The US Food and Drug Administration (FDA) plans to update the black box warning on menopause hormone therapies soon, commissioner Dr Martin Makary has said.

The move follows years of debate over safety alerts that have limited access to treatment for millions of women with menopause symptoms.

“We are in serious discussions now about what to do about the black box warning, and I think you’ll hear something on it very soon,” Makary told CNN’s Dr Sanjay Gupta on the Chasing Life podcast.

The black box warning – the FDA’s strongest safety alert – has appeared on oestrogen-containing menopause treatments since 2003, including pills, patches, sprays and creams.

It warns that their use can increase the risk of uterine and breast cancers, strokes, blood clots and dementia in women over 65.

The label was added after a large government-funded study found that women taking oestrogen pills after menopause had higher risks for certain cancers, heart disease and stroke compared with those given a placebo.

The participants had an average age of 63, meaning many were already past menopause when they began therapy.

After the study and label change, prescriptions for hormone replacement therapy (HRT) dropped by more than 70 per cent, and many doctors became reluctant to prescribe them.

“It’s really a tragedy. It’s maybe one of the greatest screw-ups of modern medicine,” Makary said.

“It’s resulted in 50 million women being denied this incredible therapy.”

The result has been undertreatment of symptoms that can be debilitating for women in midlife.

In the late 1990s, more than one in four postmenopausal women took hormones to manage symptoms such as hot flushes (sudden sensations of heat), mood swings and night sweats.

By 2020, that figure had dropped to about one in 25.

Newer analyses of the original Women’s Health Initiative data have since found that hormone therapy started in women under 60, or within 10 years of starting menopause, may safely help manage symptoms such as hot flushes and poor sleep, provided they do not have specific contraindications such as a history of hormone-sensitive breast or uterine cancer.

Makary said HRT may also have benefits including reducing bone loss, lowering heart disease risk and helping preserve memory.

“Women live longer and feel better on hormone replacement therapy when started before age 60,” Makary told Gupta.

The potential change follows a July meeting of experts convened by the FDA to discuss the benefits and risks of hormone replacement therapy.

The panellists urged the agency to remove the warning label.

“I am begging the FDA, and all of us are begging, please remove the box label,” said Dr JoAnn Pinkerton, professor of obstetrics and gynaecology at the University of Virginia School of Medicine.

“And please stop harming women.”

Some women’s health experts say the FDA overstepped when it applied the boxed warning to all forms of oestrogen replacement.

“That is a real mistake,” said Dr JoAnn Manson, professor at Harvard Medical School and one of the principal investigators of the Women’s Health Initiative study.

Some forms do not raise oestrogen levels in the blood, so they are unlikely to increase cancer risk.

For example, studies have found that low doses of oestrogen delivered by vaginal tablets, creams or rings can safely treat symptoms of dryness, painful sex and urinary tract infections in postmenopausal women, Manson said.

However, the black box warning may still deter women from using them.

“It scares them away. And even after they purchase the product, they just don’t take it,” Manson said.

“This is really where women are being tremendously undertreated and are suffering unnecessarily due to a boxed warning that is just class labelling.

“All hormone therapy products get exactly the same boxed warning, and it is really harming women,” said Manson, who is chief of the Division of Preventive Medicine at Brigham and Women’s Hospital.

Manson said it would also be reasonable for the FDA to consider removing the warnings from oestrogen-containing therapies delivered through the skin in patches, sprays or creams to relieve menopause symptoms such as hot flushes and night sweats.

These deliver hormones into the bloodstream, but observational studies suggest they have a more favourable balance of risks and benefits than pills.

She was less certain about removing the boxed warning from oestrogen-containing pills taken by mouth.

“I think that’s where it’s evidence-based and justified,” she said.

A 2022 review by the US Preventive Services Task Force concluded that, in women past menopause, there was no net benefit to taking either oestrogen alone – prescribed for women who have had their uterus removed – or a combination of oestrogen and progestin – typically prescribed for women who still have their uterus – to prevent chronic conditions such as heart disease and dementia.

What remains unclear is whether women who start hormone therapy during perimenopause (the transition before menopause) need to stay on it long-term to gain potential heart, brain and bone benefits.

“It’s a very good question,” said Dr Roberta Diaz Brinton, a neuroscientist who studies oestrogen’s effects on the brain at the University of Arizona.

“We need to answer that.”

Other experts say there is still not enough scientific evidence to support long-term use of hormones to prevent heart disease, Alzheimer’s disease or osteoporosis.

Four medical societies – the American College of Obstetricians and Gynecologists, the Menopause Society, the Endocrine Society and the American Association of Clinical Endocrinology – support the use of hormones to relieve menopausal symptoms but do not recommend continued use to prevent chronic conditions such as heart disease.

Dr Leslie Cho, who runs Cleveland Clinic’s women’s cardiovascular centre, said she supports lifting the warning from vaginal oestrogen cream.

“It’s never made sense on the cream,” she said.

But Cho warned that some of the proposed benefits are based on after-the-fact analyses of studies that were not designed to measure them.

“I’m so glad to hear the FDA chair talk about this, because then, if that’s the case, they should do a study.

“They should fund a study,” she said.

With the rise of online hormone prescriptions, Cho warned that some women could start taking hormones despite having risk factors such as high blood pressure, obesity or high cholesterol, which could outweigh potential benefits.

Even in younger women, studies show that hormones may increase the risk of blood clots.

“Women have to talk to their physicians about hormone replacement therapy before they believe in all the hype that’s currently ongoing, because so much of it is hype,” she said.