Study: Hormone Restores Menstrual Cycle In Women With Little Body Fat

You hear about it happening to gymnasts and runners, dancers and anorexics. A woman's — or girl's — body fat gets so low that she stops having periods; her reproductive cycle shuts down.

You can imagine how evolution may have worked it this way. In ancient times, if conditions were so bad that you were down to skin and bones, that was not the time to try to feed a baby. But in modern times, women with extremely low body fat may face unwanted infertility, and they have been found to be at higher risk for osteoporosis.

Today, researchers report that leptin — a hormone famed for its role in appetite and obesity — is a key to that loss of menstruation, known as "hypothalamic amenorrhea," and that giving women synthetic leptin can restore their reproductive function and possibly protect their bones.

The paper's lead author, Dr. Sharon H. Chou of Beth Israel Deaconess Medical Center, summed up the findings:

Women with hypothalamic amenorrhea, or loss of menstrual periods from excessive exercise, excessive stress, or decreased food intake, have additional neuroendocrine abnormalities and experience bone loss. These women also are found to have low leptin levels, which can be seen as a marker of energy stores. This study shows that replecement of leptin in these women restores menstrual periods, corrects some of the neuroendocrine abnormalities, and may improve bone loss.

And this from a Beth Israel press release:

The findings are reported on-line in the Proceedings of the National Academy of Sciences (PNAS), the week of April 4.
“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,” explains senior author Christos Mantzoros, MD, Dsc, 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.” Without leptin, he explains, menstrual periods cease, the body becomes chronically energy-deprived and women experience bone loss and an increased risk of bone fractures.

Circulating leptin levels reflect the amount of energy stored in fat cells, as well as acute changes in energy intake. Shortly after leptin was discovered in 1994, the hormone generated widespread attention as a possible way to suppress the appetites of obese individuals. But studies soon found that overweight individuals had plenty of leptin and that adding more was of no benefit.
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 researchers followed 20 young women with low body fat whose periods had stopped. One group received leptin shots, the other group received shots of a placebo, and neither the subjects nor the researchers knew who was in which group. Beth Israel reports:

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,” notes 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.”

So does this mean a neat new fix for women with low body fat whose periods stop? Not so fast, said Sharon Chou in an email. More studies are needed.

This is a small study. With larger and longer studies, metreleptin [synthetic leptin] may be given to induce the return of menstrual cycles. Our lab also has a longer study planned looking to see if metreleptin will increase bone mineral density in these women with hypothalamic amenorrhea.

My question: Leptin is seen as a bit of a "bust" for fighting obesity so far, not the magic bullet some had hoped; is this part of a sort of "rehabilitation," showing that in fact it can still be highly useful in various ways, and do you see other promise for it?

Sharon's answer:

Yes, leptin can be effective in a population that is sensitive to leptin, specifically women with hypothalamic amenorrhea and patients with lipodystrophy. Obese patients are resistant to leptin but if there is a way to sensitize them to leptin, then leptin may be more effective for obesity.