Fifty years ago, hormones were advertised as a cure-all. In his 1966 bestseller, “Feminine Forever,” physician Robert Wilson declared that menopause was a disease, and he had the cure: hormones, without which women would be “condemned to witness the death of their own womanhood.”
The magic of hormone therapy wasn’t just that it could make a menopausal woman whole again in the eyes of men like Wilson, who apparently received funding from Wyeth (the pharmaceutical maker of the hormones he was promoting).
For a while, it seemed that hormones such as estrogen might also protect against heart disease and keep women’s minds healthy, too.
What was then called “hormone replacement therapy” seemed so powerful that in 1993 researchers initiated the Women’s Health Initiative (WHI), a randomized clinical trial of more than 10,000 women ages 50 to 79 to test whether taking estrogen, either alone or with progesterone, continuously after menopause could help women prevent heart disease, stroke and cognitive decline.
In 2002, the WHI study released startling news — women assigned to take the hormones had a higher risk of cardiovascular disease and breast cancer than women who received placebos. It took a randomized, controlled trial — the gold standard in medicine — to show that hormones weren’t making women healthier in old age. Instead, hormone-takers were healthier to begin with.
After those findings were released, the use of hormone therapy plummeted by as much as 80 percent.
Those 2002 findings weren’t wrong, but they were reported in a “very alarmist way,” says Stephanie Faubion, medical director of the North American Menopause Society (NAMS) and author of “Mayo Clinic: The Menopause Solution.” News headlines implied that hormone therapy would give women cancer or heart attacks, but that was an oversimplification, she says.
The study convincingly showed that hormones shouldn’t be taken long term for disease prevention, but it did not directly address their short-term use to manage hot flashes and other symptoms of menopause.
“A lot of nuance got lost along the way,” says JoAnn Manson, chief of Preventive Medicine at Brigham and Women’s Hospital and a lead investigator in the WHI. The risk of breast cancer, heart disease and other conditions varied depending on how old the woman was when she started the therapy and whether she took progesterone along with the estrogen. (Women with an intact uterus are advised to take progesterone, too, to prevent the endometrial lining from building up and potentially developing cancer.)
Increased vs. lowered risks
The WHI has found that women in the study who took estrogen and progesterone in combination had an increased risk of coronary heart disease, stroke, deep vein thrombosis and breast cancer, but women who took estrogen alone actually had reduced risks of coronary heart disease and breast cancer. All of the women who took hormones had reduced risk of colorectal cancer, fractures, diabetes and all-cause mortality.
Those increases in heart disease and breast cancer risk sound scary, but in absolute numbers, the risks are pretty small, Manson says.
An analysis of the WHI data Manson and her colleagues published in 2017 found that women in the study who used hormone therapy (whether estrogen alone or with progesterone) for five to seven years did not have an increased risk of all-cause, cardiovascular or cancer mortality during the 18-year follow-up. And for women in their 50s, there was actually a trend toward a reduced risk of mortality, Manson says.
But perhaps the most important thing to understand, Manson says, is that the WHI was not designed to look at hormones used to address menopause symptoms. Instead, it was examining whether they could reduce chronic conditions such as stroke, heart disease and cognitive decline. It is like the difference between asking whether aspirin is safe to take for a headache vs. whether it is safe and effective to take it on a daily basis in hopes of preventing heart attacks.
The WHI results overturned the idea that hormones should be taken long term to stave off chronic disease in postmenopausal women, but it was not specifically set up to assess the safety of taking hormones short term for relieving menopause symptoms, Manson says.
The average age at which women in the WHI started hormone therapy was 63. That is 12 years after the average age of menopause, which means that using the results of that study to predict what will happen to women who begin hormones when menopause symptoms start and then cease them when their symptoms have ended is essentially comparing apples and oranges.
There has never been much doubt that hormones are a highly effective way of treating symptoms such as hot flashes, night sweats, mood swings and all the problems like sleep disruption that come with them.
“As of 2020, hormone therapy is still the best way to relieve menopause symptoms,” says Nanette Santoro, chair of the department of obstetrics and gynecology at the University of Colorado Anschutz Medical Campus.
NAMS, the American Society for Reproductive Medicine, and the Endocrine Society all take the position that hormone therapy is appropriate for relief of hot flashes and vaginal dryness for most healthy women who are recently menopausal.
Hormones prescribed to menopausal women are no longer called “hormone replacement therapy,” because the purpose is not to replace what the ovary previously made or to use them indefinitely, but to manage menopause symptoms, which can be debilitating and disruptive, Faubion says.
“There’s plenty of data to show that this presents a financial burden to society in general and women personally,” she says. “We do women a disservice by patting them on the head and saying you’ll be all right, don’t worry about it.”
Not an elixir of youth
Hormone therapy is not a magic bullet or an elixir of youth, and it shouldn’t be used willy-nilly, Manson says.
But women who are suffering with menopause symptoms should not be denied hormone therapy, she says, unless they are at increased risk of cardiovascular disease, breast cancer or other estrogen-sensitive cancers. (NAMS has a free app, MenoPro, that can help women determine their risk profile.)
“The pendulum has swung widely from the perception that hormone therapy is good for all women to the perception that it’s all bad for all women, to now a more appropriate place in between where hormone therapy is perceived to be good for some but not all women,” Manson says. “We’re recommending that hormone therapy be used for the duration that it’s needed to address symptoms at the lowest effective dose and with ongoing reassessment of the balance of risks and benefits.”
