 19%, P <.05) the contraction induced only by unactivated PMNs. Moreover, the supernatant from unactivated, but not that from activated, PMNs elicited a contractile response comparable to that from the addition of cells. We observed a significant correlation between the Mac-1/L-selectin ratio of activated PMNs and the contractile response they generated (r = 0.77, P <.05). The activated PMN response had an endothelium-dependent component, whereas the unactivated PMN response was endothelium-independent. These results suggest that human PMNs of varying activation states have the capacity to modulate vascular smooth muscle tone via distinct mechanisms. Unactivated PMNs appear to modulate tone via a secreted product, whereas the more activated phenotype modulates vascular tone via a cognate interaction with the endothelium.

  9. Effects of Kaempferia parviflora Wall. Ex Baker on endothelial dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Malakul, Wachirawadee; Thirawarapan, Suwan; Ingkaninan, Kornkanok; Sawasdee, Pattara

    2011-01-27

    The aim of the present study was to investigate an ethanolic extract of Kaempferia parviflora (KPE) reduces oxidative stress and preserves endothelial function in aortae from diabetic rats. Diabetes was induced in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.). Vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence, respectively. Eight weeks after STZ treatment blood glucose was elevated compared to citrate treated control rats and there was an increased aortic generation of superoxide anion. In aortic rings acetylcholine-induced relaxation was impaired whereas endothelium-independent relaxation to sodium nitroprusside was unaffected. When aortic rings were acutely exposed to KPE (1, 10 and 100 μg/ml) there was a significant reduction in the detection of superoxide anion and enhanced relaxation to acetylcholine. Two separate groups of rats (control and diabetic) were orally administered daily with KPE (100 mg/kg body weight) for 4 weeks. KPE treatment reduced superoxide generation and increased the nitrite levels in diabetic aortae, and enhanced acetylcholine-induced relaxation. In the presence of N(G)-nitro-L-arginine (L-NNA), the relaxation to acetylcholine in aortic rings of diabetic rats was only partially inhibited, but was totally abolished in aortic rings from the KPE-treated diabetic rats. Indomethacin did not affect relaxation to acetylcholine in aortic rings of any group. These results suggest that KPE, acutely in vitro or after 4 weeks administration in vivo, reduces oxidant stress, increases NO bioavailability and preserves endothelium-dependent relaxation in aortae from diabetic rats. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. 左炔诺孕酮宫内缓释系统治疗子宫腺肌病的新进展%The Progress of Levonorgestrel-releasing Intrauterine System (LNG-IUS) Treat Adenomyosis

    Institute of Scientific and Technical Information of China (English)

    杨丹鹤; 付强; 丛丽莉; 王俊文

    2016-01-01

    左炔诺孕酮宫内缓释系统(levonorgestrel-releasing intrauterine system,LNG-IUS,商品名:曼月乐)是一种激素宫内避孕系统.近年来,发现其除了具有长期避孕效果外,对一些妇科疾病也具有治疗效果,尤其是子宫腺肌病.它具有作用时间长、疗效明显及不良反应小等优点.现就左炔诺孕酮宫内缓释系统的作用机制、疗效及副作用进行综述.

  11. 左炔诺孕酮宫内缓释系统治疗子宫腺疾症的疗效分析%Curative effect analysis of levonorgestrel releasing Intrauterine system which is used in adenomyosis

    Institute of Scientific and Technical Information of China (English)

    刘侠

    2014-01-01

    Objective To study curative effect of Levonorgestrel releasing Intrauterine system which is used in the treatment of adenomyosis.Method Follow the 60 cases of adenomyosis treated with levonorgestrel-releasing intrauterine system from October,2011 to October,2012. The follow-up of two years,Before treatment and after treatment 3,6,12,24 months Visual analog scale (VAS),serum carcinoembryonic antigen (CA125) value,changes and treatment of endometrial menstrual quantity,2 years of patient satisfaction.Results The placement of levonorgestrel releasing intrauterine system after the symptoms of dysmenorrhea patients obviously relieved, menstrual quantity obvious reduction, the menstrual period is shortened obviously,ultrasound examination of the endometrial thickness was significantly thinner,Compared with before treatment, the difference had statistical significance;Compared with before treatment, no significant difference of serum CA125 level and the size of the uterus. The main adverse reactions are:vaginal spotting, a little off the ring, amenorrhea,At the end of 2 satisfaction is 94.58%,the continuation rate was 100%.Conclusion Levonorgestrel releasing intrauterine system is an effective method for treatment of uterine adenomyosis,or suitable for dysmenorrhea and menorrhagia patients with adenomyosis.%目的:探讨子宫腺疾症患者宫内放置左炔诺孕酮宫内缓释系统(LNG-IUS)的临床疗效。方法随机选取2011年10月—2012年10月因子宫腺肌症就诊于我院的患者60例,均放置左炔诺孕酮宫内缓释系统。随诊两年,观察治疗前,治疗后3,6,12和24个月时视觉模拟评分(VAS)、血清癌抗原(CA125)值,月经量、子宫内膜变化及治疗2年患者满意度。结果放置左炔诺孕酮宫内缓释系统后患者痛经症状明显缓解,月经量明显减少,经期明显缩短,超声复查子宫内膜厚度明显变薄,与治疗前比较,差异有统计学意义;血清CA125水

  12. 左炔诺孕酮宫内缓释系统的非避孕作用的临床研究%Clinical study of non-contraception effection for levonorgestrel-releasing intrauterine system

    Institute of Scientific and Technical Information of China (English)

    程玉梅

    2010-01-01

    @@ 左炔诺孕酮宫内缓释系统(delayed levonor-gestrel-releasing intrauterine system, LNG-IUS)是一种有效的长效避孕药物,国内现有的商品名为曼月乐,内含52 mg左炔诺孕酮(levonorgestrel, LNG),每日释放20 μg,直接作用于宫腔,抑制子宫内膜的生长,使宫颈黏液变稠,抑制精子活动机能,从而阻止受孕,达到与绝育术相媲美的避孕效果[1],有效期至少5年,目前在全球120多个国家被批准用于避孕.

  13. Endothelial dysfunction and increased responses to renal nerve stimulation in rat kidneys during rhabdomyolysis-induced acute renal failure: role of hydroxyl radical.

    Science.gov (United States)

    Cil, Onur; Ertunc, Mert; Gucer, Kadri Safak; Ozaltin, Fatih; Iskit, Alper Bektas; Onur, Rustu

    2012-01-01

    Rhabdomyolysis is an important cause of acute renal failure (ARF) and renal vasoconstriction is the main mechanism in the pathogenesis of ARF. Lipid peroxidation due to hydroxyl radical (.OH) formation and redox cycling of myoglobin also have a role. We investigated the disturbance in renal vascular reactivity to reveal the mechanisms leading to ARF. Female Wistar rats (n = 7) were injected with glycerol (10 mL/kg, 50% in saline) intramuscularly to induce rhabdomyolysis, and then the kidneys were isolated and perfused. We investigated acetylcholine (ACh)-induced endothelium-dependent and papaverine (PAP)-induced endothelium-independent vasodilation responses and renal nerve stimulation (RNS)-induced vasoconstrictions. These were also investigated both in rats which received either .OH scavenger, dimethylthiourea (DMTU: 500 mg/kg before glycerol injection and 125 mg/kg 8 h after glycerol injection, n = 7), or myoglobin redox cycling inhibitor, acetaminophen (ApAP: 100 mg/kg 2 h before glycerol injection and 100 mg/kg each 4 h, and 22 h after glycerol injection, n = 7). ACh-induced responses in glycerol group were decreased (p group. DMTU restored both endothelium-dependent vasodilation and RNS-induced vasoconstriction. ApAP had no effect on vascular responses. Both DMTU and ApAP exerted a partial protective effect in renal histology without restoring serum creatinine and blood urea nitrogen (BUN) levels or creatinine clearance. This study showed that endothelial dysfunction and increased vasoconstriction developed during rhabdomyolysis. .OH plays an important role in the development of these vascular responses. These findings suggest that decreased endothelium-dependent vasodilation and augmented renal sympathetic tonus contribute to the development of renal vasoconstriction during rhabdomyolysis-induced ARF.

  14. Mecanismos de acción de la anticoncepción hormonal de emergencia: efectos del levonorgestrel anteriores y posteriores a la fecundación Mechanisms of action of emergency contraception

    Directory of Open Access Journals (Sweden)

    Marta Durand

    2009-06-01

    Full Text Available El mecanismo de acción del levonorgestrel (LNG como anticonceptivo de emergencia (AE es aún controvertido. Para quienes consideran que el embarazo inicia antes de la implantación, todo compuesto capaz de interferir con etapas posteriores a la fecundación y anteriores a la implantación se considera abortivo. Investigaciones previas sugieren que en seres humanos este método actúa también después de la fecundación. Sin embargo, en la actualidad existe sólida evidencia que demuestra que los efectos anteriores a la fecundación son en realidad los que explican la acción anticonceptiva del LNG. En este artículo se revisa la evidencia acumulada sobre los mecanismos de acción propuestos. Los consensos derivados de la información disponible establecen que los mecanismos prefecundación (inhibición o retardo de la ovulación son los que explican la efectividad anticonceptiva de los AE de progestina sola.There is still controversy regarding the mechanism of action of levonorgestrel (LNG for emergency contraception (EC. For those who state that pregnancy starts prior to implantation, any compound able to interfere with post-fertilization and pre-implantation stages, should be considered as abortifacient. Previous research suggests that EC in humans acts predominantly after fertilization. Current evidence with LNG-only EC supports a pre-fertilization mechanisms to explain its action. There are many potential mechanisms of action, which could vary pending on the day during the fertilization window of the ovarian cycle at which the contraceptive is given. This paper reviews the evidence for each potential mechanism of action. According to the most recently statements, it is concluded that the primary and possible the only mechanism of action of LNG-only EC is preventing or delaying ovulation.

  15. 左炔诺孕酮宫内缓释系统治疗子宫腺肌病疗效观察%Curative effect and observation of adenomyosis treated with levonorgestrel-releasing intrauterine device

    Institute of Scientific and Technical Information of China (English)

    杨丽晔; 崔友红; 张梅; 费华

    2011-01-01

    Objective To investigate the clinical effection of levonorgestrel-releasing intrauterine device (LNG IUS) in the treatment of adenomyosis.Methods Before LNG-IUS insertion and after 3, 6, 12, 18 months, 74 cases were asked to complete a visual analog scale ( VAS) form regarding pelvic pain, pictorial blood loss assessment chart (PBAC) form regarding menstrual blood volume and volume of uterus.Results After the 18-month visit, VAS score,PBAC score and volume of uterus were 0.74, 42.7, 206.5cm3, respectively.There were decreased significantly before LNG-IUS insertion(P<0.05).Conclusion Levonorgestrel intrauterine device is a preferable effective method in the treatment of adenomyosis.%目的 观察子宫腺肌病患者放置左炔诺孕酮宫内缓释系统(LNG-IUS;商品名:曼月乐)后的临床效果.方法 观察74例子宫腺肌病患者放置LNG-IUS前,放置后3、6、12、18个月痛经评分(VAS)、PBAC法月经量评分、子宫体积的变化.结果 痛经评分、经量评分和子宫体积大小在放置后18个月分别为0.74、42.7和206.5 cm3,与放置前相比差异有统计学意义(P<0.05).结论 曼月乐是治疗子宫腺肌病的一种较为有效且安全的方法.

  16. Palm oil tocotrienol fractions restore endothelium dependent relaxation in aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats.

    Science.gov (United States)

    Muharis, Syed Putra; Top, Abdul Gapor Md; Murugan, Dharmani; Mustafa, Mohd Rais

    2010-03-01

    Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.

  17. Application analysis of levonorgestrel intrauterine device in treatment of young and middle-aged people with adenomyosis%左炔诺孕酮宫内节育器在中青年子宫腺肌症治疗中的应用分析

    Institute of Scientific and Technical Information of China (English)

    涂小娥; 刘强

    2014-01-01

    目的:探析左炔诺孕酮宫内节育系统在中青年子宫腺肌症治疗中的临床效果。方法选取我院就诊治疗子宫肌腺患者28例子宫腺肌患者,观察在放置左炔诺孕酮宫内节育器前后痛经、月经量、子宫体积、子宫内膜厚度、血清CA125、血清性激素水平的变化情况,比较治疗前后患者临床症状、激素水平的变化及不良反应。结果左炔诺孕酮宫内节育器放置12个月后,患者的痛经程度降低,子宫体积和子宫内膜厚度明显减小,CA125水平明显减低,与放置前相比差异有统计学意义(P<0.05)。结论利用左炔诺孕酮宫内节育器可明显改善子宫腺肌症中痛经、月经量等临床症状,值得临床进一步研究进而推广。%Objective To explore the clinical effects of levonorgestrel intrauterine device in the treatment of young and middle-aged people with adenomyosis.Methods Twenty-eight patients with adenomyosis treated in our hospital were selected.Changes of the patients'dysmenorrhea,menstrual blood volume,uterine volume, endometrial thickness,serum CA125 and serum sex hormone levels after placing the levonorgestrel intrauterine device were observed.The clinical symptoms,hormone level changes and adverse reactions of the patients before and after the placement of levonorgestrel intrauterine device were compared.Results After placing the levonorgestrel intrauterine device for 12 months, the patients'dysmenorrhea degree decreased,uterine volume and endometrial thickness significantly reduced, and CA125 level significantly lowered,with significant differences to those before placing (P<0.05).Conclusion The application of levonorgestrel intrauterine device can significantly improve the clinical symptoms such as dysmenorrhea and menstrual blood volume in adenomyosis,thereby worthy of further clinical study and subsequent promotion.

  18. The clinical efficacy of levonorgestrel intrauterine device on endometriosis patients after surgery%子宫内膜异位症术后置左炔诺孕酮宫内节育器的临床疗效

    Institute of Scientific and Technical Information of China (English)

    李瑞珠

    2013-01-01

    目的 观察子宫内膜异位症术后置左炔诺孕酮宫内节育器的临床疗效.方法 选择经手术和病理确诊的子宫内膜异位症患者84例,均行腹腔镜手术,按随机数字表法分为对照组和治疗组,每组42例.对照组术后仅予短期药物治疗,治疗组在对照组治疗的基础上术后放置左炔诺孕酮宫内节育器.术后随访1年,比较两组疗效. 结果 治疗组随访1年时的疼痛评分为0分,低于对照组的(1.5±0.2)分,差异有统计学意义(P<0.05);治疗组术后术后月经量占术前的比例及癌抗原125水平明显低于对照组[(1l±3)%比(45±6)%、(7.01±2.97) U/L比(38.79±31.43) U/L],差异有统计学意义(P<0.05);治疗组术后病灶复发率为2.38%(1/42),低于对照组的28.57%(12/42),差异有统计学意义(P<0.05).结论 子宫内膜异位症术后置左炔诺孕酮宫内节育器能明显缓解患者术后疼痛,减少月经量,降低病灶复发率,临床疗效显著.%Objective To observe the clinical efficacy of levonorgestrel intrauterine device (IUD) on endometriosis patients after surgery.Methods Eighty-four endometriosis patients diagnosed by pathological and surgery were divided into control group and treatment group by random digits table with 42 cases each group.The control group was accepted only short-term drug treatment,while the treatment group was placed levonorgestrel intrauterine device on the basis of control group,then comparing the efficacy after followed up for one year.Results The mean pain score of treatment group was 0,control group was (1.5 ±0.2) points,the difference was statistically significant (P< 0.05).The menstrual blood volume and CA125 levels in treatment group were significantly lower than those in control group [(11 ± 3)% vs.(45 ± 6)%,(7.01 ±2.97) U/L vs.(38.79 ±31.43) U/L] (P <0.05).The recurrence rate in treatment group was significantly lower than that in control group [2.38% (1/42) vs.28.57% (12/42),P

  19. The efficacy of 36 cases of dysfunctional uterine bleeding treatment by levonorgestrel%左炔诺孕酮对36例功能失调性子宫出血的疗效观察

    Institute of Scientific and Technical Information of China (English)

    黎凝; 朱海棉

    2012-01-01

    Objective To study the clinical efficacy of levonorgestrel (brand name:Yu Ting) in treatment for dysfunctional uterine bleeding (DUB).Methods 56 cases diagnosed as peri-menopausal patients with anovulatory DUB by gynecology outpatient department in our hospital from January 2009 to January 2011 were treated with oral administration of norethisterone,but no good effect was found in 36 cases, then changed to take levonorgestrel for 3 menstrual cycles.The bleeding time,1 month after treatment,3 months follow-up observation of menstrual flow,menstrual cycle changes were observed,and the levels of Hb,ALT,AST,BUN and CRE before and after treatment were also monitored.Results The rapid hemostatic rate of Yu Ting orally taking for 6 hours was 69.44%,hemostatic rate during 24 ~ 48 hours was 30.56%.The effective rate 1 month after treatment was 91.66%,the one of 3 months was 72.22%,there was a significant difference among them (P< 0.05); 3 months before and after treatment,the levels of Hb,ALT,AST,BUN and CRE were compared,Hb level significantly increased after treatment,with a significant difference (P< 0.05); there was no significant changes in levels of ALT,AST,BUN and CRE (P > 0.05).Conclusion Levonorgestrel has good effects in treatment for dysfunctional uterine bleeding,obvious results in hemostasis,a low incidence rate of side effects during treatment,but longterm effects need further observation.%目的 探讨左炔诺孕酮(商品名:毓婷)治疗功能失调性子宫出血的临床疗效.方法 选择2009年1月-2011年1月期间我院妇科门诊诊断为围绝经期无排卵性功血患者56例,用炔诺酮(妇康片)口服治疗效果不理想者36例,改用毓婷口服治疗3个月经周期.观察止血时间,停药后1个月、3个月随访观察月经量、月经周期变化;并对用药前后Hb、ALT、AST、BUN、CRE进行监测.结果 毓婷口服6小时内迅速止血率为69.44%,24~48小时内止血率为30.56%,停药后1

  20. 左炔诺孕酮宫内缓释系统治疗子宫内膜息肉临床分析%Clinical Analysis of Levonorgestrel-Releasing Intrauterine System in the Treatment of Endometrial Polyps

    Institute of Scientific and Technical Information of China (English)

    刘琛姝; 王永莉; 尹淑杰

    2014-01-01

    目的:对子宫内膜息肉患者采用左炔诺孕酮宫内缓释系统治疗,探讨和分析其临床治疗效果。方法:选择12个月内宫腔镜确诊子宫内膜息肉发生2次或2次以上患者40例,随机分为两组,试验组20例,采用宫腔镜下子宫内膜息肉电切后同时放置曼月乐环1枚;对照组20例,采用宫腔镜下子宫内膜息肉电切术后口服优思明治疗。所有患者均选择术后每3个月复查阴道B超,术后1年常规宫腔镜检查,进而比较两组子宫内膜增生及子宫内膜息肉复发的情况。结果:试验组和对照组子宫内膜息肉复发率分别为5.0%(1/20)、25.0%(5/20);此外,左炔诺孕酮宫内缓释系统放置前后月经量及内膜厚度的变化进行比较,差异具有统计学意义(P0.05)。结论:对子宫内膜息肉患者采用宫腔镜下子宫息肉电切术治疗,同时放置左炔诺孕酮宫内缓释系统治疗,可有效地防止患者复发,且不良反应少,值得在临床上应用。%Objective:To investigate and analyze the clinical effect of levonorgestrel-releasing intrauterine system in the treatment of endometrial polyps. Method:40 patients of endometrial polyps occurred 2 times or more than 2 times diagnosed with hysteroscopy were selected and randomly divided into two groups.The experimental group(20 patients) was given hysteroscopic endometrial polypectomy and one Mirena ring while the control group(20 patients)were given hysteroscopic endometrial polyp resection and Yasmin. After surgery,all patients were given vaginal B every 3 months ,and were given routine hysteroscopy in 1 year later. Endometrial hyperplasia and endometrial polyps recurrence in two groups was compared. Result:The experimental group and the control group of endometrial polyp recurrence rates were 5%(1/20),25%(5/20),respectively. Before and after Levonorgestrel-releasing intrauterine system placed,the menstrual flow and endometrial

  1. 左炔诺孕酮宫内缓释系统对子宫腺肌症患者卵巢功能的影响%Effect of levonorgestrel releasing intrauterine system to adenomyosis ovarian function in patients

    Institute of Scientific and Technical Information of China (English)

    朱允英

    2016-01-01

    Objective To observe the effect of levonorgestrel releasing intrauterine system to adenomyosis ovarian function in patients. Methods Patients with adenomyosis hospital from March 2014 to June 2015 were treated 70 cases, according to the chronological order of admission into two groups, control group and the observation group, 35 patients in each. The control group were treated with mifepristone treatment, the observation group were treated with levonorgestrel-releasing intrauterine system for treatment, the two groups were observed menstrual menstruation and ovarian case index level. Results The observation group patients menstrual period, menstrual cycle and dysmenorrhea degree than the control group, the difference was significant (P<0.05);observation group patients ovarian function level indicator values than the control group, the difference was significant (P<0.05). Conclusion Levonorgestrel releasing intrauterine system used in the treatment of patients with adenomyosis, ovarian function in patients with good impact and improve patient menstrual cycle and menstrual pain situation, worthy of promotion and application.%目的::观察左炔诺孕酮宫内缓释系统对子宫腺肌症患者卵巢功能的影响。方法:选取本院2014年3月~2015年6月收治的子宫腺肌症患者70例,按入院时间顺序分为两组,对照组及观察组,各35例。对照组患者给予米非司酮进行治疗,观察组患者给予左炔诺孕酮宫内缓释系统进行治疗,观察两组患者月经经期情况及卵巢指标水平。结果:观察组患者治疗后月经期、月经周期及痛经程度明显优于对照组,差异显著(P<0.05);观察组患者治疗后卵巢功能水平指标数值明显优于对照组,差异显著(P<0.05)。结论:左炔诺孕酮宫内缓释系统应用于子宫腺肌症患者治疗,对患者卵巢功能影响好,且有效改善了患者经期周期及经期疼痛情况,值得推广及应用。

  2. Clinical observation of levonorgestrel-releasing intrauterine system on endometrial hyperplasia disease%左炔诺孕酮宫内缓释系统治疗子宫内膜增生症的临床观察

    Institute of Scientific and Technical Information of China (English)

