Long-Term Menopausal Hormone Therapy Not Linked to Mortality Risk

Five to 7 years of menopausal hormone therapy was not associated with long-term risks for all-cause and cause-specific mortality, according to the findings of a recent study.

In their observational follow-up study, the researchers analyzed data from 27,347 women between 50 and 79 years of age who were involved in 2 Women’s Health Initiative Hormone Therapy trials. In the first trial, 8506 women were randomly assigned to receive conjugated equine estrogens (CEE, 0.625 mg/d) and medroxyprogesterone acetate (MPA, 2.5 mg/d) and 8102 were assigned to receive placebo for a median 5.6 years. In the second trial, 5310 women were randomly assigned to receive CEE alone and 5429 women were assigned to receive placebo for a median 7.2 years. The main study outcomes included all-cause mortality and cause-specific mortality in the 2 trials pooled and in each trial individually.
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A total of 7489 women died over the cumulative 18 years of follow-up, with 1088 deaths occurring during the intervention and 6401 deaths occurring post-intervention.

Among women who received hormone therapy, the all-cause mortality rate was 27.1% compared with 27.6% among women who received the placebo. The hazard ratios were 0.99 for all-cause mortality for the overall pooled cohort of women receiving hormone therapy, 1.02 for the CEE and MPA group, and 0.94 for the CEE alone group.

The pooled cohort cardiovascular mortality rate was 8.9% for the hormone therapy group compared with 9% for the placebo group, with an HR of 1. Likewise, total cancer-related mortality rate was 8.2% for the hormone therapy group compared with 8% for the placebo group, with an HR of 1.03. For all other causes of death, the rate was 10% for the hormone therapy group and 10.7% for the placebo group, with an HR of 0.95. These results did not differ significantly between trials.

In addition, the researchers found in an analysis of the pooled cohort that compared younger women (aged 50 to 59 years) to older women (70 to 79 years of age) that the ratio of nominal HRs for all-cause mortality was 0.61 during the intervention phase and 0.87 during follow-up. They did not find any significant heterogeneity between trials.

“Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years,” the researchers concluded.

—Melissa Weiss

Reference:

Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials [published online September 12, 2017]. JAMA. doi:10.1001/jama.2017.11217.