Normal reproductive function in leptin-deficient patients with lipoatropicdiabetes

To further examine the relationships between leptin and female reproductive axis, we conducted hormonal studies in two patients with lipoatropic diabe tes that occurred before puberty. Despite complete atrophy of sc and viscer al adipose tissue, menarche occurred in these two patients between 11-12 yr of age, followed by regular menstrual cycles. One patient had been pregnan t three times, giving birth to children who did not develop the disease. In our two patients, repeated analysis revealed leptin levels below 1 ng/mL ( normal range for 20 insulin-treated diabetic women, 2-23 ng/mL for body mas s index of 14-39 kg/m(2); personal data). We measured peripheral levels of estradiol, progesterone, FSH, LH, free testosterone, and androstenedione wi thin the first 5 days of the menstrual cycle, and we tested the reactivity of pituitary after iv injection of 100 mu g GnRH. The variation in body tem perature in the morning before arising was also analyzed. We showed that 1) all measured levels of hormones were in the normal range for both patients ; and 2) low levels of leptin did not impair the development of reproductiv e function in one patient and was associated with normal gonadal function i n both patients. We conclude that puberty and fertility can occur despite c hronic low serum levels of leptin. This suggests that leptin is not fundame ntal to the maintenance of normal reproductive function in humans.