{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T01:14:37Z","timestamp":1794532477138,"version":"4.9.1"},"reference-count":57,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Sport Exerc Med"],"accepted":{"date-parts":[[2021,6,18]]},"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To systematically review the literature of randomised controlled trials (RCTs) assessing the effect of oestrogen oral contraceptives (OCP), conjugated oestrogens (CE) and transdermal estradiol (TE) on BMD in premenopausal women with functional hypothalamic amenorrhoea (FHA) due to weight loss, vigorous exercise and\/or stress.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data extraction and synthesis<\/jats:title>\n                  <jats:p>Two authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcomes<\/jats:title>\n                  <jats:p>Difference in BMD (g\/cm<jats:sup>2<\/jats:sup>) at the lumbar spine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nine RCTs comprising 770 participants met the inclusion criteria; five studies applied OCP, two CE and two TE. Four RCTs (two OCP, two TE) found an increased BMD in premenopausal women with FHA, and five (three OCP, two CE) found a decreased BMD compared with controls. A meta-analysis showed no difference in BMD between the treatment and control groups, (standardised mean difference (SMD) 0.30, 95%\u2009CI \u22120.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95%\u2009CI \u22120.16 to 0.51). No serious adverse events were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The literature suggests that TE might increase lumbar BMD in premenopausal women with FHA, but pooled results revealed no effect of the intervention. The findings do not support oestrogen therapy to improve BMD in these patient groups.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjsem-2021-001112","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T13:53:11Z","timestamp":1625665991000},"page":"e001112","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-999X","authenticated-orcid":false,"given":"Karoline","family":"Aalberg","sequence":"first","affiliation":[{"name":"Atlasklinikken, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Stavem","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Akershus University Hospital, Lorenskog, Norway"},{"name":"Department of Pulmonary Medicine, University of Oslo, Akershus University Hospital, Lorenskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frode","family":"Norheim","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Oslo, Institute of Basic Medical Sciences, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Bj\u00f8rn","family":"Russell","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Akershus University Hospital, Lorenskog, Norway"},{"name":"Head and Neck Research Group, Division for Research and Innovation, Akershus University Hospital, Lorenskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2566-5984","authenticated-orcid":false,"given":"Aleksander","family":"Chaibi","sequence":"additional","affiliation":[{"name":"Head and Neck Research Group, Division for Research and Innovation, Akershus University Hospital, Lorenskog, Norway"},{"name":"Department for Interdisciplinary Health Sciences, Institute of Health and Society, University of Oslo Faculty of Medicine, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"key":"2025083110583898000_7.3.e001112.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5919(05)70201-5"},{"key":"2025083110583898000_7.3.e001112.2","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2013-093218"},{"key":"2025083110583898000_7.3.e001112.3","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2018-099193"},{"key":"2025083110583898000_7.3.e001112.4","doi-asserted-by":"crossref","first-page":"414???419","DOI":"10.1249\/00005768-199404000-00003","article-title":"Risk and trigger factors for the development of eating disorders in female elite athletes","volume":"26","author":"Sundgot-Borgen","year":"1994","journal-title":"Med Sci Sports Exerc"},{"key":"2025083110583898000_7.3.e001112.5","doi-asserted-by":"publisher","DOI":"10.1080\/09513590701807381"},{"key":"2025083110583898000_7.3.e001112.6","doi-asserted-by":"publisher","DOI":"10.1249\/00005768-199307000-00003"},{"key":"2025083110583898000_7.3.e001112.7","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.10.1672"},{"key":"2025083110583898000_7.3.e001112.8","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.412"},{"key":"2025083110583898000_7.3.e001112.9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.75.3.692"},{"key":"2025083110583898000_7.3.e001112.10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.6.1775"},{"key":"2025083110583898000_7.3.e001112.11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.14310\/horm.2002.1300","article-title":"Menstrual function in sports","volume":"10","author":"Roupas","year":"2011","journal-title":"Hormones"},{"key":"2025083110583898000_7.3.e001112.12","doi-asserted-by":"crossref","first-page":"i68","DOI":"10.1136\/bjsm.2007.038018","article-title":"The female football player, disordered eating, menstrual function and bone health","volume":"41 Suppl 1","author":"Sundgot-Borgen","year":"2007","journal-title":"Br J Sports Med"},{"key":"2025083110583898000_7.3.e001112.13","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0039"},{"key":"2025083110583898000_7.3.e001112.14","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2005.020065"},{"key":"2025083110583898000_7.3.e001112.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-007-0518-6"},{"key":"2025083110583898000_7.3.e001112.16","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1210\/js.2017-00102","article-title":"Treatments to prevent bone loss in functional hypothalamic amenorrhea: a systematic review and meta-analysis","volume":"1","author":"Altayar","year":"2017","journal-title":"J Endocr Soc"},{"key":"2025083110583898000_7.3.e001112.17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/eat.20687","article-title":"Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: a systematic review and meta-analyses","volume":"43","author":"Sim","year":"2010","journal-title":"Int J Eat Disord"},{"key":"2025083110583898000_7.3.e001112.18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jpsychores.2017.05.011","article-title":"Pharmacological treatment options for low bone mineral density and secondary osteoporosis in anorexia nervosa: a systematic review of the literature","volume":"98","author":"Robinson","year":"2017","journal-title":"J Psychosom Res"},{"key":"2025083110583898000_7.3.e001112.19","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.447"},{"key":"2025083110583898000_7.3.e001112.20","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2018-099723"},{"key":"2025083110583898000_7.3.e001112.21","doi-asserted-by":"crossref","DOI":"10.7326\/0003-4819-151-4-200908180-00136","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration","volume":"151","author":"Liberati","year":"2009","journal-title":"Ann Intern Med"},{"key":"2025083110583898000_7.3.e001112.