Objective: In recent studies serum leptin levels were significantly higher in the luteal phase than in the follicular phase, but the mechanism of changing leptin levels are unknown. Several research lines indicate a potential role for tumor necrosis factor (TNF-alpha) in ovulation and reproductive events. As TNF-alpha appears to regulate leptin secretion, we speculated that TNF-alpha might be involved in leptin variations during the menstrual cycle.
Design and methods: Nine healthy never obese and ten overweight normally cycling women were studied. TNF-alpha action - through the plasma levels of the soluble fraction of the tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) - and leptin concentrations were measured in the follicular (F), peri-ovulatory (PO) and luteal phases (L) of their menstrual cycles.
Results: Circulating leptin levels were significantly associated with the stage of the menstrual cycle (P<0.001), being higher in PO and L phases. However, only three of ten overweight subjects vs eight of nine lean women (Chi square P=0.014 after Fisher's exact test) showed significantly higher leptin levels in the PO and L than in the F phase (95% confidence interval (95% CI) of the differences, 3.7 to 10.2 ng/ml, paired t-test P=0.001). In these women (group 1), the changes in leptin levels parallelled the variations observed in plasma sTNFR1 (2.50+/-0.1 vs 2.11+/-0.05 ng/ml, P<0.0001, 95% CI, 0.21 to 0.56) and sTNFR2 levels (5.19+/-0.28 vs 4.55+/-0.25 ng/ml, P<0.0001, 95% CI, 0. 47 to 0.81). In the remaining women (group 2), leptin (95% CI, -1 to 9.2 ng/ml, P=not significant (NS)), sTNFR1 (95% CI, -0.3 to 0.14 ng/ml, P=NS) and sTNFR2 levels (95% CI, -0.95 to 0.39 ng/ml, P=NS) were essentially unaltered throughout the menstrual cycle. Group 2 women were similar in age (36.1+/-2.9 vs 37.3+/-1.4 years) and significantly overweight (body mass index 31+/-2.9 vs 23.9+/-1. 2 kg/m(2)) compared with group 1 women. A negative correlation was observed between leptin levels in the follicular phase and the change in plasma leptin from F to L phase in all subjects (r=-0.67, P=0.002).
Conclusions: Circulating leptin and sTNFRs levels change significantly during the menstrual cycle of most lean women. In contrast, the levels of these molecules remain essentially unaltered during the F, PO and L phases in the majority of overweight women. Obesity might be associated not only with blunted diurnal excursions and dampened pulsatility, but also with blunted excursions during the menstrual cycle.