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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.

Mental health

Neuroscience-backed journaling for women’s mental health

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AI-powered journaling app Véa is supporting mental health by helping women to understand their thoughts, triggers and behavioural patterns. 

Winner of the Brain and Mental Health Innovation Award at this year’s Femtech World Awards, Véa is designed to address the emotional gap in women’s health technology.

The journal – which has been built by a female team and trained on women’s health papers – tracks inner states, provides personalised insights and somatic practices, and utilises AI to explain complex neuroscience in relatable terms.

Described by its founders as a “protector, seeker, and sculptor”, Véa provides a longitudinal map of women’s emotional journeys, integrating journaling with therapy and both in-person and online community support.

The journal’s goal is to improve women’s mental health without replacing professional care. 

Zahra Bhatti, co-founder and CEO and Katrina Zalcmane , co-founder and growth lead speak to Femtech World about the technology, winning a Femtech World Award and their plans for the future.

Women’s health and wellbeing technology has grown so rapidly over the last few years, but is largely focused around physical health. What was the emotional gap that you saw that inspired you to create the journal? 

“Women’s health has been focused on reproductive health and physical health, but it is all one ecosystem – it always starts with the mind,” says Zahra.

“Whatever you feel down here, you feel up there too, and the hormones reflect that. 

“With Véa, it was actually built from our own personal experience of burnout. 

“We wanted to make a space where women could feel safe and were able to reflect what’s on their mind, but also understand their mind the same way that women understand their hormones. 

“Women need to understand what happens in our minds. Véa helps women to understand cognitive distortions, why they feel the way they feel, black and white thinking – we wanted to really surface that for them. 

“For example, when you’re in your luteal phase, your serotonin levels drop, so that means you’re going to be a bit more nervous. 

“You’re going to be more reactive. You’re going to be taking things more deeply, and that’s something that your rational mind wouldn’t normally do if you’re in your ovulation phase. 

“So that’s what Véa does – she reflects that back to you, so you understand your body and thought processes.”

Véa describes itself as a journal that’s designed for the female mind. What does that mean in practice, and how does the experience differ from using traditional journaling?

“The majority of our team is female, so Véa has been built from all of our lived experiences, and the AI itself is trained on women’s health papers,” says Katrina. 

“It takes into account what having a certain condition means for individuals. For example, if you have endometriosis or PCOS, We’ve trained our AI on womens health data and research, which gets reflected back to the woman in a simple and effective way

“We have a clinical board, who are all also women, who look through the AI and the language. They ensure that all outputs are evidence based, ethical and take into account the various therapies which are proven to work for women.

“We also have somatic practices which are focused on women which we call “rituals”. We have a self-inquiry ritual, a confidence mirror ritual, or we have one of our psychotherapists on the board who does therapy through novels, for example. 

“These aim to make you the protagonist of your story. 

“Generic journaling apps are one size fits all, but women are not one size fits all, and that’s what we’ve made sure to put in the forefront of Véa.”

Instead of conventional mood tracking, you are focused on the inner states of women. How do you develop that approach, and what kind of insights has it revealed about how women reflect on their emotions? 

Katrina says: “Mood plays a part in our inner state and Véa checks in on that. 

“It allows you to have a journey across time. For example, on a good day, maybe their “protector” aspect is good at setting boundaries, but on a bad day, it could be really closed off. 

“It’s a richer approach, and these inner states are tied to specific prompts which are then linked in the journaling.”

“As women, we are fluid,” adds Zahra. 

“We are not one entity. 

“For example, you might be in a state where you’re really overthinking, but actually, you’re seeking new perspectives, and that’s why within Véa, the inner state is called a “seeker”. 

“When you converse with Véa in your seeker mode, she will challenge you in a Socratic way.

“However, the next day, you might be a “protector”, and then Véa will adjust her voice for a reflective and exploratory tone compared to when you were a seeker.

“Another state which I love is the “sculptor” which is when you’re feeling confident. 

“When you’re a sculptor, Véa will talk about how you can be creative, asking questions such as ‘what did you create today?’ ‘How did that make you feel?’ and ‘How would you describe that if you could put a shape to this color, this feeling?’, for example. 

“Véa goes into all of these different modes, and it builds a longitudinal map of the woman as well. So, throughout weeks, months and years, you can see how you’ve changed across time.”

How did you approach designing an AI companion that feels supportive without replacing human connection or professional care? 

“For the past six years, I’ve been a product manager. So I’ve seen how all of these web apps and applications have been built, and I’ve worked quite deeply with AI so I knew what was missing and like what women truly needed,” says Zahra.

“The key thing for us is that we want to bring “URL to IRL” [in real life]. 

“We have a community that goes alongside Véa. This includes a WhatsApp community and events. 

“We turn the rituals inside Véa into in-person workshops at our events with our clinical board and with professionals in the space. 

“We are not neuroscientists, but there are neuroscientists who have helped us build the app, and we make sure that AI is there to support you, but AI will never replace that human touch.

“That’s something that’s very close to us, and we want to make sure we connect people together and help people reflect in a safe space. 

“As well as AI, there is the option to talk to the clinical board, to use their rituals, to reflect with the community, and go to our events.” 

Katrina adds: “The key is that whatever the touch point is, whether it’s the app or it is an event or even our online community, we don’t want women to feel alone. We want them to feel together, grow together, and process together.”

People may often start journaling with good intentions, but struggle to stick with the practice. What have you learned about building habits and how those insights have shaped the experience of your product? 

Zahra says: “I think everyone wants to gamify things – what helps us is the community aspect. 

