Of the placebo-controlled trials of hormone replacement therapy (HRT) after menopause, the two main Women’s Health Initiative (WHI) trials were large enough and well-enough designed to assess HRT’s ability to prevent coronary heart disease (CHD), stroke, and venous thromboembolic desease (VTE, aka large blood clots in deep veins of your legs or lungs).

A wise patient’s first questions should be who were studied and what treatment was studied. In this case, WHI recruited women 50 to 79 years old and from several locations in the U.S. Women who no longer had a uterus were randomized to a placebo versus oral estrogen, and women who still had a uterus were randomized to placebo v oral estrogen plus a progestin (in this case medroxyprogesterone; since taking estrogen without a progestin is known to promote uterine cancer).

The results surprised most everyone! Both trials were stopped early by their Safety Boards because bad things were happening in excess in the group taking hormones. Safety Boards, by the way, are select groups of people privileged to secretly access early results and propose an early stop if they find exceptional risk or exceptional benefit going on.

The estrogen-only trial was stopped early because of increase risk for stroke in the estrogen group after an average follow-up of 6.8 years.

The estrogen plus progestin trial was stopped early because of increase risk for CHD, stroke, pulmonary embolism (blood clot to lung), and breast cancer in the estrogen plus progestin group after an average follow-up of 5.2 years.

Needless to say, the use of HRT as “protection” against chronic disease has plummeted in the wake of these findings.

Less is known about the safety of HRT used short-term within women who are currently transitioning through menopause and dealing with highly annoying symptoms such as hot flashes and sleep problems. In most women, some HRT used short-term to decrease such symptoms is probably safe. However, decisions about HRT need to be personalized to each woman’s health, health risks, and values.

That is the basic story, thus far, of long-term hormone replacement therapy and dangerous vascular disease among post-menopausal women.

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