Norethindrone antisera: anomalous cross-reactivities with use of 3H-tetrahydro-reduced norethindrone as radioligand

International Nuclear Information System (INIS)

Watanabe, H.; Menzies, J.A.; Jordan, N.; Loo, J.C.

1983-01-01

Anomalous cross-reactions with the dihydro- and tetrahydro-reduced metabolites of norethindrone were observed utilizing antisera raised against norethindrone-3-bovine serum albumin. Whereas displacement of 3H-norethindrone from the antiserum by the metabolites was generally minimal, where one of the metabolites was used as radiotracer, displacement by the metabolites was equal to or greater than that achieved by norethindrone. This unexpected finding was examined for its usefulness in developing a radioimmunoassay system for norethindrone metabolites in plasma. The sensitivity of the resulting standard curve was such as to permit quantitation of pg amounts of the reduced metabolites

Destruction of liver haem by norethindrone. Conversion into green pigments

OpenAIRE

White, Ian N. H.

1981-01-01

1. Factors affecting the norethindrone-mediated conversion of hepatic haem into green pigments have been studied in the rat. Concentrations of haem and green pigments were estimated spectrophotometrically after esterification and separation by silica gel high-pressure liquid chromatography (h.p.l.c.). 2. Accumulation of green pigments in the liver was dependent on the dose of steroid and the time after dosing, maximum values being reached after 4–8h. Phenobarbitone pretreatment of rats result...

Simple and rapid determination of norethindrone in human plasma by supported liquid extraction and ultra performance liquid chromatography with tandem mass spectrometry.

Science.gov (United States)

Gong, Zhilong; Chandler, Kiresha; Webster, Stephen; Kerley, Remy; Buist, Susan; McCort-Tipton, Melanie

2012-03-15

We report for the first time an ultra performance liquid chromatographic method with tandem mass spectrometric detection (UPLC/MS/MS) for the determination of norethindrone alone in human plasma over the concentration range of 50.0-25000 pg mL(-1) using a sample volume of 0.250 mL. Norethindrone and its internal standard (ISTD), norethindrone-(13)C(2), were extracted from human plasma by supported liquid extraction (SLE). After evaporation of the organic solvent, samples were reconstituted and analyzed on an UPLC/MS/MS system. The UPLC system used a Waters BEH C18 (100 mm × 2.1mm, 1.7 μm) column with mobile phase A of 0.05% formic acid in water:acetonitrile (65:35, v/v) and mobile phase B of 0.05% formic acid in methanol:acetonitrile (50:50, v/v). The flow rate was 0.500 mL min(-1). The method was fully validated. The inter-run accuracy and precision at the lower limit of quantitation (LLOQ), low, mid and high quality control (QC) concentration levels were 99.2-108.4% with a <8.1% CV (coefficient of variation), respectively. The validated method has been successfully applied to analysis of thousands of pharmacokinetic samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical analysis of fish bile extracts for monitoring endocrine disrupting chemical exposure in water: Bisphenol A, alkylphenols, and norethindrone.

Science.gov (United States)

Wu, Minghong; Pan, Chenyuan; Yang, Ming; Xu, Bentuo; Lei, Xiangjie; Ma, Jing; Cai, Ling; Chen, Jingsi

2016-01-01

The present study determined concentrations of estrogenic bisphenol A (BPA), nonylphenol, octylphenol (4-tert-octylphenol), butylphenol (4-tert-butylphenol), and progestogenic norethindrone by liquid chromatography-tandem mass spectrometry in bile extracts from field fish from the Xin'an River and market fish in Shanghai, China. Compared with the field fish, endocrine disrupting chemical (EDC) concentrations in market fish bile were at relatively high levels with high detectable rates. The average concentrations of BPA, nonylphenol, 4-tert-octylphenol, 4-tert-butylphenol, and norethindrone in field fish bile were 30.1 µg/L, 203 µg/L, 4.69 µg/L, 7.84 µg/L, and 0.514 µg/L, respectively; in market fish bile they were 240 µg/L, 528 µg/L, 76.5 µg/L, 12.8 µg/L, and 5.26 µg/L, respectively; and in the surface water of Xin'an River they were 38.8 ng/L, 7.91 ng/L, 1.98 ng/L, 2.66 ng/L, and 0.116 ng/L, respectively. The average of total estrogenic activity of river water was 3.32 ng/L estradiol equivalents. High bioconcentration factors (BCFs) were discovered for all 5 EDCs (≧998-fold) in field fish bile. Furthermore, the authors analyzed the BCF value of BPA in fish bile after 30-d exposure to environmentally relevant concentrations of BPA in the laboratory, and the analysis revealed that BCF in fish bile (BCF(Fish bile)) changed in an inverse concentration-dependent manner based on the log10-transformed BPA concentration in water. Strikingly, the data from the field study were well fitted within this trend. The data together suggested that analysis of fish bile extracts could be an efficient method for assessing waterborne EDCs exposure for aquatic biota. © 2015 SETAC.

Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate.

Science.gov (United States)

Rible, Radhika D; Taylor, DeShawn; Wilson, Melissa L; Stanczyk, Frank Z; Mishell, Daniel R

2009-03-01

Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate. Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7. Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mm diameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups. In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC.

Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis.

Science.gov (United States)

Morotti, Matteo; Venturini, Pier Luigi; Biscaldi, Ennio; Racca, Annalisa; Calanni, Luana; Vellone, Valerio Gaetano; Stabilini, Cesare; Ferrero, Simone

2017-06-01

To study the efficacy of long-term treatment with norethindrone acetate (NETA) in patients with rectovaginal endometriosis. This retrospective cohort study included 103 women with pain symptoms caused by rectovaginal endometriosis. Patients received NETA alone (2.5mg/day up to 5mg/day) for 5 years. Primary outcome was the degree of satisfaction with treatment after 5 years of progestin therapy. Secondary outcomes were the assessment of any variation in pain symptoms and the volumetric assessment of the disease by magnetic resonance imaging (MRI). Sixty-one women completed the 5-year follow-up (61/103, 59.2%) with 16 women withdrawing because of adverse effects (38.1%). Overall, 68.8% (42/61) of the women who completed the study were satisfied or very satisfied of this long term NETA treatment. This represents a 40.8% (42/103) of the patients enrolled. Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (pendometriosis under NETA treatment. Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological profile, it represents a good candidate for long-term treatment in this setting. Copyright © 2017 Elsevier B.V. All rights reserved.

The degradation behaviour of nine diverse contaminants in urban surface water and wastewater prior to water treatment.

Science.gov (United States)

Cormier, Guillaume; Barbeau, Benoit; Arp, Hans Peter H; Sauvé, Sébastien

2015-12-01

An increasing diversity of emerging contaminants are entering urban surface water and wastewater, posing unknown risks for the environment. One of the main contemporary challenges in ensuring water quality is to design efficient strategies for minimizing such risks. As a first step in such strategies, it is important to establish the fate and degradation behavior of contaminants prior to any engineered secondary water treatment. Such information is relevant for assessing treatment solutions by simple storage, or to assess the impacts of contaminant spreading in the absence of water treatment, such as during times of flooding or in areas of poor infrastructure. Therefore in this study we examined the degradation behavior of a broad array of water contaminants in actual urban surface water and wastewater, in the presence and absence of naturally occurring bacteria and at two temperatures. The chemicals included caffeine, sulfamethoxazole, carbamazepine, atrazine, 17β-estradiol, ethinylestradiol, diclofenac, desethylatrazine and norethindrone. Little information on the degradation behavior of these pollutants in actual influent wastewater exist, nor in general in water for desethylatrazine (a transformation product of atrazine) and the synthetic hormone norethindrone. Investigations were done in aerobic conditions, in the absence of sunlight. The results suggest that all chemicals except estradiol are stable in urban surface water, and in waste water neither abiotic nor biological degradation in the absence of sunlight contribute significantly to the disappearance of desethylatrazine, atrazine, carbamazepine and diclofenac. Biological degradation in wastewater was effective at transforming norethindrone, 17β-estradiol, ethinylestradiol, caffeine and sulfamethoxazole, with measured degradation rate constants k and half-lives ranging respectively from 0.0082-0.52 d(-1) and 1.3-85 days. The obtained degradation data generally followed a pseudo-first-order-kinetic model

Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

Science.gov (United States)

Jayaraman, Anusha; Pike, Christian J

2014-03-25

Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Degradation of progestagens by oxidation with potassium permanganate in wastewater effluents.

Science.gov (United States)

Fayad, Paul B; Zamyadi, Arash; Broseus, Romain; Prévost, Michèle; Sauvé, Sébastien

