Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

Science.gov (United States)

Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

2017-07-15

OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

Tamoxifen for one year versus two years versus 6 months of Tamoxifen and 6 months of megestrol acetate: A randomized comparison in postmenopausal patients with high-risk breast cancer (DBCG 89C)

DEFF Research Database (Denmark)

Andersen, Jørn; Kamby, C.; Ejlertsen, B.

2008-01-01

From January 1, 1990 to December 31, 1994, DBCG conducted a randomised trial in 1 615 postmenopausal women with operable, high-risk, receptor-positive or -unknown breast cancer. The patients were after surgery randomised to Tamoxifen for 1 year (TAM1), Tamoxifen for 2 years (TAM 2) or Tamoxifen...... for 6 months followed by megestrol acetate for 6 months (TAM/MA). When the preplanned sample size of 1 500 patients was reached it was decided to continue randomisation to TAM1 or TAM2 and the study was finally closed December 31, 1996. With a median follow-up of more than 10 years...... in hazard ratios for DFS or OS among the three arms. Sideeffects were rare but more common in the TAM2 and TAM/MA arms Udgivelsesdato: 2008...

Supportive use of megestrol acetate (Megace) with head/neck and lung cancer patients receiving radiation therapy

International Nuclear Information System (INIS)

McQuellon, Richard P.; Moose, Dawn B.; Russell, Gregory B.; Case, L. Douglas; Greven, Katherine; Stevens, Michael; Shaw, Edward G.

2002-01-01

Purpose: The purpose of this study was to measure the effect of megestrol acetate (MA) on weight loss and quality of life (QOL) in patients with cancer of the lung or head and neck undergoing curative radiation therapy. Methods and Materials: This was a Phase III, placebo-controlled, double-blind randomized study. Patients received either 800 mg/day of MA (20 milliliters po qAM) or placebo over a 12-week period. Patients received radiation of the head and neck or thorax using a dose of at least 50 Gy, either alone or with chemotherapy. Weight was assessed weekly, whereas QOL was assessed at baseline and at 4, 8, and 12 weeks. Results: Patient characteristics on the MA arm (16 lung, 12 head/neck; mean age: 60 years) were similar to those on the placebo arm (17 lung, 11 head/neck; mean age: 65.8 years). Patients in the MA group had a mean weight loss over 12 weeks of 2.7 pounds, whereas the placebo group had a mean weight loss of 10.6 pounds. There was a significant time by treatment interaction (p=0.001), with the difference in weight between treatment groups being most pronounced after 6 weeks. Although overall QOL was similar in both arms of the study, several QOL subscale items did differ significantly. Compared to the placebo-treated patients, head-and-neck cancer patients in the MA arm reported the ability to eat as much as they liked (p=0.02 at 12 weeks), and lung cancer patients in the MA arm reported significantly better appetite at 4 weeks (p=0.03) and 8 weeks (p=0.001). Conclusion: MA used prophylactically is useful as an appetite stimulant; it can help patients maintain weight over the course of curative radiotherapy of the head and neck or lung and can improve specific aspects of QOL

A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy.

Science.gov (United States)

Cuvelier, Geoff D E; Baker, Tina J; Peddie, Elaine F; Casey, Linda M; Lambert, Pascal J; Distefano, Dianne S; Wardle, Marlene G; Mychajlunow, Beth A; Romanick, Marcel A; Dix, David B; Wilson, Beverly A

2014-04-01

Megestrol acetate (MA) is an appetite stimulant with efficacy in promoting weight gain in adults with cancer-associated anorexia-cachexia. Studies documenting MA efficacy in children, however, are limited. We present the first randomized, double-blind, placebo-controlled clinical trial of MA versus placebo in children with cancer and weight loss. Subjects nutrition, and toxicities. Twenty-six patients were randomly assigned (13 MA, 13 placebo). The MA group experienced a mean weight gain of +19.7% compared to a mean weight loss of -1.2% in the placebo group, for a difference of +20.9% (95%CI: +11.3% to +30.5%, P = 0.003) in favor of MA over placebo. MA subjects experienced significant increases in weight for age z-scores, body mass index z-scores, and mid upper arm circumference compared to placebo. DXA scanning suggested disproportionate increases in fat accrual. Adrenal suppression was the main toxicity of MA. In children with high-risk malignancies, MA resulted in significant increases in mean percent weight change compared to placebo. Further studies of MA should be pursued to better delineate the effect on nutritional status. © 2013 Wiley Periodicals, Inc.

Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.

Science.gov (United States)

Bines, J; Dienstmann, R; Obadia, R M; Branco, L G P; Quintella, D C; Castro, T M; Camacho, P G; Soares, F A; Costa, M E F

2014-04-01

As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR). Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. local trial number, related to the approval by the IRB: CEP 108/06.

Tratamento Clínico e Seguimento das Hiperplasias de Endométrio Clinical Treatment and Follow-up of Endometrial Hyperplasia

Directory of Open Access Journals (Sweden)

Anaglória Pontes

2000-01-01

Full Text Available Objetivos: avaliar a eficácia do acetato de medroxiprogesterona e do acetato de megestrol nas hiperplasias de endométrio. Métodos: foram incluídas, retrospectivamente 47 pacientes com sangramento uterino anormal, submetidas a curetagem uterina diagnóstica e/ou biópsia de endométrio, cujo achado histopatológico foi de hiperplasia de endométrio. Nas pacientes com hiperplasia sem atipia foi iniciado a terapêutica com acetato de medroxiprogesterona por via oral, na dose de 10 mg/dia durante 10-12 dias por mês. Nas com atipia, era utilizado o acetato de megestrol por via oral, dose de 160 mg/dia, uso contínuo. O período de tratamento variou de 3 a 18 meses. Biópsia de endométrio e/ou curetagem uterina de controle foram realizadas entre três e seis meses do início do tratamento e periodicamente para avaliar a resposta terapêutica. Resultados: foram analisadas 42 pacientes com hiperplasia endometrial sem atipia e cinco com atipia. A média de idade das pacientes foi de 49,5 ± 10,6 anos, sendo 70,2% com idade superior a 45 anos. O acetato de medroxiprogesterona foi eficaz em fazer regredir as hiperplasias sem atipias em 83,2% (35/42 e o acetato de megestrol em 80% (4/5 das hiperplasias com atipia. Em 16,8% (7 casos das hiperplasias sem atipia e em 20% (1 caso das com atipia, ocorreu persistência das lesões, apesar do tratamento. Em nenhum caso ocorreu progressão para câncer de endométrio, durante o período de seguimento que foi de 3 meses a 9 anos. No acompanhamento dessas pacientes, verificamos que 18 (38,3% apresentaram amenorréia, em 12 (25,5% ocorreu regularização do ciclo menstrual e 17 (36,2% permaneceram com sangramento uterino anormal, sendo submetidas a histerectomia total abdominal. O exame anatomopatológico mostrou a persistência da lesão hiperplásica em oito casos, leiomioma em quatro, adenomiose em três, mio-hipertrofia uterina difusa em um caso e útero normal em outro, tendo havido regressão das les

21 CFR 520.1341 - Megestrol acetate tablets.

Science.gov (United States)

2010-04-01

... dogs in proestrus accept a male. (7) Do not use prior to or during first estrus cycle. (8) Do not use in pregnant animals. (9) Do not use in the presence of a disease of the reproductive system or with...

Effects of Nutritional Support in Patients with Colorectal Cancer during Chemotherapy

OpenAIRE

Dobrila Dintinjana, Renata; Guina, Tina; Krznarić, Željko; Radić, Mladen; Dintinjana, Marijan

2008-01-01

Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients. In our study we tried to assess the influence of nutritional support (counseling, oral liquids, megestrol acetate) on nutritional status and symptoms prevalence in patients ...

Progestogens and Cushing's syndrome.

LENUS (Irish Health Repository)

Harte, C

2012-02-03

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing\\'s syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg\\/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg\\/day but Cushing\\'s syndrome has been reported in patients taking 400 mg\\/day. Neither the glucocorticoid-like effects or Cushing\\'s syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing\\'s syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing\\'s syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.

