Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 

The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

https://www.ihs.gov/california/tasks/sites/default/assets/File/BP2014-14_PolycysticOvarySyndrome_Karakas.pdf

Polycystic Ovary Syndrome

Objective: Our objective was to develop clinical practice guidelines for the evaluation and treatment of hirsutism in premenopausal women. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, two methodologists, and a medical writer. The Task Force received no corporate funding or remuneration. Evidence: Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used “recommend” for strong recommendations, and “suggest” for weak recommendations. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the Task Force with the help of a...

https://endosuem.org.uy/wp-content/uploads/2015/05/Hirsutismo.-Endocrine-Society-2008.pdf

Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline

The effect of major epidemiologic risk factors for ovarian cancer has been reviewed in the light of several hormonal hypotheses, including the gonadotropin, androgens, progesterone, estrogens, insulin-like growth factor-I, and insulin hypotheses. The role of inclusion cyst formation and Mullerian epithelium differentiation in the pathology of the disease are also briefly outlined. Although based on limited data, the observed tendency in current evidence suggests possible etiologic roles for elevated androgens and estrogens and decreased progesterone in the pathogenesis of ovarian cancer. A direct effect of gonadotropins cannot be entirely ruled out, but it is plausible that their effect on ovarian cancer risk is mediated by stimulation of ovarian steroidogenesis. Insulin-like growth factor-I also emerges as a hormone that may be directly involved in the pathogenesis of the disease, but thus far only one prospective study has examined this association. Hyperinsulinemia is an unlikely risk factor for ovarian cancer. The observed tendency for an increased risk with androgens from ovarian origin (in premenopausal women), the lack of association with adrenal androgens, and the relatively weak associations observed with obesity, hormonal replacement therapy use, and endogenous hormones after menopause suggest that ovarian synthesis of sex steroids rather than their circulating levels may be etiologically important. More data from prospective studies will be crucial to improve our understanding of the etiologic role of endogenous hormones in the pathogenesis of ovarian cancer. Such data will ultimately provide opportunities for research targeted; at early detection and preventive interventions.

https://cebp.aacrjournals.org/content/cebp/14/1/98.full.pdf

Endogenous Hormones and Ovarian Cancer: Epidemiology and Current Hypotheses

The authors examined the hypothesis that rhesus monkeys with extreme fight frontal electroencephalographic activity would have higher cortisol levels and would be more fearful compared with monkeys with extreme left frontal activity. The authors first showed that individual differences in asymmetric frontal electrical activity are a stable characteristic. Next, the authors demonstrated that relative fight asymmetric frontal activity and cortisol levels are correlated in animals 1 year of age. Additionally, extreme fight frontal animals had elevated cortisol concentrations and more intense defensive responses. At 3 years of age, extreme fight frontal animals continued to have elevated cortisol concentrations. These findings demonstrate important relations among extreme asymmetric frontal electrical activity, cortisol levels, and trait-like fear-related behaviors in young rhesus monkeys. Considerable evidence demonstrates that individual differences in temperament are associated with differences in brain and peripheral physiological functioning (e.g., Davidson & Tomarken, 1989; Kagan, Reznick, & Snidman, 1988). Thus, temperament can no longer be viewed simply as a stable trait-like behavioral and emotional style but should be considered as a constellation of stable behavioral, emotional, and physiological characteristics. How these different characteristics interact and the mechanisms underlying the formation of individual differences in temperament are important questions that remain to be answered. To begin to unravel these issues, we have used rhesus monkeys to more completely characterize the physiological concomitants of behavioral responses associated with fearful temperaments. Eventually, this information will guide studies aimed at elucidating the mechanisms underlying the development of individual differences in fear-related temperaments.

Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys.

Effect of four different oral contraceptives on various sex hormones and serum-binding globulins

Changes in Androgens During Treatment with Four Low-Dose Contraceptives

Changes in endogenous androgen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives (OCs). One hundred women were randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4) 30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded, and plasma levels of the following variables were recorded: sex-hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and hydroxyprogesterone. The free androgen index was also calculated. These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles. There were no statistically significant differences in androgenic variables among the four OCs. The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations (20% vs. 45%). Concentrations of SHBG and CBG increased significantly in all four groups (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations (about 100%). The four modern, low-dose OCs tested had similar impacts on endogenous androgen metabolism, yielding significant decreases in testosterone, dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be beneficial in women with androgen-related syndromes such as acne and hirsutism. Large studies are under way to establish which of the third-generation OCs is the least androgenic. In vitro studies suggest that norgestimate has the least androgenic profile.

R. Rolland

Papers

Changes in Androgens During Treatment with Four Low-Dose Contraceptives

Comparative evaluation of the androgenicity of four low-dose, fixed-combination oral contraceptives