Leptin was give twice daily to eight of the 14 women in amounts that raised the leptin levels in their blood to that of normal women. They continued the treatment until either they responded or three months has passed. No treatment was received by the remaining six women who served as controls. These women were observed for eight months. All of the participants were observed both as hospital in-patients and out-patients.
Dramatic results were seen in all the women who received leptin within three months of leptin therapy. Dr. Mantzoros explained, Levels of reproductive hormones were raised, and womens menstrual periods and normal ovarian functioning were restored. In addition, when serum markers [reflecting bone density] were measured, we found significant improvement among the treated women. No change was seen in the condition of the women in the control group.
Dr. Mantzoros stressed that the results of this study are significant for women with normal reproduction development, as well as women coping with diseases related to negative energy balance. He suggests that the onset of puberty in adolescent girls may be dependant on leptin.
It appears that normal, healthy girls gain weight immediately prior to puberty, says Mantzoros. This suggests that leptin levels which rise in response to the increase in body fat are letting the body know that there is enough energy available to sustain a pregnancy. Because of this, the bodies of women with particularly low energy availability revert to a state similar to that of an adolescent girl.
The leptin molecule was first discovered in 1994 by Jeffrey M. Friedman, M.D., Ph.D., a Howard Hughes Medical Institute investigator at Rockefeller University. According to Dr. Friedman, This research is important in understanding both normal human physiology as well as the mechanisms leading to several different disease states. This study proves the concept that low leptin levels are responsible for the neuroendocrine abnormalities observed in energy-deficient states, such as anorexia nervosa, strenuously exercising female athletes and extremely thin women with hypothalamic amenorrhea. This is a landmark study that will improve many patients lives in many ways. Because of the results of this study, Dr. Mantzoros adds, Were in the process of designing larger and longer studies to determine the safety, dose and efficacy of leptin treatment in these populations of women. This could eventually prove beneficial to patients with anorexia nervosa, competitive athletes with brittle bones, and last but not least, to approximately 30 percent of women whose <link url=http://infertility.about.com]infertility, problems can be attributed to hypothalamic dysfunction.
Besides Dr. Mantzoros, other lead authors of the leptin study are Jean Chan, MD of BIDMC and Corrine Welt, MD of MGH, co-authors include John Bullen, BA, and Aspasia Karalis, BS, of BIDMC; Patricia Smith, BS, of MGH; and Robyn Murphy, MS, and Alex DePaoli, MD, of Amgen, Inc.
This study was funded by grants from the National Institute of Health, Institute of Diabetes and Digestive and Kidney Diseases; the National Center for Research Resources; the Harvard Clinical Nutrition Research Center; the Harvard Center for Womens Health; and Amgen, Inc.
Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Care Center.