Stress Hormones and their Regulation in a Captive Dolphin Population

Science.gov (United States)

2015-09-30

out-of- water stress protocol. The observed response to the stress protocol was similar to that of ACTH administrations (see Parent Project for...CD, Booth R, Wasser S, Cotte L, Jensen E, Crocker D, Houser D (2013). The progestin megestrol acetate suppresses the HPA axis in bottlenose dolphin...Kellar, N.M., Cockrem, J., Romano, T., Booth, R.K. and Wasser , S.K. (2015) Natural variation in stress hormones, comparisons across matrices, and

Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting1234

Science.gov (United States)

Gullett, Norleena P; Hebbar, Gautam

2010-01-01

This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting. PMID:20164318

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...

Estimation of Cachexia among Cancer Patients Based on Four Definitions

Directory of Open Access Journals (Sweden)

Kathleen M. Fox

2009-01-01

Full Text Available Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1 ICD-9 diagnostic code of 799.4 (cachexia, (2 ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3 prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4 ≥5% weight loss. Patients with cancer of the stomach, pancreas, lung, colon/rectum, head/neck, esophagus, prostate, breast, or liver diagnosed between 1999 and 2004 were followed for cachexia. Results. Of 8541 cancer patients (60% men and 55% Caucasian, cachexia was observed in 2.4% of patients using the cachexia diagnostic code, 5.5% expanded diagnoses, 6.4% prescription medication definition, and 14.7% with ≥5% weight loss. Conclusions. The proportion of patients with cachexia varied considerably depending upon the definition employed, indicating that a standard operational definition is needed.

Dual drug encapsulated thermo-sensitive fibrinogen-graft-poly (N-isopropyl acrylamide) nanogels for breast cancer therapy.

Science.gov (United States)

Rejinold, N Sanoj; Baby, Thejus; Chennazhi, K P; Jayakumar, R

2014-02-01

5-FU/Megestrol acetate loaded fibrinogen-graft-PNIPAAm Nanogels (5-FU/Meg-fib-graft-PNIPAAm NGs) were prepared for thermo responsive drug delivery toward α5β1-integrins expressing breast cancer cells in vitro (MCF-7 cells). The 60-100 nm sized fib-graft-PNIPAAm nanogels (LCST=35 °C) were prepared by CaCl2 cross-linker. 5-FU/Meg-fib-graft-PNIPAAm NGs showed particle size of 165-195 nm size. The drug loading efficiency with 5-FU was 60% and 70% for Meg. "Drug release was greater above the lower critical solution temperature (LCST). Above LCST, drug release system triggers apopotosis and enhance toxicity to MCF-7 cells when compared to the equivalent dose of the free drug. This effect was due to the greater uptake of the drug by MCF-7 cells". 5-FU/Meg-fib-graft-PNIPAAm NGs is portrayed here as a new combinatorial thermo-responsive drug delivery agent for breast cancer therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

76 FR 11488 - Determination That MEGACE (Megestrol Acetate) Tablets and Nine Other Drug Products Were Not...

Science.gov (United States)

2011-03-02

... products that have been discontinued from marketing for reasons other than safety or effectiveness... for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice... document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

Pathophysiology of anorexia in the cancer cachexia syndrome.

Science.gov (United States)

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-12-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Simultaneous Determination of Hormonal Residues in Treated Waters Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry

Directory of Open Access Journals (Sweden)

Rayco Guedes-Alonso

2013-01-01

Full Text Available In the last years, hormone consumption has increased exponentially. Because of that, hormone compounds are considered emerging pollutants since several studies have determinted their presence in water influents and effluents of wastewater treatment plants (WWTPs. In this study, a quantitative method for the simultaneous determination of oestrogens (estrone, 17β-estradiol, estriol, 17α-ethinylestradiol, and diethylstilbestrol, androgens (testosterone, and progestogens (norgestrel and megestrol acetate has been developed to determine these compounds in wastewater samples. Due to the very low concentrations of target compounds in the environment, a solid phase extraction procedure has been optimized and developed to extract and preconcentrate the analytes. Determination and quantification were performed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS. The method developed presents satisfactory limits of detection (between 0.15 and 9.35 ng·L−1, good recoveries (between 73 and 90% for the most of compounds, and low relative standard deviations (under 8.4%. Samples from influents and effluents of two wastewater treatment plants of Gran Canaria (Spain were analyzed using the proposed method, finding several hormones with concentrations ranged from 5 to 300 ng·L−1.

