The Metabolic Status Modulates the Effect of Metformin on the Antimullerian Hormone-Androgens-Insulin Interplay in Obese Women with Polycystic Ovary Syndrome.

Context: In the adult ovary, antimullerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles and negatively regulates folliculogenesis. AMH is overproduced in the polycystic ovary and was recently proposed to play a role in the ovulatory dysfunction of polycystic ovary syndrome (PCOS). Objective: The aim of the study was to investigate the effects of metformin administration on AMH levels in relation with the clinical and endocrine-metabolic parameters in obese women with PCOS. Design and Setting: We conducted a pilot prospective study in an academic research environment. Patients: We studied 28 obese PCOS women. Interventions: We performed ultrasonographic pelvic exams, hirsutism score evaluation, hormonal profile assays, oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and lipid profile at baseline and after 6 months of metformin treatment (850 mg twice a day orally). Main Outcome Measures: We measured AMH, hormonal assays, ultrasound aspect of the ovaries, and indexes of glucose and insulin metabolism. Results: Insulin secretion and body mass index significantly decreased after treatment. Almost 70% of subjects experienced an amelioration of menstrual irregularities. Mean androstenedione, testosterone, and 17-hydroxyprogesterone levels and hirsutism score were significantly improved by metformin. However, no significant changes in AMH levels occurred. Data were further analyzed after dividing patients on the basis of pretreatment insulinemic response to the oral glucose tolerance test; metformin was effective in reducing insulin secretion, AMH levels, and, interestingly, ovarian volume exclusively in PCOS patients with hyperinsulinism; none of these changes occurred in the normoinsulinemic group. Conclusions: Metformin differentially affects the interplay between insulin and the ovarian function in obese PCOS women; the presence of hyperinsulinemia seems to be predictive of the efficacy of the treatment.