A new study has found that the hormone leptin plays a key role in women’s reproductive and neuroendocrine health and suggests a future for the hormone in treating a number of conditions including exercise-induced bone loss, anorexia and in some cases of infertility.
Leptin is known to be produced by the body's fat tissues and to signal brain cells to reduce appetite and food intake and increase energy expenditures. First discovered in 1994, leptin is probably best recognized as an appetite and weight regulation hormone. But leptin also functions to signal the brain and other organs about dangerous states of very low energy availability. Leptin also plays a permissive role in female puberty, which usually will not proceed until an adequate body mass has been achieved.
Led by researchers at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, the findings are described in the September 2 issue of The New England Journal of Medicine.
“There are three populations of women for whom this study has particular relevance,” explains senior author Christos Mantzoros, MD, Director of the Human Nutrition Research Unit and Clinical Research Overseer of the Department of Endocrinology at BIDMC and Associate Professor of Medicine at Harvard Medical School.
“The largest group,” he explains, “is made up of extremely thin women who are dealing with problems of infertility; the second group consists of competitive athletes and dancers whose thin frames put them at risk for developing osteoporosis and suffering bone fractures; and the smallest – but most extreme – group is women who are battling eating disorders, such as anorexia nervosa.” The common thread among all of these women, he adds, is that their conditions are characterized by extremely low levels of body fat.
“We know that leptin is produced by the body’s fat tissue and is secreted into the bloodstream in proportion to the amount of energy stored in fat,” explains Mantzoros. “From there, it travels to the brain where it communicates exactly how much energy is available.” In so doing, he adds, leptin regulates several key physiological functions that depend on adequate energy balance, including reproduction, metabolism, and bone formation.
Consequently, Mantzoros adds, in situations in which body fat is severely diminished – after extreme dieting or exercise or in the case of an eating disorder, for example – a woman’s body enters a state of “negative energy balance,” such that her reproductive and metabolic health are adversely affected. “Women stop menstruating and develop hypothalamic amenorrhea, their ovaries cease to function, and their levels of estrogen and other reproductive hormones drop dramatically,” he says. Amenorrhea is also associated with abnormal levels of thyroid hormones and growth factors and loss of bone mass, which can lead to osteoporosis and bone fractures.
To test whether administering leptin would restore positive energy balance and thereby reverse these adverse conditions, the researchers recruited 14 competitive female athletes (whose body fat measures approximately 40 percent less than the average woman). All of the subjects had been diagnosed with hypothalamic amenorrhea and had stopped menstruating on average five and one-half years prior to the start of the study.
Eight of the 14 subjects received leptin twice a day, in doses that raised their blood leptin levels to those of normal women. Treatment continued until they responded, or up to three months. The remaining six subjects served as controls and received no treatment; they were observed for eight months. The subjects were observed both in a hospital setting and as outpatients.