Article Text

Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: a systematic review and meta-analysis
  1. Karoline Aalberg1,
  2. Knut Stavem2,3,
  3. Frode Norheim4,
  4. Michael Bjørn Russell2,5,
  5. Aleksander Chaibi5,6
  1. 1Atlasklinikken, Oslo, Norway
  2. 2Institute of Clinical Medicine, Akershus University Hospital, Lorenskog, Norway
  3. 3Department of Pulmonary Medicine, University of Oslo, Akershus University Hospital, Lorenskog, Norway
  4. 4Department of Nutrition, University of Oslo, Institute of Basic Medical Sciences, Oslo, Norway
  5. 5Head and Neck Research Group, Division for Research and Innovation, Akershus University Hospital, Lorenskog, Norway
  6. 6Department for Interdisciplinary Health Sciences, Institute of Health and Society, University of Oslo Faculty of Medicine, Oslo, Norway
  1. Correspondence to Dr Karoline Aalberg; karoline_aalberg{at}


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.

  • female athlete triad
  • bone mineral density
  • osteoporosis
  • eating disorders

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  • Contributors KA conceived the review and drafted the initial manuscript. KA and AC performed the methodological assessment of the included studies. KA, MBR and AC synthesised the data in table. KS performed the statistical analysis. All authors have revised the paper for critical content and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.