    王植红

    2013-01-01

    Objective To discuss the therapeutic effect of levonorgestrel-releasing intrauterine system ( LNG-IUS)on endometrial hyperplasia disease. Methods 100 cases of pctients who admitted to our hospital from January 2011 to January 2012 were chose and divided into conventional hormone group and LNG-IUS group randomly,50 cases in each group. Conventional group was given progestational hormone (medroxyprogesterone) after 5 days of diagnostic dilatation and LNG-IUS group was placed levonorgestrel-releasing intrauterine system after 5 days of diagnostic dilatation. The change of menstrual quantity, hemoglobin levels, endometrial thickness and adverse reactions of the two groups were compared before and after treatment. Results After one course of treatment, there were 21 cases of patients in conventional group whose menstrual quantity was too much,and its cure rate was 58% ,while there were 4 cases of patients in LNG-IUS group whose menstrual quantity was too much,its cure rate was 92% .there was significant difference between the two groups(P<0. 05 ). The hemoglobin levels of LNG-IUS group were 12% , higher than that of conventional group, its endometrial thickness was 8 % , lower than that of conventional group after one course of treatment, the adverse reactions of conventional group included weight gain, nausea, swirl and liver/kidney damages, while LNG-IUS group's adverse reaction was uterine irregular punctate hemorrhage. Conclusion Levonorgestrel-releasing intrauterine system has better effects on endometrial hyperplasia disease than conventional oral progestational hormone and has fewer adverse reactions.%目的 探讨左炔诺孕酮宫内节育系统(LNG-IUS)对子宫内膜增生症的治疗作用.方法 2011年1月至2012年1月我院收治的100例子宫内膜增生症患者,随机分为对照组(孕激素组)和试验组(LNG-IUS组)各50例.对照组于诊断性刮宫术后第5天给予孕激素(醋酸甲羟孕酮),试验组于诊断性刮宫术后第5天宫

  3. 左炔诺孕酮宫内释放系统治疗子宫腺肌症28例临床观察%Levonorgestrel Releasing Intrauterine System in Treatment of Adenomyosis Clinical Observation of 28 Cases

    Institute of Scientific and Technical Information of China (English)

    昌新霞

    2015-01-01

    目的:探讨左炔诺孕酮宫内释放系统治疗子宫腺肌症临床观察。方法选取我院就诊的子宫腺肌症患者60例,随机分为实验组28例、对照组32例,实验组患者刮宫后按操作要求放置左炔诺孕酮宫内释放系统进行治疗,对照组患者采用米非司酮口服治疗。结果实验组患者的治愈率为32.1%、有效率为96.4%;对照组患者的治愈率21.9%、有效率为75%,两组数据差异具有统计学意义(P<0.05)。结论本文通过对左炔诺孕酮宫内释放系统治疗子宫腺肌症患者临床效果的对比研究,进一步证实了LNG-IUS为患有子宫腺肌症的患者进行临床治疗提供了新的选择方案,它不但能避孕,还使患者的月经情况得到显著改善、痛经指数大大降低、子宫体积也日渐减小,临床效果非常可观。%Objective To investigate the clinical observation of levonorgestrel releasing intrauterine system in treatment of adenomyosis. Methods 60 patients with adenomyosis in our hospital were selected,randomly divided into the experimental group of 28 cases,32 cases in the control group,atients in the experimental group after curettage according to operational equirements placed levonorgestrel releasing intrauterine system in treatment,the control group were treated by mifepristone. Results The patients in the experimental group. The cure rate was 32.1%,effective rate was 96.4%; the control group patients 21.9% cure rate,effective rate was 75%,statistical y significant differences between the two groups(P< 0.05)data. Conclusion Through comparative study on release system for the treatment of adenomyosis patients clinical effect of levonorgestrel releasing intrauterine,further confirmed the LNGIUS with adenomyosis patients provides a new selection scheme for clinical treatment,it can not only contraception,also make menstruation,dysmenorrhea patients obtained significant improvement is greatly reduced,the uterus index

  4. The Effect Observation of Levonorgestrel-releasing Intrauterine System in Adenomyosis%左炔诺孕酮宫内缓释系统治疗子宫腺肌症的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    吴小平; 林美丽

    2014-01-01

    Objective:To study clinical effect of Levonorgestrel-releasing Intrauterine System in adenomyosis.Method:40 cases of uterine adenomyosis patients in our hospital from January 2012 to March 2013 were admitted for the study,the Levonorgestrel-releasing Intrauterine System was placed into the patient utero,the menstrual flow,dysmenorrhea of the degree,uterine size change were observed and analysed before and after treatment.Result:Before treatment the dysmenorrhea score,menstrual flow,CA125,uterine size were (84.12±4.90)points,(212.01±53.01)ml,(70.38±68.50)U/ml,(190.16±90.04)cm3,placed 3 months in patients with dysmenorrhea score,menstrual flow,CA125,respectively (21.50±8.11)points,(48.21±14.88)ml,(26.01±25.42)U/ml,the difference were statistically significant(P0.05).In addition,patients had no significant adverse reactions.Conclusion:The effect of Levonorgestrel-releasing Intrauterine System in the treatment of adenomyosis is obvious,this method can effectively improve patient menstrual flow,dysmenorrhea and other symptoms,and safe,reliable,it is worthy of clinical application.%目的:观察左炔诺孕酮宫内缓释系统治疗子宫腺肌症的临床疗效。方法:选取2012年1月-2013年3月笔者所在医院收治的40例子宫腺肌症患者为研究对象,将左炔诺孕酮宫内缓释系统放置到患者宫内,对放置前后患者月经量、痛经程度、子宫大小变化等进行全面的观察和分析。结果:放置前患者痛经评分、月经量、CA125、子宫大小分别为(84.12±4.90)分、(212.01±53.01)ml、(70.38±68.50)U/ml、(190.16±90.04)cm3,放置后3个月患者痛经评分、月经量、CA125分别为(21.50±8.11)分、(48.21±14.88)ml、(26.01±25.42)U/ml,差异有统计学意义(P0.05)。此外,患者均无出现明显不良反应。结论:左炔诺孕酮宫内缓释系统治疗子宫腺肌症效果明显,能有效改善患者月经量、痛经等症状,且安全可靠,值得在临床上推广应用。

  5. Variação de peso em usuárias de sistema intra-uterino liberador de levonorgestrel, DIU T-cobre e acetato de medroxiprogesterona no Brasil Weight variation in users of the levonorgestrel-releasing intrauterine system, of the copper IUD and of medroxyprogesterone acetate in Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Angerame Yela

    2006-02-01

    Full Text Available OBJETIVO: Determinar a variação de peso corpóreo em mulheres usuárias de sistema intra-uterino liberador de 20 mg/dia de levonorgestrel (SIU-LNG, Mirena® e compará-la com a variação de peso de usuárias de dispositivo intra-uterino T cobre 380A (DIU Tcu e usuárias de acetato de medroxiprogesterona de depósito (AMP-D ao longo de cinco anos. MÉTODOS: Foram analisadas 163 mulheres usuárias de SIU-LNG que tiveram a inserção do mesmo em 1998 durante a admissão para o estudo. Cada mulher foi pareada por peso (± 1kg e por idade (± 1 ano no início do estudo, com as usuárias de DIU Tcu e AMP-D. Todas as mulheres foram seguidas por até cinco anos. Nesse período foram medidos seus pesos e calculados os índices de massa corpórea (IMC. RESULTADOS: A média de idade das usuárias de SIU-LNG foi 27±6,7 anos, enquanto que das usuárias de DIU Tcu foi 28±6,6 anos e das usuárias de AMP-D foi de 26,9±6,5 anos. O peso inicial era 62,9 ± 0,8 kg, 62,8 ± 0,8 kg e 62,5 ± 0,9 kg para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente. O IMC no início do estudo era 25 (±0,3, 26,4 (±0,3 e 25,5 (±0,4 para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente. Foi observado um aumento de peso de 3,1 kg, 4,9 kg e 8,2 kg para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente, ao final do quinto ano (p=0,009. O IMC também apresentou um aumento em todos os grupos (IMC final de 26,3 ± 0,7, 28,5 ± 0,8 e 28,7 ± 1,3 para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente. A análise multivariada mostrou que o uso de AMP-D e seu tempo de uso foram significativos em relação ao ganho de peso. CONCLUSÃO: O uso de SIU-LNG não mostrou aumento significativo no ganho de peso ao longo dos cinco anos, bem como diferença na variação de peso quando comparado com o uso de DIU Tcu.BACKGROUND: Assess weight variations in Brazilian users of the 20 µg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena® for

  6. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant.

    Science.gov (United States)

    Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

    2016-11-01

    Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2-1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more

  7. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant

    Science.gov (United States)

    Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

    2016-01-01

    STUDY QUESTION Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? SUMMARY ANSWER The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. WHAT IS KNOWN ALREADY The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. STUDY DESIGN SIZE, DURATION For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan–Meier (K–M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. PARTICIPANTS/MATERIALS, SETTING, METHODS The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K–M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95

  8. A clinical observation of therapeutic effect of levonorgestrel-releasing intrauterine system for 129 women%129例曼月乐的临床应用观察

    Institute of Scientific and Technical Information of China (English)

    解秀珍

    2009-01-01

    Objective To observe clinical efficacy and safety of levonorgestrel-releasing intrauterine system (LNG-IUS). Methods 81 healthy women who only required contraception, 32 women with adenomyosis (AM) who required contraception and treatment, 6 women after conservative operation for endometriosis (EMs) who wanted an attempting treatment and 10 women with dysfunctional uterine bleeding (DUB) presenting menorrhagia (confirmed by diagnostic curettage and pathological examination) required treatment were inserted LNG-IUS into their uterine cavity timely and were regularily followed-up for contraceptive effect, menstruation, dysmenorrhea severity, size of uterine and endometrial thickness. Results The pregnancy rate in women carring LNG-IUS was 0. After 12 months treatment of LNG-IUS, the menstrual amounts of all women were reduced significantly to (8±3)% of that before treatment (P<0.01). The serum level of CA125 of the patients with AM dropped from 72±50kU/L to 31±24kU/L, and the difference was statistically significant (t=2.373,P<0.05). The endometrial thickness of patients with DUB was thinned from 13.2±5.1mm to 5.9±1.9mm, and the difference was statistically significant (t=3.452,P<0.01). The symptom dysmenorrhea of healthy women and patients with AM was completely remitted, while that of 4 patients with EMs was completely or remarkably remitted, and that of 2 patients with EMs was partly remitted. Conclusion LNG-IUS presents significant contraceptive effect and therapeutic effect for AM and DUB, also, it exerts certain therapeuitc effect for EMs.%目的 探讨曼月乐的临床应用疗效.方法 对于健康妇女单纯要求避孕者81例,子宫腺肌症患者要求避孕及治疗者32例,子宫内膜异位症患者保守手术后要求尝试治疗者6例,月经过多的功能性子宫出血(经诊刮病理确诊)患者要求治疗者10例,适时宫内放置曼月乐,定期随访观察避孕效果、月经、痛经程度、子宫腺肌症患者子宫大小、

  9. A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls.

    Science.gov (United States)

    Bahamondes, Luis; Brache, Vivian; Meirik, Olav; Ali, Moazzam; Habib, Ndema; Landoulsi, Sihem

    2015-11-01

    Is there any difference in the clinical performance of the 3-year one-rod etonogestrel (ENG)- and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception, in particular complaints possibly related to hormonal contraceptives? The cumulative contraceptive effectiveness after 3 years and method continuation through 2.5 years were not significantly different between ENG and LNG implants, but both outcomes were significantly worse in the non-randomized age-matched group of IUD users than in the combined implant group. ENG- and LNG-releasing implants are safe and highly efficacious contraceptives with pregnancy rates reported to be 0.0-0.5 per 100 women-years (W-Y). No head-to-head comparative study of the two implants has been undertaken, and little information is available on comparisons of complaints of side effects of implant and copper IUD users. This was an open parallel group RCT with 1:1 allocation ratio of the ENG and the LNG implants with non-randomized control group of women choosing TCu380A IUD to address lack of reliable data on common side effects typically attributed to the use of progestogen-only contraceptives. After device(s) placement, follow-ups were at 2 weeks, 3 and 6 months, and semi-annually thereafter for 3 years or until pregnancy, removal or expulsion of the implant/IUD occurred. The study took place in family planning clinics in Brazil, Chile, Dominican Republic, Hungary, Thailand, Turkey and Zimbabwe. Women seeking long-term contraception were enlisted after an eligibility check and informed consent, and 2982 women were enrolled: 1003, 1005 and 974 in the ENG-implant, LNG-implant and IUD groups, respectively; 995, 997 and 971, respectively, were included in the per protocol analysis reported here. ENG and LNG implants each had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y [95% confidence interval (CI) 0.1-1.4]. A weight

  10. Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation.

    Science.gov (United States)

    Colussi, Gian Luca; Di Fabio, Alessandro; Catena, Cristiana; Chiuch, Alessandra; Sechi, Leonardo A

    2011-08-01

    Benzodiazepine (BDZ) infusion has been shown to reduce blood pressure in both humans and animals. Although the inhibitory effects of BDZ on the central nervous system have been well documented, less is known about the direct effects of BDZ on the vascular bed. The aims of this study were to assess the effects of the BDZ midazolam on the vascular system in C57/BL6 mouse aortic rings and to investigate the mechanisms of its direct vascular action. We found that midazolam induced reversible, dose-dependent vasodilation in potassium- and phenylephrine-precontracted rings. In rings that were precontracted with potassium or phenylephrine, treatment with 10 μmol l(-1) midazolam increased vasodilation by 15 and 60%, respectively, compared with baseline. Vasodilation increased by 80 and 87%, respectively, after treatment with 50 μmol l(-1) midazolam. Only the low concentration of midazolam (10 μmol l(-1)) induced endothelium-dependent vasodilation in phenylephrine-precontracted rings. Vasodilation increased by 60% in rings with endothelium and by 20% in rings without endothelium. Conversely, only the high concentration of midazolam (50 μmol l(-1)) reduced the CaCl(2)-induced vasoconstriction of aortic rings with EC(50) (the concentration giving 50% of the maximal effect) values of 1 and 6 mmol l(-1) for vehicle- and midazolam-treated rings, respectively. Furthermore, the incubation of phenylephrine-precontracted rings with an inhibitor of the nitric oxide synthase (NOS) NG-nitro-L-arginine methyl ester or the inhibitors of central or peripheral type BDZ receptors (flumazenil or PK 11195, respectively) produced no change in midazolam-induced vasodilation. Thus, low concentrations of midazolam induce vasodilation via an endothelium-dependent mechanism that does not involve NO production. In contrast, high concentrations of midazolam induce vasodilation via an endothelium-independent mechanism that implies reduced sensitivity of aortic rings to calcium ions. Additionally

  11. Use of contraception by women with induced abortion in Italy.

    Science.gov (United States)

    Cagnacci, A; Carluccio, A; Piacenti, I; Olena, B; Arangino, S; Volpe, A

    2014-12-01

    Aim of the present study was to investigate type of contraception, if any, used by women with induced abortion. Retrospective analysis on the medical records of 1782 women with induced abortion performed at the University Hospital of Modena (Italy) between 2009 and 2011. Some kind of contraception was used by 81.1% of women with induced abortion. At time of conception most of these women (39%) had used withdrawal, 19% natural methods, 15.2% condom, 7% hormonal contraception (95% estrogen plus progestin for any route) and 0.4% copper-IUD. None was using implants or levonorgestrel-IUD. Figures of past use of hormonal contraception were much higher than those present at the time of the unwanted pregnancy (50.3% vs. 7%; Pabortion (22.2% vs. 14.2%; Pabortion infrequently use long term or hormonal contraception. In half of the cases the latter has been used at least once in life, but then it has been abandoned. Appropriate education and contraceptive counselling, personalization and follow-up may reduce induced abortion.

  12. Development of endometrioid adenocarcinoma despite Levonorgestrel-releasing intrauterine system: a case report with discussion and review of the RCOG/BSGE Guideline on the Management of Endometrial Hyperplasia.

    Science.gov (United States)

    van der Meer, A C L; Hanna, L S

    2017-02-01

    Obesity is a significant risk factor for the development of endometrial hyperplasia and cancer. More conservative prevention and management strategies are attractive due to the increased surgical risk and complication rates associated with obesity. The Levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) has been shown to reduce the risk of developing endometrial cancer. The recent joint Green Top Guideline on the Management of Endometrial Hyperplasia published by the Royal College of Obstetricians and Gynaecologists (RCOG) with the British Society for Gynaecological Endoscopy (BSGE) recommends the LNG-IUS for the medical management of endometrial hyperplasia without atypia. This case study reports on the development of endometrioid adenocarcinoma despite the presence of an LNG-IUS following a negative hysteroscopy in a 56-year-old woman with morbid obesity. This report highlights the need for patients and clinicians to remain vigilant to the early warning signs of developing endometrial cancer, especially in those at an increased risk secondary to obesity. © 2016 World Obesity Federation.

  13. Effects of hormone therapy on the endometrium in postmenopausal women: a one year randomized trial of low dose oral estradiol in association with a levonorgestrel-releasing intrauterine system or drospirenone

    Directory of Open Access Journals (Sweden)

    Luiza Schvartzman

    2013-09-01

    Full Text Available OBJECTIVES: to compare the endometrial effects and uterine bleeding patterns associated with treatment using (1 levonorgestrel-releasing intrauterine system (LNG-IUS and estradiol (1 mg/day, p.o. or (2 orally administered drospirenone (2 mg/day andestradiol (1 mg/day. METHODS: thirty-four patients (aged 52.53 ± 4.44 in the LNG-IUS group and 53.15 ± 4.018 in the DRSP group were randomized. The severity of menopausal symptoms was evaluated using the Kupperman index every three months. Transvaginal ultrasound, hysteroscopy and histological evaluation were repeated after 12 months. During this period, patients kept menstrual calendars. All categorical variables were described as percentages. Variables were tested for normal distribution and Student's t test was applied for independent samples and ANOVA forrepeated measures when appropriate. Data were considered to be significant when p<0.05. RESULTS: slight vaginal bleeding was reported in the first month of treatment by 53.3% of patients from the LNG-IUS/estradiol group compared with 7.7% of patients from the drospirenone/estradiol group. There were no differences in endometrial thickness between the two groups throughout the study period. End-of-study histological findings showed atrophic endometrium in 53.3% of patients in the LNG-IUS/estradiol group compared with 76.9% of patients in the drospirenone/estradiol group. CONCLUSIONS: our results suggest good endometrial protection with both HT regimens.

  14. 左炔诺孕酮宫内缓释系统治疗子宫内膜异位症的研究进展%Research Progress in Levonorgestrel Intrauterine Releasing System Treating Endometriosis

    Institute of Scientific and Technical Information of China (English)

    李水莲

    2013-01-01

    左炔诺孕酮宫内缓释系统(LNG-IUS),以20 μg/d的剂量释放高效孕激素,使子宫内膜腺体萎缩,间质蜕膜样变,黏膜变薄,能有效缓解子宫内膜异位症(EMs)患者痛经、深部性交痛及慢性盆腔痛,可缩小子宫体积,减少月经量,降低保守性手术后中/重度痛经复发率.近年来,LNG-IUS用于缓解EMs和防止其复发均取得了较好效果.%Levonorgestrel intrauterine releasing system( LNG-IUS ),through releasing 20 μ g/d dose of efficient progestational hormone, making the endometrial glands atrophy, interstitial decidual change, mucous membrane thinned,can effectively relieve EMs patients dysmenorrhea, deep sexual pain and chronic pelvic pain,reduce uterine volume,reduce menstrual quantity,and reduce the moderate/severe dysmenorrhea recurrence rate of conservative surgery. In recent years, LNG-IUS has achieved good effect in relieving EMs and preventing the recurrence.

  15. The TCu-380A (AG), MLCu375, and Nova-T IUDs and the IUD daily releasing 20 micrograms levonorgestrel--four pillars of IUD contraception for the nineties and beyond?

    Science.gov (United States)

    Chi, I C

    1993-04-01

    With recent studies repeatedly showing results clearing the IUDs from their formerly suspected role in causing pelvic inflammatory disease (PID), very likely IUD use will further increase worldwide. While most previous IUDs have been withdrawn from the US market during the 1980s, newer and more effective IUDs have subsequently been developed; and some, marketed. Four of these devices will probably become the pillars for future IUD contraception worldwide. This review evaluates the relative performance and safety of these four devices. Consistent findings have proven the Copper-T 380A (Ag) and the Multiload-375 (MLCu375) IUDs to be safe with high and long-lasting efficacy. The Nova-T IUD showed favorable results in some studies, but showed deteriorated efficacy after three years of use in others; more studies are needed. Studies show that the IUD that daily releases 20 micrograms levonorgestrel (LNG-20) is associated with the highest efficacy in preventing accidental pregnancy among the four devices, but it has a uniquely high medical removal rate because of amenorrhea. This steroid-releasing device could be a high-performance IUD if this type of medical removal can be reduced through patient counseling devised according to local cultural background.

  16. Effect of mesenchymal precursor cells on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Laura M Dooley

    Full Text Available Mesenchymal precursor cells (MPC are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model.Arthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction.Arthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls, and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs

  17. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Poulsen, Henning Kvist; Teisner, Børge

    1993-01-01

    Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood...... presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG. Udgivelsesdato: 1993-Sep...

  18. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B

    1993-01-01

    Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood...... presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG....

  19. 左炔诺孕酮宫内缓释系统预防子宫内膜息肉复发的临床观察%The clinical observation of levonorgestrel intrauterine system in preventing recurrence of endometrial polyp

    Institute of Scientific and Technical Information of China (English)

    宋芷霜; 郭宝芝; 刘爱珍

    2015-01-01

    目的:探讨子宫内膜息肉( endometrial polyps ,EP)电切术后宫内放置左炔诺孕酮宫内缓释系统( levonorgestrel intrauterine system , LNG-IUS,又称曼月乐)预防息肉复发的临床疗效。方法收集整理2010年1月至2012年5月郑州市妇幼保健院收治的120例EP电切术后患者的临床资料,根据不同处理方法分为对照组45例、黄体酮组40例、曼月乐组35例。比较3组术后出血情况、术后2年EP复发情况。结果术后出血患者比例由高到低依次为:曼月乐组45.7%(16/35)、对照组33.3%(15/45)、黄体酮组22.5%(9/40)。术后2年曼月乐组复发率2.9%(1/35),低于对照组8.9%(4/45)及黄体酮组5.0%(2/40)(P<0.05)。结论 EP电切术后宫内放置LNG-IUS预防息肉复发的疗效显著。%Objective To investigate the clinical efficacy of levonorgestrel intrauterine system ( LNG -IUS ) in preventing recurrence of endometrial polyp ( EP ) after endometrial polyp resection .Methods Data of 120 patients with endometrial polyp resection in Zhengzhou Maternal and Child Health Hospital from Jan 2010 to May 2012 were collected , all cases were divided into the control group (n=45), progesterone group (n=40), the Mirena group (n=35).The postoperative bleeding, recurrence rate of EP after 2 years between three groups were compared .Results The rate of postoperative bleeding from high to low were Mirena group 45.7%(16/35), control group 33.3% (15/45), progesterone group 22.5% (9/40).The recurrence rate of EP after 2 years in Mirena group was 2.9%(1/35), which was lower than the control group 8.9%(4/45) and progesterone group 5.0%(2/40) (P<0.05).Conclusion The effect of LNG-IUS in preventing recurrence of EP is remarkable after endometrial polyp resection .

  20. Expulsions and adverse events following immediate and later insertion of a levonorgestrel-releasing intrauterine system after medical termination of late first- and second-trimester pregnancy: a randomised controlled trial.

