Hormone Replacement Therapy (HRT) and Cardiac Risk

Stock Shop Photography/E+/Getty Images

Question: Hormone Replacement Therapy (HRT) and Cardiac Risk

I am a 51 year-old woman having a rough menopause, and I'm confused about hormone replacement therapy. I like the idea of using HRT to relieve my hot flashes and other symptoms, but I've read that HRT can cause heart attacks, and I'm also worried about the cancer risk. My doctor says it would be OK to use HRT for a few years. I'd like to believe her but I'm afraid. Is my doctor right?

Answer: I'm not surprised you are confused, as the recommendations regarding hormone replacement therapy (HRT) for menopause have gone through a very confusing transition over the past decade. Those recommendations have changed from strongly encouraging HRT, to strongly discouraging it, to (now) somewhere in between. The good news is that, from what you describe, your doctor seems to be on top of things, and her recommendation to you appears to track with the current thinking on HRT.

What Is HRT?

With the onset of menopause, the ovaries stop making the female hormone estrogen. The drop in estrogen levels can produce several uncomfortable symptoms including hot flashes, night sweats, poor sleeping patterns, and vaginal dryness. HRT attempts to restore estrogen levels to the point that such symptoms no longer occur.

Most women on HRT must take both estrogen (which relieves the symptoms of menopause) and progestin.
The progestin is necessary because estrogen alone causes the lining of the uterus to grow excessively, thus increasing the risk of uterine cancer. Adding progestin substantially reduces the excess risk of uterine cancer. In women who have had their uterus removed, on the other hand, HRT will consist of estrogen alone.

The Evolution of HRT Recommendations

Originally it was thought that HRT would protect women from heart disease.
This assumption followed from two observations. First, the incidence of coronary artery disease (CAD) in women rises substantially after estrogen levels fall during menopause. Second, using HRT in menopausal women causes a favorable change in cholesterol levels and in other cardiac risk factors. So, doctors thought, the drop in estrogen which accompanies menopause was contributing to the development of CAD in older women; replacing estrogen (with HRT) should help to prevent CAD. And for many years HRT was widely recommended (and widely used) in menopausal women.

But then, early in the last decade, this nice, tidy story was greatly disrupted by data from the Women's Health Initiative (WHI) study. The WHI (which, ironically, was designed to "prove" that HRT is good for the heart) showed instead that women who received HRT with estrogen and progestin actually had a significantly higher risk of heart attacks and strokes, as well as an increase in blood clots and breast cancer.

Women who were able to receive estrogen-only HRT (because they had no uterus) did not have an increase in heart attacks or breast cancer, but had an increase in strokes and blood clots.

This result - that HRT increased rather than decreased risk - was quite stunning to the medical community (not to mention to most women), and it completely changed the thinking on HRT. And for a while HRT was discouraged altogether, for virtually all women.

But more recently, further analysis of the available data has tempered this broad prohibition on HRT. The WHI study, for instance, had enrolled mostly older women (women over the age of 60), many of whom had gone through menopause years before their enrollment. And in these women HRT clearly increased cardiac risk. But when the data was analyzed for the younger women who had been enrolled in the WHI study, the increase in cardiac risk was not seen. Specifically, in women below the age of 60, or whose menopause had begun within the previous 10 years, HRT did not appear to increase cardiac risk.

So today, experts generally agree that HRT can be prescribed - if necessary - to women under 60, or in women who are still within 10 years of the onset of menopause.

Why Is HRT RIskier in Older Women?

Nobody really knows why HRT produces cardiac risk in older women, but the leading theory goes like this. Estrogen probably does delay the onset of CAD, as previously believed. So giving HRT right after the onset of menopause likely does not worsen cardiac risk (and may even reduce it). But, if HRT is delayed for several years after menopause, and then is started once a woman has already developed CAD, HRT apparently somehow destabilizes the plaques in the coronary arteries, and thus increases the chance of a heart attack.

So: When Should HRT Be Used?

Today, HRT is recommended for women under the age of 60, or whose menopause is of recent onset, who have particularly bothersome symptoms of menopause, such as hot flashes, night sweats, inability to sleep, and vaginal dryness. HRT is quite effective in eliminating or reducing these symptoms. And in these younger women, the risk of heart attack does not appear to be increased with HRT.

HRT should be avoided in any woman who has had breast cancer, CAD, heart attack, stroke, or blood clots.

Finally, experts warn that HRT should be limited to less than five years in duration.

Why Does HRT Have To Be Temporary?

The hormones used in HRT increase the risk of breast cancer. It looks like it takes about 10 years of therapy with estrogen alone to produce an increase in breast cancer, but only five years or so for the combination of estrogen and progestin to bump up the risk of breast cancer. So virtually all experts recommend that, if HRT is to be used, it should be used for less than five years.

In summary, from what you describe it sounds like the suggestions being made by your doctor are compatible with current guidelines. You will have to decide for yourself whether the symptoms you are experiencing are disruptive enough to warrant HRT.


Taylor HS, Manson JE. Update in hormone therapy use in menopause. J Clin Endocrinol Metab 2011; 96:255.

Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.

Continue Reading