“We’ve created a tribe through the community, and because it’s so hyper personalised, you help shape the app, the app doesn’t shape you. You have full control, which makes people want to come back. 

“Véa remembers what you said yesterday as well as six weeks ago, and she will surface that. 

“We do have “streaks”, but our streaks are very gentle – every time you get a streak, you get a neuroscience fact along with it. 

“Something else we have built in that helps retention is “breakthroughs”. When Véa detects a shift in language, and will highlight, for example, that you have shifted from overthinking to certainty.”

“I think people are sick of data, they’re sick of data that they can’t interpret from. Véa interprets for you. 

“Soon we will evolve even more and add more features such as cycle tracking, wearable tracking and hormone tracking, to build out that ecosystem.”

What does success look like for Véa and how do you see the app and the community evolving as you move forward? 

“We want to launch across so many different markets. Our next target is the US,” explains Katrina.

“We want to bring our events over there as well. We do a lot of corporate events too. We have one with NatWest coming up – we know that work stress is a big thing, especially amongst females. 

“I think there’s a real space for that in the corporate world, so that’s one of our key focuses.”

Zahra adds: “Growing in markets and keeping going with our communities. We have just launched a supper club which sold out in three days in Manchester, which is absolutely amazing. We’re doing some in London and Amsterdam as well in the next few months. We are focused on growth, growing our board as well, and keeping the female mind at the center.”

What does it mean to win the Femtech World Award? 

Katrina says: “When you are so passionate and truly believe in something, you do it for that reason, but that external validation of seeing that it also matters for others in the wider space means so much. 

“Especially, in Femtech – it is a whole category that has been growing, but when it comes to funding and recognising women’s issues, there is still a lot of awareness that needs to be raised. 

“Being recognised gives us that fuel to continue and drive forward, and that it really does matter.”

“We want to be at the forefront of women’s mental wellness as a whole, and have put many sleepless nights into developing the app, so it is a big testament to that,” adds Zahra.

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Features

Gender gap in treatment persists even when men and women have same condition

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Women with the same medical conditions as men were less likely to receive the same treatment across several specialties, a global research review found.

The review found differences in care for conditions including cardiovascular disease, kidney disease and Parkinson’s, with women less likely to receive some active treatments.

Of 38 studies analysed, 33 found women were less likely than men to be offered active treatment.

Researchers at the University of St Andrews found women with myocardial infarction, heart failure or an irregular heartbeat were more likely to receive medication, while men were more likely to undergo coronary bypass surgery, stenting or other surgical treatment.

Women were also less likely to be prescribed statins.

Men with Parkinson’s were more likely to be referred for deep brain stimulation.

Men with liver failure were more likely to receive a transplant, while women with kidney disease requiring dialysis were less likely to receive permanent access and spent longer using a catheter.

Women were also less likely to receive opioids for pain management.

The researchers found no significant difference between women and men in treatment for stroke or diabetes, while women were more likely to receive treatment for dementia.

None of the studies identified clinical guidelines recommending different treatment based on sex.

Researchers said this suggested the differences could not be explained by the need for different clinical approaches to women’s health.

Dr Andrew O’Malley, who co-led the study, said: “For clinicians, the findings are a prompt to check whether treatment is being offered on clinical grounds rather than assumption.”

He said studies showed doctors more often attributed women’s symptoms to anxiety and made more diagnostic errors with female patients, even when test results were positive.

Dr Miriam Veenhuizen, honorary lecturer in the School of Medicine at St Andrews, said: “While the direction of the findings was not a surprise, the consistency was. The same pattern appeared in cardiology, surgery, transplant medicine and emergency care, and it survived statistical adjustment in most studies.”

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Pregnancy

Women with multiple health conditions face higher pregnancy risks, study shows

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Women entering pregnancy with multiple long-term health conditions face higher risks of miscarriage and other complications, a UK study found.

Those with two or more pre-existing physical or mental health conditions had a 20 per cent higher risk of miscarriage than women with no long-term conditions.

They also had more than twice the risk of venous thromboembolism and around four times the risk of antenatal anxiety and depression.

The UK-wide research team analysed 2,225,701 pregnancies and birth events recorded between 2000 and 2022 across five datasets covering England, Scotland, Wales and Northern Ireland.

Women with multiple long-term conditions had a 69 per cent higher risk of nausea and vomiting during pregnancy and a 42 per cent higher risk of pre-eclampsia.

The women also had a 32 per cent higher risk of placental abruption and a 26 per cent higher risk of gestational diabetes.

Risks rose as the number of existing conditions increased.

Among women with three or more long-term conditions, the risk of venous thromboembolism was more than three-and-a-half times that of women with no long-term conditions.

Researchers said the findings had implications for maternity services, where care pathways are largely centred on individual conditions and may not adequately meet the needs of women with multiple long-term conditions.

Dr Kelly-Ann Eastwood, joint senior author and honorary lecturer at Queen’s University Belfast and consultant obstetrician at St Michael’s Hospital, Bristol NHS Foundation Trust, said the results “help define” the urgent clinical challenges facing women entering pregnancy with multiple long-term conditions and the clinicians caring for them across the UK.

“These findings highlight the pressing need to restructure existing maternity services to improve antenatal outcomes,” she added.

The authors cautioned that the study was observational and relied on routinely collected health records, meaning some conditions and outcomes may have been under-recorded, while residual confounding could not be excluded.

The researchers plan to examine birth and child outcomes and identify which combinations of long-term conditions carry the greatest risk.

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