November 09, 2016
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WHI: No increase in fracture risk after stopping hormone therapy

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Postmenopausal women who discontinue hormone therapy experience a loss of protection against hip fracture, but there is no “rebound increase” in risks for hip fracture or total fracture vs. those assigned a placebo, according to an analysis of the Women’s Health Initiative.

“The diminishing benefit on fracture reduction after HT discontinuation was remarkably consistent irrespective of age, ethnicity, years since menopause, BMI, duration of previous HT, smoking, alcohol intake, physical activity level, prior fracture, falls in the past year, calcium intake, vitamin D intake or use of bone-active medications,” Nelson Watts, MD, FACP, MACE, director of Mercy Health Osteoporosis and Bone Health Services in Cincinnati, and colleagues wrote. “These data do not further elucidate whether this loss of protection against fracture reflects increased bone turnover, accentuated bone loss or other yet unidentified factors.”

Nelson Watts
Nelson Watts

Watts and colleagues analyzed data from 15,187 women who participated in one of two randomized, placebo-controlled trials in the WHI who continued active HT (either conjugated equine estrogen plus medroxyprogesterone acetate or conjugated equine estrogen alone) or placebo through the intervention period and did not take HT in the post-intervention period. Researchers assessed hip fractures and total fractures though 5 years after discontinuation via semiannual questionnaires, interviews or clinical exams.

Researchers found that the rates of hip fracture were similar between the two trials and between groups assigned either HT or placebo (2.5 per 1,000 patient-years).

In the conjugated equine estrogen plus medroxyprogesterone acetate trial, there were no between-group differences in total fracture rates for women who stopped HT (28.9 per 1,000 person-years) or placebo (29.9 per 1,000 person-years), for an HR of 0.97 (95% CI, 0.87-1.09). In the trial of conjugated equine estrogen alone, however, researchers observed a possible residual benefit of HT against total fracture, as total fractures were higher among former placebo users (36.9 per 1,000 person years) vs. former HT users (31.1 per 1,000 person years; HR = 0.85; 95% CI, 0.73-0.98).

“We have shown that discontinuation of HT results in a rapid dissipation of benefit for hip fracture reduction after medication discontinuation, but no rebound increase in fracture risk, and possible residual benefit against total fractures for women stopping [conjugated equine estrogen] alone,” the researchers wrote. “These findings should help to inform clinicians and women about the effects of discontinuation of HT on fracture risk.” – by Regina Schaffer

Disclosure: Watts reports serving as a consultant to AbbVie, Amgen and Radius and has received honoraria from Amgen and Shire. Please see the full study for the other authors’ relevant financial disclosures.