Leptin sucessfully treats hypothalamic amenorrhea in lean women

A synthetic form of the hormone leptin can treat hypothalamic amenorrhea (HA) in women with extremely low body fat, restoring fertility and lowering the risk of osteoporotic fracture, researchers report.

The international double-blinded, placebo-controlled trial investigated 20 women between 18 and 35 years of age who had had HA for a mean duration of 4 to 5 years. Over 36 weeks, the women received daily subcutaneous injections of either metreleptin (synthetic leptin) or placebo. Menstruation resumed in 7 of the 10 women receiving metreleptin (4 of the 7 ovulated); the hormone replacement also corrected abnormalities in gonadal, thyroid, adrenal, and growth hormones. The women who received metreleptin also exhibited higher levels of biomarkers indicating new bone formation.

“If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA,” the authors write. The study results expand on pilot data from a 2004 study that demonstrated that women with HA have chronically low energy and serum leptin levels.

“Our findings prove beyond a doubt that leptin is the missing link in women with significantly diminished body fat, and that this in turn results in numerous hormonal abnormalities,” says senior author Christos Mantzoros, MD, DSc.

Although the study showed improvement in biomarkers of bone metabolism, it did not find changes in bone mineral density over its short duration. “Going forward, we will continue to examine whether metreleptin impacts not only bone markers, but also bone density and bone mineral content-key factors in helping to prevent dangerous stress fractures and osteoporosis,” says Mantzoros.

The study was published online April 4 in the Proceedings of the National Academy of Sciences.