    Science.gov (United States)

    Korjamo, R; Mentula, M; Heikinheimo, O

    2017-07-10

    To compare expulsions and adverse events (AEs) between immediate and delayed insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) following medical termination of pregnancy (MTOP). Randomised controlled trial. Helsinki University Hospital, Finland, January 2013-December 2014. Cohorts of 102 (gestational age 64-84 days, late first trimester) and 57 (gestational age 85-140 days, second trimester) women requesting MTOP and LNG-IUS contraception. LNG-IUS insertion occurred immediately (same day) or 2-4 weeks following MTOP. Follow-up visits were at 2-4 weeks, 3 months, and 1 year. LNG-IUS expulsion by 3 months and 1 year. AEs and bleeding profiles within 3 months. Following late first-trimester MTOP the LNG-IUS expulsion rates by 3 months were 14 (27.5%) in the immediate-insertion group and two (4.0%) in the delayed-insertion group (risk ratio, RR 6.86; 95% confidence interval, 95% CI 1.64-28.66). By 1 year the expulsion rates were 17 (33.3%) and six (12.0%) (RR 2.78, 95% CI 1.19-6.47). Following second-trimester MTOP LNG-IUS expulsion rates by 3 months and 1 year were five (18.5%) in the immediate-insertion group and one (3.6%) in the delayed-insertion group (RR 5.19, 95% CI 0.65-41.54). No differences in AEs and bleeding profiles emerged between the groups. Immediate LNG-IUS insertion after late first- or second-trimester MTOP is feasible, does not increase the complication rate, or alter the uterine bleeding patterns; however, immediate insertion increased the expulsion rate, which may limit the cost-effectiveness. Immediate insertion of LNG-IUS following MTOP at 9-20 weeks of gestation is feasible and safe. © 2017 Royal College of Obstetricians and Gynaecologists.

  1. Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard® gel: a randomized, cross-over, pharmacokinetic study☆

    Science.gov (United States)

    Brache, Vivian; Croxatto, Horacio; Kumar, Narender; Sitruk-Ware, Regine; Cochón, Leila; Schiappacasse, Veronica; Sivin, Irving; Muñoz, Carla; Maguire, Robin; Faundes, Anibal

    2010-01-01

    Background The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard® gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner. Study Design This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner. Results Time concentration curves for serum LNG levels showed a mean Cmax of 7.8±5.5 and 8.3±5.7 nmol/L, a mean Tmax of 6.2±5.9 and 7.5±5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners. Conclusion Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible. PMID:19135574

  2. Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium

    Directory of Open Access Journals (Sweden)

    Raffai G

    2014-05-01

    Full Text Available Gábor Raffai,1 Byungkuk Kim,1 Sanga Park,1 Gilson Khang,1 Dongwon Lee,1 Paul M Vanhoutte1,21World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea; 2Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, ChinaBackground and purpose: Cinnamaldehyde, a major component of cinnamon, induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects, but its short half-life limits its clinical use. The present experiments were designed to compare the acute relaxing properties of cinnamaldehyde with those of self-assembling polymer micelles either loaded with cinnamaldehyde or consisting of a polymeric prodrug [poly(cinnamaldehyde] that incorporates the compound in its backbone.Methods: Rings of porcine coronary arteries were contracted with the thromboxane A2 receptor agonist U46619 or 40 mM KCl, and changes in isometric tension were recorded.Results: Cinnamaldehyde induced concentration-dependent but endothelium-independent, nitric oxide synthase (NOS-independent, cyclooxygenase-independent, soluble guanylyl cyclase (sGC-independent, calcium-activated potassium-independent, and TRPA1 channel-independent relaxations. Cinnamaldehyde also inhibited the contractions induced by 40 mM KCl Ca2+ reintroduction in 40 mM KCl Ca2+-free solution or by the Ca2+ channel opener Bay K8644. Cinnamaldehyde-loaded control micelles induced complete, partly endothelium-dependent relaxations sensitive to catalase and inhibitors of NOS or sGC, but not cyclooxygenase or TRPA1, channels. Cinnamaldehyde-loaded micelles also inhibited contractions induced by 40 mM KCl Ca2+ reintroduction or Bay K8644. Poly(cinnamaldehyde micelles induced only partial, endothelium-dependent relaxations that were reduced by inhibitors of NOS or sGC and by

  3. LC -MS/MS 法测定人血浆中左炔诺孕酮的浓度及其药代动力学研究%Determination of concentration of levonorgestrel in human plasma by liquid chromatography-tandem mass spectrometry and study on its pharmacokinetics

    Institute of Scientific and Technical Information of China (English)

    蔡珺; 陈新; 郑恒

    2013-01-01

      建立LC-MS/MS方法测定人血浆中左炔诺孕酮的浓度,研究其在健康女性体内的药代动力学.以甲基睾丸酮为内标,血浆样品经乙醚液液萃取处理,色谱柱为Ultimate C18,流动相为甲醇∶乙腈∶0.1%甲酸水溶液=80∶8∶12,流速为0.3 mL・ min-1,用于定量分析的离子对为左炔诺孕酮:m/z 313.10—245.20,甲基睾丸酮:m/z 303.20—97.10,采用液相-串联质谱法进行浓度测定.测定20名健康女性受试者单剂量口服1.5 mg左炔诺孕酮片的血药浓度,并计算主要药代动力学参数.结果表明:左炔诺孕酮血药浓度在0.2375 ng・ mL-1~23.75 ng・ mL-1(r=0.9971)范围内线性关系良好,最低定量限为0.2375 ng・ mL-1,日内、日间RSD均小于3%.主要药代动力学参数Tmax为(1.975±0.525)h,Cmax为(11.672±1.809) ng・ mL-1,T1/2为(24.372±14.43)h,AUC0-t为(166.722±56.893)ng・ h・ mL-1,AUC0-∞为(191.86±73.353)ng・ h・ mL-1.该方法专属性强,快速,准确,适用于左炔诺孕酮血药浓度的检测和临床药代动力学的研究.%Objective:To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of concentration of levonorgestrel in human plasma , and study on its pharmacokinetics in healthy female volunteers.Methods:Levonorgestrel and the internal standard , methyltestosterone, were isolated from plas-ma by liquid-liquid extraction with ether.The separation of levonorgestrel was performed on an Ultimate C 18 col-umn using a mobile phase consisting of methanol -acetonitrile-0.1%formic acid buffer solution (80∶8∶12), at a flow rate of 0.3 mL・ min-1 .Mass charge ratio of ion pair levonorgestrel m/z 313.10—245.20 and that of metheyltestosterone m/z 303.20—97.10.A single dose of 1.5mg levonorgestrel was given to 20 female healthy vol-unteers.The concentration of levonorgestrel was determined by LC -MS/MS and the main pharmacokinetic param-eters were calculated.Results:The linear concentration

  4. Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2009-02-01

    Full Text Available Abstract Background Exposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines. Methods We investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/- with different degree of atherosclerosis. Results The aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice. Conclusion Treatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.

  5. 自制左炔诺孕酮片溶出度、生物利用度与国外制剂比较研究%Comparative study on the dissolution and bioavailability between self-made levonorgestrel tablets and foreign preparation

    Institute of Scientific and Technical Information of China (English)

    余春梅; 陈兰; 徐洁; 杨秀丽; 周成林; 陈仲祥

    2013-01-01

    Objective To compare the dissolution and bioavailability with foreign preparation, and to imitate better quality of levonorgestrel tablets with equal to foreign preparation. Methods The dissolution was investigated with paddle method. In an open randomized controlled crossover design,20 healthy volunteers received reference and tested tablets. The plasma concentration of levonorgestrel was determined by HPLC MS/MS detection. Results The peak areas and concentrations of levonorgestrel presented a good linear relationship within the range of 0~13. 2μg·mL-1 ;the linear equation was A= —0. 90+65. 33C,the average recov ery rate of levonorgestrel was (101. 7±1. 5) % ,the similarity factor(f2) of the dissolution curves for our levonorgestrel tablets and the reference preparations(made by Hungary Gedeon Richter Plc) was 83. 0,the relative bioavailability of the test to the reference was 103. 5 ±30. 1. Conclusion The dissolution cruves of the tested tablets(made by our company) and reference preparation(made in Hungary) were similar,and two preparations were bioequivalent in healthy volunteers.%目的 通过溶出度、生物利用度与国外制剂比较研究,仿制出达到国外制剂质量的左炔诺孕酮片.方法 采用浆法测定左炔诺孕酮片的溶出度;采用开放、随机、自身对照双周期交叉设计方法,将20名受试者随机等分为A、B两组,参比制剂和受试制剂口服给药,HPLC-MS/MS测定方法测定受试者给药后血浆中左炔诺孕酮的浓度.结果 左炔诺孕酮在0~13.2 μg·mL-1的浓度范围内峰面积与浓度呈良好的线性关系,线性方程为:A=-0.90+65.33C;回收率为(101.7±1.5)%;自制左炔诺孕酮片与匈牙利Gedeon Richter Plc生产的参比制剂溶出曲线的相似因子f2=83.0;相对生物利用度为103.5±30.1.结论 参比制剂与参比制剂溶出行为相似、在健康人体内具有生物等效性.

  6. Satisfaction and health-related quality of life in women with heavy menstrual bleeding; results from a non-interventional trial of the levonorgestrel-releasing intrauterine system or conventional medical therapy

    Directory of Open Access Journals (Sweden)

    Xu L

    2014-05-01

    Full Text Available Ling Xu,1 Byung Seok Lee,2 Shaheena Asif,3 Peter Kraemer,4 Pirjo Inki51Department of Gynecology and Obstetrics, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Korea; 3Department of Gynaecology and Obstetrics, Surgimed Hospital, Lahore, Pakistan; 4Global Medical Affairs Excellence and Operations, 5Global Medical Affairs Women's Healthcare, Bayer HealthCare, Berlin, GermanyPurpose: To evaluate the patient satisfaction and health related quality of life (HRQoL for levonorgestrel-releasing intrauterine system (LNG-IUS versus conventional medical treatments ([CMTs] combined oral contraceptives, oral progestins, and antifibrinolytics, alone or in combination in Asian women with heavy menstrual bleeding (HMB.Patients and methods: A total of 647 patients diagnosed with HMB were recruited to this non-interventional study from the eight participating countries in Asia. Patient satisfaction was recorded at the last visit (at 12 months or premature discontinuation. At each visit (at 3, 6, and 12 months, patients completed the menorrhagia multi-attribute scale (MMAS to assess HRQoL.Results: A total of 83.5% of patients on the LNG-IUS were “very satisfied” or at least “satisfied” with the therapeutic effect of HMB treatment, compared with 59.2% of patients with CMTs (P<0.05. The mean (± standard deviation MMAS score increased from 41.4±24.5 to 87.7±21.4 in the LNG-IUS arm, and from 44.1±24.9 to 73.1±25.3 in the CMTs arm. This increase was significantly higher in patients on the LNG-IUS, as compared with those on CMTs (P<0.05. The improvement in HRQoL in both treatment groups correlated with the body mass index of the patient, with larger improvement obtained in women with a higher body mass index.Conclusion: The majority of women using the LNG-IUS or CMTs for HMB were satisfied with their treatment

  7. Overcoming barriers to levonorgestrel-releasing intrauterine system placement: an evaluation of placement of LNG-IUS 8 using the modified EvoInserter® in a majority nulliparous population.

    Science.gov (United States)

    Gemzell-Danielsson, Kristina; Apter, Dan; Lukkari-Lax, Eeva; Roth, Katrin; Serrani, Marco

    2017-08-24

    To report placement success rate, and ease and pain associated with placement, of the levonorgestrel-releasing intrauterine system (LNG-IUS) 8 using the modified EvoInserter® placement device. This was a pooled analysis using data from three previously reported Phase III studies in nulliparous (83.3%) or parous (16.7%) women aged 12-35 years (N=965). LNG-IUS 8 was placed using the modified Evolnserter®. The main outcomes assessed were placement success, ease of placement as reported by healthcare professionals (HCPs), pain at placement as reported by participants, and assessment of the EvoInserter® placement device by HCPs. LNG-IUS 8 placement using the modified EvoInserter® with an insertion tube diameter of 3.8 mm was successful in 99.5% of subjects. HCPs rated the placement procedure as "easy" in 91.6% of cases. Placement pain was reported as absent by 19.1% of participants, as mild by 39.3%, as moderate by 31.6%, and as severe by 10.0%. Overall 89.2% of HCPs completely agreed that the device was easy to prepare and 85.7% completely agreed that placement of an LNG-IUS was easy/simple with the EvoInserter®. Post hoc exploratory analyses indicated a significant association between ease/pain of placement and patient age and between pain of placement and parity. The modified Evolnserter® was associated with a high placement success rate, ease of placement, and manageable pain, and was assessed to have a user-friendly design. These findings suggest that the EvoInserter® may remove some concerns among HCPs about difficult placement of LNG-IUSs, thereby encouraging increased uptake of an effective contraceptive. Results reported in this study further strengthen evidence of the high placement success rate, ease of deployment, and manageable pain associated with the modified EvoInserter® placement device. These findings might reduce concerns among HCPs about placement of LNG-IUSs, meaning uptake of such contraceptives is increased. Copyright © 2017 The Authors

  8. A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

    Science.gov (United States)

    Fan, Guangsheng; Kang, Sukho; Ren, Mulan; Weisberg, Edith; Lukkari-Lax, Eeva; Roth, Katrin; Shin, SoYoung

    2017-04-01

    The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region. Copyright © 2016. Published by Elsevier Inc.

  9. The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.

    Directory of Open Access Journals (Sweden)

    Kristina Gemzell-Danielsson

    Full Text Available Two low-dose levonorgestrel intrauterine contraceptive systems (LNG-IUSs; total content 13.5 mg [average approx. 8 μg/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 μg/24 hours over the first year; LNG-IUS 13] have previously been shown to be highly effective (3-year Pearl Indices: 0.33 and 0.31, respectively, safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18-25 vs 26-35 years, or body mass index (BMI, <30 vs ≥30 kg/m2.Nulliparous and parous women aged 18‒35 years with regular menstrual cycles (21‒35 days requesting contraception were randomized to 3 years of LNG-IUS 8 or LNG-IUS 13 use.In the LNG-IUS 8 and LNG-IUS 13 groups, 1432 and 1452 women, respectively, had a placement attempted and were included in the full analysis set; 39.2%, 39.2% and 17.1% were 18-25 years old, nulliparous and had a BMI ≥30 kg/m2, respectively. Both systems were similarly effective regardless of age, parity or BMI; the subgroup Pearl Indices had widely overlapping 95% confidence intervals. Placement of LNG-IUS 8 and LNG-IUS 13 was easier (p < 0.0001 and less painful (p < 0.0001 in women who had delivered vaginally than in women who had not. The complete/partial expulsion rate was 2.2-4.2% across all age and parity subgroups and higher in parous than in nulliparous women (p = 0.004. The incidence of pelvic inflammatory disease was 0.1-0.6% across all age and parity subgroups: nulliparous and younger women were not at higher risk than parous and older women, respectively. The ectopic pregnancy rate was 0.3-0.4% across all age and parity subgroups. Across all age and parity subgroups, the 3-year completion rate was 50.9-61.3% for LNG-IUS 8 and 57.9-61.1% for LNG-IUS 13, and was higher (p = 0.0001 among older than younger women in the LNG-IUS 8 group only.LNG-IUS 8 and LNG-IUS 13 were highly effective, safe and well tolerated regardless of age or

  10. Clinical efficiency of Levonorgestrel-releasing intrauterine system in the treatment of 69 cases with adenomyosis%左炔诺孕酮宫内节育系统治疗子宫腺肌病的临床观察

    Institute of Scientific and Technical Information of China (English)

    居蓉

    2014-01-01

    Objective To evaluate the clinical efficiency of Levonorgestrel-releasing intrauterine system(LNG-IUS) in the treatment of adenomyosis. Methods Sixty-nine patients with adenomyosis were treated with LNG-IUS during March 2011 to June 2013. The menstrual quality,menstrual period,VAS and VRS score were carried out before treatment and at one,three and six months after treatment. The amount and period of menstruation were valued by test. Results Among 69 patients, menstrual quality were reduced, dysmenorrhea and chronic pelvic pain were alleviated, which were significantly different from those before treatment(P<0.05).Conclusion LNG-IUS inserting inside uterine cavity can significantly alleviate the clinical symptoms of adenomyosis and improve the patients quality.%目的:观察左炔诺孕酮宫内节育系统(LNG-IUS)治疗子宫腺肌病所致痛经、月经过多及慢性盆腔痛的临床疗效。方法选取2011年3月~2013年6月门诊确诊子宫腺肌病患者69例,排除禁忌证后给予放置左炔诺孕酮宫内节育系统治疗,随访6个月,观察患者的月经量、月经期、痛经及慢性盆腔痛的改善情况。结果与放置左炔诺孕酮宫内节育系统前相比,放置后患者月经量明显减少,痛经程度、慢性盆腔痛明显改善,差异均具有统计学意义(P<0.05)。结论左炔诺孕酮宫内节育系统可以有效缓解子宫腺肌病临床症状,提高患者生活质量。

  11. Application analysis of levonorgestrel-releasing intrauterine device in the treatment of young and middle-aged patients with adenomyosis%左炔诺孕酮宫内节育器在中青年子宫腺肌症治疗中的应用分析

    Institute of Scientific and Technical Information of China (English)

    徐红云

    2015-01-01

    目的 探讨临床上使用左炔诺孕酮宫内节育器治疗中青年子宫腺肌症的疗效. 方法 选取2013年1月至2014年9月鄢陵县人民医院收治的24例子宫腺症患者为研究对象,于宫内置左炔诺孕酮宫内节育器,随访1年,观察记录节育器放置前和放置后4、8、12 个月时患者的月经量、痛经程度、子宫大小、子宫内膜厚度、血清CA125及性激素变化情况. 结果 连续放置1年后患者月经量显著减少、痛经程度明显减轻、子宫大小和子宫内膜厚度显著降低、CA125水平显著降低,与放置前比较差异有统计学意义( P0.05). 结论 左炔诺孕酮宫内节育可显著改善中青年子宫腺肌症患者的月经量并缓解痛经,是一种较好的治疗中青年子宫腺肌症的保守治疗手段.%Objective To investigate the clinical effect of levonorgestrel-releasing intrauterine device on young and middle-aged patients with adenomyosis .Methods Twenty-four patients with adeno-myosis from January 2013 to September 2014 were selected and treated by levonorgestrel-releasing intrau-terine device .The menstrual capacity , dysmenorrhea of the degree , uterine size , endometrial thickness , serum CA125 and serum sex hormone levels were detected before and 4 , 8 , 12 months after treatment . Results After treatment for 12 months, the menstrual capacity , dysmenorrhea of the degree , uterine size, endometrial thickness, serum CA125 were changed significantly (P0.05).Conclusions The application of levonorgestrel-releasing intrauterine device is good to im-prove the clinical symptoms such as menstrual capacity and dysmenorrhea of the degree in adenomyosis , which can be a good conservative treatment method for the treatment of young and middle-aged patients with adenomyosis .

  12. The Observation of Clinical Effect of Levonorgestrel-releasing Intrauterine System in the Treatment of Endometrial Hyperplasia%左炔诺孕酮宫内节育系统治疗子宫内膜单纯性增生过长的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    胡树群; 张海艳; 栾继红; 李晓红

    2015-01-01

    目的:对左炔诺孕酮宫内节育系统治疗子宫内膜单纯性增生过长的临床价值进行探究。方法于2013年4月7日~2014年12月7日,随机选取我院接诊的60例子宫内膜单纯性增生过长患者,采用抽签方法将其平均分为实验组(n=30)和对照组(n=30),实验组患者实行左炔诺孕酮宫内节育系统治疗,对照组患者实行孕激素治疗,对实验组和对照组两组患者的生活质量状况、不良事件发生率以及临床效果等进行分析和统计。结果经过对两组患者临床疗效分析对比来看,实验组患者其临床效果优于对照组患者(P<0.05),差异具有统计学意义。结论左炔诺孕酮宫内节育系统治疗子宫内膜单纯性增生效果显著。%Objective To explore the clinical value of Levonorgestrel-releasing intrauterine system in the treatment of endometrial hyperplasia. Methods Randomly selected 60 cases of endometrial hyperplasia patients in our hospital from April 7,2013 to December 7,2014. The patients were divided into experimental group (n=30)and control group(n=30)by lottery. The patients of experimental group are treated with Levonorgestrel-releasing intrauterine system while that of control group were treated with progesterone. The patient's life quality,incidence of adverse events and clinical ef ect were analysed. Results By comparing the clinical ef icacy of two groups of patients,the clinical ef ect of experimental group was better than that of control group(P<0.05),the result had significant dif erence. Conclusion Levonorgestrel-releasing intrauterine system has a remarkable ef ect in the treatment of simple endometrial hyperplasia.

  13. Comparison of the Clinical Effect of Mirena and Levonorgestrel in the Treatment of Endometrial Hyperplasia%曼月乐及左炔诺孕酮治疗子宫内膜增生症的临床效果比较

    Institute of Scientific and Technical Information of China (English)

    林燕霞

    2016-01-01

    Objective To compare the clinical effect of mirena and levonorgestrel in the treatment of endometrial hyperplasia. Methods From May 2014 to May 2015, 70 cases of patients with endometrial hyperplasia treated in the gynecology and obstetrics department of our hospital were selected and divided into observation group (35 cases) and control group (35 cases) according to the admission sequence. The control group was treated with levonorgestrel, the observation group was treated with mirena. The clinical efficacy and incidence of adverse reactions were compared between two groups. Results The endometrial thickness of observation group two and three months after treatment was significantly less than that of control group, with statistically significant difference (P0.05). Conclusions Compared with levonorgestrel , mirena can effectively reduce the menstrual blood volume, promote the decrease of endometrial thickness, reduce the complications, which can be used as an effective method to treat endometrial hyperplasia in clinic.%目的:比较曼月乐及左炔诺孕酮治疗子宫内膜增生症的临床效果。方法选取2014年5月至2015年5月我院妇产科收治的70例子宫内膜增生症患者为研究对象,按入院顺序将患者分为观察组(35例)和对照组(35例)。对照组患者采用左炔诺孕酮治疗,观察组患者采用曼月乐治疗。对比两组患者的治疗效果以及不良反应发生情况。结果观察组患者治疗后2个月、3个月子宫内膜厚度与对照组相比明显较小,差异具有统计学意义(P0.05)。结论曼月乐与左炔诺孕酮相比,能有效减少患者月经量,促进子宫内膜厚度减小,可将其作为临床治疗子宫内膜增生症的有效方法推广应用。

  14. Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43

    Directory of Open Access Journals (Sweden)

    Xiaomiao Zhao

    2015-01-01

    Full Text Available Objects. To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. Methods. Cell proliferation and apoptosis of human endometrial stromal cells (HESCs and glandular cells (HEGCs treated with LNG in a dose- and time-dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. Results. 5 × 10−5 mol/L LNG revealed a time-dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 × 10−5 mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. Conclusions. LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment.

