Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities, specifically menstrual dysfunction and anovulation in conjunction with elevated pre-antral follicle number and arrested follicular maturation. Although anti-müllerian hormone (AMH), an inhibitor of follicle recruitment and maturation, is increased in women with PCOS, the usefulness of circulating AMH levels as a clinical predictor of menstrual response to weight loss in PCOS is not known. Overweight women with PCOS (n = 26, age 32.9 +/- 5.8 yr, weight 98.9 +/- 20.8 kg, body mass index 36.1 +/- 7.0 kg/m(2), mean +/- sd) followed an 8-wk weight loss and 6-month weight maintenance program. Net reductions in weight (4.6 +/- 4.8 kg), waist circumference (6.0 +/- 5.3 cm), testosterone (0.3 +/- 0.6 nmol/liter), fasting insulin (3.7 +/- 7.6 mU/liter), and the homeostasis model assessment of insulin sensitivity (0.7 +/- 1.3) occurred for all subjects over the entire study duration. Of 26 subjects, 15 (57.7%) responded to the intervention with improvements in menstrual cyclicity (responders). Compared to nonresponders, responders had lower AMH levels at baseline (23.6 +/- 12.0 vs. 37.9 +/- 17.8 pmol/liter; P = 0.021). Only responders had reductions in fasting insulin (6.1 +/- 5.9 mU/liter; P = 0.001) and homeostasis model assessment (1.3 +/- 5.9; P = 0.002) with acute weight loss (wk 0-8). Baseline AMH was most strongly predicted by baseline ghrelin, free testosterone, and insulin (r(2) = 0.528; P = 0.002). Overweight women with PCOS who respond to weight loss with menstrual improvements have significantly reduced preweight loss AMH and demonstrate improvements in surrogate measures of insulin resistance with weight loss. Pretreatment AMH is a potential clinical predictor of menstrual improvements with weight loss in PCOS.