The time to start therapy is as soon as the symptoms start. “Intervening earlier, rather than later, actually seems to carry less risk,” Santoro says.
Once symptoms start, they are unlikely to get better soon. On average, the menopause transition lasts about four years, Santoro says. Some women have symptoms that persist even longer, however. Although there are exceptions, most women won’t go through menopause before 45, Santoro says.
“If you’re 45 or older and starting to have hot flashes, night sweats or mood or sleep changes, it could be your hormones and it might be time to start some active management,” she says.
More choices now
Today, more options exist for hormone treatments than when the WHI study began. Women can now choose pills, skin patches, vaginal delivery products and others. Vaginal estrogen is effective for treating vaginal dryness that interferes with sex, Santoro says, “and it’s a therapy that women can take long term with little concern about any major side effects as best we can tell.”
The optimal intervention depends on the individual, but if a woman needs birth control, a hormonal contraceptive can be a nice way to “cruise through menopause,” Santoro says. Dosing and hormone type are important to consider. Birth control pills typically have higher doses of hormones than those given exclusively to treat symptoms of menopause, but other hormonal contraceptives may have less.
Some of Santoro’s patients who are taking birth control pills opt to stay on them continuously, without taking the week off each month for a period. During perimenopause, that pill-free week can make women miserable with symptoms, so staying on the pill continuously is one way to ease the transition, Santoro says.
She works with patients to estimate when they might be menopausal based on their family history (your mother’s age at menopause is a decent proxy for your own) and their own menstrual pattern.
“If you’re over 45 and have gone 60 days without a period and you used to cycle normally, you’ve got a 90 percent chance of being menopausal within four years,” Santoro says.
No test exists for menopause. Levels of anti-Müllerian hormone can be predictive about the timing of menopause, but it’s not an exact science, Santoro says. The medical definition is that the woman has gone one year without a period, which means it can be confirmed only in retrospect.
Such uncertainty can feel daunting for someone going through menopause, but information can help.
“Women need to be empowered to know what’s coming and that they can do something about it,” Faubion says. It can be hard to find a health-care provider who is well-versed in menopause medicine, but NAMS’s website, Menopause.org, can help women find providers who have passed an exam demonstrating their knowledge about menopause.
There is a lot of negative messaging about menopause, but what is less often extolled are the many upsides, Santoro says. Many women are happy to be done with their periods and relieved of having to deal with contraception.
While nothing is as effective as hormones, experts say, there are other treatment options for women who cannot take them. The Food and Drug Administration has approved a low-dose form of the antidepressant paroxetine (Brisdelle) for menopause symptoms, and it can take the edge off hot flashes, Stephanie Faubion, medical director of the North American Menopause Society, says. Some doctors also prescribe other low-dose antidepressants, although these come with risks that should be discussed ahead of time.
Faubion and her colleagues recently completed a study suggesting that Oxybutinin, a nonhormonal drug for treating overactive bladders, reduced the frequency and severity of hot flashes compared with a placebo. If the finding is confirmed, it could offer another alternative.
There are also promising studies underway testing whether NK3-inhibitors, drugs that target brain receptors involved in hot flash generation, can provide another alternative to hormones.
Unfortunately, no lifestyle or herbal remedy has ever been proven to work, Faubion says. But that is not to say that some women do not swear by these treatments, because the placebo response for hot flashes is high.
“If you give women a sugar pill, and tell her it will help with your hot flashes, it will reduce anxiety associated with hot flashes and therefore reduce the hot flashes,” she says.
Two behavioral approaches with some evidence to back them — cognitive behavioral therapy and hypnosis — probably work by reducing anxiety, Faubion says.
— Christie Aschwanden
Look for FDA-approved 'bioidenticals'
The Internet is awash with experts promoting custom compounded “bioidentical” hormones.
The word “bioidentical” refers to hormones that are similar to what the body naturally produces vs. ones derived from animal urine or produced synthetically. The expectation is that because bioidenticals are more similar to what the body naturally produces, they might have some advantage, says JoAnn Manson, chief of Preventive Medicine at Brigham and Women’s Hospital and a lead investigator in the Women’s Health Initiative (WHI).
But “bioidentical” has become a marketing term, and many of the products called “bioidentical hormones” are compounded drugs, which are neither approved nor subject to oversight by the Food and Drug Administration, Manson says.
The “FDA does not have evidence that compounded ‘bioidentical hormones’ are safe and effective, or safer or more effective than FDA-approved hormone therapy,” according to an FDA fact sheet. In 2008, the agency sent warning letters to several compounding pharmacies, calling them out for making unsubstantiated claims about their “hormonal’ products.
Compounded bioidenticals also run the risk of containing contaminants and impurities, and they may provide inconsistent doses.
Unless someone has an allergy to an ingredient in the product, experts say there is no good reason to use a compounded bioidentical product instead of one of the FDA-approved bioidenticals available at a regular pharmacy in numerous forms — oral estradiol, transdermal estradiol patches, gels, sprays, lotions, estradiol vaginal creams, tablets, rings and inserts, and micronized oral or vaginal progesterone.
These products are produced with strict manufacturing oversight, sold at regular pharmacies and come with package inserts that include a black box warning about potential risks.
— Christie Aschwanden