Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome

Objective: To determine the degree to which E-2 hyperresponsiveness to FSH and antimullerian hormone (AMH) overproduction in normal-weight women with polycystic ovary syndrome (PCOS) correlate with increased antral follicle number (AFN), hyperandrogenism, and/or metabolic dysfunction. Design: Prospective cohort study. Setting: Academic medical center. Patient(s): Seven normal-weight women with PCOS (1990 National Institutes of Health criteria) ages 20-34 years and 13 age-and body mass index-(BMI-; 18.5-25 kg/m(2)) matched normoandrogenic ovulatory women were studied. Intervention(s): All women underwent basal serum hormone and metabolic measurements, FSH stimulation testing with transvaginal ovarian sonography, frequently sampled IV glucose tolerance testing, and whole-body dual-energy x-ray absorptiometry. Main Outcome Measure(s): Serum hormone/metabolite levels, 24-hour serum E-2 response to 150 IU recombinant human (rh) FSH infusion, AFN, insulin sensitivity, and body mass measurements. Result(s): Serum E-2 responsiveness to rhFSH and AMH levels were greater in women with PCOS than in BMI-and age-matched control women, as were serum androgen levels, AFN, and abdominal fat mass. In all women combined, serum E-2 responsiveness to rhFSH was associated with AFN. Serum AMH levels, however, positively correlated with AFN but remained positively correlated with serum LH and free T levels and negatively correlated with total body fat and percent body fat, adjusting for AFN. Conclusion(s): In normal-weight women with PCOS, serum E-2 hyperresponsiveness to rhFSH represents increased AFN, while elevated serum AMH levels reflect opposing effects of stimulatory reproductive (hyperandrogenism and increased AFN) versus inhibitory metabolic (body fat) factors. Given the small number of subjects reported, additional follow-up studies are required to confirm these data. (C) 2017 by American Society for Reproductive Medicine.