The Food and Drug Administration (FDA) announced on March 15, 2024, that it will remove a long-standing boxed warning from hormone-based medications used to treat menopause symptoms. This decision affects over 20 products, including pills, patches, and creams containing estrogen and progestin, which are commonly prescribed for managing hot flashes and night sweats.
The FDA justified the removal of the warning by citing recent studies indicating that hormone therapy poses fewer risks when initiated before the age of 60 or within 10 years of the onset of menopause symptoms. Marty Makary, the FDA Commissioner, emphasized the need for a more nuanced and evidence-based approach to communicating the risks of hormone therapy. In a commentary published in the Journal of the American Medical Association, he stated, “We’re challenging outdated thinking and recommitting to evidence-based medicine that empowers rather than restricts.”
The previous warning had advised healthcare providers that hormone therapy could increase the risks of serious health issues, including blood clots and heart problems. This caution stemmed from data published over 20 years ago, which many healthcare professionals now consider outdated. The FDA’s revised labeling is expected to encourage more women to consider hormone therapy, a move supported by several physicians and pharmaceutical companies.
While the removal of the warning has received backing from some in the medical field, others have expressed concerns about the process. Critics argue that the FDA should have convened an independent advisory panel to thoroughly evaluate the evidence before making such a significant change. These experts assert that the potential risks associated with hormone therapy should not be overlooked, particularly given the contentious history surrounding these medications.
Current medical guidelines generally recommend hormone therapy for younger women experiencing early or mid-stage menopause, provided they do not have complicating health factors such as a history of breast cancer or heart disease. The updated prescribing information from the FDA aligns with this approach, yet Makary and others have posited that the benefits of hormone therapy extend beyond symptom relief.
In his commentary, Makary cited figures suggesting that hormone therapy may contribute to reduced rates of heart disease, bone fractures, and Alzheimer’s disease. He noted, “With the exception of antibiotics and vaccines, there may be no medication in the modern world that can improve the health outcomes of older women on a population level more than hormone therapy.”
The debate surrounding the efficacy and safety of hormone therapy has a long and complex history. In the late 1990s, millions of women in the United States took estrogen or combined estrogen-progestin therapies under the belief that these drugs would not only alleviate menopause symptoms but also lower the risk of heart disease and dementia. However, a landmark study involving over 26,000 women published in 2002 revealed that certain hormone therapies were associated with increased risks of stroke, blood clots, and breast cancer. Following these findings, prescriptions for hormone therapies significantly declined and have not rebounded in the past two decades.
New analyses of the original 2002 data have provided a more nuanced understanding of hormone therapy’s risks, particularly among different age groups. A recent study indicated that women in their 50s taking estrogen-based medications did not experience an increased risk of heart problems, while older women in their 70s did. The findings for women in their 60s were less clear, leading researchers to advise caution.
Additionally, advancements in hormone therapy formulations have emerged since the early 2000s. New options, such as vaginal creams, rings, and lower-dose tablets, provide alternative delivery methods that may pose different risks compared to traditional pills and patches. The FDA plans to update the labeling for these newer products to reflect their unique benefits and risks.
While the original boxed warning language will still be accessible to prescribers, it will be positioned lower in the prescribing information. The FDA will retain a boxed warning advising women who have not undergone a hysterectomy to use a combination of estrogen and progestin due to the associated risks of uterine cancer.
The FDA’s approach to revising the hormone therapy warning has raised questions about transparency and credibility. Instead of engaging a standing advisory committee on women’s health or drug safety to review the evidence, Makary opted to invite a select group of supportive doctors and researchers to discuss the benefits of hormone replacement drugs. Many of the invited participants have ties to the Unboxing Menopause campaign, which advocates for the removal of the warning label.
In response to the FDA’s decision, nearly 80 researchers signed a letter urging the agency to hold an official advisory committee meeting to ensure that all scientific viewpoints are thoroughly examined. Critics like Diana Zuckerman, president of the National Center for Health Research, have accused the FDA of undermining its own credibility by not subjecting the decision to rigorous scientific scrutiny.
As hormone therapy continues to be a contentious topic in women’s health, the FDA’s recent decision marks a significant shift in how these medications are regulated and perceived. The long-term implications for women’s health outcomes and treatment options will be closely monitored in the coming years.
