Comparison between 1 year oral and transdermal oestradiol and sequential norethisterone acetate on circulating concentrations of leptin in postmenopausal women

BACKGROUND: Oral and transdermal postmenopausal hormone replacement therapy (HRT) affects lipid and glucose metabolism differently, which is of significance in the release of leptin by adipocytes. Moreover, oestrogen and progesterone can stimulate leptin secretion in women of reproductive age. Therefore, we compared the effects of oral and transdermal oestrogen plus progestin regimen on plasma leptin in 38 healthy postmenopausal women with normal body mass index (BMI), who wished to use HRT to control incapacitating climacteric symptoms. METHODS: The women were randomized to treatment with oral HRT (2 mg oestradiol on days 1–12, 2 mg oestradiol plus 1 mg norethisterone acetate (NETA) on days 13–22, and 1 mg oestradiol on days 23–28, n = 19), or with transdermal HRT (50 μg/day of oestradiol on days 1–13, and 50 μg oestradiol plus 250 μg/day NETA on days 14–28, n = 19) for 1 year. Plasma samples were collected before and at oestradiol + NETA phase after 2, 6 and 12 months treatment and were assayed for leptin. RESULTS: The baseline leptin, ranging from 3.3 to 34.9 μg/l, was significantly associated with BMI (r = 0.78, P < 0.0001 ), but showed no difference between women in oral HRT (geometric mean 13.9 μg/l, 95% confidence interval (CI) 10.1–17.6 μg/l) or transdermal HRT group (geometric mean 12.0 μg/l, 95% CI 9.7–14.3 μg/l). Neither oral nor transdermal oestradiol + NETA caused any significant changes in plasma leptin (or BMI) after 2, 6, or 12 months of treatment. CONCLUSION: Leptin is an unsuitable factor to detect oestradiol + NETA-induced metabolic changes in postmenopausal women.