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FDA plans to revise black box warning on menopause hormone therapies

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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.

Wellness

Weekly app monitoring reduces breast cancer fatigue, study shows

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Weekly app monitoring can reduce fatigue and improve daily life for women with metastatic breast cancer, according to a study.

The approach involves regularly asking patients about their wellbeing through an app and responding quickly when problems are identified.

Germany’s Federal Joint Committee, known as the G-BA, has recommended that the treatment model be incorporated into standard care.

Professor Maria Karsten, senior attending physician at the Charité Breast Cancer Center and initiator of the PRO B project, said: “The new medications often no longer need to be administered at the hospital but can be taken at home.

“As a result, we see patients less frequently at the hospital, and our medical oversight has become somewhat incomplete.

“In order to close this gap and provide patients with close support in spite of the distance, we have developed the PRO B digital treatment concept.”

Around 68,000 women in Germany are living with metastatic breast cancer, meaning the disease has spread to other organs.

At this stage, the cancer is generally considered incurable. Modern treatments can, however, temporarily control the disease and extend life expectancy by several years, with some women able to continue working.

At the centre of PRO B is an app that asks women up to 52 structured questions once a week about their symptoms, daily life and emotional wellbeing.

Questions include whether they have experienced pain, felt too tired to carry out their usual activities or experienced shortness of breath.

An algorithm analyses the answers and immediately alerts the treatment team when relevant changes are detected.

The team then contacts the patient within 48 hours to decide whether any action is needed.

Karsten said: “During these phone calls, for example, we discuss whether the dosage of anti-nausea medication should be adjusted or offer practical tips for managing the various symptoms.

“But we also detect serious side effects more quickly – such as those indicated by a seemingly harmless symptom like fatigue – and can immediately schedule the patient for an appointment at the hospital.”

The study involved 909 women with metastatic breast cancer aged 19 to 81 across 52 breast cancer centres in Germany and followed them for one year.

Around half received PRO B care alongside drug-based cancer treatment.

The other half answered questions about their wellbeing once every three months and were not contacted by their treatment teams in response.

Women receiving PRO B care reported significantly less fatigue, which refers to physical, emotional or mental exhaustion that can severely restrict daily life.

They also rated their physical functioning more positively and required fewer hospital admissions.

Karsten said: “These are effects that have a noticeable impact on the patients’ daily lives; the women are more capable and better able to manage their lives.

“We even have evidence that the PRO B approach extends the remaining lifespan for some patients. We are achieving all of this not through a new medication, but simply by regularly and systematically assessing the women’s well-being and responding accordingly.”

More than 90 per cent of women in the PRO B group said after the study that they wanted the approach to become part of routine care.

Stephanie Neumann-Johnston, 51, who took part in the study, said: “I feel like the app has saved my life several times.

“There are so many situations and incidents that you can’t make sense of – you have so many questions.

“With the app, I can look up common problems and find medically reviewed information, for example, about fatigue. That way, I can help myself, also on the weekends.

“And the personal contact provides me with emotional and medical support.

“For example, I can find out whether I’m allowed to take certain medication for a fever, or get an assessment of my situation: Should I go to the emergency department with these symptoms or not? The app takes a huge weight off your shoulders.”

Based on the medical findings and a health economic analysis, the G-BA recommended in June that PRO B should be incorporated into standard care.

This would allow patients with statutory health insurance to access the model in future when they receive the relevant diagnosis.

PD Dr Christoph Kowalski, department director at the German Cancer Society and a co-author, said: “This recommendation must now be implemented as quickly as possible.

“If a new care concept offers medical and economic benefits, we should not withhold it from the most seriously ill women.”

The health insurance companies involved in the project are also planning further developments so affected women can receive routine PRO B care before its wider introduction into standard care, with access expected to begin this autumn.

The care model will continue under the name “ida”, led by Karsten and her team.

The PRO B project ran from 2020 to 2024 and received around €4.8m from the Innovation Committee of the Federal Joint Committee.

The project was led by Karsten, with consortium partners BARMER, mkk – meine krankenkasse, DAK-Gesundheit, the German Cancer Society and OnkoZert GmbH.

Breast cancer is the most common cancer among women in Germany, with around one in eight expected to develop the disease during their lifetime.

Worldwide, breast cancer is the leading cause of cancer-related deaths.

Despite advances in treatment, 30 per cent of women with early-stage breast cancer and up to 70 per cent of those with lymph node involvement in later stages develop distant metastases, which typically make the disease incurable.

For patients with metastatic breast cancer, treatment aims to prolong life while maintaining the best possible quality of life.

Since 2016, the G-BA has been responsible for supporting new forms of care that go beyond existing standards, as well as health services research aimed at improving healthcare quality in Germany.

Its Innovation Fund is financed through contributions from statutory health insurance plans and the Health Fund.

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Fertility

Higher doses of common fertility drug may increase pregnancy risks

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Higher cumulative doses of common fertility drug clomiphene citrate may increase pregnancy loss risks, according to new research.

Around one in six people experience infertility, with irregular or absent ovulation among the most common causes.

Clomiphene citrate has long been a mainstay of fertility treatment, but Adelaide University research has raised concerns about higher cumulative doses.

The new study found that high doses of clomiphene citrate accumulated over multiple fertility treatment cycles could increase the risk of pregnancy loss.

