Menopausal Hormone Therapy and Long-Term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials

This study was a further investigation of the data accumulated in the hormone trials of the Women's Health Initiative (WHI). While the general results derived from theWHI hormone trials have been reported previously, this study focused on the long-term follow-up of the all-cause mortality rates. The WHI ran 2 large random, controlled hormone trials from 1993 to 1998 of postmenopausal women. If the women still had their uterus, they received either conjugated equine estrogens (CEEs) plus medroxyprogesterone acetate (MPA, n = 8506) or a placebo (n = 8102) for approximately 5 1/2 years. In the second study, women without their uterus received CEE alone (n = 5310) or a placebo (n = 5429) for a bit over 7 years. This current study set up a long-term follow-up of the more 27,000 women placed into these trials through the end of 2014. Mortality data were available for more than 98% of them. In the 18-year period after the initial trials, deaths by all causes were 27.1% of the women who received hormones versus 27.6% of the women in the placebo group for a hazard ratio of 0.99. Breaking the treatment group risks down by type showed that the CEE-plus-MPA group had a hazard ratio (HR) = 1.02, and the CEE group had an HR = 0.94 for deaths by all causes. Deaths by cardiovascular disease were 8.9% for the treated group versus 9.0% for the placebo group (HR = 1.00). By treatment type, for cardiovascular disease, CEE plusMPA had an HR = 1.08, and the CEE-alone group had an HR = 1.01 compared with placebo groups. Deaths due to cancer were 8.2% for the hormone treatment group versus 8.0% for the placebo group (HR = 1.02). The CEE-plus-MPA group had an HR = 1.06, and the CEE-alone group HR = 0.99 compared with placebo groups. Breast cancer deaths were less than those in the placebo group for the CEE-alone group (HR = 0.55) and greater than those in the placebo group for the CEE-plus-MPA group (HR = 1.44), but because of heterogeneity of risk issues, these data were not pooled into the results. Deaths by all other causes were 10% for the hormone therapy group and 10.7% for the placebo group (HR = 0.95), with no significant differences between the 2 treatment groups. No trends were seen by age stratification analyses. Among the women in the WHI hormone therapy trials, the risk of death from all causes, by cardiovascular disease, or by cancer was not significantly different from placebo groups though the 18-year follow-up period.