Background: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. The association with obesity and insulin resistance is well established. Steroid hormones play a central role in the regulation of both ovarian function and body composition. This study aims to assess the influence of known functional polymorphisms in genes that are responsible for the production, metabolism and signal transduction of steroid hormones on the susceptibility to and phenotype of PCOS.
Methods: We included 518 Caucasian women with anovulatory PCOS (2003 Rotterdam criteria) and 2996 population-based controls. Functional polymorphic variants were selected in genes that affect the production of estradiol and cortisol [aromatase (CYP19), 11-beta-hydroxysteroid dehydrogenase type I (HSD11B1) and hexose-6-phosphate dehydogenase (H6PD)] and in genes for signal transduction proteins [estrogen receptor (ESR1 and ESR2) and glucocorticoid receptor (GCR)].
Results: Genotype-frequencies were similar in PCOS cases and population-based controls. We observed possible associations between GCR genotype and LH levels that suggest an inhibitory influence of GCR, i.e., lower LH levels in association with GCR alleles that are known to increase receptor sensitivity (rs6195 and rs41423247) and higher LH levels in GCR variants that may inhibit receptor sensitivity (rs6190 and rs6198).
Conclusions: The present study did not identify risk alleles for PCOS, although the study was limited by an absence of endocrine data for the population-based controls. However, GCR variants may influence gonadotrophin levels in women with anovulatory PCOS. We hypothesize that glucocorticoids can affect the function of the hypothalomo-pituitary-gonadal axis in humans.