Lead author associate professor Sheree Boulet said the findings showed a clear dose-response relationship, meaning the risks increased as cumulative exposure rose.

She said: “Women who received higher cumulative doses of clomiphene citrate experienced progressively greater risks of adverse pregnancy outcomes.

“We examined more than 21,000 embryo transfer cycles across four cumulative dose categories and found that increasing the dose did not significantly improve the chance of a live birth.

“Our findings suggest there may be a point where increasing the dose offers little additional benefit while exposing women to greater risk, highlighting the importance of carefully balancing effectiveness with safety when making treatment decisions.”

Supported by the NHMRC and conducted in partnership with Boston University and the Centers for Disease Control and Prevention, researchers analysed 21,004 IVF embryo transfer cycles in the US.

Women receiving cumulative doses of 500mg to 749mg of clomiphene citrate had a 12 per cent higher risk of miscarriage, while those receiving 750mg to 999mg had a 38 per cent higher risk.

Women receiving cumulative doses of 750mg or more were also more than twice as likely to have twins or other multiple births.

Rates of spontaneous abortion, another term for miscarriage, increased as the dose rose.

Researchers also recorded more than a threefold increase in stillbirth at the highest dose, although the finding was not statistically significant because that dose was rare. Larger studies are needed to confirm the association.

The finding is consistent with an earlier Adelaide University study that showed a doubling of neonatal death in pregnancies involving clomiphene citrate. Neonatal death means the death of a baby shortly after birth.

Higher cumulative doses did not improve the chance of a live birth, but did increase twinning, which raises the risk of adverse outcomes for both mother and child.

Clomiphene citrate is one of the world’s most widely prescribed fertility drugs. It has been prescribed to millions of women worldwide since 1967 and remains a recommended first-line treatment for ovulation induction.

The drug is recognised as an essential medicine by the World Health Organization. It works by stimulating the ovaries to release eggs, increasing the chance of pregnancy.

Women who do not respond to lower doses, or who require multiple treatment cycles, may receive progressively higher cumulative doses over time.

The findings build on a series of studies from Adelaide University’s Robinson Research Institute linking clomiphene citrate with increased risks of pregnancy loss, stillbirth, perinatal death and some birth defects.

Experimental studies in mice supported these findings, showing that higher doses reduced successful pregnancies and were associated with pregnancy loss, impaired fetal growth and developmental abnormalities.

Professor Michael Davies, senior researcher and co-author of all the studies, said the latest work builds on more than two decades of Adelaide-led research into the safety of fertility treatments.

He said: “Clomiphene citrate has been used by many women since 1967, but it has never been comprehensively evaluated in large prospective clinical trials.

“Our studies indicate that women respond differently to clomiphene citrate and that increasing cumulative doses may increase the risk of adverse pregnancy outcomes without improving the likelihood of a live birth.

“The findings confirm and extend our previous studies in both human and mouse models which highlight the need to better understand the dose-response relationship and whether more personalised dosing strategies could improve safety.

“Until we can better understand these differences, it remains important that clinicians rigorously follow manufacturer’s safety recommendations and avoid unnecessarily increasing cumulative doses.

“The same questions are now being asked of newer ovulation-inducing medications, so any move away from clomiphene citrate should also be guided by robust evidence rather than assumptions about safety.”

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Entrepreneur

Women’s Health Week Europe 2026 releases fully populated agenda ahead of October summit

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Women’s Health Week Europe 2026 has released its fully populated speaker and session lineup ahead of the event’s return to The Emirates Stadium in London on 7–8 October, with 80+ speakers now confirmed across two dedicated stages.

The programme

The agenda runs across two dedicated stages in parallel, plus two pitch competitions across both days.

The Global Stage opens with a keynote from Merete Clausen (EIF) before moving into sessions on funding trends, AI, the gender data gap, the wearable revolution, and European policy.

Standout sessions include The Age of Digital TransformAItion featuring Nichole Young-Lin (Google), Frida Polli (MIT), and Sapna Shah (Sie Ventures); Lone Wolf or Pack Leader on collaboration versus fragmentation, with Eirini Rapti (Inne), Tatum Getty (Thena Capital), Novo Nordisk, and Jen Roberts-Woods (Borski Fund); and a live debate on whether the women’s health label helps or hinders founders. Day one closes with a keynote from Alison Cave, Chief Safety Officer at the MHRA.

The Scale Stage runs a practical playbook track in parallel, with sessions covering regulatory approval pathways, international expansion, the founder’s legal playbook, PR strategy, and implementing AI into a women’s health business.

The Reverse Pitch flips the usual format: investors and corporates pitch the room on what they are actively looking to fund, acquire, or partner on right now.

View the full agenda and speaker lineup

Pitch competitions

The WHW Europe pitch competitions are back, taking place in front of the audience across both days on the mainstage. 16 finalists will compete across two categories: Consumer & Tech on day 1 and Medical Devices & Therapeutics on day 2.

Any company treating a condition that affects women exclusively, differently, or disproportionately is eligible to apply.

Applications and close 28 August 2026.

Previous alumni include Circe, who secured £100k from Innovate UK, BoobyBiome, who closed a £2.5M seed round post-WHW Europe, and Amilis, who secured £1M at London Tech Week after winning at WHW USA 2026.

Apply to pitch

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