Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis

Background Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake.Objective To systematically review the literature of randomised controlled trials (RCTs) assessing the effect of oestrogen oral contraceptives (OCP), conjugated oestrogens (CE) and tr...

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Main Authors: Knut Stavem, Michael Bjørn Russell, Aleksander Chaibi, Karoline Aalberg, Frode Norheim
Format: Article
Language:English
Published: BMJ Publishing Group 2021-09-01
Series:BMJ Open Sport & Exercise Medicine
Online Access:https://bmjopensem.bmj.com/content/7/3/e001112.full
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author Knut Stavem
Michael Bjørn Russell
Aleksander Chaibi
Karoline Aalberg
Frode Norheim
author_facet Knut Stavem
Michael Bjørn Russell
Aleksander Chaibi
Karoline Aalberg
Frode Norheim
author_sort Knut Stavem
collection DOAJ
description Background Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake.Objective 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.Methods A comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020.Data extraction and synthesis Two authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis.Main outcomes Difference in BMD (g/cm2) at the lumbar spine.Results 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% CI −0.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95% CI −0.16 to 0.51). No serious adverse events were reported.Conclusion 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.
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spelling doaj-art-6f44e2e496fc401880a66ceefd1e0ab72025-08-20T02:11:34ZengBMJ Publishing GroupBMJ Open Sport & Exercise Medicine2055-76472021-09-017310.1136/bmjsem-2021-001112Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysisKnut Stavem0Michael Bjørn Russell1Aleksander Chaibi2Karoline Aalberg3Frode Norheim4Institute of Clinical Medicine, University of Oslo, Lørenskog, NorwayInstitute of Clinical Medicine, Akershus University Hospital, Lorenskog, Norwaysenior researcherAtlasklinikken, Oslo, NorwayDepartment of Nutrition, University of Oslo, Institute of Basic Medical Sciences, Oslo, NorwayBackground Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake.Objective 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.Methods A comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020.Data extraction and synthesis Two authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis.Main outcomes Difference in BMD (g/cm2) at the lumbar spine.Results 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% CI −0.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95% CI −0.16 to 0.51). No serious adverse events were reported.Conclusion 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.https://bmjopensem.bmj.com/content/7/3/e001112.full
spellingShingle Knut Stavem
Michael Bjørn Russell
Aleksander Chaibi
Karoline Aalberg
Frode Norheim
Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
BMJ Open Sport & Exercise Medicine
title Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
title_full Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
title_fullStr Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
title_full_unstemmed Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
title_short Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
title_sort effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea a systematic review and meta analysis
url https://bmjopensem.bmj.com/content/7/3/e001112.full
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