Postmenopausal women receiving hormone therapy with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for 5.6 years or 7.2 years of CEE alone may not have a risk of all-cause cardiovascular or cancer mortality when compared with woman receiving placebo, according to a study published in JAMA.

Researchers retrospectively reviewed data from 2 randomized clinical trials (the Women’s Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials; identifier: NCT00000611) that occurred between 1993 and 1998, in addition to post trial follow-up data through 2014. Investigators identified 27,347 postmenopausal women aged 50 to 79 years, and randomly assigned women with a uterus (n=16,608) to receive either daily oral CEE plus MPA (n=8506) or placebo (n=8102) for 5.6 years, and women who had undergone a hysterectomy (n=10,739) to receive either oral CEE alone (n=5310) or placebo (n=5429) for 7.2 years. The primary outcome observed was all-cause mortality; cause-specific mortality was also an observed outcome.

Study results revealed 7849 deaths; 1088 occurred during the intervention phase, and 6401 deaths occurred during the 18-year follow-up. The primary outcome of all-cause mortality in the hormone therapy and placebo groups was 27.1% and 27.6%, respectively (hazard ratio, 0.99; 95% CI, 0.94-1.03). Hazard ratios of women treated with CEE plus MPA and women treated with CEE alone were 1.02 (95% CI, 0.96-1.08) and 0.94 (95% CI, 0.88-1.01), respectively.

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Limitations of this study include only 1 dose, formulation, and route of hormone therapy studied, thereby limiting the generalizability of the study findings. In addition, 80.6% of participants were racially identified as “white,” limiting the generalizability of the findings in other racial populations.

Researchers concluded that during a cumulative 18-year follow-up of these 2 hormone therapy clinical trials, hormone therapy with CEE plus MPA for 5.6 years and CEE alone for 7.2 years in postmenopausal women “was not associated with risk of all-cause, cardiovascular, or cancer mortality” when compared with placebo.

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Based on these results, clinicians can discuss multiple hormone therapy treatment options with postmenopausal women without concern for higher all-cause mortality in any group.


Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the women’s health initiative randomized trials. JAMA. 2017;318:927-938.