Menopausal Hormone Therapy Not Associated With Risk of Long-Term All-Cause Mortality

Among postmenopausal women, hormone therapy with estrogen plus progestin for a median of 5.6 years or with estrogen alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular or cancer mortality, according to a study published Sept. 12 in the Journal of the American Medical Association.

JoAnn E. Manson, MD, DrPH, et. al., assessed postmenopausal women between 50 – 79 years old who were enrolled in two randomized Women’s Health Initiative clinical trials between 1993 and 1998. The participants were followed through December 2014 and measured on all-cause mortality and cause-specific mortality such as cardiovascular disease mortality, cancer mortality and other major causes of mortality. It also assessed the potential difference by age.

Among the 27,347 women in the study (mean age 63.4 years old/80.6 percent white), 16,608 women with a uterus were randomized to receive daily oral conjugated equine estrogens (CEE) plus medroxyprogesterone acetate progestin (MPA) or placebo. Additionally, 10,739 women with hysterectomy were randomized to receive daily oral CEE alone or placebo.

During the cumulative 18-year follow-up, 7,489 deaths occurred – 1,088 during the intervention phase and 6,401 during the postintervention phase. Mortality follow-up was available for more than 98 percent of participants.

Results showed all-cause mortality was 27.1 percent in the hormone therapy group versus 27.6 percent in the placebo group (hazard ratio [HR], 0.99 [95 percent CI, 0.94-1.03]) in the overall pooled cohort. For the individual trials, all-cause mortality was 26.4 percent for CEE plus MPA, compared to 26.0 percent for placebo (HR, 1.02 [95 percent CI, 0.96-1.08]). All-cause mortality in the CEE alone group was 28.3 percent compared to 30.0 percent for placebo (HR, 0.94 [95 percent CI, 0.88-1.01]).

In the overall pooled cohort, cardiovascular mortality was 8.9 percent in the hormone therapy group vs. 9.0 percent in the placebo group (HR, 1.00 [95 percent CI, 0.92-1.08]), with no differences between trials. Total cancer mortality was 8.3 percent for the CEE plus MPA group vs. 7.9 percent for the placebo group (HR, 1.06 [95 percent CI, 0.95-1.18]). Additionally, cancer mortality was 8.0 percent for the CEE group compared to 8.1 percent for the placebo group (HR, 0.99 [95 percent CI, 0.86-1.13]). Mortality from other causes also did not differ significantly between the hormone therapy group (10 percent) and the placebo group (10.7 percent).

When examined by 10-year age group (50 – 59 years old vs. 70 – 79 years old) the ratios of nominal HRs for all-cause mortality in the pooled cohort were 0.61 (95 percent CI, 0.43-0.87) during the intervention phase and 0.87 (95 percent CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. The trend by age group was significant during the intervention phase but not during the cumulative follow-up period.

In an accompanying editorial comment, Melissa McNeil, MD, MPH, notes, "This information will be helpful in counseling women considering whether to start hormone therapy and hopefully will alleviate concerns that many patients and physicians have about the initiation of hormone therapy." She adds, "For women with troubling vasomotor symptoms, premature menopause, or early-onset osteoporosis, hormone therapy appears to be both safe and efficacious."

Keywords: Estrogens, Conjugated (USP), Medroxyprogesterone Acetate, Progestins, Menopause, Premature, Postmenopause, Follow-Up Studies, Estrogens, Hormone Replacement Therapy, Hysterectomy, Uterus, Osteoporosis, Counseling, Cardiovascular Diseases, Neoplasms

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