Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women

BACKGROUND: Previous studies have alluded to a role for both oestradiol and progesterone in the secretion of leptin from fat cells in the human, although direct evidence has yet to be obtained. The study aim was to assess serum leptin concentrations in normally cycling women receiving exogenous oestradiol and progesterone. METHODS: Normally cycling women were investigated in an untreated spontaneous cycle (control, n = 10), a cycle treated with oestradiol (oestradiol cycle, n = 10) and a cycle treated with oestradiol plus progesterone (oestradiol + progesterone cycle, n = 6). Oestradiol was given to the women through skin patches on cycle days 2, 3 and 4, and progesterone intravaginally on cycle days 3, 4 and 5. Serum concentrations of leptin, oestradiol, progesterone, FSH and LH were measured in daily blood samples. RESULTS: During the treatment, serum oestradiol and progesterone concentrations increased significantly. In the oestradiol cycles, leptin concentrations were not affected by treatment and did not differ from those in controls. In the oestradiol+progesterone cycles, leptin concentrations (mean +/- SEM) increased in all women from cycle day 3 (8.6 +/- 1.1 ng/ml) to days 5 (12.2 +/- 1.8 ng/ml, P < 0.01) and 6 (11.9 +/- 2.0, P < 0.05), and were at these points significantly higher than in the control cycles (P < 0.05). The mean percentage increase from day 3 to the peak concentration on days 5 or 6 was 62.6 +/- 6.8%. Leptin concentrations returned to the pretreatment value on day 7, together with the concentrations of oestradiol and progesterone. In the oestradiol+progesterone cycles, leptin concentrations correlated significantly with oestradiol and progesterone concentrations, but not with FSH and LH concentrations. CONCLUSIONS: These results show, for the first time, that leptin secretion can be stimulated in women by the administration of oestradiol plus progesterone. This may explain the increased concentrations of leptin during the luteal phase of the normal menstrual cycle.