Susan Stone is the creator and presenter of It's a Jungle, exploring the people, science, and ideas shaping our health and wellbeing. Here she explores the FDA's decision to overhaul boxed warnings on menopausal hormone therapy - and what that means for Irish women.
Fifty million women - that is the scale of the impact neuroscientist Dr Jennifer Garrison believes emerges from the data on what happened after the Women's Health Initiative (WHI) study.
She points to analyses estimating that around 50 million women worldwide have avoided or been denied hormone therapy since 2003 because of fear; fear generated by warnings the FDA has now acknowledged were inaccurate. "That's 50 million women who have potentially suffered unnecessarily," she told me.
On 10 November 2025, the FDA announced it would remove long-standing boxed warnings about heart disease, stroke, breast cancer and probable dementia from systemic menopausal hormone therapy, while retaining a warning about endometrial cancer on estrogen-only products.
According to the FDA, studies show that women who initiate HRT within 10 years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures. Women may also reduce their risk of cardiovascular diseases by as much as 50%, Alzheimer's disease by 35%, and bone fractures by 50-60%.
FDA Commissioner Dr Marty Makary called the way menopausal hormone therapy was handled "one of the greatest mistakes in modern medicine," arguing that, aside from vaccines and antibiotics, no other medication can improve the health of women on a population level more than appropriately used hormone therapy.
Though the starting time of HRT and duration of use are decisions made between the prescriber and the individual patient, the FDA's labelled recommendation will be to start HRT within 10 years of menopause onset or before 60 years of age for systemic HRT.
The Scientist Who Saw It Coming
When I interviewed Dr Jennifer Garrison earlier this year - months before the FDA announcement - she was already describing the WHI fallout as a generation-long failure, claiming that the trial recruited the wrong women at the wrong time, tested older hormone formulations, and spawned an outsized fear narrative from relatively small absolute risks.
In her view, a whole generation of women was scared away from treatment that could have protected their bones, brains and hearts, while doctors were left practising defensive medicine under the shadow of a boxed warning.
Why did it take 23 years for the scientific consensus to translate into regulatory action?
"The WHI study was misinterpreted," Garrison posits, "and there was a lot of inaccurate information that was publicised about it."
What makes this particularly frustrating, she notes, is that the Women's Health Initiative itself is incredibly valuable; it has generated over 3,000 published studies.
"But the first one that was published using that data set, unfortunately, had a lot of misinformation in it." The problem wasn't the research; it was the communication of that first paper, and the fear narrative it spawned.
The Panic That Changed Everything
To understand why this matters, you have to go back to 2002. The WHI trial, a large US study of menopausal hormone therapy, was stopped early after preliminary findings suggested that combined estrogen–progestin therapy increased the risks of breast cancer, heart disease and stroke in the women studied.
Before the full scientific papers were published, the results were unveiled at a press conference and amplified across front pages and evening news bulletins worldwide.
The effect was immediate and profound. The FDA added a boxed warning - the most stringent type of safety warning in US drug regulation - to estrogen-containing products.
Prescribing rates collapsed globally: in the United States, the proportion of women in their early 50s using menopausal hormone therapy dropped within a few years. Ireland and the UK saw similar declines.
In a statement responding to the 2025 FDA decision, the European Menopause and Andropause Society (EMAS) put it bluntly: the original interpretation of the WHI results was "overly broad and, in several important respects, misleading," and this contributed to a long-lasting under-use of menopausal hormone therapy for suitable women.
What They Got Wrong
The test subjects. The average age of women entering WHI's hormone-therapy arms was around 63 - more than a decade beyond the typical age when menopause begins and when hormone therapy is usually initiated today.
Since then, a "window of opportunity" has been recognised: when systemic hormone therapy is started within about 10 years of menopause onset or before age 60, the balance of benefits and risks appears substantially more favourable. The updated FDA labelling now explicitly highlights that age and time since menopause are key to the risk-benefit profile.
Exaggerated risk communication. The WHI results were widely reported as relative risks: headlines about a "26% increase in breast cancer" sound terrifying, but they conceal the fact that the absolute excess risk seen in the trial was on the order of eight additional cases per 10,000 women per year - less than one extra case per 1,000 women each year. Presented without that context, women and clinicians heard only "increased risk of cancer" and understandably recoiled.
The "Bioidentical" Myth
Before discussing what the WHI actually tested, Garrison wants to clear up a term that causes endless confusion. "The word 'bioidentical' is a nonsensical marketing term," she says bluntly. "It doesn't actually mean anything. It's kind of like if you call something 'natural'—what does that actually mean?"
The real issue is molecular structure. "Estradiol is a chemical that has a physical structure. If you change one single atom on that structure, it becomes a different molecule."
The estradiol in modern hormone therapy is the same molecule whether it comes from pharmaceutical synthesis or soybeans - the question is what else comes along with it during production.
The WHI tested conjugated equine estrogens, Premarin, isolated from pregnant horse urine, combined with a synthetic progestin that binds to progesterone receptors differently than progesterone itself.
"There certainly is estradiol present in Premarin," Garrison explains, "but there are dozens, if not hundreds of other molecules there in different amounts. And we don't know exactly what those were doing."
