FDA removes black-box warnings from three more estrogen patches without convening an advisory committee

The Food and Drug Administration will remove black-box warnings about cardiovascular disease, breast cancer and probable dementia from three estradiol transdermal patches, federal health officials said today, Oct. 30.

The agency did not convene an advisory committee. It also offered few specifics on the scientific basis during a media briefing. When reporters asked for the evidence, officials said it could be provided later. The Department of Health and Human Services did not immediately provide brand names for the three patches.

What the officials said

Sarah Ibrahim, deputy center director for regulatory programs at the FDA's Center for Drug Evaluation and Research, said the old warnings "painted a broad and, in some cases, overstated pictures of risk." She said updated evidence shows that for many healthy women under 60 and within 10 years of menopause onset, "the risk-benefit profile looks meaningfully different than older warnings conveyed."

The action follows February 12, when the FDA approved label changes for six menopause hormone products: Prometrium, Divigel, Cenestin, Enjuvia, Estring and Bijuva. Those changes came after HHS announced in November 2025 that it would eliminate the broad boxed warnings.

The February changes did not strip every boxed warning. The endometrial cancer warning stays on systemic estrogen-alone products, and heart disease and breast cancer risks are still described in other sections of the labels. According to a summary of the FDA's list, 29 companies have submitted label changes.

Ibrahim said the FDA is working "expeditiously" with applicants on labeling changes for the remaining menopause hormone products.

The supply problem

The patches are hard to find. Ibrahim acknowledged that after the February label changes, demand for estradiol patches "increased significantly, and patients in many areas found it difficult to get their usual patches at their usual pharmacy." She added: "I want you to know that we hear you."

Dorothy Fink, deputy director of the National Institute of Child Health and Human Development, said estrogen patch output has doubled over the past year and manufacturers continue to expand capacity. Ibrahim said the FDA has expedited review of 10 manufacturing supplements this year, two of them approved within the past week. Those are requests from manufacturers to make changes that could expand production.

The FDA has worked with manufacturers since September to boost supply. It has not designated the patches as being in shortage. Patients still report stock-outs, and some injectable and vaginal estrogen products have also been in short supply, according to Reuters.

Loosening warnings tends to raise demand, and the FDA itself says demand jumped after February. Officials have not said how the added label changes will affect supply.

The dispute over evidence

Critics are not objecting to the warnings' removal in principle so much as to how it was done. Reshma Ramachandran, an assistant professor and health services researcher at Yale School of Medicine, said: "I have been concerned by the lack of transparency behind these decisions. The blanket removal of black-box warnings regarding risks of breast cancer and cardiovascular disease without clear justification can be misleading for patients and underplays real potential harms."

Ramachandran noted that certain groups carry particular risk, including patients with histories of hormone-sensitive cancers.

The pharmacology is not in dispute. Estradiol patches are generally considered lower risk than oral synthetic hormones because the hormone enters the bloodstream without first passing through the liver. Research shows risks from patches rise at higher doses.

The original warnings trace to the Women's Health Initiative trials, stopped in 2002 and 2004. HHS's Office on Women's Health notes the average participant was 63 and that the trials tested specific products: conjugated equine estrogens, with or without medroxyprogesterone acetate. The FDA says only about 2 million women ages 46 to 65 received a hormone therapy prescription in 2020, in a population of roughly 41 million women ages 45 to 64.

Medical groups have moved too

The agency is not acting alone. In October, the American College of Obstetricians and Gynecologists and the American College of Physicians each upgraded hormone therapy to the most effective treatment for hot flashes, night sweats and sleep disturbances.

Dr. Jan Carney, president of the American College of Physicians, said these symptoms affect as many as 80 percent of women in menopause. The guidelines recommend starting before age 60 or within 10 years of menopause, generally limiting treatment to three to five years. Women with a uterus should take estrogen with a progestogen. The guidelines say hormone therapy is not recommended for women with a history of cardiovascular disease, breast cancer or certain blood clots.

That is a more conditional message than the one from some federal officials. At the November 2025 announcement, Alicia Jackson, director of the Advanced Research Projects Agency for Health, said: "The science is clear: Hormone therapy is safe and effective. And it is hugely beneficial to the vast majority of women."

A conflict-of-interest question

Jackson's role drew separate scrutiny from ProPublica, which obtained her disclosure records. They show she is the founder and former CEO of Evernow, an online menopause care platform, and kept at least $115,000 in Evernow stock plus an unknown amount of stock options after joining the government. ProPublica reported that Evernow launched a nationwide expansion months after the warning removal was announced.

ProPublica said it is unclear what role Jackson played in the decision. The FDA, not ARPA-H, regulates drugs, and an FDA expert panel had recommended ending the warning requirement months before Jackson arrived in government.

Ethics experts told ProPublica the endorsement was a problem anyway. Virginia Canter, who served as an ethics lawyer under four presidents, said it "puts her within the zone of a potential violation." Federal law bars employees from participating "personally and substantially" in matters that could affect their finances, which can include public statements at a press conference. No finding of a violation has been reported.

What comes next

Officials have said the evidence behind today's decision could be provided later, but they have not said when. The labels for the remaining hormone therapy products are still pending. Whether more patients can fill prescriptions will depend on whether the doubled manufacturing output keeps pace with demand.