Clinical Review

2017 Update on bone health

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Another WHI update: No increase in fractures after stopping HT

Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.

The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.

Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?

Details of the study

Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.

Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.

No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).

Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.

Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."

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