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0004-9514(14)60281-6"},{"key":"2025083110583898000_7.3.e001112.23","doi-asserted-by":"crossref","unstructured":"Nakano T , Tabata Y , Umakoshi Y . Texture and Bone Reinforcement. In: Encyclopedia of materials: science and technology. Elsevier, Oxford, 2005.","DOI":"10.1016\/B0-08-043152-6\/02061-1"},{"key":"2025083110583898000_7.3.e001112.24","first-page":"1155","article-title":"Bone turnover in cortical and trabecular bone in normal women and in women with osteoporosis","volume":"35","author":"Israel","year":"1994","journal-title":"J Nucl Med"},{"key":"2025083110583898000_7.3.e001112.25","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4036(199912)41:8<901::AID-BIMJ901>3.0.CO;2-W"},{"key":"2025083110583898000_7.3.e001112.26","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1482"},{"key":"2025083110583898000_7.3.e001112.27","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-25"},{"key":"2025083110583898000_7.3.e001112.28","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/jrsm.1297","article-title":"Methods for evidence synthesis in the case of very few studies","volume":"9","author":"Bender","year":"2018","journal-title":"Res Synth Methods"},{"key":"2025083110583898000_7.3.e001112.29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jrsm.1319","article-title":"Methods to calculate uncertainty in the estimated overall effect size from a random-effects meta-analysis","volume":"10","author":"Veroniki","year":"2019","journal-title":"Res Synth Methods"},{"key":"2025083110583898000_7.3.e001112.30","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"2025083110583898000_7.3.e001112.31","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7121.1533"},{"key":"2025083110583898000_7.3.e001112.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(97)70396-X"},{"key":"2025083110583898000_7.3.e001112.33","doi-asserted-by":"publisher","DOI":"10.1007\/s001980050228"},{"key":"2025083110583898000_7.3.e001112.34","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.6.2883"},{"key":"2025083110583898000_7.3.e001112.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jadohealth.2006.09.010"},{"key":"2025083110583898000_7.3.e001112.36","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0b013e318074e532"},{"key":"2025083110583898000_7.3.e001112.37","first-page":"875","article-title":"Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives","volume":"46","author":"Castelo-Branco","year":"2001","journal-title":"J Reprod Med"},{"key":"2025083110583898000_7.3.e001112.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(03)00660-5"},{"key":"2025083110583898000_7.3.e001112.39","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-012-0436-7"},{"key":"2025083110583898000_7.3.e001112.40","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-011-0296-6"},{"key":"2025083110583898000_7.3.e001112.41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020369"},{"key":"2025083110583898000_7.3.e001112.42","first-page":"39","article-title":"Amenorrhea: a systematic approach to diagnosis and management","volume":"100","author":"Klein","year":"2019","journal-title":"Am Fam Physician"},{"key":"2025083110583898000_7.3.e001112.43","unstructured":"Substance Abuse and Mental Health Services Administration. In: Disturbance D-CIfCSE, ed. US: Rockville (MD): Substance Abuse and Mental Health Services Administration (US), 2016:Table 19, DSM-IV to DSM-5 Anorexia Nervosa Comparison."},{"key":"2025083110583898000_7.3.e001112.44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.18773\/austprescr.2016.020","article-title":"Bone mineral density: testing for osteoporosis","volume":"39","author":"Sheu","year":"2016","journal-title":"Aust Prescr"},{"key":"2025083110583898000_7.3.e001112.45","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0025-6196(12)65502-5","article-title":"Comparison of dual-energy X-ray absorptiometry and dual photon absorptiometry for bone mineral measurements of the lumbar spine","volume":"63","author":"Wahner","year":"1988","journal-title":"Mayo Clin Proc"},{"key":"2025083110583898000_7.3.e001112.46","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1986.03380030082032"},{"key":"2025083110583898000_7.3.e001112.47","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1210\/jc.2017-00131","article-title":"Functional hypothalamic amenorrhea: an endocrine Society clinical practice guideline","volume":"102","author":"Gordon","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2025083110583898000_7.3.e001112.48","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.7.3162"},{"key":"2025083110583898000_7.3.e001112.49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1123\/ijsn.6.1.24","article-title":"Treatment of athletic amenorrhea with a diet and training intervention program","volume":"6","author":"Dueck","year":"1996","journal-title":"Int J Sport Nutr"},{"key":"2025083110583898000_7.3.e001112.50","doi-asserted-by":"publisher","DOI":"10.1249\/JSR.0000000000000077"},{"key":"2025083110583898000_7.3.e001112.51","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0035"},{"key":"2025083110583898000_7.3.e001112.52","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0723"},{"key":"2025083110583898000_7.3.e001112.53","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-410473-0.00009-X"},{"key":"2025083110583898000_7.3.e001112.54","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(90)90034-S"},{"key":"2025083110583898000_7.3.e001112.55","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-72-2-374"},{"key":"2025083110583898000_7.3.e001112.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)01691-5"},{"key":"2025083110583898000_7.3.e001112.57","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0560"}],"container-title":["BMJ Open Sport &amp; Exercise Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjsem-2021-001112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T17:58:51Z","timestamp":1756663131000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopensem.bmj.com\/lookup\/doi\/10.1136\/bmjsem-2021-001112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,7,7]]},"published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1136\/bmjsem-2021-001112"],"URL":"https:\/\/doi.org\/10.1136\/bmjsem-2021-001112","relation":{},"ISSN":["2055-7647"],"issn-type":[{"value":"2055-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7]]}}}