Women who take hormones to ease menopausal symptoms are at no greater risk for early mortality than women who skip them, according to new long-term findings. The findings have just been announced by researchers with the Women’s Health Initiative (WHI), and they come from the largest, longest-term study conducted to date on hormone therapy—either estrogen by itself or, more commonly, an estrogen/progestin combination.
In the hormone wars, you might call it a draw. On the one hand, the new data confirm that earlier dire warnings about increased health risks for all women who take these drugs don’t translate into shorter lives. On the other hand, this study provides the strongest evidence to date that hormone therapy, while it helps with symptoms, won’t provide protection for all women against heart disease and stroke.
The devil, of course, is in the details. Health risks are different depending on how old a woman is when she begins hormone therapy. Younger women (those in their 50s when they enrolled) turned out to have a 30% lower risk for premature death with hormone therapy than without it, but there was no reduction in risk for premature death for women who began the therapy when they were in their 60s and 70s. And the new study leaves unanswered many questions that some women and their doctors are still struggling with. For starters, many “hormone therapy” options are different now than in the 1990s, when they were almost always moderate-to-high doses of conjugated equine estrogens (Premarin)—a complex of estrogenic compounds that are not exactly the same chemically as human estrogen—and medroxyprogesterone (Provera), a synthetic form of the hormone progesterone.
In the years since the study began, the way ob-gyns and other physicians prescribe hormone therapy to menopausal women has been transformed. Today, lower doses of the above drugs are more common. Plus, besides the pills that used to be the only way to take hormone therapy, there are now FDA-approved patches that deliver hormones directly into the blood, vaginal inserts that deliver hormones locally to vaginal tissue, bioidentical hormones that are (as the name implies) identical in structure to what a woman produces herself, hormone precursors such as vaginal DHEA and many other options for women experiencing menopausal symptoms.
To clarify how the new research affects a woman’s decision about hormone therapy, we interviewed Bottom Line menopause expert JoAnn Manson, MD, DrPH, a professor at Harvard Medical School and Brigham and Women’s Hospital and lead author of the new research.
Background: When a now-famous large WHI study of estrogen plus progestin that started in 1993 was abruptly halted in 2002—because it seemed so clear that the risks of the hormone therapy outweighed any benefits— many women panicked. For years, women going through menopause had been taking hormones because it not only treated hot flashes but also might protect them from osteoporotic fractures and heart attacks. It did help to reduce bone fractures and type 2 diabetes but also appeared to increase the risk for heart attack and stroke in some women. Estrogen plus progestin increased breast cancer risk, while estrogen alone reduced this risk. Use of hormone therapy plummeted after the 2002 WHI report.
Then in 2013, new data from the same study revealed that the risks were mostly among the women who had begun hormone therapy 10 years or more after menopause. For women who had begun hormone therapy around the time of menopause, there were fewer risks than for older women and even some long-term health benefits. But we still didn’t know whether hormone treatment affected lifespan, including the long-term effects on overall death (all-cause mortality) or death from any specific disease (cause-specific mortality). Now, the latest analysis sheds more light on this question.
Latest study: Researchers picked up where the earlier studies stopped and followed the women for another dozen years—for an average follow-up of 18 years. Overall, 7,489 of the WHI participants have died since the study began.
Results: On average—meaning not accounting for the age at which each woman started hormone therapy—there was no statistically different rate of all-cause, cardiovascular or cancer mortality between women who took hormones and those who took placebos. But age made a difference. For all-cause mortality over 18 years, the data suggested a 21% reduced risk with estrogen alone, and minimal reduction for estrogen plus progestin, for women who started hormones before age 60, compared to placebo.
Surprising finding: Deaths from Alzheimer’s disease and other forms of dementia were 26% lower among women who used estrogen alone compared with placebo. The finding was intriguing because some earlier studies had suggested that using hormones may actually increase risk for dementia. The researchers point out the possibility that the beneficial effects of hormone therapy on insulin resistance and diabetes, both major determinants of cognitive decline, may have contributed to this surprising finding. Estrogen-only therapy is an option only for women who have had a hysterectomy, however. (To learn more, see Bottom Line’s “Hormone Therapy and the Risk for Alzheimer’s Disease.”)
THE HORMONE DECISION: WHAT DO TO NOW
This latest, longer-term study provides reassuring evidence that the hormone treatment used in the WHI didn’t lead to excess mortality and remains a reasonable option for management of menopausal symptoms, especially for women in early menopause. However, the treatment should not be used to try to prevent cardiovascular disease or other chronic diseases of aging. Although the same medications used in the study dating back to the 1990s still are available, women have more treatment options now. These include lower doses, different formulations, non-oral routes of hormone delivery, and nonhormonal choices. The North American Menopause Society (NAMS) has a free mobile app (MenoPro, for iOS and Android devices) that helps women work together with their clinicians to individualize decision making about treatment options. What’s right for you depends on your menopausal symptoms and how much they are bothering you, your personal medical history and risk factors and, just as important, your personal preferences. The more you know, the better your conversation with your doctor can be—and the more likely that your decision will be right for you.