The “black box” label is long outdated—and doing away with it opens up room for more nuanced conversations.
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Much to the delight of ob-gyns long espousing the upsides of hormone therapy (a.k.a. hormone replacement therapy, or HRT) for menopause, the FDA announced today that HRT products will no longer have a “black box” warning. Originally added in 2003, the label called out risks of conditions like breast cancer, heart attack, stroke, and dementia based on a large study called the Women’s Health Initiative (WHI)—it was stopped short the year prior when researchers first spotted such potential for poor outcomes. But in the decades since, it’s been well-established that the data didn’t support the warning that followed.
In a press conference today, FDA commissioner Marty Makary, MD, said that at the time, the FDA “reacted out of fear, not gold-standard science,” and that “instead of correcting the record, the medical establishment doubled down in groupthink.” It only makes sense that HRT prescriptions and usage plummeted in the years after the warning label was added—down from about a quarter of eligible women to roughly 5% today.
That equates to millions of women who may have suffered needlessly through menopause symptoms like hot flashes, night sweats, vaginal dryness, and insomnia that HRT could have resolved. And the effect of leaving these symptoms untreated isn’t just poor quality of life; it can trickle into relationship and career issues, not to mention risk for downstream medical problems like recurrent urinary tract infections and a slew of conditions prompted by inadequate sleep.
Even as plenty of doctors have scrambled to address the flaws of the WHI and the benefits of HRT for quelling the symptoms of menopause, women have remained, understandably, deterred by the scary warning. “That’s the hole, literally, that we’ve been trying to dig out of,” Sharon Malone, MD, a DC-based ob-gyn and certified menopause practitioner, and chief clinical director at menopause telehealth platform Alloy, tells SELF. The decision to strip the warning makes it easier for doctors and patients to weigh the pros and cons of HRT on an individual basis, without that conversation being overshadowed by outdated findings.
The results of the WHI initially suggested that women using the most commonly prescribed type of HRT, a combo of estrogen and progestin, had a slightly increased likelihood of having a heart attack, stroke, breast cancer, or dementia. But when the data were reviewed, a host of problems surfaced with the study’s design and even more so, how it was interpreted.
For starters, the population was skewed toward older women, Dr. Malone says, with participants up to age 79. That’s typically a decade-plus past menopause, when HRT is known to be less effective, and women are at higher baseline risk for all of the above conditions just due to age. When the results were broken out for women under 60? The apparent risks vanished. In fact, the data even suggested that women who used HRT under age 60 had some protection against developing and dying from heart attack and stroke. Since then, more research has reinforced the key factor of age at the time of starting HRT, uncovering lower risk of not just heart disease but also dementia and breast cancer in women who get on HRT during perimenopause (a.k.a. the lead-up to menopause).
The WHI results surrounding breast cancer, in particular, were also widely misinterpreted, Dr. Malone points out. The elevated risk was, in reality, so tiny, it wasn’t even statistically significant—less than one additional case per year for every one thousand women who took the combo estrogen-progestin pills. And what got missed in the coverage was, those who took estrogen-only pills were less likely to get and die from breast cancer, Dr. Malone adds.
Some experts attribute the difference here to the type of concentrated synthetic progestin included in HRT pills at the time, called medroxyprogesterone acetate. These days, FDA-approved versions include a kind of progesterone that matches what’s in your body instead, a.k.a. bio-identical, Sophia Yen, MD, a Sunnyvale, California-based ob-gyn and menopause specialist, and cofounder of telemedicine platform Pandia Health, tells SELF.
The original takeaways from the WHI also “painted all hormone therapy in the same light, when it only investigated an oral pill in a particular [mostly older] population,” Somi Javaid, MD, a Cincinnati-based ob-gyn, founder of women’s health care platform HerMD, and member of the plusOne wellness collective, tells SELF. The resulting black box warning was added to not just pills but all other types of systemic therapies (like patches and gels) and vaginal rings and creams, from which the estrogen isn’t even absorbed into your blood.
To be clear, no research has ever shown that such a localized form of HRT could raise your risk of any of the health conditions above, making the warning there feel particularly out of place—especially given that urologists explicitly recommend the use of vaginal estrogen for combatting UTIs and related issues that tend to crop up in menopause.
Dr. Malone equates the fallout from the WHI to “a bad game of telephone” among doctors and patients. One finding, which was weak and poorly described from the start, got passed on and on, and became increasingly misconstrued to the point where everyone began avoiding all HRT outright—when the benefits often far outweigh the risks. The correction now feels long overdue in the sense that none of this is new information, she says.
The removal of the black box warning from all types of HRT might suggest that HRT is broadly safe for anyone dealing with menopause symptoms, but as with any drug, it’s tough to make a blanket statement. Dr. Makary noted in today’s news conference that a package insert will still address the “nuance,” like potential risks and adverse effects.
One important variable is the type of HRT; while the American College of Obstetrics and Gynecology (ACOG) has long advocated for the removal of the safety warning from vaginal estrogen, a news release from the org notes that systemic options (pills, patches) have a “different safety profile.” Because the estrogen in them enters your bloodstream, research suggests it may increase your risk of blood clots, Dr. Yen notes. (It’s thought, however, that this applies largely to the oral types—due to how they’re metabolized by your liver—and not to transdermal options.) This may be why your doctor might recommend against taking systemic HRT if you’ve had a blood clot, heart attack, or stroke, or have liver disease.
But even these traditional contraindications don’t necessarily take systemic HRT off the table, Dr. Malone says. For instance, maybe your blood clot happened as a result of an injury or being immobilized for a while; you’d be less at risk for a future clot than someone with a genetic predisposition to clotting, she points out. Or “perhaps your stroke or heart attack happened 20 years ago and now you’re suffering mightily through your menopausal symptoms,” she says. “We can’t just say, ‘Sorry, this isn’t for you.’”
The same measured calculus can apply to women with a history of breast cancer, Dr. Javaid says. “Maybe it was decades ago, and you’ve had negative genetic testing and a double mastectomy,” she points out. It isn’t necessarily a flat-out “no” to systemic HRT, given what we know about the WHI’s flaws and the potential benefits of HRT, both short- and long-term. Besides alleviating many of the often debilitating symptoms of menopause and offering protection for cardiovascular and brain health (if you time it right), HRT has also been proven to help ward off osteoporosis by bolstering your bones, Dr. Javaid notes.
Hence why discussing all of these factors with your doctor in light of your personal health history is the best way to decide if or when HRT is right for you. “Guidelines aren’t rules or laws,” Dr. Malone points out. “Every doctor can use them how they see fit to treat their patients. And women are also capable of making informed decisions about their own care.”
As we find distance from decades of misleading messaging around HRT, Dr. Javaid pushes women to flip the script. “Instead of asking, ‘What will happen to me if I take hormone therapy?’, I want them to consider, ‘What will happen to me if I don’t?’”
Both Dr. Yen and Dr. Malone also highlight the need for more education about menopause in medical school and among doctors. As Dr. Yen says, “back in my day, all we were taught [about menopause] was to put your hand on the woman’s shoulder and say, ‘This will pass.’” As a result, there’s “a whole generation of doctors who have never really prescribed hormone therapy or don’t feel comfortable managing women in midlife,” Dr. Malone says. Stripping the misleading messaging from HRT is only the first step in popularizing it among these physicians—and in turn, making it accessible to any woman who might benefit.