  15. 解读世界卫生组织对左炔诺孕酮紧急避孕药的安全性声明%The interpretation on "Fact sheet declared by WHO on the safety of levonorgestrel-alone emergency contraceptive pills (LNG ECPs)"

    Institute of Scientific and Technical Information of China (English)

    吴尚纯

    2010-01-01

    @@ 今年以来针对国际上媒体所表达的群众对紧急避孕药(emergency contraceptive pills,ECP)安全性的顾虑,世界卫生组织(World Health Organization, WHO)组织相关专家,在对大量证据进行全面评价、分析和综合的基础上,通过充分讨论,达成一致共识,并于2010年6月以通俗和简明的文字,发表了对左炔诺孕酮紧急避孕药(levonorgestrel-alone emergency contraceptive pill, LNG-ECP)的安全性声明(下简称"声明").

  16. Observation of the curative effect of mifepristone combined with infertility caused left levonorgestrel releasing intrauterine system in acetone in treatment of adenomyosis%米非司酮联合左炔诺孕丙酮宫内缓释系统治疗子宫腺肌病导致不孕症疗效观察

    Institute of Scientific and Technical Information of China (English)

    施振娥

    2013-01-01

    目的:观察米非司酮联合左炔诺孕丙酮缓释系统(LNG-IUS)治疗子宫腺肌病导致不孕症的临床疗效。方法将本院2010年5月~2011年8月收治的子宫腺肌病导致的不孕症患者60例,随机分成治疗组和对照组两组。治疗组:予以米非司酮25mg,每日一次口服,连服3个月。并且所有患者均在签署知情同意书后自愿使用左炔孕丙酮宫内缓释系统。经彩超检查后,由专人于月经第3~7天在用药同时放置左炔诺孕丙酮宫内缓释系统。6个月后取出。对照组:单独给予米非司酮25mg,每日一次口服,连服3个月。观察停药后1、3、6、12个月的怀孕成功率。结果随访至12个月时统计,治疗组平均受孕率79%,对照组平均受孕率57%,治疗组总有效率明显高于对照组(P<0.05)。结论使用米非司酮联合左炔诺孕丙酮宫内缓释系统治疗子宫腺肌病可以明显提高患者的受孕率,对于子宫腺肌病导致的不孕症疗效好于其他方法,而且经济、安全,便于患者接受。%Objective To observe the curative effect of mifepristone combined with infertility caused left levonorgestrel releasing intrauterine system in acetone in treatment of adenomyosis. Methods 60 infertility patients in our hospital from 2010 May to 2011 August were adenomyosis in patients, randomly divided into treatment group and control group two groups.Treatment group was given mifepristone 25mg orally, once a day, and even served three months. And all the patients after informed consent voluntary use of levonorgestrel releasing intrauterine system in acetone, by color Doppler ultrasound examination, by hand in 3-7 days in the menstrual medication at the same time, place left levonorgestrel releasing intrauterine system in acetone, removed after 6 months. Control group was given mifepristone 25mg orally, once a day, and even served three months. The pregnancy, 3, 6, 1 and 12 months were

  17. 左炔诺孕酮宫内缓释系统治疗子宫内膜单纯性增生过长的研究%Study of Levonorgestrel Intrauterine System in the Treatment of Simple Endometrial Hyperplasia

    Institute of Scientific and Technical Information of China (English)

    奚滕滕; 崔秀娟; 孙燕娜

    2014-01-01

    目的:探讨左炔诺孕酮宫内缓释系统(曼月乐)治疗子宫内膜单纯性增生过长的疗效及可能作用机制。方法:选取2011年11月—2012年2月门诊应用曼月乐治疗子宫内膜单纯性增生过长的患者60例,观察放置曼月乐6个月后的子宫内膜活检病理变化及经阴道超声测量子宫内膜厚度、子宫动脉血流[阻力指数(RI)、搏动指数(PI)]及月经模式的改变。结果:2例由于阴道持续性点滴出血提前取出,58例子宫内膜转归正常。放置曼月乐前后子宫内膜厚度、RI分别为(1.52±0.33) cm、(0.62±0.14)cm和0.64±0.07、0.79±0.08,差异均有统计学意义(P<0.05或P<0.01),PI分别为1.98±0.51、1.96±0.04,差异无统计学意义(P>0.05)。放置曼月乐后经量明显减少,24例表现为月经稀发,32例表现为闭经。结论:曼月乐是治疗子宫内膜单纯性增生过长的简单有效方法,对子宫动脉血流的影响是其可能的作用机制。%Objective:To study the efficancy and long possible mechanism of Mirena (levonorgestrel intrauterine system ) in the treatment of simple endometrial hyperplasia. Methods:Select sixty cases of simple endometrial hyperplasia in outpatient between 2011.11 and 2012.2,we observed the menstrual patterns,the endometrial thickness and uterine arterial blood flow [resistance index (RI),pulsatility index (PI)] by transvaginal ultrasound,pathologic changes of endometrial by endometrial biopsy in 6 months after insertion of mirena. Results:2 patients were removed Mirena due to colporrhagia. Pathological examinations of 58 patients performed 6 months after the insertion showed that endometrial hyperplasia had reversed. The endometrial thickness,RI of uterine artery in 6 months after the insertion were statistically significant,respectively (1.52±0.33) cm,(0.62±0.14) cm (P0.05). After placing Mirena significantly reduced by the amount,24 cases showed

  18. Effect of levonorgestrel releasing intrauterine system on endometrial polyp recurrence%左炔诺孕酮宫内缓释系统预防子宫内膜息肉术后复发的研究

    Institute of Scientific and Technical Information of China (English)

    蔡惠兰; 丁香翠; 钱蓉蓉; 虞如芬; 孙利敏; 李强

    2011-01-01

    Objective: To explore the clinical effect of a levonorgestrel intrauterine system ( LNG - IUS) on prevention of en-dometrial polyp recurrence after endometrial polyp resection by hysteroscopy. Methods: Three hundred and three women after endometrial polyp resection by hysteroscopy were randomly divided into two groups. Women in the treatment group (n = 152) had a LNG - IUS insertion immediately after hysteroscopy. There were 103 cases of solitary endometrial polyp and 49 cases of multiple endometrial polyps in the treatment group, and 111 cases of solitary endometrial polyp and 40 cases of multiple endometrial polyps in the control group. Women were followed up for 3 years. Results: No endometrial polyp recurrence were found in the treatment group. In the control group, the endometrial polyp recurrence was found in 31 women (20.5% ) , 17 cases of solitary endometrial polyp and 14 cases of multiple endometrial polyps. There was statistically significant difference in the incidence of endometrial polyp recurrence between the two groups (P<0. 05). No hypoestrogenic symptoms, acne, hirsutism, and abnormal liver and renal functions as well as lipid metabolism were found throughout the following - up period. Conclusion ; A LNG - IUS could prevent the endometrial polyp recurrence after hysteroscopy.%目的:探讨左炔诺孕酮宫内缓释系统( LNG - IUS)预防宫腔镜子宫内膜息肉切除术后复发的临床疗效.方法:采用前瞻性随机对照研究,将303例宫腔镜子宫内膜息肉切除术(TCRP)后妇女分为两组,治疗组152例,TCRP术后立即放置LNG - IUS,其中单发性息肉103例,多发性息肉49例;对照组151例,TCRP术后无任何处理措施,其中单发性息肉111例,多发性息肉40例,门诊随访3年.结果:治疗组中无一例复发,对照组中单发性息肉有17例复发,多发性息肉有14例复发,总复发率为20.5% (31/151),两组复发率差异有统计学意义(P<0.05).在随访期间,治疗组无一例患者出

  19. Clinical effects of Levonorgestrel-Releasing Intrauterine System in 98 women%98例左诀诺孕酮宫内缓释系统临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘田雨; 柯珮琪; 梁明懿; 耿慧珍; 黄佳明

    2014-01-01

    目的 探讨子宫内膜异位症、功能失调性子宫出血(功血)及单纯避孕妇女放置左诀诺孕酮宫内缓释系统(LNG-IUS)后的临床疗效.方法 随访我院计生门诊98例子宫内膜异位症、功血及单纯避孕患者,分别于放置LNG-IUS后3、6、12个月观察其月经、副反应及患者满意度情况;同时采用口诉评分(VRS)法对47例子宫内膜异位症患者痛经程度进行评估.结果 34例功血患者放环后3、6、12个月月经量较放环前减少,差异有统计学意义(P<0.001);47例子宫内膜异位症患者放环后3、6、12个月VRS评分较放环前减小,差异有统计学意义(P<0.001).治疗12个月,无一例发生妊娠,59例(64.9%,59/91)患者对治疗的综合效果表示非常满意或满意.结论 LNG-IUS是一种治疗子宫内膜异位症、功血及避孕的安全有效方法.%Objective To evaluate the safety and efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) for the women who are suffered from endometriosis (EM),dysfunctional uterine bleeding (DUB) or simply intended to contraception.Methods Ninety-eight cases of EM,DUB or simply intending contraception were enrolled from the Department of Family Planning Clinics.The primary endpoints were defined as controlling menstruation,side effects and satisfaction after placing LNG-IUS for 3,6 and 12 months.Meanwhile,the visual analogue scale (VAS) score was used to assess the degree of dysmenorrhea.Results For the 34 DUB patients,their menstrual quantity after placing LNGIUS for 3,6 and 12 months decreased significantly compared with the levels of their baseline(P<0.001).The VAS scores of the 47 EM patients of the baseline levels were significantly different from those of the follow-up levels (P<0.001).Overall,no woman was pregnant in cases of intended to contraception.And 59 women (64.9%,59/91) were very satisfied or satisfied with the one-year treatment.Conclusion LNG-IUS is a safe and efficient method for the

  20. Clinical Study on Treatment for Uterine Fibroids with Intratumoral Injection of Methotrexate Com-bined with Levonorgestrel%甲氨蝶呤瘤体内注射联合左炔诺孕酮治疗子宫肌瘤的临床研究

    Institute of Scientific and Technical Information of China (English)

    董梅

    2015-01-01

    Objective To explore the efficacy and safety of intratumoral injection of methotrexate com-bined with levonorgestrel in treating uterine fibroids .Methods A total of 186 patients with uterine fibroids who were treated in Zoucheng People′s Hospital from Jan.2011 to Jan.2012 were selected and divided into combination group(n=92) and control group(n=94) according to random number table.Patients in combi-nation group were treated with intratumoral injection of methotrexate (50-60 mg) combined with levonorg-estrel(20 μg).While patients in control group were only treated with levonorgestrel(20 μg).Improvement of clinical symptomschanges of uterine fibroids volume,efficiency,incidences of adverse reactions were com-pared between the two groups.Results After treatment,the menstrual recovery rate,disappearance rate of lower abdomen and waist pain, disappearance rate of frequent and urgent micturition in combination group were significantly higher than those in control group (P<0.05).Six months,twelve months after treatment, the uterine myoma volumes of the combination group were significantly smaller than those of the control group [(43.7 ±18.3) cm3 vs (49.2 ±18.0) cm3,(30.4 ±17.0) cm3 vs (42.5 ±16.5) cm3,P<0.05].The efficiency of the combination group was higher than that of the control group(94.6% vs 85.1%,P<0.05). Adverse reactions occurred 1-3 days after injection of methotrexate in the combination group were mild and recovered rapidly,while no obvious adverse reaction occurred in the control group.Conclusion Treating uterine fibroids with levonorgestrel release system combined with intratumoral injection of methotrexate can reduce uterine fibroids volume and improve clinical symptoms more quickly,with better curative effect,com-pared with simple treatment with levonorgestrel release system.%目的:探讨甲氨蝶呤瘤体内注射联合左炔诺孕酮治疗子宫肌瘤的疗效及安全性。方法选择2011年1月至2012年1月于邹城市人民医院妇科

  1. Effects of levonorgestrel intrauterine system on the expressions of estrogen receptor, progesterone receptor and insulin-like growth factor-1%左炔诺孕酮宫内释放系统对雌激素受体、孕激素受体及胰岛素样生长因子-1的影响

    Institute of Scientific and Technical Information of China (English)

    吴晓杰; 刘霞; 金小英; 徐兴云

    2014-01-01

    Objective To explore the effects of levonorgestrel intrauterine system on estrogen receptor (ER) and progesterone receptor (PR),insulin-like growth factor-1 (IGF-1) of endometrial polyps and surrounding endometrial tissue.Methods A total of 250 cases of hysteroscopic resection for endometrial polyps were divided into study group (n =125) with placement of levonorgestrel intrauterine system after hysteroscopic electroresection and control group (n =125) without placement.The intraoperative and postoperative expressions of ER,PR and IGF-1 in endometrial biopsy specimens were measured by immunohistochemistry.They were followed up for 2 years to analyze the recurrence of endometrial polyp.Results All patients had successful surgery.When intraoperative and postoperative specimens were compared with regards to the expressions of ER,PR and IGF-1,significant differences existed between two groups.During a 2-year follow-up,the recurrence of endometrial polyp was 10.89% in control group versus 0 in study group.Conclusion Levonorgestrel intrauterine system may inhibit the recurrence and formation of endometrial polyp through lowering the expressions of ER,PR and IGF-1.%目的 研究左炔诺孕酮宫内释放系统对子宫内膜息肉局部及周围内膜组织雌激素受体(ER)、孕激素受体(PR)、胰岛素样生长因子(IGF)的影响.方法 选取2010至2011年在浙江省嘉兴市妇幼保健院行宫腔镜下子宫内膜息肉切除术患者,共250例.随机分组为研究组(106例)和对照组(125例).研究组术后子宫内即时放置左炔诺孕酮宫内释放系统,而对照组不予放置.分别对术中内膜组织及术后6个月子宫内膜活体组织检查,通过免疫组化方法对ER、PR、IGF-1的表达情况进行对比,且追踪随访2年,了解患者子宫内膜息肉复发情况.结果 所有患者均手术成功,研究组内膜组织对比发现ER、PR、IGF-1表达术后明显低于术中,差异有统计学意义.对照组术中及术

  2. Immediate Post-abortal Insertion of the Levonorgestrel-releasing Intrauterine System: A Systematic Review%人工流产术后即时放置左炔诺孕酮宫内缓释系统的系统评价

    Institute of Scientific and Technical Information of China (English)

    王彩燕; 黄紫蓉; 邹燕

    2013-01-01

    Objective: To evaluate the effectiveness and safety of immediate post-abortal insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS). Methods: The Medline, Embase, Cochrane Library, CJFD, CBM, VIP and Wanfangdata were searched for researches to compare immediate post-abortal insertion of the levonorgestrel-releasing intrauterme device with copper IUD (Cu IUD) or post-menstrual insertion of the LNG-IUS. Two reviewers independently extracted data and assessed the quality of the evidence. Meta analysis was conducted using RevMan 5.0. Results: Totally, 17 articles and 5 512 women were included. Comparing with immediate post-abortal insertion of the copper IUD, less pregnancy, more amenorrhea occurred among women with immediate post-abortal insertion of the LNG-IUS. Both groups experienced similar rates of expulsions and removals for medical reasons and irregular bleedings. Comparing with post-menstrual insertion, women with post-abortal insertion of the LNG-IUS experienced less irregular bleedings in 6 months after insertion (RR=0.42, 95%CI=0.22~0.83, P=0.01). In 12 months after insertion, both groups experienced similar rates of pregnancy, expulsion, removal for medical reasons, amenorrhea and irregular bleedings. Conclusion: Immediate post-abortal insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) is safe and effective.%目的:系统评价人工流产术后即时放置左炔诺孕酮宫内缓释系统(LNG-IUS)的临床疗效和安全性.方法:计算机检索Medline、Embase、Cochrane图书馆、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊数据库、万方数据资源系统.纳入比较人工流产术后即时放置LNG-IUS与人工流产术后即时放置含铜宫内节育器(CuIUD),以及人工流产术后即时放置LNG-IUS与月经期放置LNG-IUS的研究.由2位评价者独立进行文献筛选及数据提取.采用Cochrane协作网提供的RevMan5.0进

  3. 左炔诺孕酮宫内缓释系统对子宫腺肌病患者月经模式的影响%Effects of Levonorgestrel-Releasing Intrauterine System on Menstrual Patterns of Patients with Adenomyosis

    Institute of Scientific and Technical Information of China (English)

    段志珍; 洪莉; 程艳香

    2013-01-01

    Objective To explore the variation of menstrual patterns of patients who suffered from adenomyosis after the treatment with levonorgestrel via intrauterine releasing system.Methods Seventy patients with adenomyosis who were inserted with levonorgestrel-releasing intrauterine system were selected.The variation of menstrual patterns was assessed through menstrual blood loss method and dysmenorrhea scoring at beginning and 1,3, 6, 9 months after insertion.Results Sixty-five patients completed follow-up, which accounted for 92.9%.Menstrual blood volume of baseline and 1 ,3,6,9 months after therapy was (193.03±134.79), (21.08±32.13),(5.56±7.16), (2.13±4.28), (1.51 ±2.89),respectively.Compared to the baseline, the menstrual blood volume and blood clot of the patients were significantly decreased at 1,3,6,9 months after treatment.The dysmenorrhea score of 27 patients at the same time point was 1.85 ±0.82 (prior-insertion),0.48 ±0.51 (one month post-insertion),0.13 ±0.34 (three months post-insertion), 0 (six months post-insertion), respectively, and the dysmenorrheal normally occurred after vaginal ring operation was obviously relieved after insertion.Conclusion Levonorgestrel-releasing intrauterine system displays good therapeutic effect on improving the menstrual patterns of patients with adenomyosis.%目的 探讨左炔诺孕酮宫内缓释系统对子宫腺肌病患者月经模式的影响.方法 选择因子宫腺肌病放置左炔诺孕酮宫内缓释系统的患者70例.采用月经失血法、痛经评分法评价患者放置前,放置后1,3,6,9个月月经模式.结果 65例患者完成随访,随访率为92.9%.月经量评分:放置前(193.03±134.79)分,放置后1个月(21.08±32.13)分,放置后3个月(5.56±7.16)分,放置后6个月(2.13±4.28)分,放置后9个月(1.51±2.89)分,与放置前比较,放置后1,3,6,9个月患者,月经量、血块均明显减少;其中27例痛经患者痛经评分:放置前(1.85±0.82)分,放置后1个月(0.48±0.51)

  4. Preparation of hydroxypropyl-β-cyclodextrin inclusion with Levonorgestrel and Quinestrol(EP-1) and its influence on the reproductive organs Brandt's voles(Lasiopodomys brandtii)%EP-1包合物制备及其对布氏田鼠繁殖器官的影响

    Institute of Scientific and Technical Information of China (English)

    王大伟; 刘琪; 刘明; 李宁; 黄宝欢; 刘晓辉

    2011-01-01

    EP series rodent contraception is mainly composed of levonorgestrel and quinestrol. However, neither compopent do not readily dissolves in water, which limits the precision of research and application. In the present study, solubilization was measured in hydroxypropyl-β-cyclodextrin ( HPCD ) inclusion complexes of levonorgestrel and quinestrol, respectively. Afterwards, the effects of treatment times ( after 2 and 4 weeks) and doses (0, 1,2, 4 mg/kg) of EP-I inclusion complexes on reproductive organs were investigated using a gastric gavage method. The results showed that the solubility of levonorgestrel and quipestrol reached 4 mg/mL and 0. 5 mg/mL in 20% aqueous HPCD solution, respectively. For females, there were no significant differences after 2 or 4 weeks between the control and treatment groups that received gavage. For males, the average weight of reproductive organs of the group that received gavage for 2 weeks of 2 mg/kg group was less than that of the control group. Our results indicate that the solubility of EP-1 was significantly enhanced by forming inclusion complexes with HPCD; the suppressive effects on reproduction in male Brandt's voles is more obvious than those in females. Moreover, inclusion did not affect the anti-fertility effect of EP-1.%EP系列鼠类不育剂的主要成分--左炔诺孕酮和炔雌醚在常温下难溶于水,给研究和应用造成很大不便.本研究利用2-羟丙基-β-环糊精(HPCD)提高了EP不育剂的水溶性,制备包合物;设置4个浓度梯度的EP-1包合物水溶液,分别对雌雄布氏田鼠进行灌胃,并在第2周和第4周测量繁殖器官指标,评价不育效果.结果表明,在20%的HPCD水溶液中,左炔诺孕酮和炔雌醚的溶解度分别可达约4 mg/mL和0.5 mg/mL;在第2周,2 mg/kg EP-1灌胃组雄鼠的繁殖器官受到了明显抑制,但各剂量组雌鼠未表现出明显影响.本研究结果说明,HPCD与EP-1可通过形成包合物,显著增加其常温下的溶解度;EP-1

  5. 左炔诺孕酮宫内节育器治疗围绝经期功能性子宫出血50例临床分析%Levonorgestrel IUD treatment of dysfunctional uterine bleeding of perimenopausal period in 50 cases

    Institute of Scientific and Technical Information of China (English)

    徐艳; 李淑清; 周巧梅

    2009-01-01

    Objective To explore the role of levonorgestrel intrauterine device in the treatment of peri-menopausal dysfunctional uterine bleeding, to find theoretical basis for effective and rational treatment of peri-menopausal dysfunctional uterine bleeding and reduce the rate of hysterectomy. Methods Fifty patients received levonorgestrel intrauterine device (treatment group) and another 50 cases were given oral Fukang tablets (control group). The rate of hysterectomy, assessment of menstrual volume and endometrial thickness were observed between the two groups. Results In treatment group, 1 (2%) patient was performed hysterectomy, 2 (4%) had the assessment of menstrual volume score greater than 100, while in control group, 8 (16%) were performed operations, and 12 (24%) had the assessment of menstrual volume score greater than 100. The assessment of menstrual volume scores were 131.0±51.2, 53.0±21.9, 36.7±19.7, 17.9±6.8, respectively, and endometrialt thickness reduced from (13.2±4.3) mm to (8.5±1.9)mm, (7.2±1.5)mm,(6.2±1.1)ram before or 3, 6 and 12 months after the use of the device. Conclusion The use of levonorgestrel intrauterine device can reduce the volume of menstruation and the hysterectomy rate caused by dysfunctional uterine bleeding.%目的:探讨左炔诺孕酮宫内节育器治疗围绝经期功能性子宫出血的疗效,为寻找有效、合理治疗围绝经期功能性子宫出血提供理论依据并减少子宫切除率.方法:治疗组50例患者放置左炔诺孕酮宫内节育器,对照组为口服妇康片(炔诺酮)50例患者,观察2组子宫切除率、月经量评分、子宫内膜厚度.结果:治疗组50例中1例手术(2%)、月经量评分>100分2例(4%);对照组50例中8例手术(16%)、月经量评分>100分12例(24%).治疗组子宫切除率和出血量均低于对照组;放置左炔诺孕酮宫内节育器前及放置后3,6,12个月月经量评分分别为131.0±51.2,53.0±21.9,36.7±19.7,17.9±6.8;子宫内膜由(13.2±4.3)mm

