Recombinant Human Leptin in Women With Hypothalamic Amenorrhea.

摘要

Hypothalamic amenorrhea, characterized by absent menstrual cycles and low estrogen levels, reportedly accounts for more than 30% of all cases of amenorrhea in women of reproductive age. Infertility and bone loss are possible consequences. Functional hypothalamic amenorrhea occurs when, for any reason, there is a relative energy deficit. Leptin levels are low in these patients, and the normal diurnal variation in leptin levels is absent. To determine whether low leptin levels cause neuroendocrine and reproductive dysfunction, 8 women with hypothalamic amenorrhea resulting from low body weight or strenuous exercise prospectively received recombinant human leptin for 2 to 3 months. Six control women received no treatment. Participants self-administered 0.08 mg/kg of recombinant human leptin subcutaneously each day, 40% of it in the morning and 60% in the evening.Serum leptin levels increased during treatment and body weight decreased slightly. Food intake and resting metabolic rate did not change appreciably. Three of 8 women had an ovulatory menstrual cycle while receiving leptin. Two others had a preovulatory follicle but did not ovulate. Leptin treatment significantly increased maximum follicle diameter, the number of dominant follicles, ovarian volume, and endometrial thickness. Mean levels of luteinizing hormone (LH) increased during treatment, and LH pulse patterns improved or became normal in 6 of 8 women. Thyroid hormone levels increased but remained within the normal range. Markers of bone formation, including bone alkaline phosphatase and osteocalcin, rose significantly during leptin treatment. There was no significant change in urinary N-telopeptides, a marker of bone resorption. Total bone density did not change significantly. No adverse effects were noted. Patients reported decreased appetite but felt well.In this prospective study, leptin treatment of women with hypothalamic amenorrhea normalized reproductive hormone levels, follicle development, and menstrual cyclicity. The findings suggest that leptin, which reflects the adequacy of stored energy, is necessary for normal neuroendocrine and reproductive functioning.