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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.<\/jats:p>","DOI":"10.1073\/pnas.1015674108","type":"journal-article","created":{"date-parts":[[2011,4,4]],"date-time":"2011-04-04T23:19:19Z","timestamp":1301959159000},"page":"6585-6590","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":254,"title":["Leptin is an effective treatment for hypothalamic amenorrhea"],"prefix":"10.1073","volume":"108","author":[{"given":"Sharon H.","family":"Chou","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Chamberland","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Matarese","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche and"},{"name":"Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universit\u00e0 di Napoli Federico II, Naples 80131, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyun","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianna","family":"Stefanakis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary T.","family":"Brinkoetter","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizhi","family":"Gong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Arampatzi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos S.","family":"Mantzoros","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"},{"name":"Section of Endocrinology, Boston Veterans Administration Healthcare System, Harvard Medical School, Boston, MA 02130; and"},{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,4,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(86)90274-7"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(18)30179-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.3.5551"},{"key":"e_1_3_3_4_2","first-page":"25","article-title":"Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea","volume":"83","author":"Laughlin GA","year":"1998","unstructured":"GA Laughlin, CE Dominguez, SS Yen, Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. 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