Postmenopausal hormone replacement therapy may not prevent chronic diseases in women, based on an extended study of data from the Women’s Health Initiative (WHI) studies. The trials assessed the effects of therapy on heart disease, fractures, breast cancer and colorectal cancer in more than 27,000 women across the U.S.
The most recent analysis, published in the Oct. 2 issue of JAMA, involved a longer follow-up that continued until September 2010.
“The goal of this report is to provide a comprehensive, integrated overview of findings from the 2 WHI hormone therapy trials with extended postintervention follow-up,” wrote the authors, led by JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston.
As primary efficacy and safety outcomes, the authors assessed coronary heart disease (CHD) and invasive breast cancer. They also evaluated stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture and death.
In the WHI studies, study participants with a uterus were randomized to receive oral conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (Prempro, Pfizer) or a placebo. In another trial, women who had a hysterectomy were randomized to oral CEE alone (Premarin, Pfizer) or a placebo.
“Overall, the risks of CEE plus MPA therapy during the intervention phase outweighed the benefits,” they wrote. “Most risks and benefits from CEE plus MPA dissipated postintervention; however, cardiovascular disease events remained nonsignificantly elevated,” the authors found.
In terms of the primary outcomes, the results of the two WHI studies were different. Women in the CEE plus MPA intervention group were at higher risk for CHD compared with placebo (hazard ratio [HR] 1.18). The HR was 1.8 one year after the intervention, but was not elevated as much or was neutral in the years afterward. Women who received only CEE had an HR of 0.94 compared with placebo. The HRs remained about the same in the years after the women were randomized.
During the extended follow-up period, the CHD HRs were 1.08 for CEE and MPA and 0.94 for CEE alone in comparison to placebo.
Data for MI were similar to the data for CHD. HRs increased by postmenopausal decade for the CEE and MPA group. For CEE, the HRs increased with each age decade.
CABG or PCI were included as a secondary outcome in both WHI trials. In the CEE and MPA group, the HR was 0.95 in comparison to placebo. In the CEE only group, the HR was 1 compared to placebo. For all other cardiovascular events, the HR was 1.13 in the CEE plus MPA group compared to placebo and in the CEE alone group, the HR was 1.11 compared to placebo. The risk of stroke and deep vein thrombosis were also higher in both intervention groups when compared to placebo.
However, the HRs were neutral during the postintervention phase. Data were neutral for cardiovascular death throughout the trial phases.
Younger age offered benefits to the CEE alone group. There was a more favorable risk-to-benefit ratio among younger women who had a hysterectomy, but in the CEE plus MPA group, the risks outweighed the benefits regardless of age.
The findings, the authors wrote, suggest that postmenopausal hormone therapy has complex effects on women’s health. Overall, their data do not back up the use of hormone replacement therapy for chronic disease prevention.
Even though hormone replacement therapy may be used to manage symptoms of menopause, they urged caution in the use of hormone replacement therapy among younger and older women “given the high risk of CHD and other outcomes associated with hormone therapy use in this setting.”