Leptin, the hormone best known to control appetite, also appears to play a major role in fertility and bone development in women.

A small, new study finds synthetic injections of the hormone can help young women whose naturally low levels of leptin left them thin and prone to osteoporosis, broken bones, and reproductive problems.

Low doses of leptin restored hormonal balance, improved bone density, and began menstrual cycles again, according to the study, which appears in the Sept. 2 issue of the New England Journal of Medicine.

The researchers also suspect that leptin is involved in eating disorders, although that wasn't tested in this research.

Leptin, which was discovered 10 years ago, is a protein that helps regulate body weight, metabolism and reproductive function, and it has been linked to appetite and weight regulation. Leptin plays another role as well, signaling the brain and other organs to dangerously low energy availability.

Leptin is produced in fat tissue and secreted into the bloodstream in proportion to the amount of energy stored in fat, explained lead researcher Dr. Christos Mantzoros, director of human nutrition research at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. Leptin tells the brain how much energy the body has available, he explained.

Levels of leptin regulate key body functions that depend on having adequate energy, including reproduction, metabolism and bone formation, Mantzoros said. "We are talking about three related but distinct disease states," he added. "One is anorexia nervosa."

The second group is women who exercise a lot, "such as athletes and dancers, who lose fat mass, and use more energy than the energy than they take in. These women have no periods, low estrogen levels, abnormal thyroid levels, and low levels of growth hormone," he said.

This condition, called hypothalamic amenorrhea, leads to osteoporosis and infertility. "Despite exercise, these women have osteoporosis, usually unbeknownst to them," Mantzoros said.

An even larger group is extremely thin women who have very mild abnormalities and are infertile. "The common thread in all these conditions is energy deficiency," he noted.

To find out what causes these abnormalities, Mantzoros' group looked at leptin levels in female athletes with hypothalamic amenorrhea. The researchers treated six women with low doses of leptin for three months to bring their hormonal levels into the normal range.

Another group of six women were given no treatment, but were observed for almost nine months.

"In the women not treated, nothing changed," Mantzoros said. "But in the women who were treated, all the hormone levels that were abnormal improved. Their estrogen levels went up, thyroid levels improved, and growth hormone levels improved."

The women also started having menstrual periods after not having had them for an average of 5.5 years, Mantzoros said, adding that bone density improved.

The impact of the study is that it explains why women develop these conditions, Mantzoros said: "Because leptin is missing."

The results of the study also open up new treatment options. Mantzoros's team is starting a larger trial to find out if leptin is safe and effective for treating hypothalamic amenorrhea to prevent osteoporosis and normalize all the hormone levels.

Moreover, in extremely thin women who cannot reproduce, low-dose leptin might make conception possible without having to resort to in vitro fertilization, Mantzoros said.

Mantzoros cautioned that leptin therapy is not appropriate for treating women with anorexia nervosa.

"For the first time we know the causes of these problems, and knowing the cause we can effectively treat it," Mantzoros said.

The discovery should spur more research into the disorder, said Dr. Rexford S. Ahima, an assistant professor of medicine at the University of Pennsylvania School of Medicine. "Hypothalamic amenorrhea, a disease that was first described in the 1940s and was poorly understood for decades, may finally benefit from a rebirth of investigation leading to rational therapy," Ahima wrote in an accompanying article.

"Prospective demonstration that leptin replacement for women who are in chronic negative energy balance (and thus lack sufficient adipose tissue) restores menstrual cycles and bone density has not been accomplished before," added Dr. Tamas Horvath, an associate professor of obstetrics and gynecology and neurobiology at the Yale School of Medicine.

The paper "shows a critical role for leptin in these processes," he added.

Horvath is not sure how women receiving leptin replacement will do over the long term. "Would the quasi-fooled physiological response of energy re-organization have a negative impact on functioning of other tissues, such as the heart, liver kidney and brain?" he wondered.

The study was funded by grants from the National Institutes of Health, Harvard University, and Amgen, which makes the genetically engineered hormone.

More information

Read about infertility at the American Society of Reproductive Medicine.

Reference Source 101
September 2, 2004

For more information on how to prevent other diseases, use
PreventDisease.com's "Quick Prevention Resources".