2013-01-01

This study investigated the oxidation of selected progestagenic steroid hormones by potassium permanganate at pH 6.0 and 8.0 in ultrapure water and wastewater effluents, using bench-scale assays. Second order rate constants for the reaction of potassium permanganate with progestagens (levonorgestrel, medroxyprogesterone, norethindrone and progesterone) was determined as a function of pH, presence of natural organic matter and temperature. This work also illustrates the advantages of using a novel analytical method, the laser diode thermal desorption (LDTD-APCI) interface coupled to tandem mass spectrometry apparatus, allowing for the quick determination of oxidation rate constants and increasing sample throughput. The second-order rate constants for progestagens with permanganate determined in bench-scale experiments ranged from 23 to 368 M(-1) sec(-1) in both wastewater and ultrapure waters with pH values of 6.0 and 8.0. Two pairs of progestagens exhibited similar reaction rate constants, i.e. progesterone and medroxyprogesterone (23 to 80 M(-1) sec(-1) in ultrapure water and 26 to 149 M(-1) sec(-1) in wastewaters, at pH 6.0 and 8.0) and levonorgestrel and norethindrone (179 to 224 M(-1) sec(-1) in ultrapure water and 180 to 368 M(-1) sec(-1) in wastewaters, at pH 6.0 and 8.0). The presence of dissolved natural organic matter and the pH conditions improved the oxidation rate constants for progestagens with potassium permanganate only at alkaline pH. Reaction rates measured in Milli-Q water could therefore be used to provide conservative estimates for the oxidation rates of the four selected progestagens in wastewaters when exposed to potassium permanganate. The progestagen removal efficiencies was lower for progesterone and medroxyprogesterone (48 to 87 %) than for levonorgestrel and norethindrone (78 to 97%) in Milli-Q and wastewaters at pH 6.0-8.2 using potassium permanganate dosages of 1 to 5 mg L(-1) after contact times of 10 to 60 min. This

VIP and PACAP display different vasodilatory effects in rabbit coronary and cerebral arteries

DEFF Research Database (Denmark)

Dalsgaard, Tórur; Hannibal, Jens; Fahrenkrug, Jan

2003-01-01

on the vasodilatory effects of these two peptides in cerebral and coronary vessels from female New Zealand White (NZW) rabbits.The localization and concentration of VIP and PACAP in cardiovascular tissue was evaluated using immunohistochemistry and radioimmunoassays. The vasodilatory effects of VIP and PACAP were...... investigated using myographs, allowing isometric tension recordings. In order to evaluate the influence of steroid hormones, the rabbits were ovariectomized and randomized to treatment for 4 weeks with 17beta-estradiol (E(2)), Norethindrone Acetate (NETA), E(2)+NETA or placebo. Ring segments of the posterior...

A chewable low-dose oral contraceptive: a new birth control option?

Directory of Open Access Journals (Sweden)

Weisberg E

2012-04-01

Full Text Available Edith Weisberg1,21Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, 2Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, AustraliaAbstract: A new chewable combined oral contraceptive pill containing ethinyl estradiol (EE 0.025 mg and norethindrone (NE 0.8 mg in a 24/4 regimen was approved for marketing in December 2010. Each of the four inactive tablets contains 75 mg ferrous fumarate, which has no therapeutic benefit. The tablet can be taken with food but not water as this affects the absorption of EE. The Pearl index based on intention to treat women aged 18–35 years has been reported at 2.01 (confidence interval [CI] 1.21, 3.14 and for the whole population 1.65 (CI 1.01, 2.55. The effect of a body mass index of >35 was not studied. Regular withdrawal bleeding occurred for 78.6% of women in Cycle 1, but by Cycle 13 almost half the women failed to have a withdrawal bleed. This new formulation provides an intermediate dose of an EE/NE combination that will be useful for women experiencing breakthrough bleeding on the lower-dose EE/NE pill. The convenience of a low-dose pill, which can be chewed without the need for water, will be useful to enable women who have forgotten a pill to take one whenever they remember, provided they carry it with them. The advantage of a 24/4 regimen is better suppression of follicular development in the pill-free interval and may be beneficial for women who experience menstrual cycle-related problems, such as heavy bleeding or dysmenorrhea.Keywords: combined oral contraceptive, low dose, ethinyl estradiol, norethindrone

Effects of Norethindrone and Levonorgestrel on Reproductive Parameters in a Marine Fish

Science.gov (United States)

Progestins and other hormones are continuously added to surface and ground waters through waste water treatment plant (WWTP) effluent in concentrations of low to hundreds of ng/L (Orlando and Ellestad 2014). The exposure effects of pharmaceutical progestins from oral contraceptiv...

Comparison of Norethindrone-Containing OCPs to Desogestrel OCPs and Depro-Provera in Women

Science.gov (United States)

1999-10-01

it is easy to use or because it induces amenorrhea (12,20-26). To date, however, no study has directly compared continuation rates among these... exercise may help control this weight gain, a willingness to exercise may be impeded by DMPA use as preliminary studies suggest that this method results...not induce cyclic bleeding, as with DMPA (33). Irregular bleeding may also occur with use of hormonal contraception. However, the frequency of

Direct effect of gonadal and contraceptive steroids on insulin release from mouse pancreatic islets in organ culture

DEFF Research Database (Denmark)