  6. Clinical study of levonorgestrel-releasing intrauterine system in the treatment of perimenopausal uterine bleeding.%左旋炔诺酮宫内缓释系统治疗围绝经期功血的90例疗效观察

    Institute of Scientific and Technical Information of China (English)

    李红

    2012-01-01

    Objective To observe the clinical efficacy of levonorgestrel-releasing intrauterine system in the treatment of perimenopausal uterine bleeding. Methods 90 patients with perimenopausal uterine bleeding were treated with levonorgestrel-releasing intrauterine system, and all the patients were followed up 3-7 days after menstrual for 6 months. The menstrual flow, endometrial thickness, uterine size, ovaries size, and hemoglobin changes before and after treatment were recorded. Results There were no statistically significant differences in the uterine size, ovarian volume before and after treatment (P>0.05). The endometrial thickness was (13.69±0.35) mm before treatment and (7.36±1.29) mm after treatment (P<0.05), showing statistically significant difference. The hemoglobin content was (53.66±3.22) g/L before the treatment, significantly lower than (102.96±4.62) g/L after treatment (P<0.05). Conclusion Levonorgestrel-releasing intrauterine system for treatment of perimenopausal uterine bleeding can effectively reduce the menstrual flow, control the endometrial hyperplasia, and increase hemoglobin levels, with satisfactory clinical result, which is worthy to be promoted in clinical practice.%目的 观察左炔诺孕酮宫内缓释系统治疗围绝经期功血的临床疗效.方法 对90例围绝经期功血患者采用左炔诺孕酮宫内缓释系统治疗,全部病例均于每次月经后3 ~7d内随访,共随访6个月.记录服药前后月经出血情况、子宫内膜厚度、子宫大小、双侧卵巢大小、血红蛋白含量的变化.结果 患者用药前后的子宫大小、卵巢体积比较差异无统计学意义(P>0.05);患者在用药前的子宫内膜厚度为(13.69±0.35) mm,用药后为(7.36±1.29) mm,治疗前后的子宫内膜厚度改变比较差异有统计学意义(P<0.05);患者用药前的血红蛋白含量为(53.66±3.22) g/L,治疗后为(102.96±4.62) g/L,治疗前后的血红蛋白含量改变比

  7. An observation of effect of levonorgestrel-releasing intrauterine system for inhibiting recurrence of endometriosis focus after resecting ovarian endometrial implantation cyst%卵巢子宫内膜异位囊肿剥除术后放置曼月乐的观察

    Institute of Scientific and Technical Information of China (English)

    林素霞; 何华

    2011-01-01

    目的 探讨卵巢子宫内膜异位囊肿行剥除术后放置左炔诺孕酮宫内缓释系统抑制病灶复发的有效性.方法 回顾性地分析46例卵巢子宫内膜异位囊肿患者行腹腔镜剥除术后放置左炔诺孕酮宫内缓释系统对卵巢子宫内膜异位囊肿复发的控制情况,并完成2年至2年11个月的随访,观察复发情况.随机对照同期住院行腹腔镜卵巢子宫内膜异位囊肿剥除术,且术后予口服孕三烯酮治疗6个月的患者38例.结果 随访发现5例复发,复发率为10.87%;对照组复发11例,复发率为28.95%.两组复发率比较差异有统计学意义(χ2=4.41,P<0.05).结论 左炔诺孕酮宫内缓释系统作为卵巢子宫内膜异位囊肿剥除术术后针对控制复发的后续治疗,相比较传统以孕三烯酮为代表的全身激素抑制治疗,其远期观察具有较好地控制复发的结果.%Objective To observe effect of placement of levonorgestrel-releasing intrauterine system for inhibiting recurrence of endometriosis focus after resecting ovarian endometrial implantation cyst. Methods The recurrence control situations of 46 women with ovarian endometrial implantation cyst who received laparoscopic cystectomy after placing levonorgestrel-releasing intrauterine system in a period from Oct. , 2007 to Sep. , 2008 in Quanzhou Municipal Maternal and Child Health of Fujian Province were retrospectively analyzed.All 46 patients were followed-up for 24 months to 35 months to observe their recurrence situations ( observation group). The therapeutic effects of 46 patients were compared with those of 38 women with ovarian endometrial cyst who were given orally gestrinone for 6 months after cystectomy (control group). Results 5 of 46 patients with ovarian endometrial implantation cyst who were placed levonorgestrelreleasing intrauterine system recurred after laparoscopic cystectomy, the recurrence rate was 10.87% at follow-up after 24 months to 35 months. In the control group

  8. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  9. Clinic observation of a levonorgestrel-releasing intrauterine system inserted immediately after artificial abortion%人工流产后即时放置曼月乐的临床观察

    Institute of Scientific and Technical Information of China (English)

    陈静; 王娴静; 梁艳; 金勤

    2011-01-01

    Objective To compare the contraceptive efficacies and side effects of Mirena (levonorgestrel-releasing intrauterine system,LNG-IUS)inserted immediately after artificial abortion and in the period of regular menstruation.Methods A total of 166 female subjects volunteered for the insertion of LNG-IUS.They were divided into 2 groups.Eighty-six female subjects inserted right after artificial abortion were selected as the observation group and 80 female subjects inserted during the period of regular menstruation as the control group.Follow-up was performed at one year after insertion.Contraceptive efficacies and side effects were compared between two groups.Results No pregnancy was found in both groups.No mirena expulsion occurred in neither groups.The continuation rates were 100% and 95% in the observation and control groups respectively(P >0.05).The rates of abnormal hemorrhage were 27.5% and 36.2% in observation and control groups respectively during the first three months(P <0.05).And 22.7% and 23.3% subjects suffered amenorrhea respectively in the first year.No significant difference was found in such side effects as amenorrhea,weight gain,acne and swollen breasts between two groups(P > 0.05).Conclusion Mirena is proved to be an excellent choice for contraception after artificial abortion.Secondary intrauterine surgery may be avoided.And its insertions immediately after artificial abortion or during the period of regular menstruation share the same efficacies.%目的 观察早孕人工流产后即时放置与月经后期放置左炔诺孕酮宫内缓释系统(曼月乐)的避孕效果、不良反应比较.方法 166例自愿选择放置曼月乐的已生育女性,分人工流产术后即时放置组(观察组)86例和月经后期放置组(对照组)80例,随访12个月,对其避孕效果、续用率及不良反应进行观察比较.结果 观察组与对照组的妊娠率均为0,脱环率均为0,续用率分别为100%、95%,两组比

  10. Clinical efficacy on levonorgestrel intrauterine system in treating dysfunctional uterine bleeding during peri-menopausal period%左炔诺孕酮宫内缓释系统治疗围绝经期功血的临床观察

    Institute of Scientific and Technical Information of China (English)

    何丽霞; 陈正勤

    2016-01-01

    目的:观察围绝经期功能失调性子宫出血(功血)患者宫腔内放置左炔诺孕酮宫内缓释系统(商品名:曼月乐)的临床疗效。方法:选取曼月乐治疗围绝经期功血患者72例,比较放置曼月乐前后患者月经情况、子宫内膜厚度及血红蛋白、血脂、性激素水平变化。结果:放置曼月乐后月经量减少,子宫内膜变薄,血红蛋白升高,结果均有明显差异(P <0.05),而血脂及性激素水平无明显改变,差异无统计学意义(P >0.05)。结论:曼月乐治疗围绝经期功血减少经量和纠正贫血效果确切,不影响血脂代谢和卵巢功能。%Objective To investigate the clinical efficacy on dysfunctional uterine bleeding during peri -menopausal period of levonorgestrel intrauterine system.Method Seventy -two cases of patients who were diagnosed dysfunctional uterine bleeding during peri -menopausal period were placed with mirenas during menstrual period.The menstrual conditions,endometrium width, hemoglobin,blood lipid,sex hormone level changes of these cases were measured before and after the insertion of mirena.Results After the insertion of mirena the menstrual quantity decreases,thinning of the endometrium,hemoglobin was increased.These were statistically significant(P 0.05).Conclusion Levonorgestrel intrauterine system can efficiently reduce the amount of blood and correct a-nemia but does not affect blood lipid metabolism and ovarian function.

  11. Comparison of the Efficacy and Safety of Levonorgestrel Intrauterine System and Mifepristone in the Treatment of Perimenopausal Dysfunctional Uterine Bleeding%左炔诺孕酮宫内节育系统与米非司酮治疗围绝经期功能失调性子宫出血的疗效和安全性比较

    Institute of Scientific and Technical Information of China (English)

    姜欣; 曾银花

    2016-01-01

    目的:比较左炔诺孕酮宫内节育系统与米非司酮治疗围绝经期功能失调性子宫出血的疗效和安全性。方法:200例围绝经期功能失调性子宫出血患者随机分为观察组(100例)和对照组(100例)。观察组患者放置左炔诺孕酮宫内节育系统(含左炔诺孕酮52 mg),对照组患者口服米非司酮胶囊10 mg/d。两组疗程均为3个月。观察两组患者的临床疗效和治疗前后子宫内膜厚度、月经量[根据图示应用出血评分法(PBAC)评估]、血红蛋白水平及不良反应发生情况。结果:治疗后,观察组患者总有效率显著高于对照组,不良反应发生率显著低于对照组,差异均有统计学意义(P<0.01)。治疗前,两组患者子宫内膜厚度、PBAC评分、血红蛋白水平比较差异无统计学意义(P>0.05);治疗后,两组患者子宫内膜厚度、PBAC评分显著低于同组治疗前,且观察组低于对照组,而血红蛋白水平显著高于同组治疗前,且观察组高于对照组,差异均有统计学意义(P<0.01或P<0.05)。结论:左炔诺孕酮宫内节育系统治疗围绝经期功能失调性子宫出血的疗效和安全性显著优于米非司酮。%OBJECTIVE:To compare the efficacy and safety of levonorgestrel intrauterine system and mifepristone in the treat-ment of perimenopausal dysfunctional uterine bleeding. METHODS:200 patients with perimenopausal dysfunctional uterine bleed-ing were randomly divided into observation group (100 cases) and control group (100 cases). Patients in the observation group placed levonorgestrel intrauterine system (containing levonorgestrel 52 mg),patients in control group received Mifepristone cap-sule 10 mg/d,oral,the treatment course for 2 groups were 3 months. Clinical efficacy,endometrial thickness,menstruation(PBAC score),hemoglobin level before and after treatment and incidence of adverse reaction in 2 groups were observed

  12. An introduce on the health education of levonorgestrel-releasing intrauterine system in the treatment of adenomyosis and its effect evaluation%曼月乐治疗子宫腺肌病患者的健康教育及效果评价

    Institute of Scientific and Technical Information of China (English)

    何淑明; 黄少兰

    2006-01-01

    目的:探讨健康教育程序在左旋-18甲基炔诺酮宫内缓释系统(levonorgestrel-releasing intrauterine system,LNG-IUS;商品名为"曼月乐")在治疗子宫腺肌病中的作用.方法:对48例子宫腺肌病的患者宫内放置曼月乐治疗,进行健康教育评估、诊断、制订实施健康教育计划和效果评价.结果:48例患者中有43例术前均有不同程度焦虑情绪,经教育后仅有3例存在轻度焦虑心理,无一例并发感染或有不遵医行为.结论:运用健康教育程序对曼月乐治疗子宫腺肌病进行健康教育可以增长患者知识,改变患者行为,提高患者的依从性.

  13. Effect of Levonorgestrel-releasing Intrauterine System in the Treatment of Adenomyosis:Analysis of 120 Cases%左炔诺孕酮宫内缓释系统治疗子宫腺肌症120例疗效分析

    Institute of Scientific and Technical Information of China (English)

    王莉; 王彩霞

    2013-01-01

    Objective:To observe the effect of levonorgestrel-releasing intrauterine system in treatment of adenomyosis. Methods:The changes of menstruation, uterine volume, hemoglobin and hormone levels before and after LNG-IUS placement were performed in 120 patients with AM. Results:The menstrual quantity obvious reduction;reduction of uterine volume and increased hemoglobin were observed after the placement of LNG-IUS 4,8 months in patients with anemia(P0.05). Conclusion:LNG-IUS had significant effect in the treatment of AM, had no t effect on ovarian function, worthy of clinical application.%目的:观察左炔诺孕酮宫内缓释系统(LNG-IUS,曼月乐)治疗子宫腺肌病(AM)的疗效。方法:对120例AM患者放置LNG-IUS前后月经量、子宫体积、血红蛋白和激素水平的变化进行观察。结果:放置LNG-IUS4、8个月后月经量明显减少;子宫体积缩小及贫血患者血红蛋白上升(P0.05)。结论:LNG-IUS治疗AM疗效显著,对卵巢功能无明显影响,值得临床应用推广。

  14. Use of Emergency Contraception could Halve Induced Abortion Rate in Shanghai,China

    Institute of Scientific and Technical Information of China (English)

    Chao-hua LOU; Shuang-ling ZHAO; Er-sheng GAO

    2004-01-01

    Objective To investigate and estimate the proportion of the induced abortion that could have been prevented by using emergency contraception in Shanghai Method Structured interviews were conducted in 606 women (413 married and 193unmarried) aged 18-49 years, who were attending three health care centers in Shanghai for termination of first trimester pregnancy.Results A total of 98.2% of the pregnancies were unwanted, and 63.7% of the women recognized that they were at risk of pregnancy soon after the intercourse. It is estimated that 52.2% of the induced abortion could have been prevented if the women had used levonorgestrel-only emergency contraception. Only 28.5% of the respondents were aware of emergency contraception. The most important sources of information about emergency contraception identified by respondents were books/newspapers/periodicals (38.2%), and relatives/friends (30.6%). Family planning health education on emergency contraception was noted by 28.9% of married women but only by 5.8% of unmarried women. A portion of 85.5% of all respondents reported they would be willing to use emergency contraception when needed. Those more willing to use emergency contraception included younger, better educated, and unmarried women experiencing their first pregnancy. Women preferred drugstores (60.1%) than hospitals (30.2%)for obtaining emergency contraception.Conclusion Women's needs for emergency contraception were enormous. Promotion of emergency contraception by providing information and improving service could have a substantial impact on reducing the rate of induced abortion in Shanghai.

  15. Inducing labor

    Science.gov (United States)

    Labor induction; Pregnancy - inducing labor; Prostaglandin - inducing labor; Oxytocin - inducing labor ... threaten the health of you or your baby. Oxytocin may also be started after a woman's labor has started, but her contractions have not been ...

  16. Efficacy of Oral Contraceptive or Levonorgestrel-releasing Intrauterine System after Hysteroscopic Endometrial Polypectomy in Preventing Recurrence%宫腔镜子宫内膜息肉切除术后口服避孕药或放置左炔诺孕酮宫内缓释系统对预防复发的作用

    Institute of Scientific and Technical Information of China (English)

    王威; 王晓晔

    2013-01-01

    Objective To investigate the recurrence-prevention effect of oral contraceptive or levonorgestrel-releasing intrauterine system ( Mirena) after hysteroscopic endometrial polypectomy. Methods Totally 116 patients, who received hysteroscopic endometrial polypectomy and were confirmed with endometrial polyp by postoperative pathological examination during January 2009 and October 2011 in our hospital, were enrolled into this study. The patients were divided into three groups; oral contraceptive group (n =34) was given combined oral contraceptive since one month until 12 months after the operation; Mirena group ( n = 39) received levonorgestrel-releasing intrauterine system since one month after the operation; and control group ( n = 43 ) received no treatment after hysteroscopic endometrial polypectomy. The three groups were followed up at 3, 6, and 12 months after the procedure, and the recurrence rate, menstruation, and level of hemoglobin were compared among the groups. Results No patients were lost during a 12-month follow-up. The control group showed significantly higher recurrence rate, lower proportion of low menstruation volume and lower level of hemoglobin than the oral contraceptive and Mirena groups [18.6% (8/43) vs. 2.9% (1/34) and 2.6% (1/39) , χ2 - 8. 649, P = 0. 013; P = 0. 000; and P < 0. 05, respectively]. Conclusion Oral contraceptive or levonorgestrel-releasing intrauterine system after hysteroscopy for endometrial polyps significantly decreases recurrence rate and adverse reaction, and we recommend it to be widely used.%目的 探讨子宫内膜息肉宫腔镜手术后口服避孕药或放置左炔诺孕酮宫内缓释系统(曼月乐)对预防复发的效果. 方法 2009年1月~2011年10月门诊宫腔镜子宫内膜息肉切除术且病理证实为子宫内膜息肉116例,由患者知情选择术后处理方法.34例宫腔镜手术后1个月开始应用复方短效口服避孕药12个月(避孕药组),39例宫腔镜术后1个

  17. Determination of apparent oil-water partition coefficient and equilibrium solubility of levonorgestrel and gestodene by RP-HPLC%RP-HPLC测定左炔诺孕酮与孕二烯酮表观油水分配系数及平衡溶解度

    Institute of Scientific and Technical Information of China (English)

    曾佳; 黄婷; 李芳; 朱芷涵; 陈良康; 俸灵林

    2014-01-01

    目的:分别测定第2代和第3代避孕药代表性药物左炔诺孕酮(levonorgestrel,LNG)与孕二烯酮(gestodene,GES)的表观油水分配系数及平衡溶解度,为长效避孕微球注射剂制备工艺及体外释放介质的选择提供坚实的处方前研究基础.方法:采用RP-HPLC测定LNG与GES在正辛醇-水、正辛醇-pH 1.2~8.0磷酸盐缓冲液等9种体系中的表观油水分配系数及在水、缓冲液、常用有机溶剂等19种介质中的平衡溶解度.结果:LNG与GES在水中的lgPapp值分别为3.62和3.43;在不同pH值PBS中该值相近,但在pH3.0时例外,LNG与GES的该值均增大.此外,两药均难溶于水,易溶于二氯甲烷、三氯甲烷等有机溶剂;GES的水溶性是LNG的8~ 10倍,且GES比LNG更易溶于有机试剂;两者在pH 3.0时溶解度均有下降趋势,而在其他pH值条件下无明显差别,该情况与两者表观油水分配系数的变化规律相一致.结论:表观油水分配系数结果提示:LNG与GES在微球制备过程中可获得较好的包封率,同时将延长微球在体内的释药周期.平衡溶解度结果提示:在微球体外释放评价时应添加合适的增溶剂以增加药物溶解度来满足漏槽条件;制备微球采用常规工艺的水包油(O/W)型乳剂-液中干燥法微囊化具有可行性.

  18. Predicted Value of Serum Prostaglandin E2 on the Dysmenorrheal Treatment Effect in Adenomyosis Patients with Levonorgestrel-releasing Intrauterine System%血清前列腺素E2预测左炔诺孕酮缓释系统治疗子宫腺肌病痛经效果的价值探讨

    Institute of Scientific and Technical Information of China (English)

    杨丽华; 徐勤; 胡万芹

    2013-01-01

    Objective: To explore the possibility of the serum prostaglandin E2(PGE2) level predictive value on the dysmenorrheal treatment effect in the adenomyosis (ADS) patients with levonorgestrel-releas-ing intrauterine system (LNG-IUS). Methods: Forty-one ADS patients treated with LNG-IUS because of dysmenorrhea were collected. These patients were divided into effective group (n=32) and noneffective group (n=9) according to the effect of relieving dysmenorrhea. The serum PGE2 level before and after 6 months of the LNG-IUS treatment were compared by ELISA, and the influence of serum PGE2 level caused by LNG-IUS and the correlation between the serum PGE2 level and the dysmenorrheal treatment effect with LNG-IUS were analyzed. Results: The serum PGE2 concentrations were 20.95 ± 3.07 pg/ml and 5.56 ± 1.72 pg/ml in the effective group before and after 6 months with LNG-IUS treatment, there was a significant difference between them (P<0.05). The serum PGE2 concentrations were 5.74 ±1.12 pg/ml and 4.95±1.39 pg/ml in the noneffective group before and after 6 months with LNG-IUS treatment, there was no significant difference between them. The serum PGE2 concentration in the effective group was significantly higher than that in the noneffective group (P<0.05). The change of visual analogue scale (VAS) score after 6 months of LNG-IUS treatment had a positive correlation with the serum PGE2 level before LNG-IUS treatment, the higher serum PGE2 concentration was, the more obviously the VAS score decreased (r=0.845, P<0.05). Conclusion: PGE2 might be involved in the occurrence of ADS dysmenorrhea and LNG-IUS relieved dysmenorrhea through decreasing the PGE2 level. It is suggested that the patients with high PGE2 level choose LNG-IUS to treat their dysmenorrhea and the patients with low PGE2 level use other ways to treat dysmenorrhea.%目的:探讨子宫腺肌病(adenomyosis,ADS)患者血清前列腺素E2(prostaglandin E2,PGE2)水平预测左炔诺孕酮缓释系统(levonorgestrel

  19. A systematic review of levonorgestrel-releasing intrauterine system in the treatment of primary endometriosis%左炔诺孕酮宫内缓释系统宫内节育器用于子宫内膜异位症治疗的meta分析

    Institute of Scientific and Technical Information of China (English)

    赵勤莉; 张文韬; 杨永秀

    2013-01-01

    目的 通过循证医学的方法评价左炔诺孕酮宫内缓释系统(曼月乐)治疗子宫内膜异位症的安全性及有效性.方法 计算机检索Medline、Embase、Cochrane Library、中国生物医学文献数据库、中国期刊全文数据库、中文科技期刊全文数据库,检索时间从各数据库建立至2012年4月;同时辅助其他检索方法,所检索文献由两名系统评价者独立评价纳入研究并提取资料,并用Revman 5.1软件进行统计学分析.结果 共纳入11项研究,meta分析结果显示,与促性腺激素释放激素类似物相比,曼月乐可以取得相当的缓解疼痛的效果.与子宫全切术相比,曼月乐可以明显缓解患者疼痛,且对其性生活质量影响较小.保守手术后使用曼月乐与期待疗法相比,可以缓解患者疼痛.结论 曼月乐可以有效缓解子宫内膜异位症患者的疼痛,不良反应发生率低,值得临床推广应用.%Objective To evaluate the efficacy and safety of the levonorgestrel-releasing intrauterine system (mirena) in the treatment of endometriosis.Methods Medline,Embase,The Chinese Biomedical Database (CJFD) and Chinese Science and Technology Journal Full-text Database (CSJD) from their establishment to April 2012 were employed in the study.All the studies included were evaluated by Cochrane Handbook,and homogenous studies were analyzed by Revman 5.1 software.Results Eleven studies were included.Compared with gonadotropin releasing hormone group,the mirena group had no statistical difference in visual analogue score; compared with hysterectomy group,the mirena group had statistical significance in pain relief rate; compared with expectant management group,the mirena group also had statistical significance in pain relief rate.The mirena group showed no statistical significance in adverse effect.Conclusion The mircna can significantly relieve the pain of the patients of cndometriosis,and it is worth generalization in clinical.But the related

  20. 奥利司他对肥胖高血压患者非内皮依赖性血管舒张功能的影响%Effects of orlistat on endothelium-independent vasodilation function in obese subjects with hypertension

    Institute of Scientific and Technical Information of China (English)

    刘靖; 孙宁玲; 杨松娜; 马志毅; 杨靓

    2009-01-01

    目的:观察肥胖高血压患者服用奥利司他治疗前后血压和硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能的变化.方法:30例肥胖合并轻度高血压患者(肥胖高血压组)奥利司他120mg,3次/d,共12周,服药前后诊所测量身高、体重、腰围及血压,计算BMI.并行肱动脉高解像度超声检查,舌下含服硝酸甘油0.3 mg,测定硝酸甘油介导的血管舒张(NMD)程度的变化.15例非肥胖的高血压患者作为对照组.结果:两组基线的特征具有可比性.肥胖高血压组患者治疗前与非肥胖高血压患者的NMD无差别,但BMI及腰围明显增加(P均0.05).结论:奥利司他短期治疗能降低肥胖高血压患者的体重及血压,但对硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能无作用.