Modern hormone therapy typically uses estradiol and progesterone - the same molecules the body produces. "The data using those hormones is not relevant for the hormones we're using today," Garrison concludes. "The benefits, the risks - they're completely different."
Her advice: "When you hear the word 'bioidentical,' think marketing ploy."
What the Evidence Now Shows
Two decades of follow-up studies, re-analyses and new trials have greatly refined the picture of who benefits most from menopausal hormone therapy and when. When systemic hormone therapy is started within the window of opportunity, using modern regimens in generally healthy women, the benefits are substantial.
Evidence from randomised trials and large observational cohorts shows that menopausal hormone therapy is the most effective treatment for hot flushes and night sweats, and can markedly improve sleep, mood and quality of life.
It also reduces the risk of osteoporosis and fractures, with several analyses suggesting that appropriately used systemic therapy can roughly halve the risk of certain osteoporotic fractures in eligible women.
Importantly, a pooled analysis of multiple randomised trials found no overall increase in cancer mortality among women using menopausal hormone therapy.
In its November 2025 statement, EMAS summarised the current consensus: for healthy women under 60 or within about 10 years of menopause, using appropriately selected systemic menopausal hormone therapy, the benefits generally outweigh the risks, particularly for relief of vasomotor symptoms and prevention of osteoporosis and fractures.
What This Means for Ireland
There are signs of progress closer to home. In Ireland and the UK, the prescribing of menopausal hormone therapy has risen markedly over the past decade as updated guidelines and public campaigns have reached more women and clinicians.
In a landmark policy shift, from 1 June 2025, HRT became free for women with medical cards or Drugs Payment Scheme cards at participating pharmacies in Ireland.
More than 170,000 women have already accessed free HRT in the early months of the scheme, according to implementation reports, and over 1,800 pharmacies have joined. This represents a significant step toward removing financial barriers to evidence-based care.
In Britain, the British Menopause Society has for years supported individualised prescribing, with no limit on how long otherwise healthy women can continue systemic hormone therapy when benefits clearly outweigh risks.
The European Menopause and Andropause Society welcomed the FDA's decision as an important step towards more balanced communication, while stressing that appropriate prescribing - not maximal prescribing - remains the goal.
"Prescribing of hormone therapy should be in the context of a woman's personal and family history (understanding her risk factors), symptoms, treatment goals and values, and current screening."
In Ireland, the HSE states that the benefits of hormone replacement therapy (HRT) "usually outweigh the risks" and can depend on your age, symptoms and risk factors.
They say that the evidence shows that the risks of serious side effects from HRT are very low, but that individuals should speak with their GP to make the right decision for them.
Breaking Down the Barriers
Garrison says there are two changes needed for things to change.
The affected prescribers: "From the perspective of the prescriber, there was a lot of trepidation around prescribing hormones from a legal and a liability standpoint."
The affected patients: "When you open up a prescription, and you read something that tells you this is going to cause cancer, and you should be on it for the shortest period of time possible, it really dampens your enthusiasm for using these interventions."
Whether the FDA decision will translate into changed behaviour remains to be seen. But removing these twin barriers - prescriber liability fears and patient alarm - is a necessary first step.
Flip the Script
For women who remain fearful despite the FDA's decision, Garrison has a message: flip the script.
"Hormone therapy is a band-aid," she acknowledges. "Let's be perfectly clear - it's not going to revolutionise your life and cure you of all disease."
But for women in perimenopause and beyond, "it is the best band-aid we have" for two critical purposes: addressing the over 100 symptoms associated with hormonal fluctuations, and reducing long-term risks of cardiovascular disease and osteoporosis.
This doesn't mean hormone therapy is right for everyone - Garrison emphasises that individualised care is essential. "It has so much to do with who you are as an individual, what your health history is, what your genetic risk factors are, how old you are, and what your environmental exposures have been."
Garrison also highlights the training gap that affects doctors on both sides of the Atlantic. Many received little or no formal teaching on menopause, ovarian ageing, or the nuances of hormone therapy during medical school or residency, and some report feeling under-prepared to counsel patients on current evidence.
Her advice to Irish women is simple: if your doctor seems uncomfortable discussing menopause or hormone therapy and cannot answer your questions, it is reasonable to seek out another clinician with more specialist training.
What This Means For You
If you are in perimenopause or menopause today, the evidence supporting appropriately used hormone therapy is stronger and more nuanced than it has ever been.
For healthy women who start systemic therapy within about 10 years of menopause or before age 60, major guidelines now agree that the benefits generally outweigh the risks.
Three practical steps can help you navigate your options:
- Learn about the "window of opportunity" and where you fall in relation to it, including your age, time since your last period and overall health.
- Seek out GPs or specialists with specific menopause training so you can have a detailed conversation about your individual risks and priorities.
- Ask about the risks of not taking hormone therapy - including bone health, cardiovascular risk, sleep and cognition - not just the risks of taking it.
In Ireland, access has improved significantly with free HRT now available at participating pharmacies for women with medical cards or Drugs Payment Scheme cards.
Women's health is human health, and it is long past time that our systems treated it with the same
seriousness, nuance and urgency.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ.
