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Loss of bone density and bone strength following premenopausal risk–reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study)

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Abstract

Summary

Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss.

Introduction

This prospective study investigated bone health in women following premenopausal oophorectomy.

Methods

Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up.

Results

Mean age was 42.4 ± 2.6 years (n = 30) for the surgery group and 40.2 ± 6.3 years for controls (n = 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (kbend) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all p < 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and kbend (14.8%) were observed at 24 months (all p < 0.01). HT prevented losses in kbend, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (p = 0.01).

Conclusion

This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.

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Acknowledgments

We thank all study participants for their contribution to this study. We wish to acknowledge Dr. Ashwini Kale for performing DXA and pQCT scans. We thank Dr. Gillian Mitchell, Associate Professor Bettina Meiser, and Dr. Mary-Ann Davey for their contributions in the design of the WHAM study.

Funding

MH is funded by an Australian Government National Health and Medical Research Council (NHMRC) Practitioner Fellowship (reference: APP1058935). The study was funded by NHMRC Project Grant to MH and JDW (reference: APP1048023). HJ was funded by a joint PhD scholarship by China Scholarship Council (reference: CSC201608240003) and the University of Melbourne.

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Authors and Affiliations

  1. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, 3050, Australia

    H. Jiang, C. J. Yates & J. D. Wark

  2. Department of Biomedical Engineering, University of Melbourne, Parkville, Australia

    D. L. Robinson & P. V. S. Lee

  3. Department of Obstetrics and Gynaecology, University of Melbourne and Royal Women’s Hospital, Parkville, Australia

    E. O. Krejany & M. Hickey

  4. Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville, Australia

    C. J. Yates & J. D. Wark

  5. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Australia

    C. J. Yates & J. D. Wark

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  1. H. Jiang
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  3. P. V. S. Lee
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  4. E. O. Krejany
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Corresponding author

Correspondence to J. D. Wark.

Ethics declarations

The study was conducted in accordance with the Declaration of Helsinki. Ethics approval was obtained from the respective human research ethics committee at the Royal Melbourne Hospital (ethics reference: MH2013.060), the Royal Women’s Hospital, Melbourne (ethics reference: RWH12/50), and the Peter MacCallum Cancer Centre (ethics reference: HREC/12/PMCC/24).

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Professor Martha Hickey is joint senior author.

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Jiang, H., Robinson, D.L., Lee, P.V.S. et al. Loss of bone density and bone strength following premenopausal risk–reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study). Osteoporos Int 32, 101–112 (2021). https://doi.org/10.1007/s00198-020-05608-5

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