  1. Influence of Levonorgestrel on the endometrium VEGF, ER, PR and serum hormone of patients with anovulatory functional bleeding%左炔诺孕酮对无排卵型功能失调性子宫出血患者子宫内膜血管内皮细胞生长因子、雌激素受体、孕激素受体及血清激素的影响

    Institute of Scientific and Technical Information of China (English)

    陈秀琴; 郑安桔

    2013-01-01

    Objective To study the influence of Levonorgestrel for the endometrium vascular endothelial growth factors (VEGF), estrogen receptor (ER), progesterone receptor (PR) and serum hormone of patients with anovulatory functional bleeding. Methods 28 patients with anovulatory functional bleeding treated with Marvelon from March 2011 to July 2012 were the control group, and 28 cases treated with Levonorgestrel at the same time were the observation group, then the endometrium gland and stromal VEGF, ER, PR, serum hormone before and after treatment for 1, 3 and 6 months and other related items of two groups were compared. Results The endometrium gland and stromal VEGF of observation group after treatment for 1, 3 and 6 months were 64.29%, 71.43%, 78.57% and 57.14%, 64.29%, 75.00%, serum progesterone (P) were (3.49±0.26) ng/mL, (3.80±0.29) ng/mL and (3.93±0.32) ng/mL, and they were higher than those of control group, ER, PR and serum estradiol (E2) were lower than those of control group, there were all signifi-cant differences (all P 0.05), while the endometrial thickness was smaller than that of control group, hemoglobin level was higher than that of control group, PBAC scores were all lower than those of control group, incidence of ad-verse reactions was lower than that of control group, there were all significant differences (all P < 0.05). Conclusion The influence of Levonorgestrel for the endometrium VEGF, ER, PR and serum E2, P of patients with anovulatory functional bleeding is great, and it effectively improve other related indexes of disease.%目的 探讨左炔诺孕酮对无排卵型功能失调性子宫出血(功血)患者子宫内膜血管内皮细胞生长因子(VEGF)、雌激素受体(ER)、孕激素受体(PR)及血清激素的影响.方法 选取2011年3月~2012年7月采用妈富隆进行治疗的28例无排卵型功血患者为对照组,同期采用左炔诺孕酮进行治疗的28例患者为观察组.将两组患者治疗前与治疗后1、3、6个

  2. Inducing autophagy

    DEFF Research Database (Denmark)

    Harder, Lea M; Bunkenborg, Jakob; Andersen, Jens S.

    2014-01-01

    catabolism, which has recently been found to induce autophagy in an MTOR independent way and support cancer cell survival. In this study, quantitative phosphoproteomics was applied to investigate the initial signaling events linking ammonia to the induction of autophagy. The MTOR inhibitor rapamycin was used...

  3. DEVELOPMENT OF A DEPOT INJECTION OF LEVONORGESTREL AND ESTRADIOL

    Institute of Scientific and Technical Information of China (English)

    XUEYin-Huan; JINZhao-Ying

    1989-01-01

    LNG and E2 microcrystals were prepared by the solvent conversion method. The secondary solvent system, rate of stirring and temperature were considered to have a significant effect on the forming of microcrystalline with different particle sizes.

  4. 促性腺激素释放激素激动剂联合左炔诺孕酮宫内缓释系统治疗子宫腺肌病的疗效观察%Effect of GnRH-a combined with levonorgestrel-releasing intrauterine system on the treatment of large adenomyosis

    Institute of Scientific and Technical Information of China (English)

    刘芸; 段华

    2014-01-01

    目的:探讨促性腺激素释放激素激动剂(GnRH-a)联合左炔诺孕酮宫内缓释系统(LNG-IUS)治疗较大子宫腺肌病的效果。方法入选子宫腺肌病所致中、重度痛经合并月经量过多的患者54例,宫腔深度9~12 cm, GnRH-a治疗3个疗程后放置LNG-IUS,比较治疗前,放置后3个月、6个月、12个月患者的痛经缓解程度、子宫体积变化、血红蛋白及血清CA125水平。结果47例完成研究,患者痛经的VAS评分由治疗前的(75.9±10.3)下降为治疗后的(27.1±8.6),VRS评分由(2.2±0.4)分下降为(1.1±0.2)分,子宫体积由(268.2±12.0)cm3下降为(196.3±7.2)cm3,血清CA125水平由(68.2±22.2)U/ml下降为(43.4±22.1)U/ml,血红蛋白由(87.4±10.3)g/L上升为(123.9±23.1)g/L,差异均有统计学意义(P<0.01)。且上述指标在弥漫性和局限性子宫腺肌病均有明显改善。结论 GnRH-a联合LNG-IUS治疗宫腔深度在9~12 cm的子宫腺肌病,近期内能有效缓解痛经及月经量过多的临床症状,短期内避免手术治疗可能带来的相关风险,提高生活质量,值得临床应用。但对于局限性子宫腺肌病的患者使用前应与患者充分沟通,密切随访,观察疗效,适时修改治疗方案。%Objective To evaluate the effect of gonadotropin releasing hormone agonist (GnRH-a) combined with levonorgestrel-releasing intrauterine system (LNG-IUS) on the treatment of large adenomyosis. Methods Fifty-four women with moderate or severe dysmenorrhea associated with adenomyosis were recruited, whose depth of uterine cavity was from 9 to 12 cm. All women were inserted LNG-IUS following 3 courses of GnRH-a. Three, six and twelve months af-ter the placement of LNG-IUS, the uterine size, degree of dysmenorrhea, hemoglobin and CA 125 values were compared to those before therapy. Results Forty-seven women completed the study. There were significant differences between

  5. Clinical research of oral contraceptive and levonorgestrel-releasing intrauterine system after hysteroscopic endometrial polypectomy in preventing recurrence%口服避孕药与宫腔内放置左炔诺孕酮宫内缓释系统治疗子宫内膜息肉术后复发的临床研究

    Institute of Scientific and Technical Information of China (English)

    于慧; 周海慧

    2014-01-01

    Objective To explore the recurrence-prevention effect of oral contraceptive and levonorgestrel-releasing intrauterine system (Mirena) after hysteroscopic endometrial polypectomy.Methods One hundred and seventy-four patients who received hysteroscopic endometrial polypectomy were enrolled in this research.The patients were informed and divided into three groups according to their selection:51 cases were given oral contraceptive since one month until 12 months after the surgery (oral contraceptive group); 60 cases were received Mirena since one month after the surgery (Mirena group) ; and 64 cases were received no treatment after the surgery (control group).The groups were followed up at 3,6,12 months after the surgery and compared the recurrence rate,menstruation,level of hemoglobin and complication rate.Results The recurrence rate in oral contraceptive group,Mirena group and control group was 3.9%(2/51),3.3% (2/60) and 19.0% (12/63),respectively.The recurrence rate in control group was higher than that in oral contraceptive group and Mirena group,and there was significant difference (P < 0.05).The proportion of low menstruation volume in control group was lower than that in oral contraceptive group and Mirena group,and there was significant difference (P < 0.05).The level of hemoglobin in control group was lower than that in oral contraceptive group and Mirena group [(124.55 ±9.33) g/L vs.(133.71 ± 11.03),(135.89 ±6.88) g/L],and there was significant difference (P < 0.05).The incidence of complication in Mirena group [18.3% (11/60)] was less than that in oral contraceptive group[35.3%(18/51)],and there was significant difference (P < 0.05).Conclusions Oral contraceptive and Mirena after hysteroscopy for endometrial polys significantly decrease the recurrence rate.The complication rate of Mirena is lower and it is a safe and effective way to treat and prevent the endometrial polyp.%目的 探讨子宫内膜息肉行宫腔镜手术后口服避

  6. Exercise-Induced Bronchoconstriction

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  7. 复方短效口服避孕药、左炔诺孕酮宫内缓释系统和安全套在剖宫产瘢痕妊娠清宫术后的避孕效果比较%A comparative contraceptive effect among compound short-acting oral contraceptives,levonorgestrel releasing intrauterine system and condoms after cesarean scar pregnancy curettage

    Institute of Scientific and Technical Information of China (English)

    万金华; 朱艳琼

    2016-01-01

    Objective To explore the contraceptive efficacy and safety of compound short-acting oral contraceptives,levonorgestrel re-leasing intrauterine system and condoms after cesarean scar pregnancy curettage.Methods Totally 112 CSP patients,who were treated uterine artery embolization combined with curettage,were randomized into 3 groups.Patients (39 cases)in the contraceptive pill group were treated with compound short-acting contraceptives,patients (37 cases)in mirena group were placed Mirena (levonorgestrel-relea-sing intrauterine system)after curettage immediately,and patients (36 cases)in condom group were given condoms contraception. Three groups of patients were followed up to compare ultrasonic examination results,unexpected pregnancy and menstrual flow change. Results Patients were followed up for 1 year.The total effective rates of patients in contraceptive pill group,Mirena patient group and condoms contraception group were 94.88%,100.00% and 86.11%,respectively.There wasn’t significant difference in total contracep-tive effective rate among the three groups.There was 1 case of recurrent CSP in contraceptive pills group and condoms group respectively, but there was no recurrence in Mirena group.Ultrasonic examination showed there were noincision rupture or damage,no increase in the a-mount of menstruation in the 3 groups.With chi-square division method,the menstrual changes of the three groups were compared.The de-crease of menstruation in the patients of Mirena group was significantly higher than those of the condom group and the contraceptive pill group (P <0.017)at 3,6 and 12 months postoperatively.The menstrual blood loss decreased significantly in contraceptive pill group at 3 months after curettage compared with the other two groups (P <0.017).There were no serious adverse events and complaints about asexu-al life in the 3 groups.Conclusions After uterine artery embolization combined with uterine curettage CSP patients can take marvelon and Mirena

  8. Exercise-Induced Asthma

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Exercise-Induced Asthma KidsHealth > For Parents > Exercise-Induced Asthma A A ... previous continue Tips for Kids With Exercise-Induced Asthma For the most part, kids with exercise-induced ...

  9. Placenta Micromorphology and Expressions of Steroid Receptors,Proliferating Cell Nuclear Antigen Ki67, Apoptosis Related Molecules caspase-3/8/9, Exposed to Levonorgestrel Used for Emergency Contraception%左炔诺孕酮紧急避孕失败后继续妊娠者胎盘微观形态和性激素受体及增殖核抗原Ki67和凋亡相关分子caspase-3/8/9的表达

    Institute of Scientific and Technical Information of China (English)

    张琳; 郭坤; 杨祖菁; 周赟; 程利南

    2013-01-01

    目的:明确左炔诺孕酮紧急避孕(LNG-EC)暴露是否对妊娠晚期胎盘产生相关影响.方法:选择21例末次月经后使用过LNG-EC药孕妇计划剖宫产的产后胎盘为研究组,21例正常妊娠孕产妇计划剖宫产的产后胎盘为对照组.采用电子显微镜观察胎盘绒毛和细胞器超微结构;采用免疫组织化学方法检测孕妇胎盘中雌激素受体(ER)、孕激素受体(PR)、雄激素受体(AR)和增殖核抗原Ki67、凋亡相关分子caspase-3/8/9的表达情况.结果:光学显微镜和电子显微镜下胎盘形态学组间无统计学差异(P>0.05);胎盘中ER、PR、AR、Ki67和caspase-3/8/9的表达组间无显著统计学差异(P>0.05).结论:左炔诺孕酮用于紧急避孕不影响其失败后妊娠晚期胎盘的形态结构、性激素受体表达和胎盘增殖及老化.%Objective:To evaluate the impact of exposure to levonorgestrel-only emergency contraception (LNG-EC) on late pregnancy placenta.Methods:Twenty-one samples of placenta tissues were collected from women who used the LNG-EC after last menstrual period (study group),21 cases of normal pregnant placenta were collected as control group.Electron microscope was used to investigate the micromorphology configuration,immunohistochemistry was used to investigate the function of the LNG-EC exposed placentas with PR,ER,AR,Ki67 and caspase-3/8/9.Results:There was no significant difference between study group and control group in placenta morphologic examination.The expressions of ER,PR,AR,Ki67 and caspase-3/8/9 in placenta between the two groups were not statistically different.Conclusion:There was no association between the use of levonorgestrel emergency contraception pills and the morphologic configuration in their later pregnancy placenta,LNG-EC does not interfere the main steroid hormone receptors and the aging of placenta.

  10. [Induced abortion: Guidelines for clinical practice - Text of the Guidelines (short text)].

    Science.gov (United States)

    Vayssière, C; Gaudineau, A; Attali, L; Bettahar, K; Eyraud, S; Faucher, P; Fournet, P; Hassoun, D; Hatchuel, M; Jamin, C; Letombe, B; Linet, T; Msika Razon, M; Ohanessian, A; Segain, H; Vigoureux, S; Winer, N; Wylomanski, S; Agostini, A

    2016-12-01

    Develop recommendations for the practice of induced abortion. The Pubmed database, the Cochrane Library and the recommendations from the French and foreign Gyn-Obs societies or colleges have been consulted. The number of induced abortions (IA) has been stable for several decades. There are a lot of factors explaining the choice of abortion when there is an unplanned pregnancy (UPP). Early initiation and choice of contraception in connection to the woman's life are associated with lower NSP. Reversible contraceptives of long duration of action should be positioned fist in line for the teenager because of its efficiency (grade C). Ultrasound before induced abortion must be encouraged but should not be obligatory before performing IA (Professional consensus). As soon as the sonographic apparition of the embryo, the estimated date of pregnancy is done by measuring the crown-rump length (CRL) or by measuring the biparietal diameter (BIP) from 11 weeks on (grade B). Reliability of these parameters being±5 days, IA could be done if measurements are respectively less than 90mm for CRL and less than 30mm for BIP (Professional consensus). A medical IA performed with a dose of 200mg mifepristone combined with misoprostol is effective at any gestational age (EL1). Before 7 weeks, mifepristone followed between 24 and 48hours by taking misoprostol orally, buccally sublingually or eventually vaginally at a dose of 400 ug possibly renewed after 3hours (EL1, grade A). Beyond 7 weeks, misoprostol given vaginally, sublingually or buccally are better tolerated with fewer side effects than oral route (EL1). It is recommended to always use a cervical preparation during an instrumental abortion (Professional consensus). Misoprostol is a first-line agent for cervical preparation at a dose of 400 mcg (grade A). Aspiration evacuation is preferable to curettage (grade B). A perforated uterus during an instrumental suction should not be considered as a scarred uterus (Professional

  11. Exercise-Induced Asthma

    Science.gov (United States)

    ... management of exercise-induced bronchoconstriction: A practice parameter. Annals of Allergy, Asthma & Immunology. 2010;105:S1. Krafczyk ... up exercise on exercise-induced bronchoconstriction. Medicine and Science in Sports and Exercise. 2012;44:383. Asthma ...

  12. Extrachromosomal inducible expression

    NARCIS (Netherlands)

    Veltman, Douwe M; Van Haastert, Peter J M

    2013-01-01

    Inducible expression systems are very convenient for proteins that induce strong side effects such as retardation of growth or development and are essential for the expression of toxic proteins. In this chapter we describe the doxycycline-inducible expression system, optimized for the controlled exp

  13. Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Nilas, Lisbeth; Pedersen, Susan Helene

    2004-01-01

    OBJECTIVES: To compare the acute effects of estradiol, tibolone and its metabolites on coronary arteries in vitro and to investigate possible vascular mechanisms. METHODS: Coronary artery ring segments from female rabbits were mounted in myographs for isometric tension recordings. Concentration.......05, ANOVA). CONCLUSIONS: Our data indicate that the acute relaxation induced by tibolone and its metabolites in coronary arteries in vitro are probably mediated by endothelium independent inhibition of calcium channels but may also involve an endothelium-dependent mechanism via nitric oxide. The effect...

  14. Bromazepam-induced dystonia.

    Science.gov (United States)

    Pérez Trullen, J M; Modrego Pardo, P J; Vázquez André, M; López Lozano, J J

    1992-01-01

    Benzodiazepines are drugs with a good tolerance that are widely used for the treatment of anxiety. Extrapyramidal side-effects are unusual. Diazepam is effective for the treatment of drug-induced dystonias, nevertheless there are some reports of Diazepam-induced dystonia. We report a case history of a patient who developed oromandibular dystonia after taking Bromazepam. The possible mechanisms that cause drug-induced dystonia are described.

  15. Glucocorticoid-Induced Osteoporosis

    Science.gov (United States)

    ... Cryopyrin-Associated Autoinflammatory Syndrome (CAPS) (Juvenile) Dermatomyositis (Juvenile) Familial Mediterranean Fever (Juvenile) Fibromyalgia Giant Cell Arteritis Glucocorticoid-induced Osteoperosis ...

  16. Induced radioactivity at CERN

    CERN Multimedia

    1970-01-01

    A description of some of the problems and some of the advantages associated with the phenomenon of induced radioactivity at accelerator centres such as CERN. The author has worked in this field for several years and has recently written a book 'Induced Radioactivity' published by North-Holland.

  17. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring c

  18. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring

  19. Mesalamine-Induced Myocarditis

    OpenAIRE

    Pierre-Louis Michel; Richard Dorent; Nadjib Hammoudi; Florence Pontnau; Antoine Khalil; Clement Bailly; Olivier Merceron

    2010-01-01

    Nowadays mesalamine is a common treatment for Crohn's disease and hypersensitive reactions to this product have been reported. Yet there is limited information concerning mesalamine-induced myocarditis and its mechanism is not known. We described a case of mesalamine-induced myocarditis in Crohn's disease of the colon.

  20. Mesalamine-Induced Myocarditis

    Directory of Open Access Journals (Sweden)

    Olivier Merceron

    2010-01-01

    Full Text Available Nowadays mesalamine is a common treatment for Crohn's disease and hypersensitive reactions to this product have been reported. Yet there is limited information concerning mesalamine-induced myocarditis and its mechanism is not known. We described a case of mesalamine-induced myocarditis in Crohn's disease of the colon.

  1. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  2. Bleomycin-induced pneumonitis

    NARCIS (Netherlands)

    S. Sleijfer (Stefan)

    2001-01-01

    textabstractThe cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced cytokin

  3. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring c

  4. Mania induced by opipramol

    Directory of Open Access Journals (Sweden)

    Kazhungil Firoz

    2015-01-01

    Full Text Available Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania.

  5. Topological Induced Gravity

    CERN Document Server

    Oda, Ichiro

    2016-01-01

    We propose a topological model of induced gravity (pregeometry) where both Newton's coupling constant and the cosmological constant appear as integration constants in solving field equations. The matter sector of a scalar field is also considered, and by solving field equations it is shown that various types of cosmological solutions in the FRW universe can be obtained. A detailed analysis is given of the meaning of the BRST transformations, which make the induced gravity be a topological field theory, by means of the canonical quantization analysis, and the physical reason why such BRST transformations are needed in the present formalism is clarified. Finally, we propose a dynamical mechanism for fixing the Lagrange multiplier fields by following the Higgs mechanism. The present study clearly indicates that the induced gravity can be constructed at the classical level without recourse to quantum fluctuations of matter and suggests an interesting relationship between the induced gravity and the topological qu...

  6. Optomechanically induced transparency

    CERN Document Server

    Weis, S; Deleglise, S; Gavartin, E; Arcizet, O; Schliesser, A; Kippenberg, T J

    2010-01-01

    Coherent interaction of laser radiation with multilevel atoms and molecules can lead to quantum interference in the electronic excitation pathways. A prominent example observed in atomic three-level-systems is the phenomenon of electromagnetically induced transparency (EIT), in which a control laser induces a narrow spectral transparency window for a weak probe laser beam. The concomitant rapid variation of the refractive index in this spectral window can give rise to dramatic reduction of the group velocity of a propagating pulse of probe light. Dynamic control of EIT via the control laser enables even a complete stop, that is, storage, of probe light pulses in the atomic medium. Here, we demonstrate optomechanically induced transparency (OMIT)--formally equivalent to EIT--in a cavity optomechanical system operating in the resolved sideband regime. A control laser tuned to the lower motional sideband of the cavity resonance induces a dipole-like interaction of optical and mechanical degrees of freedom. Under...

  7. Exercise-induced asthma

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000036.htm Exercise-induced asthma To use the sharing features on this page, ... such as running, basketball, or soccer. Use Your Asthma Medicine Before you Exercise Take your short-acting, ...

  8. Cold-induced metabolism

    NARCIS (Netherlands)

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic

  9. Glucocorticoid-Induced Osteoporosis

    Science.gov (United States)

    ... also is approved for treatment of glucocorticoid-induced osteoporosis. This manmade form of parathyroid hormone helps stimulate bone formation. Women planning a pregnancy should talk to their doctor about the pros ...

  10. Trauma-induced coagulopathy.

    Science.gov (United States)

    Katrancha, Elizabeth D; Gonzalez, Luis S

    2014-08-01

    Coagulopathy is the inability of blood to coagulate normally; in trauma patients, it is a multifactorial and complex process. Seriously injured trauma patients experience coagulopathies during the acute injury phase. Risk factors for trauma-induced coagulopathy include hypothermia, metabolic acidosis, hypoperfusion, hemodilution, and fluid replacement. In addition to the coagulopathy induced by trauma, many patients may also be taking medications that interfere with hemostasis. Therefore, medication-induced coagulopathy also is a concern. Traditional laboratory-based methods of assessing coagulation are being supported or even replaced by point-of-care tests. The evidence-based management of trauma-induced coagulopathy should address hypothermia, fluid resuscitation, blood components administration, and, if needed, medications to reverse identified coagulation disorders.

  11. Cold-induced metabolism

    NARCIS (Netherlands)

    van Marken Lichtenbelt, W.D.; Daanen, A.M.

    2003-01-01

    Cold-induced metabolism. van Marken Lichtenbelt WD, Daanen HA. Department of Human Biology, Maastricht University, Maastricht, The Netherlands. PURPOSE OF REVIEW: Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesi

  12. Drug-induced hepatitis

    Science.gov (United States)

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  13. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  14. Drug-induced catatonia.

