Endometrial Expression of Estrogen Receptors and the Androgen Receptor in Women With Polycystic Ovary Syndrome: A Lifestyle Intervention Study

Context: Polycystic ovary syndrome (PCOS) is a common cause of anovulation. It may also negatively affect the endometrium, which could lead to implantation failure and proliferative aberrations. Objective: Our objective was to study sex hormone receptors in the endometrium of women with PCOS. Design: This is a cross-sectional study and lifestyle intervention. Setting: Clinical and laboratory research unit was undertaken at a university hospital. Participants: Twenty overweight/obese women fulfilling all three PCOS criteria (anovulation, hyperandrogenism, and polycystic ovaries), 10 body mass index-matched regularly menstruating controls, 11 normal-weight women with PCOS, and 11 normal-weight controls. Intervention: Intervention for this study included dietary management and physical exercise. Main Outcome Measures: mRNA levels and immunostaining of estrogen receptor alpha (ER alpha) and beta (ER beta), nongenomic estrogen receptor alpha 36 (ER alpha 36), and G-protein-coupled estrogen receptor-1 (GPER), and the androgen receptor (AR) on cycle days 6-8 and cycle days 21-23. Results: Before intervention, mRNA levels of ER alpha, ER alpha 36, and the ER alpha/ER beta mRNA ratio were lower in proliferative endometrium of overweight/obese PCOS women compared with controls (P < .05). After intervention, ER alpha protein and the ER alpha/ER beta protein ratio in proliferative endometrium increased and were higher in PCOS women with improved menstrual function than in those without improvement (P < .05). In the subgroup of PCOS women with restored ovulation, only higher protein levels of GPER were found in secretory endometrium (P < .01). However, PCOS women who remained anovulatory had higher protein levels of ER alpha, GPER, and AR on cycle days 21-23 than controls (P < .05). Conclusions: Lifestyle intervention alters, but does not fully restore, ER and AR expression in proliferative and secretory endometrium of obese women with PCOS.