HRT and Heart Disease: Understanding the Connection

Like many decisions regarding your health, the decision to start hormone replacement therapy (HRT) for menopause is a very personal one. And likely one that’s not easy to make. Personally, I debated back and forth for a while about whether or not I wanted to try out HRT, and turned to menopause support groups on social media for advice.

These groups are chockfull of information on the pros and cons of HRT, and I found solace in relating to other women making the same decision. The hottest of topics, though? Whether taking estrogen protects against cardiovascular disease (i.e., diseases of the heart and blood vessels).

There’s good reason for this interest: Hundreds of thousands of women in the U.S. die from cardiovascular disease each year, and this mortality risk only increases as you age, per the American Heart Association (AHA).

When I finally went to my doctor to learn more about HRT, she informed me that supplemental estrogen may actually help protect my heart and blood vessels from disease. This fact played a huge part in my deciding to start the therapy.

What she didn’t tell me—and I didn’t know, despite being a health writer—is there’s a metaphorical “ticking clock” when it comes to HRT, meaning you may have to start taking it at a particular time in order to reap its cardioprotective benefits.

Here, learn more about the link between HRT and heart disease, the best time to start HRT for heart health, and how long HRT can be taken for without incurring any potential side effects or risks.

The estrogen-heart connection

In order to know the best time to take HRT, it helps to know how exactly estrogen and the heart are connected.

Cardiovascular disease—diseases of the heart and blood vessels caused by plaque buildup in the arteries—is the number one cause of death in the U.S. for both men and women, per the AHA. That said, women tend to develop cardiovascular risks up to seven to 10 years later than men, per a December 2010 study in Netherlands Heart Journal. This could partly be because in the pre-menopausal years, estrogen helps to protect your heart, by relaxing your arteries and promoting good cholesterol, according to Yale Medicine.

As women hit midlife and estrogen begins to decline (i.e., when menopause starts), the risk of developing heart disease goes up notably—especially after age 55, according to a November 2020 study in Circulation².

“There’s no doubt we’re looking at a sex-related hormonal effect,” says Howard N. Hodis, MD, director of the Atherosclerosis Research Unit and professor of cardiology at Keck School of Medicine at the University of Southern California. “This is important because it means the risk could be modifiable,” he adds.

Which begs the question: Can replacing lost estrogen via HRT reduce your cardiovascular disease risk? Evidence so far points toward “yes,” but as long as it’s timed the right way.

Can HRT for menopause benefit your heart?

There’s a possibility it can. In fact, a May 2022 study in The Cancer Journal, co-authored by Dr. Hodis, found that starting women on HRT before the age of 60 (who are also at or near menopause) significantly reduced both cardiovascular disease and all-cause mortality—something other prevention therapies (like statins) failed to do.

“Based on cumulative data, cardiovascular disease and all-cause mortality—including deaths from cardiovascular disease, bone fractures, cancer, and other causes—is reduced 20 to 25 percent in women who use HRT versus women who do not,” says Dr. Hodis.

Why did this happen? There’s a few reasons. First, estrogen helps stop LDL (or “bad”) cholesterol from causing plaque buildup in your blood vessel walls. Second, it helps decrease inflammation and increase vascular dilation (i.e., when blood vessels widen to allow for healthy blood flow). HRT has also been shown to reduce other cardiovascular risk factors, including obesity, insulin resistance, and high cholesterol and blood pressure levels, according to a landmark study in Diabetes, Obesity, and Metabolism.

Ultimately, “estrogen has a lot of mechanisms of activity at the cellular and tissue level that are active in limiting the progression of atherosclerosis (i.e., plaque buildup),” adds Dr. Hodis.

When a woman’s natural stores of estrogen are diminished, the cardiovascular protections from that hormone are lost, too. This phenomenon was reflected in the landmark 1976 Framingham study in the Annals of Internal Medicine, which found postmenopausal women between the ages of 40 and 54 have a two to six times greater incidence of cardiovascular disease than premenopausal women in the same group.

Though estrogen lost at any age can also pose risks to your heart. For example, the 2003 Women’s Ischemia Syndrome Evaluation (WISE) study, published in the Journal of the American College of Cardiology and sponsored by the National Heart, Lung, and Blood Institute, found that young women with estrogen deficiency have a sevenfold increase in coronary artery risk compared to those without estrogen deficiency.

All this is to say, getting estrogen HRT (in pill or patch form) may help restore those cardioprotective benefits, while also treating menopause symptoms like hot flashes, night sweats, sleep issues, vaginal dryness, and mood swings, says Taniqua Miller, MD, a board-certified OB/GYN, CEO of Revival Telemedicine, and adviser to virtual menopausal care platform Evernow. (Just keep in mind: If you still have a uterus, you’ll likely need to take progesterone, too, to help prevent uterine overgrowth and endometrial cancer risk, per the University of Rochester.)

Getting HRT during what experts call “the window of opportunity,” however, is when you’ll reap the greatest cardiovascular benefits. (More on this below.)

