Is short-term hormone replacement therapy reasonable?

- Jennifer Middleton, MD

A recent follow-up study of the Women's Health Initiative (WHI) trial is bringing hormone replacement therapy (HRT) back into the news. The WHI aimed to demonstrate that HRT improved cardiovascular outcomes in women, but instead they found not only an increased risk of coronary artery disease (CAD) and stroke but also breast cancer and venous thromboembolism (VTE) in participants taking HRT compared to those who were not taking HRT. The WHI intervention trial was stopped due to these findings, but researchers continued following these women for the next several years. They found that all-cause mortality did not differ between groups who had and had not been taking HRT when the intervention was halted.

When the WHI intervention was halted, women with a uterus who were taking estrogen and progesterone (and their corresponding control group taking placebo) had been enrolled for a median of 5.6 years, and women without a uterus taking estrogen only (and their corresponding control group taking placebo) had been enrolled for a median of 7.2 years. Following all of these women for a median of 18 years after the intervention groups stopped taking their HRT,* the hazard ratio (HR) for all-cause mortality in the estrogen and progesterone group compared to placebo was 1.02 (95% confidence interval 0.96-1.08); for the estrogen only group compared to placebo, the HR was 1.00 (95% confidence interval 0.88-1.01). HRs for deaths due to cardiovascular disease and cancer were similarly non-significant.

Breast cancer, CAD, stroke, and VTE are all serious conditions that certainly give me pause before prescribing HRT, and I have done so for only a small number of women. That small number of women, however, have disabling symptoms from menopause, and they have been willing to accept the risk of those complications in exchange for the ability to function during the day and sleep restfully at night. It is somewhat reassuring to know that, while their risk of these complications is significant, their overall mortality risk appears to be unchanged compared to women not taking HRT.

Using HRT to prevent chronic conditions still has a D grade from the United States Preventive Services Task Force (USPSTF), and this new study won't have me rushing to prescribe HRT to women with mild to moderate menopausal symptoms. There are several safer alternatives to ameliorate hot flashes and vaginal dryness as described in this 2016 AFP article on "Hormone Therapy and Other Treatments of Menopause." If you'd like to read more, there's also an AFP By Topic on Menopause.

*Less than 4% of enrolled women reported taking HRT at some point after the WHI intervention was halted in 2002.