What Should Doctors Know About FDA’s Black Box Change for Hormone Replacement Therapy Drugs? 

A Keck Medicine of USC breast surgeon discusses the FDA’s decision — and whether using HRT to treat menopause symptoms actually affects breast cancer risk. 

Why was there a stigma around HRT before?  

Two decades ago, the FDA began requiring HRT medications to come with a black box warning about potential increased health risks in women. This came after the Women’s Health Initiative (WHI) study seemed to link HRT to a higher risk of breast cancer, as well as heart attack, stroke and blood clots. Apprehensive about HRT’s potential risks to patients, some physicians avoided prescribing HRT to women who may have otherwise benefited from the intervention.  

At the same time, Woodworth says, many women who have been on HRT have felt like they are “living in the shadows because they always had to defend their use of HRT against stigmas about the black box warning.” She adds that the warning could even discourage some women from seeking routine breast cancer screenings for fear that they would be questioned about their HRT use. 

The FDA now aims to update the language featured on HRT product labeling to remove references to risks of cardiovascular disease, breast cancer and probable dementia. (It is, however, retaining a boxed warning related to endometrial cancer for systemic estrogen-alone products.) 

Woodworth says the news has reinvigorated conversations about the need to help women manage menopause symptoms. “The FDA’s decision is allowing us to have these conversations about women’s health openly,” she notes. “Before, there was a major stigma everywhere around HRT. I was in medical school right when the black box warning was implemented. At the time, medical students weren’t even being taught much about menopause symptoms, and we definitely weren’t learning that HRT could be a beneficial treatment.” 

“With this decision from the FDA, I’m very glad that we are taking off the black veil around menopause, its symptoms and potential treatments,” she says. 

What does the latest science say about HRT and breast cancer risk?  

General practitioners should reevaluate their biases regarding HRT and menopause treatments, Woodworth advises. She also highlights the need for more research on HRT and other interventions for menopause symptoms. 

“As a breast surgeon, I’ve completely changed my views on HRT after reading the latest research,” she says. “Many doctors have had it engrained in them since medical school that HRT is not an acceptable treatment. It’s important to look at the new research and come up with modern-day best practices for our patients.” 

Making the best decision for each patient 

Every patient’s breast cancer risk looks different, whether or not they are engaged in HRT. “The science around breast cancer risk is very nuanced,” Woodworth says.  

Typically, whenever someone talks about an increased risk of breast cancer in the setting of HRT, they are referring to low-grade, hormone-sensitive breast cancer, she explains. These types of cancer are usually caught early during regular screenings and are highly treatable.  

Another important factor is whether the HRT prescribed is systemic or topical. If someone is just taking localized, vaginal HRT to treat chronic urinary tract infections, this type of HRT does not pose an increased risk of breast cancer, even for women with a history of low-grade, hormone-sensitive breast cancers.  If, however, someone is experiencing hot flashes, weight changes, brain fog or other full-body symptoms, they’ll likely be prescribed systemic HRT, Woodworth says. 

The data on systemic HRT has changed significantly over the past two decades, she says. A recent meta-analysis of 30 trials on 26,708 female participants found that HRT use was not associated with increased cancer mortality. Moreover, the data actually suggests that women who started HRT before age 60 appeared to have a decreased mortality risk. Other studies have also shown that HRT benefits women by reducing their risk of all-cause mortality, fractures, Alzheimer’s disease and heart attacks. 

“Hormone responsibly”  

That said, Woodworth notes that HRT is not a cure-all for all patients. Instead, providers need to assess the individual risks and benefits for each patient.  

“I think sometimes people are very quick to jump to conclusions that one treatment will fix everything, and I get a bit concerned by that type of thinking,” she says. “It’s great that women who can benefit from HRT now have easier access to it, but it’s also important to acknowledge that not all menopause-like symptoms may be caused by menopause. For instance, sometimes a hot flash can result from very high blood pressure. As doctors, we need to make sure that we’re still considering all the possible diagnoses — and not just throwing HRT at everything as a solution.”  

“What I always tell my patients is to use hormone replacement therapy responsibly and to keep the nuances of each unique situation in mind,” Woodworth says. For instance, in the case of assessing breast cancer risk, it’s important to remember that HRT can increase breast density, and higher breast density can increase a patient’s risk of developing breast cancer. These are the variables doctors need to take into account for each patient.  

“We need to get a picture of what each individual’s risk for developing breast cancer is and make sure that we’re recommending the appropriate screening based on that person’s risk,” she adds. 

Meanwhile, a situation in which Woodworth would not recommend HRT as a safe option is if a woman has a history of hormone-sensitive, invasive breast cancer. “The concern is that if you are taking hormones and you have dormant, hormone-sensitive breast cancer cells, could HRT wake up those cells and allow them to reactivate? That’s a big concern.” 

Women who have had triple-negative breast cancer, on the other hand, might benefit from HRT, Woodworth says. “Many of these women have undergone removal of their tubes and ovaries, because they’re at risk of ovarian or tubal cancers,” she says. “These women are going to need some sort of hormonal support. They’re usually very young, and we should be reexamining whether systemic HRT could benefit them after they’ve been in remission for a few years.” 

Overall, Woodworth says it’s important for doctors to stay updated on the latest research. “Reread the data. Also, look at your own biases of why you feel a certain way, and really examine why you think that way,” she says. “It’s okay to shift your views. It doesn’t mean that you were wrong before or that you provided bad medicine; it actually means that you’re willing to examine how you practice, and that you’re offering the most up-to-date treatment.” 

And, if in doubt about whether HRT is a good choice for your patient or not, you can always reach out to a breast cancer expert for consult. “If a patient is at high risk for breast cancer, but they are interested in starting HRT, then they should be referred to a breast specialist,” Woodworth says. “We have to evaluate each patient as an individual.”  

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