The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women

Controversial effects of weight reduction on gonadotropin secretion in obes ity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring L H and FSH concentrations. We studied follicular phase nocturnal urinary (nu ) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsu linemic clamp) during 1 menstrual cycle/30-day period before and after weig ht reduction in 10 severely overweight infertility patients (age, 29 +/- 3. 1 yr; body mass index, 37.1 +/- 3.3 kg/m(2); +/-SEM). A 6-week. very low ca lorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH su rge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6 .06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), w hich was accounted for by a significant increase in nonoxidative glucose di sposal (P = 0.003). Serum sex hormone-binding globulin concentrations incre ased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protei n-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin con centrations decreased by 38%, those of leptin by 37%, those of androstenedi one by 32%, those of testosterone by 20% tall P ( 0.01), and those of dehyd roepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH co rrelated negatively with glucose uptake (r = -0.76; P < 0.01) and the incre ase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positi vely with the percent change in waist to hip ratio (r = 0.79; P < 0.01). Th e absolute nu-LH levels after weight reduction correlated significantly wit h fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were fou nd between absolute levels or changes in nu-LH concentrations and leptin, I GF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH conce ntrations, a reduction in the LH/FSH ratio, and FSH predominance favoring f olliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.