    Science.gov (United States)

    Duggal, Harpreet S; Singh, Ira

    2005-09-01

    Catatonia is a heterogeneous syndrome that varies in etiology, presentation, course and sequelae. Initially conceptualized as a subtype of schizophrenia, catatonia is now recognized to occur not only with other psychiatric conditions but also with medical conditions and drug-induced and toxic states. While drug-induced catatonia is now a recognized entity, most studies club it with catatonia due to general medical conditions or organic catatonia, thus precluding any meaningful interpretation of such cases. The literature on drug-induced catatonia mostly draws from scattered case reports. This article attempts to review the available literature in this realm and integrate the information in an attempt to explore the epidemiology, etiology, mechanism and treatment of drug-induced catatonia.

  15. Carbamazepine-Induced Diarrhea

    OpenAIRE

    J Gordon Millichap

    1992-01-01

    Intractable diarrhea induced by carbamazepine (CBZ) in 3 patients and necessitating discontinuation of the drug is reported from the Departments of Neurology and Medicine, University of Louisville School of Medicine, Kentucky.

  16. Lorazepam-induced diplopia.

    Science.gov (United States)

    Lucca, Jisha M; Ramesh, Madhan; Parthasarathi, Gurumurthy; Ram, Dushad

    2014-01-01

    Diplopia - seeing double - is a symptom with many potential causes, both neurological and ophthalmological. Benzodiazepine induced ocular side-effects are rarely reported. Lorazepam is one of the commonly used benzodiazepine in psychiatric practice. Visual problems associated with administration of lorazepam are rarely reported and the frequency of occurrence is not established. We report a rare case of lorazepam-induced diplopia in a newly diagnosed case of obsessive compulsive disorder.

  17. Lorazepam-induced diplopia

    Directory of Open Access Journals (Sweden)

    Jisha M Lucca

    2014-01-01

    Full Text Available Diplopia - seeing double - is a symptom with many potential causes, both neurological and ophthalmological. Benzodiazepine induced ocular side-effects are rarely reported. Lorazepam is one of the commonly used benzodiazepine in psychiatric practice. Visual problems associated with administration of lorazepam are rarely reported and the frequency of occurrence is not established. We report a rare case of lorazepam-induced diplopia in a newly diagnosed case of obsessive compulsive disorder.

  18. Terahertz field induced electromigration

    DEFF Research Database (Denmark)

    Strikwerda, Andrew; Zalkovskij, Maksim; Iwaszczuk, Krzysztof;

    We report the first observation of THz-field-induced electromigration in sub-wavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm.......We report the first observation of THz-field-induced electromigration in sub-wavelength metallic gap structures after exposure to intense single-cycle, sub-picosecond electric field transients of amplitude up to 400 kV/cm....

  19. Paroxetine-induced galactorrhea.

    Science.gov (United States)

    Gulati, Prannay; Chavan, B S; Das, Subhash

    2014-10-01

    Drug-induced galactorrhea has been reported with agents such as antidopaminergic antiemetics, antipsychotics, etc., with few case reports of galactorrhea with selective serotonin reuptake inhibitors, including paroxetine, being reported in last few decades. Prolactin levels have been found to be either raised or normal in these cases. We here report a case of paroxetine induced galactorrhea in a 48-year-old female patient of obsessive compulsive disorder, having hyperprolactinemic and euprolactinemic galactorrhea at different time with a pituitary incidentaloma.

  20. Paroxetine-induced galactorrhea

    OpenAIRE

    Gulati, Prannay; Chavan, B.S.; Das, Subhash

    2014-01-01

    Drug-induced galactorrhea has been reported with agents such as antidopaminergic antiemetics, antipsychotics, etc., with few case reports of galactorrhea with selective serotonin reuptake inhibitors, including paroxetine, being reported in last few decades. Prolactin levels have been found to be either raised or normal in these cases. We here report a case of paroxetine induced galactorrhea in a 48-year-old female patient of obsessive compulsive disorder, having hyperprolactinemic and euprola...

  1. Contrast-induced nephropathy

    Directory of Open Access Journals (Sweden)

    Ricardo A. García Hernández

    2016-06-01

    Full Text Available Contrast-induced nephropathy is an important complication associated with the use of contrast media. Favoring factors for the development of contrast-induced nephronpathy have been widely described, being diabetes mellitus and previous renal disease the greatest risk. The pathophysiology is a complex process where the medullary hypoxia represents the trigger element. Previous hydration and the use of low osmolality contrast are the most recommended measures to prevent its development.

  2. Optically Induced Transparency

    CERN Document Server

    Zheng, Yuanlin; Shen, Zhenhua; Cao, Jianjun; Chen, Xianfeng; Liang, Xiaogan; Wan, Wenjie

    2015-01-01

    Light-matter-light interactions serve as the backbone technology of all-optical information processing for both on-chip and long-haul communication purposes. The representative example of electromagnetically induced transparency has its unique ability of optically controlling transparency windows with relative low light in atomic systems, though its practical applications are limited due to rigid experimental requirements. Here we demonstrate a new form of optically induced transparency in a micro-cavity by introducing four-wave mixing gain in order to couple nonlinearly two separated resonances of the micro-cavity in ambient environment. A signature Fano-like resonance is also observed owing to the nonlinear interference of two coupled resonances. Moreover, we show that the unidirectional gain of four-wave mixing can lead to non-reciprocal transmission at the transparency windows. Optically induced transparency may offer a unique platform for a compact, integrated solution to all-optical processing and quant...

  3. [Radiation induced tumors].

    Science.gov (United States)

    Gutiérrez Bayard, L; Delgado López, L; Tirado Bejarano, C; Gómez Puerto, A; García Fernández, J L

    1998-04-01

    Radiations at cellular level produce different effects, depending on type of radiation and irradiated tissue. The radiation-induced cancers are associated to non-letals genetics mutations, and to classify like radiation induced tumors is necessary that appear in the treatment volume, a long latency period (years), histolo-different to the primary lesion, enough doses quantitatively and that exists a greater incidence in the irradiated populations. The genetics mutations affect at tumoral suppressors gen(Gen RB I, p53, BRCA I, BRCA 2) and repressors gen (hMSH 2, hMLH I,...), they could be longer and multifocals mutations, and produce lack of cellular control and a greater predisposition to develop tumors and a probable risk of increment of radiosensitivity. We present some of the more representatives studies about radiation-induced tumors.

  4. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest

    2012-01-01

    Time-domain-induced polarization has significantly broadened its field of reference during the last decade, from mineral exploration to environmental geophysics, e.g., for clay and peat identification and landfill characterization. Though, insufficient modeling tools have hitherto limited the use...... of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function......%. Furthermore, the presence of low-pass filters in time-domain-induced polarization instruments affects the early times of the acquired decays (typically up to 100 ms) and has to be modeled in the forward response to avoid significant loss of resolution. The developed forward code has been implemented in a 1D...

  5. Crystalglobulin-induced nephropathy.

    Science.gov (United States)

    Gupta, Vinay; El Ters, Mireille; Kashani, Kianoush; Leung, Nelson; Nasr, Samih H

    2015-03-01

    Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.

  6. Gravitationally induced quantum transitions

    Science.gov (United States)

    Landry, A.; Paranjape, M. B.

    2016-06-01

    In this paper, we calculate the probability for resonantly inducing transitions in quantum states due to time-dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultracold neutrons, which are organized according to the energy levels of the Schrödinger equation in the presence of the Earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency ω . The driving force is created by oscillating a macroscopic mass in the neighborhood of the system of neutrons. The neutron lifetime is approximately 880 sec while the probability of transitions increases as t2. Hence, the optimal strategy is to drive the system for two lifetimes. The transition amplitude then is of the order of 1.06 ×10-5, and hence with a million ultracold neutrons, one should be able to observe transitions.

  7. Gravitationally induced quantum transitions

    CERN Document Server

    Landry, A

    2016-01-01

    In this letter, we calculate the probability for resonantly induced transitions in quantum states due to time dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultra cold neutrons (UCN), which are organized according to the energy levels of the Schr\\"odinger equation in the presence of the earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency $\\omega$. The driving force is created by oscillating a macroscopic mass in the neighbourhood of the system of neutrons. The neutrons decay in 880 seconds while the probability of transitions increase as $t^2$. Hence the optimal strategy is to drive the system for 2 lifetimes. The transition amplitude then is of the order of $1.06\\times 10^{-5}$ hence with a million ultra cold neutrons, one should be able to observe transitions.

  8. Induced Norm Control Toolbox

    DEFF Research Database (Denmark)

    Beran, Eric Bengt

    1996-01-01

    This paper describes the basic nature of the InducedNorm Control Toolbox (INCT). The toolbox is a set of Matlab-filesusing LMITOOL and the Semidefinite Programming package(SP). Thetoolbox is public domain. The INCT provides a series of analysisand synthesis tools for continuous time-invariant lin......This paper describes the basic nature of the InducedNorm Control Toolbox (INCT). The toolbox is a set of Matlab-filesusing LMITOOL and the Semidefinite Programming package(SP). Thetoolbox is public domain. The INCT provides a series of analysisand synthesis tools for continuous time...

  9. Olmesartan-Induced Enteropathy.

    Science.gov (United States)

    Adike, Abimbola; Corral, Juan; Rybnicek, David; Sussman, Daniel; Shah, Samir; Quigley, Eamonn

    2016-01-01

    Olmesartan-induced enteropathy mimics celiac disease clinically and pathologically. As in celiac disease, the pathologic findings are villous atrophy and increased intraepithelial lymphocytes. Clinical presentation of olmesartan-induced enteropathy includes diarrhea, weight loss, and nausea. In contrast to celiac disease, tissue transglutaminase is not elevated and there is no response to a gluten-free diet. Including this entity in the differential diagnosis of sprue-like enteropathy is critical for its early diagnosis since replacing olmesartan with an alternative antihypertensive drug can simplify the diagnostic workup and provide both clinical and histologic improvement.

  10. Rosuvastatin-induced pemphigoid.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2012-01-01

    Statins are widely prescribed medications and very well tolerated. Rosuvastatin is another member of this drug used to treat dyslipidaemia. It is a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Immunobullous disease is usually idiopathic but can be drug-induced. Both idiopathic and iatrogenic forms share common clinical and immunohistological features. The authors report a case of pemphigoid induced by rosuvastatin, a commonly prescribed medication. To our knowledge, there is limited report on rosuvastatin associated with pemphigoid in the literature.

  11. Wheat induced urticaria

    Directory of Open Access Journals (Sweden)

    Uppal Monica

    2004-09-01

    Full Text Available Wheat is widely consumed all over India in various forms - flour, daliya, maida, suji and wheat bran. Very few cases of wheat induced urticaria have been reported. This may be due to unusual features of wheat related hypersensitivity. A 35 year old female presented to us with history of chronic urticaria and angioedema. History revealed correlation between wheat intake and urticaria episodes. Prick testing was done with wheat antigen in the standard series and derivatives of raw wheat. Normal saline and histamine were used as controls. Prick testing was positive. Oral challenge induced urticaria within half an hour. This report discusses clinical features of wheat related hypersensitivity.

  12. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

    2014-01-01

    INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled tr...

  13. Advertising-Induced Embarrassment

    NARCIS (Netherlands)

    Puntoni, S.; Hooge, de I.E.; Verbeke, W.J.M.I.

    2015-01-01

    Abstract Consumer embarrassment is a concern for many advertisers. Yet little is known about ad-induced embarrassment. The authors investigate when and why consumers experience embarrassment as a result of exposure to socially sensitive advertisements. The theory distinguishes between viewing potent

  14. Ergotamine-induced colitis.

    Science.gov (United States)

    Wörmann, B; Höchter, W; Seib, H J; Ottenjann, R

    1985-07-01

    We report on a 45-year-old woman with ulcerative colitis of the rectum that arose after the use of up to 6 suppositories of a preparation containing ergotamine daily over a period of 6 years. On the basis of a review of the literature the clinical, endoscopic and histological features of the ergotamine-induced colitis are characterized.

  15. Induced Angular Momentum

    Science.gov (United States)

    Parker, G. W.

    1978-01-01

    Discusses, classically and quantum mechanically, the angular momentum induced in the bound motion of an electron by an external magnetic field. Calculates the current density and its magnetic moment, and then uses two methods to solve the first-order perturbation theory equation for the required eigenfunction. (Author/GA)

  16. Amlodipine induced gingival enlargement

    Directory of Open Access Journals (Sweden)

    Shankar Gittaboyina

    2016-01-01

    Full Text Available Drug-induced gingival overgrowth or enlargement is an abnormal growth of the gingiva due to an adverse drug reaction in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers (CCBs. CCBs are considered as one of the etiologic factors among patients seeking dental care for drug-induced gingival enlargement or overgrowth. This enlargement can be localized or generalized and can range from mild to extremely severe, affecting patient's appearance, and function. CCBs are one of the most commonly used drugs for the management of cardiovascular disorders and are known for causing gingival over growth. Amlodipine is a new CCB and has been used with increasing frequency in the management of hypertension and angina. Although amlodipine is considered as a safe drug, very rarely it may induce gingival overgrowth. A rare case of amlodipine-induced gingival overgrowth has been reported herein a 45-year-old female patient. The treatment aspect included scaling and root planing, substitution of the drug, the surgical excision, and the maintenance and supportive therapy resulting in an excellent clinical outcome.

  17. Cold-induced metabolism

    NARCIS (Netherlands)

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic respon

  18. Geomagnetism and Induced Voltage

    Science.gov (United States)

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it…

  19. Inducible laryngeal obstruction

    DEFF Research Database (Denmark)

    Halvorsen, Thomas; Walsted, Emil Schwarz; Bucca, Caterina

    2017-01-01

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenc...

  20. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  1. Advertising-Induced Embarrassment

    NARCIS (Netherlands)

    Puntoni, S.; Hooge, de I.E.; Verbeke, W.J.M.I.

    2015-01-01

    Abstract Consumer embarrassment is a concern for many advertisers. Yet little is known about ad-induced embarrassment. The authors investigate when and why consumers experience embarrassment as a result of exposure to socially sensitive advertisements. The theory distinguishes between viewing potent

  2. Injection-induced earthquakes.

    Science.gov (United States)

    Ellsworth, William L

    2013-07-12

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  3. Understanding induced seismicity

    NARCIS (Netherlands)

    Elsworth, Derek; Spiers, Christopher J.; Niemeijer, Andre R.

    2016-01-01

    Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where seismi

  4. Pyrazinamide induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Kant Surya

    2010-01-01

    Full Text Available Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs.

  5. Understanding induced seismicity

    NARCIS (Netherlands)

    Elsworth, Derek; Spiers, Christopher J.; Niemeijer, Andre R.

    2016-01-01

    Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where

  6. Hyperthermia-induced apoptosis

    NARCIS (Netherlands)

    Nijhuis, E.H.A.

    2008-01-01

    This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this

  7. Calotropis procera -induced keratitis

    Directory of Open Access Journals (Sweden)

    Pandey Nidhi

    2009-01-01

    Full Text Available Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  8. Drug-induced uveitis

    Science.gov (United States)

    2013-01-01

    A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates. PMID:23522744

  9. Injection-induced earthquakes

    Science.gov (United States)

    Ellsworth, William L.

    2013-01-01

    Earthquakes in unusual locations have become an important topic of discussion in both North America and Europe, owing to the concern that industrial activity could cause damaging earthquakes. It has long been understood that earthquakes can be induced by impoundment of reservoirs, surface and underground mining, withdrawal of fluids and gas from the subsurface, and injection of fluids into underground formations. Injection-induced earthquakes have, in particular, become a focus of discussion as the application of hydraulic fracturing to tight shale formations is enabling the production of oil and gas from previously unproductive formations. Earthquakes can be induced as part of the process to stimulate the production from tight shale formations, or by disposal of wastewater associated with stimulation and production. Here, I review recent seismic activity that may be associated with industrial activity, with a focus on the disposal of wastewater by injection in deep wells; assess the scientific understanding of induced earthquakes; and discuss the key scientific challenges to be met for assessing this hazard.

  10. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  11. Uterine contraction induced by Tanzanian plants used to induce abortion

    DEFF Research Database (Denmark)

    Nikolajsen, Tine; Nielsen, Frank; Rasch, Vibeke

    2011-01-01

    Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect.......Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect....

  12. Viral induced demyelination.

    Science.gov (United States)

    Stohlman, S A; Hinton, D R

    2001-01-01

    Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus-specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the

  13. Hormone replacement therapy and hypercoagulability. Results from the Prospective Collaborative Danish Climacteric Study

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, Jørgen; Andersen, Lars F.

    2003-01-01

    norethindrone acetate, (E). E(2) combined with local delivery of levonorgestrel and (F). E(2)V plus medroxyprogesterone. HRT-induced changes in the concentration of inhibitors of coagulation and markers of fibrin turnover during 12 months of treatment. RESULTS: Significant decreases of antithrombin and protein...

  14. Topiramate Induced Excessive Sialorrhea

    Directory of Open Access Journals (Sweden)

    Ersel Dag

    2015-11-01

    Full Text Available It is well-known that drugs such as clozapine and lithium can cause sialorrhea. On the other hand, topiramate has not been reported to induce sialorrhea. We report a case of a patient aged 26 who was given antiepileptic and antipsychotic drugs due to severe mental retardation and intractable epilepsy and developed excessive sialorrhea complaint after the addition of topiramate for the control of seizures. His complaints continued for 1,5 years and ended after giving up topiramate. We presented this case since it was a rare sialorrhea case induced by topiramate. Clinicians should be aware of the possibility of sialorrhea development which causes serious hygiene and social problems when they want to give topiramate to the patients using multiple drugs.

  15. Tulipalin A induced phytotoxicity.

    Science.gov (United States)

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-04-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure.

  16. Curvature-induced dissipation

    CERN Document Server

    Debus, J -D; Succi, S; Herrmann, H J

    2015-01-01

    By inspecting the effect of curvature on a moving fluid, we find that local sources of curvature not only exert inertial forces on the flow, but also generate viscous stresses as a result of the departure of streamlines from the idealized geodesic motion. The curvature-induced viscous forces are shown to cause an indirect and yet appreciable energy dissipation. As a consequence, the flow converges to a stationary equilibrium state solely by virtue of curvature-induced dissipation. In addition, we show that flow through randomly-curved media satisfies a non-linear transport law, resembling Darcy-Forchheimer's law, due to the viscous forces generated by the spatial curvature. It is further shown that the permeability can be characterized in terms of the average metric perturbation.

  17. Induced Charge Capacitive Deionization

    CERN Document Server

    Rubin, S; Biesheuvel, P M; Bercovici, M

    2016-01-01

    We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electrostatic field. The external electric field induces an electric dipole in the porous particle, leading to capacitive charging of its volume by both cations and anions at opposite poles. This regime is characterized both by a large RC charging time and a small electrochemical charge relaxation time, which leads to rapid and significant deionization of ionic species from a volume which is on the scale of the particle. We show by theory and experiment that the transient response around a cylindrical particle results in spatially non-uniform charging and non-steady growth of depletion regions which emerge around the particle's poles. Potentially, ICCDI can be useful in applications where fast concentration changes of ionic species are required over large volumes.

  18. Induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Siddhartha Bhowmik; LI Yong

    2011-01-01

    Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

  19. Ofloxacin induced hypersensitivity reaction

    Directory of Open Access Journals (Sweden)

    Hari Babu Ramineni

    2015-01-01

    Full Text Available Ofloxacin is a commonly used antimicrobial agent to combat various infections. The adverse profile of quinolones includes gastrointestinal symptoms, which are the most frequent, neuropsychiatric symptoms, hematologic abnormalities are less common. We report a rare case of ofloxacin induced hypersensitivity reaction in a 57 year old female patient with complaints of rashes over the axilla, upper limb and back, abdomen, thorax associated with exfoliation of skin all over the axilla associated with severe itching. Based on history and clinical examination patient was diagnosed as ofloxacin induced hypersensitivity reaction and was successfully treated with antihistamines and corticosteroids. Pharmacovigilance should be a part of patient care in order to reduce occurrence of adverse drug reaction and also encourage practitioners in reporting so as to gather more and more data regarding adverse drug reactions. [Int J Res Med Sci 2015; 3(1.000: 349-351

  20. Sepsis-induced Cardiomyopathy

    Science.gov (United States)

    Romero-Bermejo, Francisco J; Ruiz-Bailen, Manuel; Gil-Cebrian, Julián; Huertos-Ranchal, María J

    2011-01-01

    Myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to 70%. During the sepsis-induced myocardial dysfunction, both ventricles can dilate and diminish its ejection fraction, having less response to fluid resuscitation and catecholamines, but typically is assumed to be reversible within 7-10 days. In the last 30 years, It´s being subject of substantial research; however no explanation of its etiopathogenesis or effective treatment have been proved yet. The aim of this manuscript is to review on the most relevant aspects of the sepsis-induced myocardial dysfunction, discuss its clinical presentation, pathophysiology, etiopathogenesis, diagnostic tools and therapeutic strategies proposed in recent years. PMID:22758615

  1. Cyanamide-induced granulocytopenia.

    Science.gov (United States)

    Ajima, M; Usuki, K; Igarashi, A; Okazaki, R; Hamano, K; Urabe, A; Totsuka, Y

    1997-09-01

    We report a 64-year-old male with granulocytopenia and dermatitis due to cyanamide treatment. We administered cyanamide for alcoholism. After about one month he suffered from scaly erythema over his whole body and granulocytopenia (granulocyte; 140/microliter) with maturation arrest in bone marrow. After cessation of cyanamide and the start of granulocyte colony-stimulating factor administration, the skin eruption ameliorated gradually, and the peripheral blood granulocyte counts increased. Cyanamide showed positive results in the drug lymphocyte stimulation test (198%) and the patch test led to the diagnosis of granulocytopenia and dermatitis induced by cyanamide. After restarting glibenclamide and diazepam administration, his granulocytopenia did not reoccur. To our knowledge, this is the first report of a case with granulocytopenia induced by cyanamide.

  2. Inducement Prizes and Innovation.

    OpenAIRE

    Brunt, Liam; Lerner, Josh; Nicholas, Tom

    2011-01-01

    We examine prizes as an inducement for innovation using a novel dataset of awards for inventiveness offered by the Royal Agricultural Society of England from 1839 to 1939. At annual shows the RASE held competitive trials and awarded medals and monetary prizes (exceeding one million pounds in current prices) to spur technological development. We find large effects of the prizes on contest entries, especially for the Society’s gold medal. Matching award and patent data, we also detect large eff...

  3. Drug-induced diarrhoea.

    Science.gov (United States)

    Chassany, O; Michaux, A; Bergmann, J F

    2000-01-01

    Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several

  4. Inducement prizes and innovation

    OpenAIRE

    Brunt, Liam; Lerner, Josh; Nicholas, Tom

    2011-01-01

    We examine prizes as an inducement for innovation using a novel dataset of awards for inventiveness offered by the Royal Agricultural Society of England from 1839 to 1939. At annual shows the RASE held competitive trials and awarded medals and monetary prizes (exceeding one million pounds in current prices) to spur technological development. We find large effects of the prizes on contest entries, especially for the Society’s gold medal. Matching award and patent data, we also detect large eff...

