Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin

Objective: To address the effect of leptin in the modulation of change in b ody weight after hormone replacement therapy (HRT), we prospectively examin ed the responses of body weight and serum leptin after estrogen-progestin r eplacement in postmenopausal women. Patients: Subjects consisted of 63 post menopausal women aged 54-82 years on HRT for osteoporosis. Design: Thirty t hree of the subjects received 0.3 mg of conjugated equine estrogen (CEE) (g roup 1) while 30 were on 0.625 mg of CEE daily (group 2). All subjects also took 5 mg of medrogestone acetate and 750 mg elemental calcium supplement daily. Measurements: Fasting serum leptin was measured by RIA at baseline, 1 and 3 months after treatment. Data were expressed as mean +/- S.E.M. Resu lts: Serum leptin was highly related to body weight both at baseline (r = 0 .40, P < 0.001) and after 3 months of HRT (r = 0.42, P < 0.001). When divid ed the subjects into three equal groups according to baseline leptin levels , it was found that serum leptin significantly decreased in subjects with h igh baseline leptin at 3 months (- 9.4 +/- 5.7%, P < 0.05) while it increas ed in subjects whose baseline leptin levels were in the lowest tertile at 1 month (33.2 +/- 8.3%, P < 0.001) and 3 month (27.8 +/- 8.3%, P < 0.01). In regards to body weight, those with leptin in the highest tertile demonstra ted a reduction of body weight at 3 (- 1.9 +/- 0.6%, P < 0.05) and 12 month s ( - 3.2 +/- 0.5%, P < 0.05) after HRT while those whose serum leptin leve ls were in the lowest and middle tertiles did not demonstrate change in bod y weight. By repeated measured analysis of variance, it was found that the decrease in body weight in subjects with high serum leptin was independent of the doses of estrogen. Conclusion: Postmenopausal hormone replacement do es not cause weight gain. However, it results in a small reduction in body weight particularly in subjects with higher basal leptin concentrations. (C ) 1998 Elsevier Science Ireland Ltd. All rights reserved.