Nielsen, Jens Høiriis

1984-01-01

Sex steroids are supposed to contribute to the normal glucose homeostasis and to the altered glucose and insulin metabolism in pregnancy and during contraception. In the present study isolated mouse pancreatic islets were maintained in tissue culture medium RPMI 1640 supplemented with 0.5% newborn...... calf serum and 100 ng/ml of one of the following steroids: oestradiol, progesterone, testosterone, megestrol acetate, medroxyprogesterone, chlormadinone acetate, norethynodrel, norethindrone acetate, and ethynyloestradiol. Release of insulin to the culture medium was measured during a 2 week culture...... in the presence of oestradiol, progesterone, or testosterone were subjected to 30 min stimulation with 5.5, 11, 22 mmol/l glucose, only the progesterone-treated islets released more insulin in response to glucose than the control islets. It is concluded that progesterone and its derivatives have a direct effect...

Use of [125I]-iodohistamine-labelled steroid derivatives as radioligands for radioimmunoassay of natural and synthetic steroids

International Nuclear Information System (INIS)

Stanczyk, F.Z.; Goebelsmann, U.

1981-01-01

[ 125 I]-Iodohistamine-labelled steroid derivatives were prepared and utilized as radioligands in radioimmunoassays of progesterone, testosterone, estradiol, estriol, estriol-16α-glucuronide, levonorgestrel, norethindrone and medroxyprogesterone acetate. The binding of these iodinated radioligands was compared to that of the corresponding tritiated steroids and their effect on the sensitivity and slope of standard curves was examined. The results demonstrate that much higher antibody dilutions could be used with iodinated than with tritiated radioligands. In general, standard curves obtained with iodinated radioligands were more sensitive than those obtained with tritiated steroids, but standard curves had steeper slopes when tritiated rather than iodinated radioligands were used. The data, summarizing our 5-year experience with steroid-[ 125 I]-iodohistamine derivatives, indicate that these tracers play an important role in radioimmunoassay systems for both natural and synthetic steroids. (author)

RNA interference mediated pten knock-down inhibit the formation of polycystic ovary.

Science.gov (United States)

Ouyang, Jie-Xiu; Luo, Tao; Sun, Hui-Yun; Huang, Jian; Tang, Dan-Feng; Wu, Lei; Zheng, Yue-Hui; Zheng, Li-Ping

2013-08-01

Pten (phosphatase and tensin homolog deleted on chromosome 10), a kind of tumor suppressor gene, plays important roles in female reproductive system. But its expression and roles in the formation of polycystic ovaries are yet to be known. In this study, we constructed a rat model of PCOS using norethindrone and HCG injections and found the expressions of pten mRNA and PTEN protein increased significantly in the polycystic ovary tissue by immunohistochemistry, RT-PCR, and western blot. Furthermore, the results showed that in vivo ovaries could be effectively transfected by lentiviral vectors through the ovarian microinjection method and indicated that pten shRNA may inhibit the formation of polycystic ovaries by pten down-regulation. Our study provides new information regarding the role of PTEN in female reproductive disorders, such as polycystic ovary syndrome.

Sex hormone studies by radioimmunoassay in pregnant and non-pregnant women and in women treated with hormonal contraceptives

International Nuclear Information System (INIS)

Tafurt, C.A.

1980-12-01

Blood concentration profiles for follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, testosterone, estradiol, estriol, progesterone, cortisol and sex hormonebinding globulin throughout a menstrual cycle were derived from measurements by radioimmunoassay and related procedures on serial blood samples from 16 normal women as controls. Similar studies were then performed on 9 normal women receiving a low-dose oral contraceptive combination of D-norgestrel and ethynlestradiol. Further studies were performed on 9 out of 16 normal women in whom progestational contraception was carried out with orally administered lynestrenol or intramuscularly administered norethindrone enathate and on 12 normal pregnant women from the 28th to the 38th week of pregnancy. Additional studies embracing chorionic gonadotropin progesterone and 17-hydroxyprogesterone were performed on 10 normal pregnant women from the 6th to the 12th week of pregnancy. Detailed results are presented and their significance discussed

Norethindrone acetate and testosterone interactions in mammary gland, uterus and seminal vesicles of mice

Czech Academy of Sciences Publication Activity Database

Škarda, Josef

2002-01-01

Roč. 71, - (2002), s. 463-471 ISSN 0001-7213 R&D Projects: GA ČR GA524/02/0406; GA AV ČR KSK5020115 Keywords : Bioassay * steroid hormones * agonist Subject RIV: ED - Physiology Impact factor: 0.370, year: 2002

Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis.

Science.gov (United States)

Barra, Fabio; Scala, Carolina; Ferrero, Simone

2018-04-01

Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women' pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis. Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis. Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

International Nuclear Information System (INIS)

Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2004-01-01

Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations