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Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial
  1. Kathryn E Ackerman1,2,
  2. Vibha Singhal1,3,
  3. Charumathi Baskaran1,3,
  4. Meghan Slattery1,
  5. Karen Joanie Campoverde Reyes1,
  6. Alexander Toth1,
  7. Kamryn T Eddy4,
  8. Mary L Bouxsein5,6,
  9. Hang Lee7,
  10. Anne Klibanski1,
  11. Madhusmita Misra1,3
  1. 1 Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Divisions of Sports Medicine and Endocrinology, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
  3. 3 Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA
  4. 4 Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  5. 5 Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  6. 6 Division of Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  7. 7 Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Kathryn E Ackerman, Divisions of Sports Medicine and Endocrinology, Boston Children’s Hospital, Boston MA 02115, USA; kathryn.ackerman{at}childrens.harvard.edu

Abstract

Objective Normal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was to determine the effects of transdermal versus oral oestrogen administration on bone in OAA engaged in weight-bearing activity.

Methods 121 patients with OAA aged 14–25 years were randomised to receive: (1) a 17β-estradiol transdermal patch continuously with cyclic oral micronised progesterone (PATCH), (2) a combined ethinyl estradiol and desogestrel pill (PILL) or (3) no oestrogen/progesterone (NONE). All participants received calcium and vitamin D supplementation. Areal BMD was assessed at the lumbar spine, femoral neck, total hip and total body less head using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. Intention-to-treat (ITT) and completers analyses were performed.

Results Randomised groups did not differ for age, body mass index or BMD Z-scores at baseline. For ITT analysis, spine and femoral neck BMD Z-scores significantly increased in the PATCH versus PILL (p=0.011 and p=0.021, respectively) and NONE (p=0.021 and p=0.033, respectively) groups, and hip BMD Z-scores significantly increased in the PATCH versus PILL group (p=0.018). Similar findings were noted in completers analysis.

Conclusion Transdermal estradiol over 12 months improves BMD in young OAA, particularly compared with an ethinyl estradiol-containing contraceptive pill/oral contraceptives.

Trial registration number NCT00946192; Pre-results

  • female athlete triad
  • endocrine
  • bone mineral density
  • adolescent
  • bone

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Footnotes

  • Contributors MM conceived the project and designed the study. MM, KEA and MLB contributed to study protocol and key data interpretation. KEA, MM, VS, CB, MS, KJCR, AT and KE were involved in patient assessments, visits and study coordination. HL and MM performed the statistical analysis. KEA wrote the initial draft of the paper. MM, KEA, MLB, HL and AK critically edited and revised the paper.

  • Funding This study was funded by National Institutes of Health grants R0I HD060827, K24 HD071843 and UL1TR001102 and S10 RR023045.

  • Competing interests MM has served on the Scientific Advisory Board of Novo Nordisk, is a coinvestigator on an investigator-initiated grant from Novo Nordisk and is a consultant for Sanofi Pharmaceuticals.

  • Patient consent Obtained.

  • Ethics approval Massachusetts General Hospital.

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

  • Data sharing statement These data have not been previously published and are original data. In addition, no other entity has permission to use these data.

  • Correction notice This article has been corrected since it published Online First. The patient consent statement has been corrected.

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