told their hearts are fine while living with the evidence that they are not
For decades, a form of heart disease affecting millions of women has hidden in plain sight — too small for standard tests to detect, too often dismissed as nothing at all. Coronary microvascular dysfunction damages the heart's tiniest vessels, striking most commonly after menopause, yet cardiovascular medicine built its knowledge and treatments largely around men. Now a UNSW-led team, backed by $75 million in global funding, is mounting the first clinical trial designed to treat not the symptoms of this invisible disease, but its underlying biology — a quiet reckoning with a long and costly oversight.
- Up to 70% of women presenting with chest pain are sent home with clear angiograms and no diagnosis, while a real and damaging condition continues undetected in their heart's smallest vessels.
- The human cost accumulates quietly — reduced working hours, early retirement, eroded mental health, and a four-fold elevated risk of major cardiovascular events for those living with CMD.
- Every treatment currently offered to these women was designed for a different disease in a different body, addressing symptoms without ever touching the root cause.
- The RESTORE trial will enroll 132 post-menopausal women across three Australian cities to test whether transdermal oestrogen and structured exercise can physically repair damaged microcirculation over 16 weeks.
- Backed by Wellcome Leap's VISIBLE program, the trial represents a structural shift — women's cardiovascular health moving from the margins of research priority to its centre.
A woman arrives at hospital with chest pain. Her angiogram comes back clear. She is sent home reassured — but the pain, the breathlessness, and the fatigue remain. She is one of roughly seven in ten women with chest pain who receive this same verdict, because the disease she carries exists in vessels too small for standard tests to see.
Coronary microvascular dysfunction — CMD — damages the heart's tiniest blood vessels and is far more common in women, particularly after menopause. For decades it has been systematically overlooked by a cardiovascular medicine that developed its understanding and treatments largely around men's hearts. Women diagnosed with CMD are typically offered medications designed for blocked arteries in male patients — treatments that address symptoms but not the condition itself.
Now a UNSW Sydney team led by Associate Professor Erin Howden has secured $75 million through Wellcome Leap's VISIBLE program to run the RESTORE trial — the first study designed to treat CMD's underlying biology. Over 16 weeks, 132 post-menopausal women across Sydney, Melbourne, and Adelaide will receive transdermal oestrogen, structured exercise training, or both. Advanced cardiac MRI will track changes in the heart's smallest vessels.
The reasoning is grounded in biology: CMD surges after menopause, when oestrogen — which plays a key role in blood vessel health — drops sharply. Combined with the known cardiovascular benefits of exercise, oestrogen replacement may restore what menopause has damaged. Success would mean the first approved treatment that addresses what is actually wrong, rather than managing how it feels.
For Howden, the stakes reach beyond the trial. CMD has long exemplified how women's heart disease has been treated as secondary — a sub-specialty rather than a priority. Millions of women worldwide live with a condition affecting the majority of those presenting with chest pain and clear arteries, with no approved remedy in sight. RESTORE, and the program funding it, signals something larger: that women's cardiovascular health is finally being treated as a scientific priority of the highest order.
A woman arrives at the hospital with chest pain. The doctors run an angiogram—a standard test that looks for blockages in the heart's major arteries. The results come back clear. She is sent home reassured, told there is nothing wrong with her heart. But the pain persists. So does the breathlessness, the fatigue, the sense that something is genuinely broken inside her body. She is one of roughly seven in ten women with chest pain who receive this same verdict: your arteries are fine, so you must be fine too.
The problem is that her heart disease exists in a place the standard test cannot see. Coronary microvascular dysfunction—CMD, sometimes called invisible heart disease—damages the tiniest blood vessels that feed the heart muscle. These vessels are too small to appear on an angiogram. The condition is far more common in women, particularly after menopause, and for decades it has been systematically overlooked by cardiovascular medicine, which developed its understanding and treatments largely around men's heart disease.
Now a team at UNSW Sydney has secured $75 million in global funding to change that. The money comes through Wellcome Leap's VISIBLE program, a research initiative dedicated to women's cardiovascular health. Associate Professor Erin Howden will lead the RESTORE trial, which aims to test the first treatment designed specifically for CMD's underlying biology rather than merely masking its symptoms.
