For most women, hormone replacement therapy (HRT) is a safe and effective option for relieving menopause symptoms, which can be near disabling and can last for years. And yet, there have been mixed messages about the risks of HRT since the early 2000s when the Women’s Health Initiative (WHI) suddenly stopped research in its tracks due to concerns about safety.
Experts have since come to question these concerns and have found, for the great majority of women, HRT is a net benefit to health.
A Little History
By the 1990s, HRT was widely known to significantly reduce many symptoms of menopause. Symptoms include hot flashes, night sweats, poor sleep, mood disorders, trouble concentrating, and problems with sex. There was even some evidence that HRT may be linked to lower risks of age-related conditions like heart disease and dementia. By the turn of the millennium, about 40% of postmenopausal women in the U.S. were using HRT.
But in the early 2000s, the Women’s Health Initiative released results from two large clinical trials meant to assess the preventive health benefits of oral HRT – either estrogen alone (referred to as ET) or estrogen plus progesterone (EPT) – in almost 30,000 postmenopausal women. The results appeared unexpectedly grim.
According to the WHI, women who received HRT had significantly less osteoporosis and colorectal cancer. But they also reported an apparent higher risk of health conditions such as breast cancer and stroke. The authors made the broad conclusion that HRT poses more risks than benefits and shouldn’t be used to prevent disease. The research was stopped due to safety concerns. New prescription guidelines stated that doctors should prescribe HRT only as a last resort, and then only in the smallest effective amount for the shortest possible time. Predictably, prescriptions for oral HRT quickly plummeted.
In retrospect, many experts think the WHI conclusions were overly general and the results were sensationalized. “It was a well-conducted study. It’s just that it’s more nuanced,” says Jennifer Howell, MD, an OB/GYN and menopause specialist at Duke Health in Durham, NC. “The study was interpreted more broadly than it should have been.”
Large swaths of women needlessly scaled back or stopped their HRT cold turkey. “It was a roller coaster,” says Susan Reed, MD, an OB/GYN and menopause research specialist at the University of Washington in Seattle. “I had a lot of people coming in very, very worried.”
A Reassessment of HRT and the WHI trials
The WHI studies included women within a fairly wide age range of 50 to 79. Most of these women were postmenopausal, something the authors didn’t take care to emphasize. Furthermore, none of the women in the study had menopause symptoms.
Applying the same conclusion across the board was a mistake, Howell says. The risks depend heavily on timing. “When you look at it based on age of initiation, actually, those bad things are only happening to the older women in the study,” she explains. For younger women in good health, HRT is still the first-line treatment for menopause symptoms.
Several experts say concerns about increased breast cancer risk may have been overemphasized by the Women’s Health Initiative. ET – which is used only for women who have had a hysterectomy – had no negative effect on breast cancer risk. In fact, follow-up studies show estrogen can actually protect those women from breast cancer.
EPT – which is more common and is used in women who still have a uterus – did appear to increase breast cancer risk by 26% in the WHI studies. That may sound like a lot, says Reed, but it equates to an increase of less than 1 in 1,000 women per year. Put another way, for a 50-year-old overweight person, she explains, the baseline risk of breast cancer is about 6%. Taking EPT for 5 years puts that risk at about 8% over 20 years – only two percentage points higher. “We need to use absolute risk differences when we interpret our findings for our patients,” Reed says. “Period, end of story.”
WHI authors themselves noted in the study that the 26% increase in breast cancer rates “almost reached” statistical significance, but not quite. This means the apparent increase could still be due to chance. Certain common lifestyle habits are known to increase breast cancer risk about the same amount or more, including smoking, alcohol use, and a poor diet.
In addition, the risk appears only to develop after about 5-10 years of EPT, then appears to go up slowly with each year of treatment. Further studies have shown that the risk is lower for younger women. More research is needed to find out if HRT is the cause of this increased risk and if it holds true for all women.
There are some real concerns for some women on HRT, says Howell. As a woman gets older and further past menopause, it might be dangerous to reintroduce estrogen after many years without it. In women with arterial plaque buildup, estrogen may cause clotting that, in an already narrowed blood vessel, could lead to a stroke, heart attack, or dementia. Women with breast cancer, heart disease, or who are at a higher risk of getting heart disease may also need to be more cautious with HRT. Talk with your doctor to learn more about your individual risks.
But overall, the research is clear that HRT is safe for most women who start it within about 10 years of their last menstrual period, Howell says. For those women, there are actually more benefits than risks, especially in the first 5 years of treatment. A careful analysis of the WHI and other data shows that estrogen actually protects women under 60 from heart disease and osteoporosis, she says.
A New Era for HRT
The fear surrounding HRT persisted for years after the WHI studies were published, despite many more studies aiming to clarify the issue, including papers by the WHI itself that separated women by age. None were as highly publicized as the originals. For 2 decades, countless women were under-informed and under-treated for menopause symptoms.
Finally, just in the past year or two, an explosion of media coverage has begun to shift the public’s opinion to favor hormones again. Some studies suggest estrogen may help prevent Alzheimer’s disease, although more data is needed. It’s well-established that HRT can significantly improve your risks of osteoporosis, a major health factor for women as they age.
Though research is still ongoing, HRT might actually have a protective effect on the heart in some younger women, and while risks to the heart and blood vessels are a key concern in older women, that can sometimes be lessened by using skin patches instead of pills, says Reed. And nothing compares to HRT for relieving menopause symptoms.
But in some ways, the pendulum may have swung too far, says Howell. Many of her patients are getting more and more of their wellness information from social media. Some of them are now under the impression that the WHI trial should be dismissed wholesale and that hormones can be taken at any point without adverse effects.
“What I see now is more people saying, ‘No, that study was debunked! I may be 70, but I’m ready to go on my estrogen,’ ” she says. “Some patients get mad at me if I disagree with some influencer that they’ve been following. It’s so hard to do your job.”
For-profit anti-aging clinics, in particular, have seized the opportunity to market hormonal supplements, including to women who shouldn’t be using them, says Howell. “The predatory wellness industry is kind of telling everybody they should be on hormones – they’re backing this with half-truths and touting hormones in a very different way from what the actual science is,” she says.
People trying to promote their health in “natural” ways end up doing themselves harm by taking unregulated hormonal pills or pellets and spending money out of pocket on unnecessary tests, she says. Some of them end up in Howell’s clinic with bleeding or other problems. “I’ve seen cancers, I’ve seen patients with testosterone levels [unintentionally] in the male range, I’ve seen all sorts of things,” she says.
“We’ve been fighting this for at least 5 to 10 years,” says Reed. “Menopause became a business, and people are making money off of people with symptoms.”
It’s important to remember that while the message about estrogen continues to evolve, it’s only one piece of the puzzle. Along with the timing, risks and benefits also vary depending on your weight, your bone health, whether you have diabetes, and more. It’s also not yet clear whether the risks are different for women of different races, as there’s a lack of data on HRT in non-White women.
Ultimately, deciding whether to start HRT, and how long to continue it, is highly specific to each person. As you reach menopause, the best way forward depends on your age, how long it’s been since your last period, your risks of disease, your heart health, and how severely your menopause symptoms are affecting your quality of life. Talk with your doctor about what the most up-to-date research says, and if you have doubts, see a specialist who can give you the best advice possible.