  5. Fluoroscopy-induced radionecrosis

    OpenAIRE

    Tchanque-Fossuo, Catherine N.; Kamangar, Faranak; Ho, Baran; Chang, Shurong; Dahle, Sara E.; Schulman, Joshua M.; Isseroff, R Rivkah

    2016-01-01

    Complications from radiation exposure during fluoroscopic guidance of cardiac catheterization may occur. With repeated procedures, the risk for cutaneous injuries increases. Herein, we describe a 59-year-old man with extensive coronary artery disease, who had undergone multiple revascularization procedures and developed a non-healing ulcer on his left inferior scapula. The patient’s medical history, physical exam findings, and histopathology gave clues to a case of radiation-induced dermatiti...

  6. Environment induced incoherent controllability

    OpenAIRE

    Romano, Raffaele; D'Alessandro, Domenico

    2005-01-01

    We prove that the environment induced entanglement between two non interacting, two-dimensional quantum systems S and P can be used to control the dynamics of S by means of the initial state of P. Using a simple, exactly solvable model, we show that both accessibility and controllability of S can be achieved under suitable conditions on the interaction of S and P with the environment.

  7. OXYTOCIN INDUCED NEONATAL HYPERBILIRUBINEMIA

    Directory of Open Access Journals (Sweden)

    Smita S.

    2015-05-01

    Full Text Available INTRODUCTION: Hyperbilirubinemia is one of the most common causes of health problems, observed in 60% of term and 80% of preterm infants in the first week of life . Hyperbilirubinemia leads to neurotoxicity in severe condition. Some studies suggests that liberal use of oxytocin for inducing labour is one of the factor which lead to neonatal hyperbilirubinemia. OBJECTIVE: To compare the effect of oxytocin and neonatal bilirubin levels with spontaneous vaginal delivery . MATERIALS AND METHOD S : 100 full term parturients were selected for this study. The subjects were divided into two groups. 50 healthy babies of women who had oxytocin induced labour and 50 healthy babies of women with normal vaginal delivery following spontaneous onset of labour formed the control group. Neon atal serum bilirubin was measured on day 1, 3 and 5 after delivery. Bilirubin was measured by spectrophotometry. Data was analysed in ms excel sheet using spss 19.0v. Statistical analysis was done by using unpaired‘t’ test. RESULTS: There was significant i ncrease in bilirubin level in oxytocin induced group compared to control group on day 1 and 3. There was insignificant increase in bilirubin level in oxytocin induced group on day 5. However the level of serum bilirubin is within normal limits as bilirubin level normally rises on till 4 th day and decreases thereafter. CONCLUSION: Neonatal hyperbilirubinemia may be due to oxytocin administration by continues IV infusion which results in erythrocyte swell and rupture. Increase in bilirubin level in oxytocin i nduced group is within physiological limits

  8. Cisplatin Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  9. Polarization induced doped transistor

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Huili (Grace); Jena, Debdeep; Nomoto, Kazuki; Song, Bo; Zhu, Mingda; Hu, Zongyang

    2016-06-07

    A nitride-based field effect transistor (FET) comprises a compositionally graded and polarization induced doped p-layer underlying at least one gate contact and a compositionally graded and doped n-channel underlying a source contact. The n-channel is converted from the p-layer to the n-channel by ion implantation, a buffer underlies the doped p-layer and the n-channel, and a drain underlies the buffer.

  10. Ketamine-Induced Hallucinations.

    Science.gov (United States)

    Powers, Albert R; Gancsos, Mark G; Finn, Emily S; Morgan, Peter T; Corlett, Philip R

    2015-01-01

    Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At subanesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations, a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine. Here we present data from a set of healthy participants who received moderately dosed, placebo-controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging (MRI) scanner. We highlight the phenomenological experiences of 3 participants who experienced particularly vivid hallucinations. Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner. We interpret the observation of ketamine-induced auditory verbal hallucinations in the context of the reduced perceptual environment of the MRI scanner and offer an explanation grounded in predictive coding models of perception and psychosis - the brain fills in expected perceptual inputs, and it does so more in situations of altered perceptual input. The altered perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine. Such circumstances induce aberrant percepts, including musical and auditory verbal hallucinations. We suggest that these circumstances might represent a useful experimental model of auditory verbal hallucinations and highlight the impact of ambient sensory stimuli on psychopathology. © 2015 S. Karger AG, Basel.

  11. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... America Information For… Media Policy Makers Noise-Induced Hearing Loss Recommend on Facebook Tweet Share Compartir Hearing plays ... sounds over an extended period. Preventing Noise-Induced Hearing Loss Hearing loss caused by exposure to loud sound ...

  12. Induced QCD I: Theory

    CERN Document Server

    Brandt, Bastian B; Wettig, Tilo

    2016-01-01

    We explore an alternative discretization of continuum SU(N_c) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N_b auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N_b can be as small as N_c. In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U(N_c) to SU(N_c), (ii) derive refined bounds on N_b for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the ga...

  13. Induced QCD I: theory

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, Bastian B. [Institute for Theoretical Physics, Goethe-University of Frankfurt,60438 Frankfurt (Germany); Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany); Lohmayer, Robert; Wettig, Tilo [Institute for Theoretical Physics, University of Regensburg,93040 Regensburg (Germany)

    2016-11-14

    We explore an alternative discretization of continuum SU(N{sub c}) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N{sub b} auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N{sub b} can be as small as N{sub c}. In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U(N{sub c}) to SU(N{sub c}), (ii) derive refined bounds on N{sub b} for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the gauge fields to arrive at a dual formulation of lattice QCD.

  14. Ethanol-induced analgesia

    Energy Technology Data Exchange (ETDEWEB)

    Pohorecky, L.A.; Shah, P.

    1987-09-07

    The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.

  15. Induced abortion and psychosexuality.

    Science.gov (United States)

    Bianchi-Demicheli, F; Kulier, R; Perrin, E; Campana, A

    2000-12-01

    Little information exists on the impact of induced abortion on psychosexuality. Negative psychological effects and psychiatric complications due to termination of pregnancy seem to be rare. The objective of this study was to review the impact of induced abortion on sexuality and couple relationships. A systematic search of the literature was performed. Studies had to report a quantitative or qualitative evaluation of sexuality after pregnancy termination. Four studies were included. In the one prospective study using a control group, no difference in sexual functioning between groups after 1 year was reported. In the remaining observational studies, sexual dysfunction was reported in up to 30% of women after termination. Women undergoing abortion had significantly more conflicts in their partnerships. This was similar in all studies. Separation occurred in about one-quarter of all couples. Some studies report sexual dysfunction after termination of pregnancy. In about half of the couples separated after termination, abortion seemed not to have led to the separation. Psychological factors, together with relationship problems, might have played a role in failed contraception. The impact of induced abortion on sexuality needs to be studied in greater detail with rigorous methodology to draw firm conclusions.

  16. Duxorubicin-induced cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Mukund Joshi

    2015-02-01

    Full Text Available The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the and ldquo;toxicity that affects the heart. and rdquo; This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX, cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the

  17. Swimming pool-induced asthma.

    Science.gov (United States)

    Beretta, S; Vivaldo, T; Morelli, M; Carlucci, P; Zuccotti, G V

    2011-01-01

    A 13-year-old elite swimmer presented with wheezing after indoor swimming training. On the basis of her clinical history and the tests performed, exercise-induced asthma and mold-induced asthma were ruled out and a diagnosis of chlorine-induced asthma was made.

  18. Sociodemographic profiles and use-dynamics of Jadelle (levonorgestrel implants in Jos, Nigeria

    Directory of Open Access Journals (Sweden)

    V C Pam

    2016-01-01

    Full Text Available Background: Contraceptive implants (including Jadelle are highly effective, safe, and easy to use and have a long duration of action. They do not interfere with intercourse with immediate return to fertility after removal. However, disruption of the menstrual bleeding pattern is almost inevitable and coercive prescription may be a problem because insertion and removal of implants are provider dependent. The objective of this study was to determine the sociodemographic profiles of acceptors of Jadelle and the reasons for discontinuation in Jos, Nigeria. Materials and Methods: This was a 6-year retrospective chart review carried out at the Jos University Teaching Hospital. Results: About 1401 women accepted Jadelle with a mean (΁standard deviation of 33.4 ΁ 5.9 years. About 88% of the women were Christians and almost three-quarters (73.5% had at least secondary school education. The means of parity and number of children still alive at the time of accepting Jadelle were 4.1 and 3.8, respectively. Half of the women (49.5% were breastfeeding and over half (55.9% had future fertility desires at the time of commencing Jadelle. About 82% had previously used other contraceptives (mostly short-acting methods such as injectables, pills, and condoms, with only 18% starting Jadelle as the first-ever contraceptive method. About 90% of the women had regular menstrual cycles. The major reason for discontinuation of Jadelle was desire for pregnancy although menstrual pattern disruption was the most common reason for removal in the first 6 months of use. Conclusion: The main reason for discontinuation of Jadelle was to have more children although menstrual pattern disruptions accounted for earlier discontinuation.

  19. Effects of Two Progestins, Norethindrone and Levonorgestrel, On Reproduction in a Marine Fish, Tautogolabrus adspersus.

    Science.gov (United States)

    Endocrine-active pharmaceuticals that enter the aquatic environment through sewage effluent may have unintended impacts on reproduction in fish, which in turn may affect the sustainability of exposed populations. Laboratory experiments were conducted with the marine fish cunner (...

  20. Sociodemographic profiles and use-dynamics of Jadelle (levonorgestrel) implants in Jos, Nigeria.

    Science.gov (United States)

    Pam, V C; Mutihir, J T; Nyango, D D; Shambe, I; Egbodo, C O; Karshima, J A

    2016-01-01

    Contraceptive implants (including Jadelle) are highly effective, safe, and easy to use and have a long duration of action. They do not interfere with intercourse with immediate return to fertility after removal. However, disruption of the menstrual bleeding pattern is almost inevitable and coercive prescription may be a problem because insertion and removal of implants are provider dependent. The objective of this study was to determine the sociodemographic profiles of acceptors of Jadelle and the reasons for discontinuation in Jos, Nigeria. This was a 6-year retrospective chart review carried out at the Jos University Teaching Hospital. About 1401 women accepted Jadelle with a mean (±standard deviation) of 33.4 ± 5.9 years. About 88% of the women were Christians and almost three-quarters (73.5%) had at least secondary school education. The means of parity and number of children still alive at the time of accepting Jadelle were 4.1 and 3.8, respectively. Half of the women (49.5%) were breastfeeding and over half (55.9%) had future fertility desires at the time of commencing Jadelle. About 82% had previously used other contraceptives (mostly short-acting methods such as injectables, pills, and condoms), with only 18% starting Jadelle as the first-ever contraceptive method. About 90% of the women had regular menstrual cycles. The major reason for discontinuation of Jadelle was desire for pregnancy although menstrual pattern disruption was the most common reason for removal in the first 6 months of use. The main reason for discontinuation of Jadelle was to have more children although menstrual pattern disruptions accounted for earlier discontinuation.

  1. Levonorgestrel and 17beta-estradiol given transdermally for the prevention of postmenopausal osteoporosis

    DEFF Research Database (Denmark)

    Warming, L; Ravn, Pernille; Christiansen, C

    2005-01-01

    AIM: To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis. METHODS: 212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S.D. of the preme......AIM: To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis. METHODS: 212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S...

  2. Migration of levonorgestrel IUS in a patient with complex medical problems: what should be done?

    Science.gov (United States)

    Soleymani Majd, Hooman; El Hamamy, Essam; Chandrasekar, Ramya; Ismail, Lamiese

    2009-03-01

    Patients with complex medical problems should be counselled about the need for highly effective contraception. As failure resulting in pregnancy, could cause significant morbidity and mortality. The LNG-IUS has gained great popularity and generally has a low side effect profile; however, perforation of the uterus and migration of the device is a potentially serious complication known to be associated with its use. The current accepted management is removal of the device from the abdominal cavity in order to prevent further morbidity. However this is not always a simple matter in patients who have complex medical problems and who are deemed unfit for surgery. Each time the patient comes for renewal of the contraceptive method, clinicians need to reassess the risks and benefits. This is particularly relevant in patients who have complex medical problems where special attention needs to be given, not only to immediate risks but also to long-term ones. Careful individualised counselling and consideration are paramount and perhaps it would have been prudent to discuss vasectomy with this patient and her husband (as the first line of contraception), as this may have avoided the ensuing complications arising from the chosen method.

  3. Levonorgestrel intrauterine contraceptive device in heavy menstrual bleeding: our experience in a tertiary level government hospital

    Directory of Open Access Journals (Sweden)

    Renuka Malik

    2016-02-01

    Conclusions: LNG-IUCD is an effective and acceptable non-surgical alternative to a common problem of HMB. The success rate was 94% in our study with only 3 patients needing hysterectomy due to expulsion. Emphasis on counseling patients of troublesome spotting and correct fundal placement is essential. [Int J Reprod Contracept Obstet Gynecol 2016; 5(2.000: 327-333

  4. PREPARATION AND RELEASE RATE OF A LEVONORGESTREL-RELEASING INTRAUTERINE DEVICE

    Institute of Scientific and Technical Information of China (English)

    LINWu; JINGZhao-Ying; ZHUGeng-Geng

    1989-01-01

    A key-shaped lcvonorgcstrcl-rclcasing intrauterine device ( LNG-IUD ) was designed and fabricated. The IUD with a hollow vcrtlcal arm was made of modified ethylene-vinyl acetate copolymcr ( EVA ). The LNG paste was cncapsulcd in the vertical arm to

  5. Sociodemographic profiles and use-dynamics of Jadelle (levonorgestrel) implants in Jos, Nigeria

    Science.gov (United States)

    Pam, V. C.; Mutihir, J. T.; Nyango, D. D.; Shambe, I.; Egbodo, C. O.; Karshima, J. A.

    2016-01-01

    Background: Contraceptive implants (including Jadelle) are highly effective, safe, and easy to use and have a long duration of action. They do not interfere with intercourse with immediate return to fertility after removal. However, disruption of the menstrual bleeding pattern is almost inevitable and coercive prescription may be a problem because insertion and removal of implants are provider dependent. The objective of this study was to determine the sociodemographic profiles of acceptors of Jadelle and the reasons for discontinuation in Jos, Nigeria. Materials and Methods: This was a 6-year retrospective chart review carried out at the Jos University Teaching Hospital. Results: About 1401 women accepted Jadelle with a mean (±standard deviation) of 33.4 ± 5.9 years. About 88% of the women were Christians and almost three-quarters (73.5%) had at least secondary school education. The means of parity and number of children still alive at the time of accepting Jadelle were 4.1 and 3.8, respectively. Half of the women (49.5%) were breastfeeding and over half (55.9%) had future fertility desires at the time of commencing Jadelle. About 82% had previously used other contraceptives (mostly short-acting methods such as injectables, pills, and condoms), with only 18% starting Jadelle as the first-ever contraceptive method. About 90% of the women had regular menstrual cycles. The major reason for discontinuation of Jadelle was desire for pregnancy although menstrual pattern disruption was the most common reason for removal in the first 6 months of use. Conclusion: The main reason for discontinuation of Jadelle was to have more children although menstrual pattern disruptions accounted for earlier discontinuation. PMID:27942097

  6. Effects of Two Progestins, Norethindrone and Levonorgestrel, On Reproduction in a Marine Fish, Tautogolabrus adspersus.

    Science.gov (United States)

    Endocrine-active pharmaceuticals that enter the aquatic environment through sewage effluent may have unintended impacts on reproduction in fish, which in turn may affect the sustainability of exposed populations. Laboratory experiments were conducted with the marine fish cunner (...

  7. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  8. Ofloxacin-induced hallucinations

    Directory of Open Access Journals (Sweden)

    Urmila Chauhan

    2013-01-01

    Full Text Available Drug-induced hallucinations are not uncommon, and may be misdiagnosed as psychiatric illness leading to unnecessary treatment with antipsychotics. If a temporal association of use of a drug having the potential to cause hallucinations is present, mere withdrawal of the drug causes complete improvement in the symptoms. There are reports of various untoward central nervous system adverse events following administration of fluoroquinolones, including delirium, hallucinations and psychosis, even after a single dose. We describe a 5-year-old girl who suffered visual hallucinations following ofloxacin use.

  9. Cannabis induced asystole.

    Science.gov (United States)

    Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

    2016-01-01

    Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. GEMCITABINE-INDUCED RETINOPATHY.

    Science.gov (United States)

    Kovach, Jaclyn L

    2016-10-31

    To report a case of Purtscher-like retinopathy associated with gemcitabine. The author reports a 68-year-old woman who presented with a 4-month history of bilateral vision loss. She had a history of diabetes, hypertension, and leiomyosarcoma, diagnosed 5 months before presentation and had completed 5 cycles of combination treatment with gemcitabine and docetaxel. Clinical examination revealed a Purtscher-like retinopathy that improved after gemcitabine cessation without the development of cystoid macular edema or retinal neovascularization. This case highlights the importance of recognizing gemcitabine-induced ischemic retinopathy that can be associated with life-threatening myocardial or renal ischemia.

  11. Sulphasalazine Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

  12. Drug-induced gynecomastia.

    Science.gov (United States)

    Eckman, Ari; Dobs, Adrian

    2008-11-01

    Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

  13. Sitagliptin-induced hemolysis

    Directory of Open Access Journals (Sweden)

    Bekur Ragini

    2010-01-01

    Full Text Available Sitagliptin is a newer oral hypoglycemic drug of the dipeptidyl peptidase-IV inhibitor class. It appears to be a promising newer oral hypoglycemic agent. The advantages are the absence of hypoglycemia when used as monotherapy and they cause less gain weight. We report a case of sitagliptin-induced hemolysis, a rare side effect, not reported in the literature. As sitagliptin is widely used in type 2 diabetes mellitus physicians should be aware of the possibility of this rare but potentially serious adverse drug reaction.

  14. Catatonia induced by disulfiram

    Directory of Open Access Journals (Sweden)

    HK Goswami

    2015-07-01

    Full Text Available Catatonia is a clinical syndrome with varieties of psychomotor abnormalities of retardation and excitement. It can occur both in psychiatric and medical conditions. The aetiology of catatonia has not been fully described. Many researchers suggest that catatonia can occur due to deficiency of cortical gamma-aminobutyric acid (GABA which is an inhibitory neurotransmitter. Disulfiram is an agent that is being used in the treatment of alcohol dependence by its aversive effect. It has been seen that disulfiram is one of the causes of catatonia. This paper aimed to report a case of catatonia induced by disulfiram with no past history of any psychiatric or medical illness.

  15. Antioxidant-Induced Stress

    Directory of Open Access Journals (Sweden)

    Robert D. Kross

    2012-02-01

    Full Text Available Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals.

  16. Docetaxel-induced neuropathy

    DEFF Research Database (Denmark)

    Eckhoff, Lise; Feddersen, Søren; Knoop, Ann

    2015-01-01

    Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...

  17. Xerostomia induced by radiotherapy

    Directory of Open Access Journals (Sweden)

    Alimi D

    2015-08-01

    Full Text Available David Alimi Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAWe read with great interest the excellent review on xerostomia induced by radiotherapy, by Pinna et al.1 The authors should be congratulated for a very detailed review of the physiopathology, clinical symptoms, and therapeutic management of an extremely difficult condition. Although we agree that the use of anticholinergic medication represents treatment, it requires the patient to have residual salivary gland function. Unfortunately, it is well established that in most cases radiotherapy destroys most of the salivary gland and associated salivary secretions.     

  18. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  19. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  20. Trauma Induced Coagulopathy

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Johansson, Per; Meyer, Martin Abild Stengaard

    2013-01-01

    It remains debated whether traumatic brain injury (TBI) induces a different coagulopathy compared to non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients were...... sampled (median of 68 min (IQR 48-88) post-injury) upon admission to our trauma centre. Plasma/serum were retrospectively analysed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue...

  1. Man-Induced Vibrations

    DEFF Research Database (Denmark)

    Jönsson, Jeppe; Hansen, Lars Pilegaard

    1994-01-01

    Human motion can cause various types of periodic or transient dynamic loads. The periodic loads are mainly due to jumping, running, dancing, walking and body rocking. Transient loads primarily result from single impulse loads, such as jumping and falling from elevated positions. The response...... concerned with spectator-induced vertical vibrations on grandstands. The idea is to use impulse response analysis and base the load description on the load impulse. If the method is feasable, it could be used in connection with the formulation of requirements in building codes. During the last two decades...

  2. Drug-induced lupus.

    Science.gov (United States)

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  3. Interferon induced thyroiditis.

    Science.gov (United States)

    Tomer, Yaron; Menconi, Francesca

    2009-12-01

    Interferon-alpha (IFNalpha) is used for the treatment of various disorders, most notable chronic hepatitis C virus (HCV) infection. One of the commonest side effects of IFNalpha therapy is thyroiditis, with up to 40% of HCV patients on IFNalpha developing clinical or subclinical disease. In some cases interferon induced thyroiditis (IIT) may result in severe symptomatology necessitating discontinuation of therapy. IIT can manifest as clinical autoimmune thyroiditis, presenting with symptoms of classical Hashimoto's thyroiditis or Graves' disease, or as non-autoimmune thyroiditis. Non-autoimmune thyroiditis can manifest as destructive thyroiditis, with early thyrotoxicosis and later hypothyroidism, or as non-autoimmune hypothyroidism. While the epidemiology and clinical presentation of IIT have been well characterized the mechanisms causing IIT are still poorly understood. It is likely that the hepatitis C virus (HCV) itself plays a role in the disease, as the association between HCV infection and thyroiditis is well established. It is believed that IFNalpha induces thyroiditis by both immune stimulatory effects and by direct effects on the thyroid. Early detection and therapy of this condition are important in order to avoid complications of thyroid disease such as cardiac arrhythmias.

  4. [Induced abortion at home].

    Science.gov (United States)

    Jørgensen, Hilde; Qvigstad, Erik; Jerve, Fridtjof; Melseth, Eldbjørg; Eskild, Anne; Nielsen, Christopher S

    2007-09-20

    Medically induced abortion through week 9 is a well established procedure. The article concerns satisfaction among women who choose to do this at home, and possible associations between satisfaction, socio-demographic--and clinical factors. 110 women with pregnancy duration questionnaires filled in before and 1 and 3 weeks after the abortion. The degree of satisfaction was recorded on a scale from 1 to 10, where 1 was not content and 10 was very content. Follow-up data were available for 105 women. 90 of 105 women were very content (> 7 on the satisfaction scale) with the treatment. Discomfort and pain during the abortion and marital status seemed to influence the results. The degree of pain varied much. No serious complications were observed. The study showed a high degree of satisfaction with medically induced abortion at home early in the pregnancy. The study has a relatively small sample size and no control group, so the results on factors affecting satisfaction are uncertain. Medical abortion at home should be an opportunity for women applying for early pregnancy termination; as long as the women are well informed, are offered sufficient pain relief and a well functioning follow-up programme.

  5. [Gluten induced diseases].

    Science.gov (United States)

    Frič, P; Zavoral, M; Dvořáková, T