More than 2.8 million Australians are diagnosed with asthma and women are roughly 40% more likely suffer from the disease. Women are also 2.3 times more likely to be admitted to hospital with severe symptoms and they’re more likely to die from an asthma attack. Yet, despite this disparity, very little research has been conducted to understand why adult women are disproportionately impacted by the disease.

Now, a groundbreaking study published by a team of researchers at HMRI and the University of Newcastle, in collaboration with teams from Imperial College London, University of Technology Sydney, The Woolcock Institute, Karolinska Institute and University of Hong Kong, has shown how female sex hormones and the oral contraceptive pill could play critical roles in modifying asthma severity.

University of Newcastle Professor Jay Horvat, from HMRI’s Immune Health Research Program, explains that one possible explanation for the sex disparity in asthma presentations involves specific female sex hormones.

“We know that natural hormonal fluctuations occurring throughout a female’s lifespan are associated with varying severity in asthma symptoms,’ he explains. “Many women, for instance, experience a worsening of their asthma symptoms during menstruation and in menopause.”

Female sex hormones, particularly estrogen and progesterone, are known to play important roles in regulating airway inflammation, airway hyperresponsiveness (AHR), and mucus production. These hormones can influence the severity of asthma by modifying metabolism in cells in the airways. Airway cells require the energy generated from cellular metabolism to promote disease. Professor Horvat’s research team has made the novel discovery that different sex hormones and the oral contraceptive pill modify the level of a protein, known as GLUT-1, that allows glucose into cells to fuel metabolic activity.

Professor Horvat and his co-research leads, University of Newcastle Professor Lisa Wood and Dr’s Alexandra Brown and Olivia Carroll, all from the HMRI Immune Health Research Team, have shown that estrogen increases, whilst progestogen and the oral contraceptive pill decrease, GLUT-1.

“Essentially, estrogen appears to worsen, while progestogen and the oral contraceptive pill appear to protect against asthma,” says Professor Horvat.

Importantly, the team has shown that GLUT-1 is increased in severe asthma and that blocking GLUT-1 protects against asthma, particularly in severe, estrogen-induced disease.

These exciting results are a significant step forward in understanding the mechanism – and potential treatment – of asthma in women and people assigned female at birth. It may also have implications for transgender women undergoing gender-affirming hormone treatments, although further research is needed in this area.

Follow-up studies are now required to develop and test transformative new therapies for asthma and other respiratory diseases that harness the protective effects of hormone responses on cellular metabolism that the team has discovered. Such therapies could be particularly beneficial for women and people assigned female at birth who experience a worsening of respiratory symptoms during menstruation and in menopause.

* Although the authors refer to females and female sex hormones they recognise that female sex hormones may be relevant for transgender people, some non-binary people, people with variations in sex characteristics or people who are intersex. The research conducted in this study and previous literature referenced has only addressed female sex hormones in female-presenting individuals.