Gonadotropins at menopause: the influence of obesity, insulin resistance, and estrogens

Obese, postmenopausal women have lower FSH levels. To determine whether thi s is due to higher estrogen exposure, we compared feedback gonadotropin sen sitivity and its relation to insulin resistance in four groups of obese and lean, postmenopausal women. Group one was treated with 400 mg troglitazone (TG) daily for two weeks; 150 clomiphene citrate (CC) was added daily for the second week. Group two received 150 mg CC daily for a week. Group three received 1000 mg metformin (MET) daily for two weeks, with 120 mg raloxife ne (RAL) added during the second week. Group four received 120 mg RAL for a week. Before and after each period, a serum pool was obtained from samples taken every minute during a 10 ml interval. The women recruited for this s tudy were categorized as obese or lean based on BMI greater than or equal t o 29 or BMI < 29, respectively. Obese, menopausal women had lower FSH (45.5 IU/l) and LH (16.2 IU/l) values than those of lean (64.1 IU/l and 23.0 IU/ l), but the obese menopausal women had higher leptin, DHEAS. glucose, insul in, and HOMA-IR levels. Log [FSH] was associated with BMI (r = -0.53, P < 0 .000001) and number of pregnancies (r = -0.37, P = 0.0009). TG treatment di d not change HOMA-IR or gonadotropin levels, but DHEAS and androstenedione levels decreased significantly. CC alone or together with TG, diminished FS H (-7.9 and -9.2) and LH (-2.5 and -3.6) concentrations, with a greater red uction in lean women. MET reduced glucose and the HOMA-IR index without aff ecting gonadotropin or steroid levels. Conclusions: obese, menopausal women have lower FSH levels due to greater estrogen exposure, by mechanisms unre lated to insulin resistance. (C) 2001 Elsevier Science Inc. All rights rese rved.