Leptin is an effective treatment for hypothalamic amenorrhea
- 4 April 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (16), 6585-6590
- https://doi.org/10.1073/pnas.1015674108
Abstract
Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.Keywords
This publication has 57 references indexed in Scilit:
- Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia NervosaJournal of Clinical Endocrinology & Metabolism, 2009
- The Effects of Recombinant Human Leptin on Visceral Fat, Dyslipidemia, and Insulin Resistance in Patients with Human Immunodeficiency Virus-Associated Lipoatrophy and HypoleptinemiaJournal of Clinical Endocrinology & Metabolism, 2009
- Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency StatesJournal of Clinical Endocrinology & Metabolism, 2008
- Prognostic Indicators of Changes in Bone Density Measures in Adolescent Girls with Anorexia Nervosa-IIJournal of Clinical Endocrinology & Metabolism, 2008
- Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrowCell and tissue research, 2006
- Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiencyJCI Insight, 2002
- Decreased Serum Leptin in Bulimia NervosaJournal of Clinical Endocrinology & Metabolism, 2000
- Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin DeficiencyThe New England Journal of Medicine, 1999
- Leptin in relation to resumption of menses in women with anorexia nervosaMolecular Psychiatry, 1998
- Nutritional and Endocrine-Metabolic Aberrations in Women with Functional Hypothalamic AmenorrheaJournal of Clinical Endocrinology & Metabolism, 1998