Postmenopausal women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for a median of 5.6 years, or with CEE alone for a median of 7.2 years had no increased risk of all-cause, cardiovascular, or cancer mortality over a cumulative follow-up of 18 years, according to the latest report from the Women’s Health Initiative hormone therapy trials.
All-cause mortality among the 27,347 participants in the two randomized, double-blind, placebo-controlled trials was 27.1% in the hormone therapy group versus 27.6% in the placebo group (hazard ratio, 0.99), JoAnn E. Manson, MD , Harvard Medical School, Boston, and her colleagues reported.
For those who received CEE plus MPA, the hazard ratio was 1.02, while for CEE alone the hazard ratio was 0.94 (JAMA. 2017 Sep;318:927-38).
Cardiovascular mortality among the pooled cohort was 8.9% with hormone therapy and 9.0% with placebo (HR, 1.00), and total cancer mortality was 8.2% and 8.0%, respectively (HR, 1.03). Mortality from other causes was 10.0% with hormone therapy, compared with 10.7% with placebo (HR, 0.95). The results did not differ significantly between the trials, the investigators noted.
An analysis by age showed that women aged 50-59 years tended to have lower hazard ratios for mortality from cardiovascular disease, cancer, and other causes during the intervention phases of the trials, but only the difference for “other” causes in the CEE-alone trial showed a statistically significant trend with age. This was influenced in part by adverse effects of the treatment in women aged 70-79 years. During cumulative follow-up, trends related to mortality across age groups were not statistically significantly different.
The trials included women aged 50-79 years who were enrolled between 1993 and 1998 and followed through 2014. Given the hormone-therapy-related risks identified in the CEE plus MPA and CEE-alone trials – which were stopped early because of increased risk of breast cancer/overall risks exceeding benefits, and for increased stroke risk, respectively – the absence of an increase in all-cause mortality during the intervention and cumulative follow-up phases of the trials is noteworthy, the investigators wrote.
“Although these findings lend support to practice guidelines endorsing use of hormone therapy for recently menopausal women with moderate to severe symptoms, in the absence of contraindications, the attenuation of age differences with longer follow-up and potential health risks of treatment would not support use of hormone therapy for reducing chronic disease or mortality,” they wrote. “Moreover, it is unclear whether benefits would outweigh risks with longer duration of treatment.”
They added that “in clinical decision making, these considerations must be weighed against the evidence linking untreated vasomotor symptoms in midlife women to impaired health and quality of life, disrupted sleep, reduced work productivity, and increased health care expenditures.”
The Women’s Health Initiative is funded by the U.S. Department of Health & Human Services. Study drugs were donated by Wyeth Ayerst. Dr. Manson reported having no financial disclosures. Several of her coauthors reported receiving grants and research funding from the National Institutes of Health, and receiving personal fees, speaking fees, and honoraria from various pharmaceutical companies.