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Normal Reproductive Function in Leptin-Deficient Patients with Lipoatropic Diabetes

Endocrinology and Diabetes Department, Hospital E Herriot (F.A., M.L., J.P.R., C.T.), 69437 Lyon; and the Diabetes Department, Hospital de Rangueil (H.H.-B., J.P.T.), 31403 Toulouse, France

Address all correspondence and requests for reprints to: Dr. F. Andreelli, Pavillon X, Hôpital E Herriot, 69437 Lyon Cedex 03, France.

To further examine the relationships between leptin and female reproductive axis, we conducted hormonal studies in two patients with lipoatropic diabetes that occurred before puberty. Despite complete atrophy of sc and visceral adipose tissue, menarche occurred in these two patients between 11–12 yr of age, followed by regular menstrual cycles. One patient had been pregnant 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 mass index of 14–39 kg/m²; personal data). We measured peripheral levels of estradiol, progesterone, FSH, LH, free testosterone, and androstenedione within the first 5 days of the menstrual cycle, and we tested the reactivity of pituitary after iv injection of 100 µg GnRH. The variation in body temperature 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 reproductive function in one patient and was associated with normal gonadal function in both patients. We conclude that puberty and fertility can occur despite chronic low serum levels of leptin. This suggests that leptin is not fundamental to the maintenance of normal reproductive function in humans.

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