Pathophysiology of anorexia in the cancer cachexia syndrome

Science.gov (United States)

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-01-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID:26675762

Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

Science.gov (United States)

Dobrila-Dintinjana, Renata; Trivanovic, Dragan; Zelić, Marko; Radić, Mladen; Dintinjana, Marijan; Petranović, Duška; Toni, Valković; Vukelic, Jelena; Matijasic, Nusa

2013-05-01

Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

Nutritional Interventions for Cancer-induced Cachexia

Science.gov (United States)

Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R.

2011-01-01

Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate. PMID:21420558

Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS.

Science.gov (United States)

Badowski, Melissa E; Perez, Sarah E

2016-01-01

Since the beginning of the HIV/AIDS epidemic, weight loss has been a common complaint for patients. The use of various definitions defining HIV wasting syndrome has made it difficult to determine its actual prevalence. Despite the use of highly active antiretroviral therapy, it is estimated that the prevalence of HIV wasting syndrome is between 14% and 38%. HIV wasting syndrome may stem from conditions affecting chewing, swallowing, or gastrointestinal motility, neurologic disease affecting food intake or the perception of hunger or ability to eat, psychiatric illness, food insecurity generated from psychosocial or economic concerns, or anorexia due to medications, malabsorption, infections, or tumors. Treatment of HIV wasting syndrome may be managed with appetite stimulants (megestrol acetate or dronabinol), anabolic agents (testosterone, testosterone analogs, or recombinant human growth hormone), or, rarely, cytokine production modulators (thalidomide). The goal of this review is to provide an in-depth evaluation based on existing clinical trials on the clinical utility of dronabinol in the treatment of weight loss associated with HIV/AIDS. Although total body weight gain varies with dronabinol use (-2.0 to 3.2 kg), dronabinol is a well-tolerated option to promote appetite stimulation. Further studies are needed with standardized definitions of HIV-associated weight loss and clinical outcomes, robust sample sizes, safety and efficacy data on chronic use of dronabinol beyond 52 weeks, and associated virologic and immunologic outcomes.

The influence of exogenous progestin on the occurrence of proestrous or estrous signs, plasma concentrations of luteinizing hormone and estradiol in deslorelin (GnRH agonist) treated anestrous bitches.

Science.gov (United States)

Sung, M; Armour, A F; Wright, P J

2006-10-01

The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02). (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.

Cancer cachexia, mechanism and treatment

Science.gov (United States)

Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Matsubara, Hisahiro; Takabe, Kazuaki

2015-01-01

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials. PMID:25897346

Cancer Cachexia: Beyond Weight Loss.

Science.gov (United States)

Bruggeman, Andrew R; Kamal, Arif H; LeBlanc, Thomas W; Ma, Joseph D; Baracos, Vickie E; Roeland, Eric J

2016-11-01

Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.

Management of Dysgeusia related to Cancer

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DURGESHWORI MUNANKARMI

2017-05-01

Full Text Available Introduction: Taste change due to cancer is a notorious side effect, adversely affecting appetite and weight. Even though taste change or dysgeusia is one of the major causes of poor nutritional status in cancer survivors, it is not addressed as a significant problem and is often left untreated. The main purpose of this review is to explore current knowledge of pharmacological and behavioral interventions for the treatment of cancer related taste change. Methods: This systematic review was conducted in accordance with PRISMA guidelines to identify original articles on taste change. Multiple databases including; Scopus, Medline, EMBASE, CINAHL, and all databases via Pro quest were searched for original articles or studies related to taste change caused by cancer or its treatment. Relevant articles were subjected to a full text evaluation and assessed by Critical appraisal skills program (CASP guidelines and the Effective public health practice project (EPHPP instrument. Results: The search revealed 12 eligible studies, six of which were randomized controlled trials. Most of the studies used a standardized validated tool to measure taste change. Dysgeusia is common in cancer, 14 to 100% cancer patient report it. Pharmacological management with zinc remains inconclusive as one study reports it as beneficial and two other studies reported null effect. Few studies suggested dietary modifications such as use of sugary, salty foods that are helpful to reduce the effect of dysgeusia. Conclusion: Dietary counseling and informing the patient well about self-care strategies before treatment has consistently shown positive results on taste change, with strong statistical power. Other potential treatments for dysgeusia such as zinc, amifostine, and megestrol acetate gave inconsistent results.

Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

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Robertson John FR

2011-09-01

Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

Successful treatment for subinvolution of placental sites in the bitch with low oral doses of progestagen.

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Voorhorst, M J; van Brederode, J C; Albers-Wolthers, C H J; de Gier, J; Schaefers-Okkens, A C

2013-10-01

Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro-oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility. © 2013 Blackwell Verlag GmbH.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

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Akturk, Halis Kaan; Chindris, Ana Maria; Hines, Jolaine M; Singh, Ravinder J; Bernet, Victor J

2018-03-01

To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS

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Badowski ME

2016-02-01

Full Text Available Melissa E Badowski,1 Sarah E Perez2 1Department of Pharmacy Practice, Section of Infectious Diseases Pharmacotherapy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Infectious Diseases Clinic, Tufts Medical Center, Boston, MA, USA Abstract: Since the beginning of the HIV/AIDS epidemic, weight loss has been a common complaint for patients. The use of various definitions defining HIV wasting syndrome has made it difficult to determine its actual prevalence. Despite the use of highly active antiretroviral therapy, it is estimated that the prevalence of HIV wasting syndrome is between 14% and 38%. HIV wasting syndrome may stem from conditions affecting chewing, swallowing, or gastrointestinal motility, neurologic disease affecting food intake or the perception of hunger or ability to eat, psychiatric illness, food insecurity generated from psychosocial or economic concerns, or anorexia due to medications, malabsorption, infections, or tumors. Treatment of HIV wasting syndrome may be managed with appetite stimulants (megestrol acetate or dronabinol, anabolic agents (testosterone, testosterone analogs, or recombinant human growth hormone, or, rarely, cytokine production modulators (thalidomide. The goal of this review is to provide an in-depth evaluation based on existing clinical trials on the clinical utility of dronabinol in the treatment of weight loss associated with HIV/AIDS. Although total body weight gain varies with dronabinol use (–2.0 to 3.2 kg, dronabinol is a well-tolerated option to promote appetite stimulation. Further studies are needed with standardized definitions of HIV-associated weight loss and clinical outcomes, robust sample sizes, safety and efficacy data on chronic use of dronabinol beyond 52 weeks, and associated virologic and immunologic outcomes. Keywords: dronabinol, weight loss, HIV/AIDS, HIV wasting syndrome, cachexia

Fatigue in cancer: A review of literature

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Vijayakumar Narayanan

2009-01-01

Full Text Available Fatigue is a common symptom of advanced cancer limiting one′s activity and affecting the quality of life. It is a multidimensional symptom complex with subjective and objective components. Hence, its definition and assessment seems arbitrary, incomplete, and elusive. Components of fatigue often merge with other ′disease states′ as anemia, depression and so on, compounding difficulty to assess it separately. Fatigue has a high prevalence rate, and lasts longer in chronic diseases like cancer. Its association with treatment modalities like chemotherapy, radiotherapy alongside the primary disease process makes it seemingly ubiquitous in many cases. Systemic manifestation of cancer causes excess demand on body resources on cell repair, uncontrolled growth with metabolite accumulation causing fatigue. Co-morbid conditions of organic and psychological nature causes fatigue. There are many assessment tools for fatigue with different uses and objectives, simple and reproducible tools like Brief Fatigue Inventory, Edmonton Symptom assessment scale seem feasible in everyday practice. Management of fatigue is not straightforward and rewarding. Although treatment of cause appears to be an attractive option, it is not possible in all cases. Therapeutic agents targeting cytokine load is in early stages of study and available results are not favorable. Specific measures aimed at pain relief, prevention/treatment of sepsis, management of depression, avoidance of drugs causing fatigue, restoring the metabolic profile are important. Methyl phenidate, megestrol, and modafinil are some drugs with promising effect to treat fatigue, though confirmatory studies are yet to be established. Non-pharmacological methods are also helpful. Forewarning patients on upcoming fatigue, active regular exercise, and stress management are some of them. Fatigue being a multidimensional entity, single mode of therapy is insufficient. Combined modality tailored to individual

Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

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Preciosa M Coloma

Full Text Available Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings.To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network.Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects': azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate.Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out.A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical

Two synthetic progestins and natural progesterone are responsible for most of the progestagenic activities in municipal wastewater treatment plant effluents in the Czech and Slovak republics.

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Šauer, Pavel; Stará, Alžběta; Golovko, Oksana; Valentová, Olga; Bořík, Adam; Grabic, Roman; Kroupová, Hana Kocour

2018-06-15

progesterone, which contributed 65-96% of such activity in samples where no antagonistic activity was found. The progestins medroxyprogesterone acetate, megestrol acetate and progesterone contributed most to the progestagenic activity detected in municipal effluents. Anti-progestagenic activities were found in some municipal effluents, but no causative agents were revealed because two analysed selective progesterone receptor modulators (SPRMs) with anti-progestagenic activities, mifepristone and ulipristal acetate, were not present in the effluents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy

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Erkurt, E.; Tunali, C. [Cukurova University Medical Faculty, Dept. of Radiation Oncology, Balcali-Adana (Turkey); Erkisi, M. [Cukurova University Medical Faculty, Dept. of Medical Oncology (Turkey)

2000-12-01

The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated further during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in the weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT plus or minus chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. >From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by the researchers. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+ 3 to + 5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status (p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). It was observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects

Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy

International Nuclear Information System (INIS)

Erkurt, E.; Tunali, C.; Erkisi, M.

2000-01-01

The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated further during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in the weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT plus or minus chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by the researchers. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+ 3 to + 5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). It was observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects, and

Simple and complex hyperplastic papillary proliferations of the endometrium: a clinicopathologic study of nine cases of apparently localized papillary lesions with fibrovascular stromal cores and epithelial metaplasia.

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Lehman, M B; Hart, W R

2001-11-01

The clinicopathologic features of nine cases of papillary proliferation of the endometrium devoid of malignant nuclear features were studied. The patients ranged in age from 33 to 71 years (median 57 years). All were postmenopausal, except the youngest. The most common symptom was postmenopausal bleeding. Two patients were receiving hormonal replacement therapy and two were taking megestrol acetate. Two lesions were incidental findings in a hysterectomy specimen. Seven were diagnosed in endometrial biopsy or curettage specimens. In six cases (67%) the lesion involved an endometrial polyp. In all cases the papillae had fibrovascular stromal cores and variable degrees of branching. Two architectural patterns were found. A simple papillary pattern with involvement of only a few glands and little epithelial proliferation occurred in five cases, including three that were entirely intracystic. A complex papillary pattern with more extensive involvement of endometrial glands, a greater degree of branching of the papillae, and cellular tufting occurred in four cases. One or more metaplastic epithelial changes occurred in all cases, including endocervical-type mucinous metaplasia in nine cases (90%), eosinophilic cell change in eight (89%), ciliated cell change in seven (70%), focal squamous metaplasia in two cases (22%), and hobnail cell change in two (22%). Mitotic figures were found in three cases. In four lesions (44%), all with a complex papillary pattern, the proliferating cells had mild nuclear atypia. Three of these patients underwent hysterectomy within 5 months. Simple nonpapillary hyperplasia and two endometrial polyps were found in one patient, complex nonpapillary hyperplasia in one, and atrophic endometrium in the other. Two patients had additional endometrial samplings within 4 months that contained small residual simple papillary lesions. One of these had another biopsy at 16 months that showed only atrophy. One patient had no subsequent diagnostic or

Progestin-only pills for contraception.

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Grimes, David A; Lopez, Laureen M; O'Brien, Paul A; Raymond, Elizabeth G

2013-11-13

levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial. Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.