Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women

Leptin and oestrogen are both involved in the regulation of adipose tissue deposition and feeding behaviour. We investigated whether 5 years of hormon e replacement therapy (HRT) affected serum leptin and body composition diff erently in 89 postmenopausal women treated with HRT compared with 178 contr ols. At baseline, leptin was significantly correlated with oestradiol (r=0. 13, P<0.05) and in multiple backward regression analysis including oestradi ol and any estimate of body fat, oestradiol remained a significant determin ant of leptin levels. In the control group, all estimates of body fat deter mined by dual energy X-ray absorptiometry (DEXA) or anthropometry were incr eased (3.6-16.9%) and leptin increased 31.3% (16.03 +/- 1.02 to 20.84 +/- 1 .2 ng/ml (S.E.M.), P<0.001). In the HRT group all estimates of body composi tion also increased during the 5-year observation but to a lesser extent th an observed in the control group (1.0-8 .5%). Leptin was raised by 19.7% (1 7.81 +/- 1.32 to 20.57 +/- 1.65 ng/ml, P<0.001). However, the DEXA scans re vealed that the control group gained 2.4-fold more fat during the 5-year ob servation (1.9 +/- 0.3 vs 0.8 +/- 0.4 kg, P<0.05), and especially the trunk fat increased (1.4 +/- 0.2 vs 0.7 +/- 0.3 kg, P<0.05). This was reflected in the increase in leptin levels, which were increased by 7.4% in the contr ol group compared with the HRT group (4.81 +/- 0.60 vs 2.76 +/- 0.87 ng/ml, P<0.05). Adjusting for the difference in adipose tissue revealed that HRT had no independent effect on leptin levels. Comparisons between obese (body mass index >25 kg/m(2)) and non-obese (<25 kg/m(2)) subjects by stratifyin g for HRT treatment using multiple Linear regression revealed that the chan ge in fat mass was significantly less among treated subjects (P=0.038) and especially in the non-obese subjects (P=0.001). The change in trunk fat was similarly correlated with treatment status (P=0.029) and with the degree o f obesity (P=0.006). In conclusion, 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region. This effect of HRT was more pronounced in non-obese as compared with obese subjects. Th e HRT-induced reduction in fat mass seems not to be mediated by leptin.