When’s the ideal time to start HRT to maintain heart health?

The best time to start HRT for heart health is before your blood vessels show any signs of plaque buildup and disease. If going off age, that’s likely between ages 50 and 59, or within six years (but no more than 10) of starting menopause, according to Dr. Hodis. This is sometimes called the “timing hypothesis” or “window of opportunity.”

This means, starting HRT while your blood vessels are still healthy is more beneficial than starting it once you’ve already shown signs of cardiovascular disease, according to The Cancer Journal study.

“We don’t really understand the biology behind the mechanisms of this window of opportunity,” says Dr. Hodis. “We do know that with age, healthy blood vessel lining will thicken and plaques will form, which can become dangerous.”

“More importantly, the vessels also lose receptiveness to estrogen molecules with age, and the number of estrogen receptors in diseased vessels drops dramatically,” he adds. This is basically like making a phone call that never gets received or answered.

Once you’ve passed the 10-year mark with menopause, you’re likely too late to reap cardiovascular benefits from HRT (though your doctor may still prescribe it solely for the symptom-relief benefits). “The data show very effectively that starting HRT has no effect on atherosclerosis if you’re more than 10 years past menopause,” says Dr. Hodis. “But if you start within six years, there’s a highly significant [risk] reduction.”

On the other end of the spectrum, there are theories (though no definitive data) that starting HRT when you already have plaque buildup will increase your cardiovascular disease risk. “This theory could be tied to the fact that studies are only looking at oral estrogen pills—like estradiol or synthetic estrogen—which have been shown to increase risk of plaque formation and blood clots in some people,” says Dr. Miller.

But “any oral estrogen processed by your liver—including birth control pills—increases your risk of blood clot formation,” she adds. This means, if you introduce estrogen to already sticky, plaque-filled blood vessels, you might increase your risk of cardiovascular events like clots, Dr. Miller adds.

Where does this leave transdermal estrogen (i.e., the kind delivered through a skin patch)? While this kind doesn’t get broken down by the liver, and comes with a lower risk of blood clotting, it’s unclear whether it offers the same cardiovascular benefits (and risks) of oral pills, says Dr. Miller. And due to limited studies on transdermal estrogen and heart health, “we can just assume the effect of patches is the same if given at the proper time,” she adds.

Bottom line: HRT cannot cure any existing markers of cardiovascular disease, but starting it within about six years of starting menopause (and when you still have healthy blood vessels) may help you maintain your heart health as you age.

The ideal time to start HRT for cardiovascular benefits is within six years (but no more than 10) of starting menopause.

Who should not take HRT?

It should be noted that the professional guidelines from the North American Menopause Society and American College of Cardiologist do not recommend prescribing HRT solely for cardiovascular disease prevention, but both do recognize the potential cardiovascular benefits if therapy is started earlier in menopause.

“If a woman is having [menopause] symptoms, I will recommend HRT over other non-hormonal therapies, if they are a candidate for it, because it can be cardioprotective” says Dr. Miller. Though she says she does not prescribe HRT to women without menopausal symptoms.

Other people who might not be candidates for HRT (especially oral estrogen) include the following, per Dr. Miller:

• Those with a history of blood clots
• Those with breast or uterine cancers
• Those with uncontrolled high blood pressure

If this is your case, your doctor will likely recommend other menopause treatment options that do not exacerbate underlying conditions.

Other ways to protect your heart during menopause

While it’s important to take care of your heart at all phases of life, it’s especially important during menopause, when your risk of cardiovascular disease climbs.

Protecting your heart requires a “comprehensive approach” that includes that may include some of the following lifestyle changes, according to Dr. Miller:

• Managing your stress levels
• Getting at least 150 hours of moderate-intensity exercise per week, or 30 minutes per day
• Eating a balanced, nourishing diet
• Getting plenty of quality sleep

“All these things are helpful in preventing disease,” she adds. In other words, “you can’t just take estrogen and wipe [all risk] out.”

Dr. Miller is also an advocate of educating yourself about menopause and its effects (including its effects on your heart), even before you go to your doctor with concerns. You can find helpful online resources from both the American Heart Association and the North American Menopause Society.

“Be a savvy consumer. Find really good resources and take that information to your clinician so you can sit down and make a shared decision,” she adds.

The bottom line

For women who are candidates for HRT, taking estrogen can help offer protection from cardiovascular disease—as long as you take it early on, optimally within six years of starting menopause and before age 60. Beyond that point, HRT may help with menopause symptoms, but might not offer the same protection for your heart and blood vessels.

If you do take it at or past the 10-year mark, talk to your doctor about benefits versus risks of taking HRT, and how long you can stay on it for. (There’s no fixed limit on when you should stop taking HRT; it’s different for every person and the severity of their menopause symptoms, per the NHS.)

And above all else, the key to reducing cardiovascular risk still lies in making healthy lifestyle changes like eating well, getting enough exercise and sleep, managing stress, and taking care of underlying health conditions. HRT can simply be a supplemental option.