Endocrine Abstracts

Polycystic Ovary Syndrome (PCOS), the most common endocrinopathy of reproductive-age women, was initially defined by the association of anovulation and clinical and/or biochemical hyperandrogenism (1990 NIH). Since Rotterdam Consensus Conference in 2003, its diagnosis requires the presence of at least two of the following features: oligo-/anovulation, hyperandrogenism and polycystic ovaries on ultrasound. However, since its introduction, this definition was strongly challenged by Androgen Excess Society, as they supported a central role of hyperandrogenism in PCOS pathogenesis, thus considering it as an essential diagnostic criterion. Indeed, theca cells of PCOS women appear to have the intrinsic property of synthesizing excessive amounts of androgens because of a possibly genetically determined hyperexpression and/or hyperactivity of steroidogenesis enzymes, notably cytochrome P450c17α, the limiting step in androgens biosynthesis in the ovary and adrenal gland. Hyperandrogenism may in turn promote adipose tissue accumulation at abdominal level, typically accompanied by insulin resistance. Compensatory increased insulin levels at the ovary can further stimulate androgens synthesis, thus creating a vicious circle. The aim of the study was to characterise androgen steroids profile in follicular fluid (FF) of PCOS women. Three groups were evaluated (n=20, each), PCOS patients diagnosed according to Rotterdam criteria, women requiring a Medically Assisted Reproduction procedure for another infertility cause (control group) and women presenting ≥12 follicles/ovary on ultrasound without other PCOS characteristic features (ECHO group). Each group of patients equally included normal weight (BMI 18-25 kg/m²) and obese (BMI>30 kg/m²) women. Androgen steroids were measured in FF by mass spectrophotometry. Follicular concentrations of testosterone, dehydroepiandrosterone (DHEA) and delta4-androstenedione were significantly higher in PCOS women (P<0.01 compared to controls). A significant difference between PCOS and ECHO groups was found for 17-OH pregnenolone (P<0.05), DHEA and delta4-androstenedione (P<0.01). Concerning adrenal androgens, PCOS patients presented lower 11-deoxycorticosterone (DOC) levels compared to controls (P<0.01). No difference was found respecting corticosterone, cortisol, 11-OH cortisol and 17-OH progesterone. Interestingly, follicular levels of testosterone, DHEA and delta4-androstenedione were positively correlated with cycle duration (P<0.05), while a negative correlation was observed between DOC concentration and plasmatic Anti-Müllerian Hormone levels (P=0.02) as well as ovarian follicles number (P=0.03). Follicular concentrations of androgen steroids seem to be increased in PCOS women independently of the presence of a systemic hyperandrogenism. Notably, we found a selective increase in ovarian androgens, further suggesting that PCOS pathogenesis is strongly linked with an initial alteration of theca cells leading to an excessive androgens biosynthesis.