Extended follow-up of the Womens Health Initiative hormone therapy trials does not support use of hormones for chronic disease prevention, although the treatment may be appropriate for menopausal symptom management in some women.
The hormone therapy trials of the Womens Health Initiative were stopped after investigators found the health risks outweighed the benefits, according to background information in the study, which was published in the Oct. 2 issue of the Journal of the American Medical Association. Menopausal hormone therapy continues in clinical use, but questions remain regarding its risks and benefits over the long-term for chronic disease prevention.
JoAnn E. Manson, MD, DrPH, of Brigham and Womens Hospital in Boston, and colleagues provide a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up and stratification by age and other important variables. The study included 27,347 postmenopausal women, ages 50 through 79, who were enrolled at 40 U.S. centers in 1993.
Women with an intact uterus received conjugated equine estrogens plus medroxyprogesterone acetate (8,506 study participants) or placebo (8,102 participants). Women with prior hysterectomy received CEE alone (5,310 participants) or placebo (5,429 participants). The intervention lasted a median of 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial, with six to eight additional years of follow-up until September 2010.
The researchers found that overall, the risks of CEE plus MPA during intervention outweighed the benefits. Risks were increased for coronary heart disease, breast cancer, stroke, pulmonary embolism, dementia (in women 65 and older), gallbladder disease and urinary incontinence. Benefits included decreased hip fractures, diabetes and vasomotor symptoms. Most risks and benefits dissipated post-intervention, although some elevation in breast cancer risk persisted during follow-up.
For CEE in women with prior hysterectomy, the benefits and risks during the intervention phase were more balanced, with increased risks of stroke and venous thrombosis, reduced risk of hip and total fractures and a reduction in breast cancer that was not considered statistically significant. Post-intervention with CEE, a significant decrease in breast cancer emerged and most other outcomes were neutral. For CEE alone, younger women (ages 50 to 59) had more favorable results for all-cause death and myocardial infarction.
Neither regimen affected all-cause mortality in the overall study group.
The findings do not support the use of either estrogen-progestin or estrogen alone for chronic disease prevention, the authors wrote. Even though hormonal therapy may be a reasonable option for management of moderate to severe menopausal symptoms among generally healthy women during early menopause, the risks associated with hormone therapy, in conjunction with the multiple testing limitations attending subgroup analyses, preclude a recommendation in support of CEE use for disease prevention even among younger women.
Current findings also suggest caution when considering hormone therapy treatment in older age groups, even in the presence of persistent vasomotor symptoms, given the high risk of coronary heart disease and other outcomes associated with hormone therapy use in this setting.