Warning labels on menopause treatments ‘scare women’, doctors tell FDA

When obstetrician JoAnn Pinkerton spoke on a Food and Drug Administration panel recently, she didn’t mince words.

“Please stop harming women,” she said.

Pinkerton argues that the FDA’s black box warning labels on hormone replacement therapies make women reluctant to take medications that can be beneficial for treating the symptoms of menopause.

Pinkerton was one of twelve doctors — many of them experts in obstetrics and women’s health — who asked the FDA to remove the warning labels for vaginal low-dose estrogen treatment.

The medication is typically prescribed to women in order to mitigate symptoms of menopause or perimenopause. Unlike other systemic hormone therapy treatments which are absorbed by the whole body, it is delivered locally — through a patch, a cream or a ring.

The black box warning is the strongest safety label the FDA can put on a prescription medication. And Pinkerton and others argue that such a warning for low-dose estrogen treatment is unnecessary.

The medication is often prescribed to prevent or address symptoms associated with menopause including frequent urinary tract infections, vaginal dryness, and pain during sexual intercourse.

“ The boxed warning is not supported by science,” says Pinkerton. “It overstates risk.”

Pinkerton described a recent patient suffering from such symptoms, for whom she had written a prescription. She pulls out the tube, “and it says warning: Endometrial cancer, cardiovascular disorders, probable dementia and breast cancer. And she looks at it, her partner or spouse looks at it and they throw it in the trash,” Pinkerton recounts.

A pendulum swing toward HRT

The consensus from the medical establishment on the safety of hormone treatment for menopause has changed dramatically in recent decades. In 2002, researchers partly halted a large study on women’s health — the Women’s Health Initiative — out of concern that hormone therapy was associated with increased risk of cancer and stroke. Breast cancer was a particular concern. Since then, researchers and doctors have determined the cancer risk was overstated.

Treatments and best practices around when to prescribe hormone therapy and what medications exactly to prescribe have evolved in recent decades.

Many doctors in women’s health have advocated for this change for years without success.  Recent studies suggest the cancer risks of some hormone therapies are quite low and there are significant benefits for women going through menopause. This is a pet issue for Dr. Marty Makary — the current FDA commissioner. Makary is a surgeon, not an obstetrician. He convened the panel.

“Fifty million plus women have not been offered the incredible potential health benefits of hormone replacement therapy,” Makary said in opening remarks at the panel, “because of medical dogma.”

Makary said his own family could have benefited from this treatment when it fell out of favor with the medical establishment.

“ One of those women was my mother,” he said, “who went through perimenopause around that time.”

Obstetricians and gynecologists interviewed for this story agreed they would like to see the black box label removed for low-dose vaginal estrogen treatments that carry lower cancer risk.

“ I usually will make a little joke about, hey, we’ve been working for many years to try to get that black box warning removed, but you know, how slow government things can take,” said Dr. Monica Christmas, who regularly prescribes such treatments to her patients. Christmas is an OBG-GYN who is also the associate medical director for The Menopause Society.

Christmas expressed reticence, however, about removing labels for systemic estrogen, which carries a different risk profile for cancer.

“ For the vast majority of people, the risk is low, even for systemic hormone therapy,” said Christmas, “but it’s not zero.”

Christmas said the black box warning can prompt doctors and patients to have necessary conversations about the risks and benefits of such medications.

The FDA panel focused primarily on low-dose estrogen, but Makary also hinted at removing the label for systemic therapy, mentioning the benefits as suggested in some studies for reduced risk of osteoporosis, among others.

“We want to learn from all of you,” Makary said to the panel members, “help guide us as we think through what should be done here at the FDA.”

“This was theater, not scientific evaluation.”

The panel was a departure from typical decision making at the FDA.

“This was theater, this was not scientific evaluation,” said Adriane Fugh-Berman a professor of Pharmacology at Georgetown University. Fugh-Berman is skeptical of removing such labels and points out that the FDA usually has a more rigorous process to inform these kinds of changes.

“That process is being undermined and distorted,” she said.

(Fugh-Berman has worked as a paid expert witness in litigation against pharmaceutical companies accused of overselling the benefits of hormone therapy and contributing to breast cancer.)

FDA decision making often involves a period of public input. Committees are appointed to study issues and make recommendations. Fugh-Berman said she would have preferred to see a period of public comment as well as an expert committee that included a wider range of experts such as epidemiologists, oncologists, and experts in public health.

Representatives from the FDA did not respond to a request for comment on this story, or offer comment on future steps in a potential process to remove the warnings from prescriptions.

At least one obstetrician celebrated the increased attention to this issue, even if it came through an unconventional process.

“I was very happy,” said Rachel Rubin, a urologist with a specialty in sexual medicine. Rubin was also a panel member. “ The fact that the head of the FDA wants to be talking about this topic is extraordinary and something we’ve all been dreaming about,” she says.

 Rubin acknowledged the departure from the level of rigor to which the FDA usually adheres.

“Were there voices missing? Of course,” she says. But given this opportunity, she said, it’s worth showing up to, “fight for something you’ve been fighting for for decades.”

OB-GYN Monica Christmas wouldn’t say whether she thought the composition of the panel should have been different or the process more rigorous. But she did express concern that enthusiasm for hormonal treatment for menopause may be eclipsing the necessary risk-benefit analysis that patients and doctors need to make when considering these medications.

“Hormone therapy has become synonymous with menopause,” she says. And she cautions that women should rule out other issues before they jump to hormone therapy.

“It’s almost like, ‘Oh, I’m in menopause,’ says Christmas, “I should have to be on hormone therapy for all of these magical or mystical benefits.”