Injections of a hormone made by fat cells can jump-start an idling reproductive system, research shows.
Extreme exercise can stop a woman's periods
Twice-daily injections of leptin restored menstruation in female athletes who had become so lean that their periods had stopped.
The Beth Israel Deaconess Medical Center team said the injections might also prevent bone loss and treat the eating disorder anorexia nervosa.
Their findings are reported in the New England Journal of Medicine.
Leptin is known to regulate appetite and weight and tells the brain how much energy is available in the body. It's role in obesity has already been studied.
Leptin is made by the body's fat and, therefore, women who are particularly thin, such as athletes with rigorous training programmes or women on very restrictive diets, produce less leptin.
In extreme cases, the woman's body enters a state of 'negative' energy balance and her reproductive system shuts down to prevent a pregnancy and conserve energy.
This is called hypothalamic amenorrhoea or dysfunction.
These women also risk bone loss because of the resultant lack of female hormones, which can lead to osteoporosis and an increased risk of fractures.
Dr Christos Mantzoros and colleagues tested whether giving women leptin would restore positive energy balance and reverse these adverse conditions.
Five out of eight female athletes, whose periods had stopped five or more years ago as a consequence of their rigorous exercise regimes, started menstruating again after receiving leptin injections twice a day for three months.
Three of these women also started to ovulate.
Furthermore, measures of bone health improved among those who received leptin.
In comparison, six female athletes given no treatment at all showed no improvement in any of the measures.
Dr Mantzoros said the benefits of leptin were three-fold.
"This could eventually prove beneficial to patients with anorexia nervosa, competing athletes with brittle bones, and last but not least, to approximately 30% of women whose fertility problems can be attributed to hypothalamic dysfunction."
The researchers plan to carry out larger and longer studies to determine the safety, dose and efficacy of leptin treatment in these types of women.
Dr Richard Fleming, an expert in reproductive endocrinology at Glasgow Royal Infirmary and member of the British Fertility Society, said: "The results are interesting and important."
"These data imply that leptin is the key, and will perform the trick even if the energy stores are not there," he said.
But he said great care would have to be taken with respect to pregnancy in these women with subnormal energy stores, as pregnancy would be high risk for both the mothers and the children.
Professor Gordana Prelevic, professor in reproductive endocrinology at the Royal Free and member of the Society for Endocrinology, said: "This is a brilliant study.
"It's proven what we suspected."
She said it could be a good treatment for a minority of infertile women whose cause of infertility was leptin deficiency through over-exercising or under-eating.
"If it proves to be useful it would have enormous clinical implications," she said.