FDA Removes Black Box Warnings from Menopause Hormone Therapy

The U.S. Food and Drug Administration (FDA) has announced the removal of black box warnings on hormone replacement therapies (HRT) for menopause, a significant policy shift that may change how these treatments are perceived and utilized. This decision, made public by the Department of Health and Human Services (HHS) on March 15, 2024, reverses a long-standing warning that linked HRT to increased risks of breast cancer, heart disease, and stroke based on research conducted in the early 2000s.

A black box warning is the FDA’s most serious notification regarding potential safety issues associated with medications. It is typically applied to entire classes of treatments based on their physiological effects. In a press conference, FDA Commissioner Marty Makary described the previous use of these warnings for HRT as “unscientific.”

As a result of the FDA’s latest decision, experts suggest that hormone therapies could become more accessible for individuals experiencing menopausal symptoms, such as hot flashes and night sweats. Since the introduction of the black box warning in 2003, subsequent research has indicated that the risks associated with HRT may have been overstated, which may have discouraged both providers and patients from considering these therapies.

Dr. Nanette Santoro, an obstetrician-gynecologist at the University of Colorado Anschutz and a leading researcher with the Women’s Health Initiative, emphasized that many women suffering from menopausal symptoms have been inadequately treated. “There are too many women who suffer in silence,” she stated. The Women’s Health Initiative, which has been investigating heart disease, cancer, and osteoporosis in postmenopausal women since 1991, has mostly received funding from the National Institutes of Health (NIH).

Despite the potential benefits of the FDA’s announcement, there is concern that it may lead to confusion regarding the safety and efficacy of hormone therapies. Deputy Secretary of Health and Human Services Jim O’Neill remarked that more women could potentially reduce their risks of fractures, heart disease, and cognitive decline while enhancing their overall vitality. However, Dr. Santoro cautioned that the evidence supporting these claims is not as robust as suggested.

The FDA’s decision comes as Makary and HHS Chief Robert F. Kennedy Jr. are scrutinizing past FDA decisions, including those related to vaccines. A panel of experts convened in July to review the scientific evidence surrounding the risks and benefits of HRT for menopause. It is important to note that not all hormone replacements are affected by this change; certain estrogen-only therapies will continue to carry warnings regarding the risk of endometrial or uterine cancer.

Menopause, characterized primarily by a decrease in estrogen levels, typically occurs after 12 months without a menstrual period. Hormone therapy can alleviate several menopausal symptoms by administering synthetic hormones, typically estrogen or a combination of estrogen and progesterone. These therapies can be delivered via oral pills, transdermal patches, gels, or vaginal rings.

Dr. Kemi Doll, a gynecologic oncologist at the University of Washington, highlighted that patients with a uterus should remain vigilant about the risks of endometrial cancer associated with estrogen-only treatments. “It’s too much estrogen stimulation,” she warned, noting that there has been an increase in preventable endometrial cancers linked to high doses of estrogen without accompanying progesterone.

In light of the FDA’s decision, the agency also announced the approval of two new drugs for menopause: a generic version of the oral hormone therapy tablet Premarin and Bayer’s Lynkuet, a non-hormonal treatment designed to alleviate menopausal symptoms such as hot flashes.

While hormone therapies do present some risks, particularly for individuals with a history of reproductive cancers or blood clots, the benefits may outweigh the risks for many women, especially those in their 50s. The recent label change could facilitate greater access to these treatments.

Dr. Santoro expressed skepticism regarding the claims being made about hormone therapy’s benefits. “I do not believe that it is the elixir of youth,” she remarked. There is a growing consensus that new research is needed to address the evolving health concerns facing women today, as much of the current discourse continues to be based on earlier studies, including those from the Women’s Health Initiative.

As the landscape of menopause treatment evolves, the implications of the FDA’s recent policy change will likely be closely monitored by both healthcare providers and patients alike.