October 16, 2013
Hormone Treatment Shouldn’t Be Prescribed for Chronic Disease Prevention in Women

Boston—Here’s the latest answer to the frequent question of how and when hormone treatment should be used for women.

An extended follow-up of the two Women’s Health Initiative hormone therapy trials suggests that hormone treatment may be appropriate for menopausal symptom management in some women but should not be prescribed for chronic disease prevention.

The study, led by researchers from Brigham and Women’s Hospital in Boston and published in the Journal of the American Medical Association, sought to determine the long-term risks and benefits of using hormones for chronic disease prevention. The initial hormone therapy trials of the Women’s Health Initiative (WHI) were stopped after investigators found that the health risks outweighed the benefits, leaving numerous unanswered questions.

The recent report provides a comprehensive overview of findings from the two WHI hormone therapy trials with extended postintervention follow-up and stratification by age and other key variables. For the study, 27,347 postmenopausal women, ranging in age from 50 through 79, were enrolled at 40 U.S. centers in 1993.

Of women with an intact uterus, 8,506 women received conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with another 8,102 getting a placebo. In the prior hysterectomy group, 5,310 received CEE alone and 5,429 were in the placebo group.

The CEE plus MPA trial lasted a median of 5.6 years, with 7.2 years in the CEE alone trial. The 6 to 8 years of additional follow-up lasted until September 30, 2010.

According to the research, risks were increased for coronary heart disease, breast cancer, stroke, pulmonary embolism, dementia (in women 65 years of age and older), gallbladder disease, and urinary incontinence in the group receiving CEE plus MPA. The authors suggest those heightened risks outweighed the benefits, which included decreased hip fractures, diabetes, and vasomotor symptoms.

The majority of both risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during follow-up, the report notes.

More balanced effects were observed with CEE use in women with prior hysterectomy; risks of stroke and venous thrombosis were increased, but risk of hip fractures and total fractures were decreased. A nonsignificant reduction in breast cancer also was detected.

Postintervention with CEE, however, a significant decrease in breast cancer was detected, although most other outcomes were neutral. For CEE alone, younger women—defined as 50 to 59 years—fared better in terms of all-cause death and heart attack, although neither regimen affected all-cause mortality overall.

“In summary, current WHI findings based on results from the intervention, post intervention, and cumulative post-trial stopping phases do not support the use of either estrogen-progestin or estrogen alone for chronic disease prevention,” the authors write.
“Even though hormone 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,” they add. “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.”

In an accompanying editorial, Elizabeth G. Nabel, MD, of Brigham and Women’s Hospital, points out that the WHI “has overturned medical dogma regarding the use of menopausal hormone therapy,” adding, “For that, women and all patients whose health depends on sound science are grateful.”

U.S. Pharmacist Social Connect