Does hormone replacement therapy increase the risk of all-cause and cause-specific mortality in postmenopausal women?

This cumulative 18-year follow-up report from the Women's Health Initiative hormone replacement therapy (HRT) trials found no significant differences in all-cause mortality, cardiovascular-related mortality, or cancer-related mortality in postmenopausal women who previously took estrogen plus progesterone or estrogen alone (with a prior hysterectomy) compared with placebo-control groups. Less than 4% of the women in the original study continued HRT after the trial was stopped. There was no increased risk of breast cancer mortality with the use of HRT and a significantly reduced risk of breast cancer mortality among the group of women who took estrogen only. (LOE = 2b)

Manson JE Aragaki AK, Rossouw JE, et al, for the WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality. The Women's Health Initiative randomized trials. JAMA 2017;318(10):927-938.  [PMID:28898378]

Randomized controlled trial (double-blinded)

Government

Concealed

Outpatient (any)

This report is a long-term follow-up of the Women's Health Initiative HRT trials that evaluated the outcomes of giving conjugated equine estrogens plus progesterone to postmenopausal women, aged 50 to 79 years, with an intact uterus and giving estrogen alone for women in the same age group with a previous hysterectomy. The original trials were stopped after 7.2 years because of an increased risk of stroke in the treatment groups compared with the placebo control group. After the original trial was stopped less than 4% of women reported continued HRT use. These investigators analyzed data about the study participants obtained from regular surveillance of the National Death Index and reports from next of kin for all deaths through December 31, 2014. Results include a cumulative follow-up of 18 years for both the estrogen-plus-progesterone and estrogen-alone trials. No significant differences occurred between the 2 treatment groups and their respective control groups in the risks of all-cause mortality, cardiovascular-related mortality, and cancer-related mortality. For breast cancer mortality, no significant difference occurred between women who took estrogen plus progesterone compared with those who took placebo, but there was a significant reduction (yes, reduction) in breast cancer mortality among the estrogen-alone group compared with the placebo group. There was also no significant difference in mortality based on 10-year age increments (ie, women aged 50 to 59 years, 60 to 69 years, and 70 to 79 years).