Researchers hope to deliver a female-specific treatment approach for a condition that has been overlooked for generations.
A team led by UNSW Sydney has secured support through Wellcome Leap’s VISIBLE, opens in a new window program, a global research initiative investing more than $75 million ($US55 million) in women’s cardiovascular health.
Associate Professor Erin Howden from UNSW Medicine & Health will lead the RESTORE trial, which aims to deliver a female-specific treatment approach for coronary microvascular dysfunction (CMD), often referred to as invisible heart disease.
CMD affects the tiny blood vessels of the heart and is too small to see on standard angiograms. It is far more common in women, particularly after menopause, and remains poorly understood and inadequately treated.
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“Up to 70% of women with chest pain who undergo angiography are told their arteries are clear, yet many will continue to live with debilitating angina, breathlessness and fatigue that limits daily life,” explained A/Prof. Howden.
Diagnostic tests for CMD are not widely available and often require invasive procedures.
“The condition can have a huge impact on women’s day-to-day lives. In addition to having debilitating symptoms, women with CMD carry an up to four-fold higher risk of major cardiovascular events,” A/Prof. Howden said.
“At a day-to-day level, experiencing angina or chest pain limits a women’s ability to work, with many reporting that they reduce hours or retire early. There are additional negative effects on mental health and social lives.”
Despite its impact, there are currently no treatments that target the underlying biology of CMD.
A new approach to treating CMD
At present, women who are told they have CMD are offered symptom-relieving medications that were developed for men with obstructive coronary artery disease.
The trial led by A/Prof. Howden will test whether two safe and accessible treatments – transdermal oestrogen and structured exercise training – can repair the damaged microcirculation and restore women’s quality of life.
“Our trial will investigate whether treating oestrogen deficiency in post-menopausal women, combined with structured exercise, can improve the function of the heart’s smallest blood vessels,” A/Prof. Howden said.
Over 16 weeks, 132 post-menopausal women across Sydney, Melbourne and Adelaide will receive one or both treatments, with advanced cardiac MRI used to measure the effect on the smallest heart vessels.
“If RESTORE shows that transdermal oestrogen and structured exercise can repair the heart’s smallest blood vessels and improve symptoms, it could lead to the first female-specific treatment for a condition that affects millions of women worldwide.
“It would also change the way CMD is understood and treated from a condition often dismissed as ‘nothing serious’, to one that can be actively managed.”
A/Prof. Howden said that receiving support from Wellcome Leap’s VISIBLE programme was transformative.
“For decades, coronary microvascular dysfunction has been one of the clearest examples of how women’s cardiovascular disease has been overlooked. It affects the majority of women with chest pain and clear arteries, yet not a single approved treatment targets its underlying biology.
“VISIBLE provides the resources to change that, and just as importantly, brings our research into a global community working on the same problem with shared data and shared research protocols. For the field more broadly, this signals something overdue – women’s cardiovascular health is now a scientific priority of the highest order, not a sub-speciality concern.”
Wellcome’s VISIBLE program
Wellcome Leap’s VISIBLE program is focused on improving the diagnosis and treatment of coronary microvascular disease in women and reducing the global burden of cardiovascular disease.
The initiative aims to dramatically increase the number of women with stable angina who receive accurate diagnosis and effective treatment for CMD, while maintaining reliable detection of obstructive coronary artery disease
Professor Cheryl Jones, Dean of UNSW Medicine & Health, congratulated A/Prof. Howden on securing the highly competitive Wellcome funding.
“CMD has too often gone unrecognised and undertreated in women. By investigating this female-specific treatment approach for this condition, the RESTORE trial has the potential to transform care for millions of women worldwide and position Australia at the forefront of women’s heart health research.”
Founded by the Wellcome Trust in 2020 as a US nonprofit, Wellcome Leap, opens in a new window builds and executes bold, unconventional programs with the urgency required to deliver breakthroughs in years, not decades. Operating at the intersection of life sciences and engineering, Wellcome Leap programs require best-in-class, multi-disciplinary, global teams assembled from universities, companies, and nonprofits working together to solve problems they cannot solve alone.
Source: University of New South Wales
Published on June 9, 2026