The human toll of this oversight is substantial. Women living with CMD experience debilitating chest pain and breathlessness that constrains their ability to work. Many reduce their hours or retire early. The condition carries a four-fold higher risk of major cardiovascular events compared to the general population. Beyond the physical symptoms, women report significant impacts on mental health and social life—the cumulative weight of being told you are fine while your body tells you otherwise.
Currently, women diagnosed with CMD are offered medications developed for men with blocked arteries—treatments that address symptoms but not the root cause. The RESTORE trial will test whether two accessible interventions can actually repair the damaged microcirculation: transdermal oestrogen patches and structured exercise training. Over 16 weeks, 132 post-menopausal women across Sydney, Melbourne, and Adelaide will receive one or both treatments. Advanced cardiac MRI will measure changes in the heart's smallest blood vessels.
The logic is straightforward: CMD is far more common in women after menopause, when oestrogen levels drop sharply. Oestrogen plays a crucial role in maintaining healthy blood vessel function. Combined with the cardiovascular benefits of structured exercise, oestrogen replacement might restore what menopause has damaged. If the trial succeeds, it would represent the first approved treatment that targets CMD's actual biology rather than its symptoms.
For Howden, the significance extends beyond the trial itself. CMD has been one of the starkest examples of how women's cardiovascular disease has been treated as a secondary concern—a sub-specialty rather than a priority. Millions of women worldwide live with a condition that affects the majority of those presenting with chest pain and clear arteries, yet not a single approved treatment addresses what is actually wrong. The VISIBLE program signals a shift: women's heart health is now being treated as a scientific priority of the highest order, not an afterthought.
If RESTORE demonstrates that oestrogen and exercise can repair the heart's smallest blood vessels and improve symptoms, it will change how CMD is understood—from a condition often dismissed as nothing serious to one that can be actively managed. It would also position Australia at the forefront of women's heart health research and open the door to treatments that could transform the lives of millions of women who have spent years being told their hearts are fine while living with the evidence that they are not.
Citas Notables
For decades, coronary microvascular dysfunction has been one of the clearest examples of how women's cardiovascular disease has been overlooked.— Associate Professor Erin Howden, UNSW Sydney
CMD has too often gone unrecognised and undertreated in women. The RESTORE trial has the potential to transform care for millions of women worldwide.— Professor Cheryl Jones, Dean of UNSW Medicine & Health
La Conversación del Hearth Otra perspectiva de la historia
Why has this condition been overlooked for so long if it affects so many women?
Because the standard test—the angiogram—can't see it. If the major arteries look clear, medicine has historically assumed the heart is fine. The condition lives in vessels too small to visualize with conventional tools. And because cardiovascular research was built around men's disease patterns, the fact that women present differently went largely unexamined.
So these women are being gaslit by medicine itself.
In a way, yes. They have real, debilitating symptoms—chest pain, breathlessness, fatigue that limits their ability to work. But they're told their arteries are clear, so the problem must be psychological or minor. That dismissal compounds the physical suffering.
Why would oestrogen specifically help repair these tiny blood vessels?
Oestrogen plays a direct role in maintaining healthy blood vessel function. After menopause, oestrogen levels drop dramatically, and CMD becomes far more common in women. The theory is that restoring oestrogen levels, combined with the cardiovascular benefits of exercise, can actually repair the damaged microcirculation rather than just treating symptoms.
And if this trial works, what changes?
Everything, potentially. Right now there is no approved treatment for CMD at all. If oestrogen and exercise can repair the vessels and improve symptoms, it becomes the first female-specific treatment for a condition affecting millions. It also signals that women's cardiovascular health is finally being treated as a top scientific priority, not an afterthought.
What's the risk if it doesn't work?
The research continues, but the women living with this now—the ones told their hearts are fine while they struggle to work, to exercise, to live normally—they're still waiting. That's the human cost of decades of overlooking this condition.