- Antiandrogen treatment ameliorates reproductive and metabolic phenotypes in the letrozole-induced mouse model of PCOS. [Journal Article]
- EEndocrinology 2018 Feb 19
- Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unkn...
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unknown, excess androgens are thought to be a critical factor driving the pathology of PCOS. We previously demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET) in mice produces many hallmarks of PCOS, including elevated testosterone (T) and luteinizing hormone (LH), anovulation, and obesity. In the present study, we sought to determine whether androgen receptor (AR) actions are responsible for any of the phenotypes observed in LET mice. C57BL/6 female mice were subcutaneously implanted with LET or placebo control (CON), and subsequently treated with the nonsteroidal AR antagonist flutamide or vehicle control. Flutamide treatment in LET females reversed elevated T levels and restored ovarian expression of Cyp17a1 (critical for androgen synthesis) to normal levels. Pituitary expression of Lhb was decreased in LET females that received flutamide treatment, with no changes in expression of Fshb or Gnrhr. Flutamide treatment also restored estrous cycling and reduced the number of ovarian cyst-like follicles in LET females. Furthermore, body weight and adipocyte size were decreased in flutamide-treated LET females. Altogether, our findings provide strong evidence that AR signaling is responsible for many key reproductive and metabolic PCOS phenotypes, and further establish the LET mouse model as an important tool for the study of androgen excess.
- Adverse effects of doping with anabolic androgenic steroids (AAS) in competitive athletics, recreational sports and bodybuilding. [Journal Article]
- MEMinerva Endocrinol 2018 Feb 19
- Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of at...
Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes und haemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhoea, secondary amenorrhoea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.
- The Diagnostic Value of Anti-Mullerian Hormone in Early Post Menarche Adolescent Girls with Polycystic Ovarian Syndrome. [Journal Article]
- JPJ Pediatr Adolesc Gynecol 2018 Feb 17
- CONCLUSIONS: The use of adult specific diagnostic methods in adolescence may result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed.
- The Root Aqueous Extract ofEntada africanaGuill. et Perr. (Mimosaceae) Inhibits Implant Growth, Alleviates Dysmenorrhea, and Restores Ovarian Dynamic in a Rat Model of Endometriosis. [Journal Article]
- EBEvid Based Complement Alternat Med 2017; 2017:8563909
- Entada africana(Mimosaceae) was reported to have analgesic and antioxidant properties. The present study is aimed at investigating the effects of the root aqueous extract ofEntada...
Entada africana(Mimosaceae) was reported to have analgesic and antioxidant properties. The present study is aimed at investigating the effects of the root aqueous extract ofEntada africana(EA) on an experimental model of endometriosis. The study was performed in rats orally treated with EA at doses of 127.5, 255, and 510 mg/kg. Microgynon® 30 served as the reference substance. Estradiol valerate and oxytocin were used to induce dysmenorrhea. Endometrial implant levels of catalase and malondialdehyde (MDA) allowed estimating tissue oxidative status. Ovarian dynamic and rat sexual behavior were assessed through histological analysis of ovaries, uterus, and vagina. EA decreased dysmenorrhea at tested doses following a 7-day treatment (p< 0.001). Endometrial implant volume decreased following the three treatment periods (p< 0.05). Catalase activity (p< 0.001) and MDA level (p< 0.01) increased only following a 3-day treatment. EA also increased antral follicles, reduced luteinized unruptured follicle number (p< 0.001), and induced animals to be in the estrus phase. In conclusion, EA prevented the progress of endometriosis, reduced dysmenorrhea, promoted ovarian follicle growth, prevented anovulation, and stimulated the special period of rat sexual desire. These results suggest thatEntada africanacould be a promising alternative option for the treatment of endometriosis.
- Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome. [Journal Article]
- OOncotarget 2018 Jan 12; 9(4):4522-4536
- CONCLUSIONS: Our study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls.
- Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway. [Journal Article]
- ETExp Ther Med 2018; 15(2):2120-2127
- Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogen...
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5'adenosine monophosphate-activated protein kinase (AMPK)/phosphoinositide-3 kinase (PI3K)/c-Jun N-terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV-induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy demonstrated great efficacy in ameliorating PCOS through regulating the AMPK/PI3K/JNK pathway.
- Association of testosterone and antimüllerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy. [Journal Article]
- FSFertil Steril 2018 Feb 07
- CONCLUSIONS: Women with higher T and AMH had more frequent anovulatory cycles but with marginal impacts on TTP or pregnancy loss. A continuum of mild inefficiency in reproductive function may be related to higher T and AMH, including in fecund women with normal menstrual cycles and no clinical diagnosis of polycystic ovary syndrome, but with unclear effects on fecundability and pregnancy loss.
- The correlation between serum AMH and HOMA-IR among PCOS phenotypes. [Journal Article]
- BRBMC Res Notes 2018 Feb 09; 11(1):114
- CONCLUSIONS: There was a positive correlation between serum AMH and HOMA IR levels. Serum AMH and HOMA IR levels were significantly different across the four PCOS phenotypes; with the highest values were present with phenotype 1.
- The numbers of 2- 5 and 6-9 mm ovarian follicles are inversely correlated in both normal women and in polycystic ovary syndrome patients: what is the missing link? [Journal Article]
- HRHum Reprod 2018 Feb 07
- Is the negative correlation between the numbers of 2-5 and 6-9 mm follicles influenced by ovarian and/or metabolic parameter(s) in young control women and in patients with polycystic ovarian syndrome...
Is the negative correlation between the numbers of 2-5 and 6-9 mm follicles influenced by ovarian and/or metabolic parameter(s) in young control women and in patients with polycystic ovarian syndrome (PCOS)?
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- Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits. [Review]
- OAOpen Access J Contracept 2017; 8:13-23
- Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of c...
Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal contraceptives (CHCs). CHCs contain estrogen that exerts antiandrogenic properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels. Moreover, the progestogen present in CHCs and in progestogen-only contraceptives suppresses luteinizing hormone secretion. In addition, some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5α reductase enzyme. However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia. This article reports a narrative review of the available evidence of the safety of hormonal contraceptives in women with PCOS. Considerations are made for the possible impact of hormonal contraceptives on endocrine, metabolic, and cardiovascular health.