Abstract
CONTEXT: The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT. OBJECTIVE: The purpose of this study was to examine fractures after discontinuation of HT. DESIGN AND SETTING: Two placebo-controlled randomized trials served as the study setting. PATIENTS: Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period. INTERVENTIONS: Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy. MAIN OUTCOME MEASURES: Total fractures and hip fractures through 5 years after discontinuation of HT were recorded. RESULTS: Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03). CONCLUSIONS: We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.