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BMAT is negatively associated with BMD in AN and more than 85% of women with AN have low bone mass and an increased risk of fracture. Although a majority of women with AN are amenorrheic, which is associated with low BMD, oral contraceptive pills, containing supraphysiologic doses of estrogen, are not effective in increasing bone mass. We performed a 6\u2010month, open\u2010label study of transdermal estradiol (0.045\u2009mg\/day)\u2009+\u2009levonorgestrel (0.015\u2009mg\/day) in 11 women with AN (mean age\u2009\u00b1\u2009SEM: 37.2\u2009\u00b1\u20092.3\u2009years) to investigate the effects of transdermal, physiologic doses of estrogen on BMD and BMAT in women with AN. We measured change in BMD by DXA, change in BMAT at the spine\/hip by <jats:sup>1<\/jats:sup>H\u2010magnetic resonance spectroscopy, and change in C\u2010terminal collagen cross\u2010links (CTX), P1NP, osteocalcin, IGF\u20101, and sclerostin after 3 and 6 months of transdermal estrogen. Lumbar spine (2.0%\u2009\u00b1\u20090.8%; <jats:italic>p<\/jats:italic> = 0.033) and lateral spine (3.2%\u2009\u00b1\u20091.1%; <jats:italic>p<\/jats:italic> = 0.015) BMD increased after 6 months of transdermal estrogen. Lumbar spine BMAT decreased significantly after 3 months (\u221213.9\u2009\u00b1\u20096.0%; <jats:italic>p<\/jats:italic> = 0.046). Increases in lateral spine BMD were associated with decreases in CTX (<jats:italic>p<\/jats:italic> = 0.047). In conclusion, short\u2010term treatment with transdermal, physiologic estrogen increases spine BMD in women with AN. Future studies are needed to assess the long\u2010term efficacy of this treatment. \u00a9 2019 The Authors. <jats:italic>JBMR Plus<\/jats:italic> published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbm4.10251","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T16:13:49Z","timestamp":1573575229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transdermal Estrogen in Women With Anorexia Nervosa: An Exploratory Pilot Study"],"prefix":"10.1093","volume":"4","author":[{"given":"Megi","family":"Resulaj","sequence":"first","affiliation":[{"name":"Neuroendocrine Unit Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-3275","authenticated-orcid":false,"given":"Sai","family":"Polineni","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erinne","family":"Meenaghan","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamryn","family":"Eddy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Lee","sequence":"additional","affiliation":[{"name":"Biostatistics Center Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-2927","authenticated-orcid":false,"given":"Pouneh K","family":"Fazeli","sequence":"additional","affiliation":[{"name":"Neuroendocrine Unit Massachusetts General Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"},{"name":"University of Pittsburgh School of Medicine  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.5.561"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)63994-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3068"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03460090081037"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650071215"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.3.898"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.6.8574"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1083-3188(02)00145-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jadohealth.2006.09.010"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.447"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0380"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1659"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01959087"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.3.774"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.12.4489"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.1.200"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-005-1972-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2532"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090805"},{"issue":"8","key":"e_1_2_7_21_1","first-page":"1620","article-title":"Potential value of vertebral proton MR spectroscopy in determining bone weakness","volume":"22","author":"Schellinger D","year":"2001","journal-title":"AJNR Am J Neuroradiol."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000137833.43248.79"},{"issue":"5","key":"e_1_2_7_24_1","first-page":"517","article-title":"A dose\u2010ranging trial of a matrix transdermal 17beta\u2010estradiol for the prevention of bone loss in early postmenopausal women","volume":"24","author":"Delmas PD","year":"1999","journal-title":"International Study Group. 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