Leptin's Role in Fertility and Bone Health

Fat hormone leptin restores fertility and reduce the risk of bone fractures in women with low body weight, according to a recent study.

Researchers at Beth Israel Deaconess Medical Center (BIDMC) offered the first definitive proof that a lack of leptin contributes to hypothalamic amenorrhea (HA) - a condition in which menstrual periods of women cease, triggering serious problems as infertility and osteoporosis.

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"This condition accounts for over 30 percent of all cases of amenorrhea in women of reproductive age, and is an important problem for which we didn't have a good solution," said senior author Christos Mantzoros, Director of the Human Nutrition Unit at BIDMC and Professor of Medicine at Harvard Medical School.

"Our findings now prove beyond any doubt that leptin is the missing link in women with significantly diminished body fat, and that this, in turn, results in numerous hormonal abnormalities," he added.

Without leptin, menstrual periods cease, the body becomes chronically energy-deprived and women experience bone loss and an increased risk of bone fractures, said Mantzoros.

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Mantzoros and his team have been examining the hormone's role from the opposite end of the energy spectrum by studying individuals with extremely low levels of body fat.

The new research - a double-blinded, placebo-controlled trial, the gold standard in scientific investigation - expands and extends pilot data from their 2004 proof-of-concept paper in the New England Journal of Medicine (NEJM), which showed that women with HA have chronically low energy and serum leptin levels.

"In this new PNAS study, we investigated 20 women between the ages of 18 and 35 who had developed HA," said Mantzoros.

"These are young, mostly college-age women, mainly runners. They watch their diets, they are slim and appear healthy. But they have abnormal hormone levels, they have ceased menstruating and stopped ovulating and they also have low bone density measures," he added.

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Over a period of 36 weeks, the study subjects were given either a synthetic form of leptin (known as metreleptin) or a placebo.

The results showed that daily subcutaneous injections of replacement leptin resulted in significantly elevated levels of the hormone within just a month of treatment.

"Seven of 10 women began to menstruate and four of the seven were found to be ovulating," said Mantzoros.

"Compared with the women who received the placebo, the women who received the metreleptin therapy were also found to have an improved hormonal profile and exhibited higher levels of biomarkers indicating new bone formation," he added.

The findings are reported online this week in the Proceedings of the National Academy of Sciences.

Source-ANI