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Description of Evidence


    The WHI Estrogen-Alone Trial was a double-masked, placebo-controlled randomized clinical trial conducted among women who have had a hysterectomy. Women aged 50 to 79 years (N = 10,739) were randomly assigned to receive either conjugated equine estrogen (CEE) or placebo. Estrogen-only preparations should only be considered among women who have had a hysterectomy since unopposed estrogen increases the risk of uterine cancer. Like the WHI combined-HT trial, this trial was stopped early because of an increased risk of stroke and no evidence of benefit as measured by a global index of risks and benefits.[37,38] After an average of 6.8 years of follow-up, the incidence of breast cancer was lower in the group receiving CEE compared with placebo but the difference was not statistically significant (HR = 0.77; 95% CI, 0.59–1.01; 26 vs. 33 cases of invasive breast cancer per 10,000 person-years [annualized rate of 0.26% vs. 0.33%], respectively). For the global index of risks and benefits (based on outcomes of stroke, pulmonary embolus, breast cancer, colorectal cancer, hip fractures, and death), there was a nonstatistically significant excess of two events per 10,000 person-years.[37] An extended follow-up for a median of 11.8 years was conducted with 78% of the trial participants consenting to take part.[38,39] Characteristics among those in the extended follow-up who were randomly assigned to receive active intervention with CEE or placebo were similar, except for slight imbalances in history of prior breast biopsy (19.8% among the CEE group and 22.3% among the placebo group) and prior hormone use (48.9% among the CEE group and 50.4% among the placebo group). At the end of the follow-up period, 151 cases of breast cancer occurred among the CEE group (0.27% per year) compared with 199 cases of breast cancer among the placebo group (0.35% per year) (HR = 0.77; 95% CI, 0.62–0.95).[38,39] Breast cancer mortality was statistically significantly lower in the CEE group (6 deaths, 0.009% per year) than in the placebo group (16 deaths, 0.024% per year) (HR = 0.37; 95% CI, 0.13–0.91). All-cause mortality was also lower in the CEE group (0.046% per year) than in the placebo group (0.076% per year) (HR = 0.62; 95% CI 0.39–0.97). Following discontinuation of CEE, the risk of stroke decreased in the postintervention period. Over the entire follow-up period, there was no increased or decreased risk of coronary heart disease, deep vein thrombosis, stroke, hip fracture, or colorectal cancer.[38] Among the subset of women in the WHI trial who initiated estrogen-only therapy within the first 5 years of onset of menopause, neither an excess nor decreased risk of developing breast cancer was observed (HR = 1.06; 95% CI, 0.74–1.51).


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