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The Women’s Health Initiative: Hormone Therapy and Calcium/Vitamin D Supplementation Trials

  • Evaluation and Management (M Kleerekoper, Section Editor)
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Abstract

The Women’s Health Initiative (WHI) was a large and complex study focused on strategies for the prevention and control of common chronic diseases of postmenopausal women. The WHI included 3 randomized controlled trials: the Hormone Therapy (HT) Trials, the Diet Modification Trial, and the Calcium/Vitamin D (CaD) Trial. Conjugated equine estrogen with or without a progestin significantly decreased hip, clinical vertebral, and all fractures. Once the intervention was stopped, the fracture benefit dissipated. However, estrogen plus progestin was associated with more risks than benefits and use of hormone therapy solely for the prevention of osteoporosis is not recommended. The CaD trial found no overall benefit for fracture reduction except in adherent women and women taking supplements for 5 or more years. Overall, the common practice of taking calcium and vitamin D supplementation with possible benefits on hip and positive evidence on bone mineral density and few risks is reasonable.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials. 1998;19(1):61–109.

    Article  Google Scholar 

  2. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701–12.

    Article  PubMed  CAS  Google Scholar 

  3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.

    Article  PubMed  CAS  Google Scholar 

  4. Wysowski DK, Golden L, Burke L. Use of menopausal estrogens and medroxyprogesterone in the United States, 1982–1992. Obstet Gynecol. 1995;85(1):6–10.

    Article  PubMed  CAS  Google Scholar 

  5. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20(1):47–63.

    Article  PubMed  CAS  Google Scholar 

  6. Lindsay R, Hart DM, Clark DM. The minimum effective dose of estrogen for prevention of postmenopausal bone loss. Obstet Gynecol. 1984;63(6):759–63.

    PubMed  CAS  Google Scholar 

  7. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995;273(3):199–208.

    Google Scholar 

  8. •• Heiss G, Wallace R, Anderson GL, et al. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–45. This paper summarizes the outcomes of the E+P trial during the intervention phase, post-intervention and overall.

  9. •• LaCroix AZ, Chlebowski RT, Manson JE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305(13):1305–14. This paper summarizes the outcomes of the E-alone trial during the intervention phase, post-intervention and overall.

    Article  PubMed  CAS  Google Scholar 

  10. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA. 2003;290(13):1729–38.

    Article  PubMed  CAS  Google Scholar 

  11. Jackson RD, Wactawski-Wende J, LaCroix AZ, et al. Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women’s health initiative randomized trial. J Bone Miner Res. 2006;21(6):817–28.

    Article  PubMed  CAS  Google Scholar 

  12. Black DM, Steinbuch M, Palermo L, et al. An assessment tool for predicting fracture risk in postmenopausal women. Osteoporos Int. 2001;12(7):519–28.

    Article  PubMed  CAS  Google Scholar 

  13. Pilon D, Castilloux AM, LeLorier J. Estrogen replacement therapy: determinants of persistence with treatment. Obstet Gynecol. 2001;97(1):97–100.

    Article  PubMed  CAS  Google Scholar 

  14. Coker LH, Espeland MA, Rapp SR, et al. Postmenopausal hormone therapy and cognitive outcomes: the Women’s Health Initiative Memory Study (WHIMS). J Steroid Biochem Mol Biol. 2010;118(4–5):304–10.

    Article  PubMed  CAS  Google Scholar 

  15. Clarkson TB, Melendez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause. 2013;20(3):342–53.

    Article  PubMed  Google Scholar 

  16. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354(7):684–96.

    Article  PubMed  CAS  Google Scholar 

  17. • Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669–83. This paper is the primary report of the calcium/Vitamin D trial and the fracture/bone mineral density outcomes.

  18. Jackson RD, LaCroix AZ, Cauley JA, McGowan J. The Women’s Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ann Epidemiol. 2003;13(9 Suppl):S98–106.

    Article  PubMed  Google Scholar 

  19. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40–9.

    Article  PubMed  CAS  Google Scholar 

  20. • Prentice RL, Pettinger MB, Jackson RD, et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int. 2013;24(2):567–80. This paper is an updated analyasis of the Calcium/Vitamin D trial on multiple outcomes.

    Article  PubMed  CAS  Google Scholar 

  21. de Boer IH, Tinker LF, Connelly S, et al. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care. 2008;31(4):701–7.

    Article  PubMed  Google Scholar 

  22. Manson JE, Allison MA, Carr JJ, et al. Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative. Menopause. 2010;17(4):683–91.

    PubMed  Google Scholar 

  23. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846–54.

    Article  PubMed  CAS  Google Scholar 

  24. Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100(22):1581–91.

    Article  PubMed  CAS  Google Scholar 

  25. Brunner RL, Cochrane B, Jackson RD, et al. Calcium, vitamin D supplementation, and physical function in the Women’s Health Initiative. J Am Diet Assoc. 2008;108(9):1472–9.

    Article  PubMed  Google Scholar 

  26. LaCroix AZ, Kotchen J, Anderson G, et al. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women’s Health Initiative calcium-vitamin D randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2009;64(5):559–67.

    Article  PubMed  Google Scholar 

  27. Rejnmark L, Avenell A, Masud T, et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab. 2012;97(8):2670–81.

    Article  PubMed  CAS  Google Scholar 

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Compliance with Ethics Guidelines

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Conflict of Interest

JA Cauley is part of an advisory board for Merck, and has given expert testimony in Fosamax litigation on behalf of Merck. Her institution has received grants from the NIH.

Human and Animal Rights and Informed Consent

The WHI protocol was approved by the Institutional Review Board (IRB) at each participating institution. All women signed written consent.

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Authors and Affiliations

  1. Graduate School of Public Health, Department of Epidemiology, University of Pittsburgh, 130 DeSoto St, Crabtree A510, Pittsburgh, PA, 15261, USA

    Jane A. Cauley

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  1. Jane A. Cauley
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Correspondence to Jane A. Cauley.

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Cauley, J.A. The Women’s Health Initiative: Hormone Therapy and Calcium/Vitamin D Supplementation Trials. Curr Osteoporos Rep 11, 171–178 (2013). https://doi.org/10.1007/s11914-013-0150-7

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  • DOI: https://doi.org/10.1007/s11914-013-0150-7

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