Testosterone treatment and respiratory medications and exacerbations in people prescribed inhaled corticosteroids: a nationwide cohort study
Abstract
Background After puberty asthma is more common and often more severe in females, indicating a potential role of sex steroids. Observational and genetic studies suggest that higher testosterone levels are associated with improved lung function and reduced asthma risk, but evidence on the clinical efficacy of exogenous androgen supplementation is limited. We aimed to investigate changes in use of inhaled corticosteroid (ICS) and short-acting β2-agonist (SABA), and exacerbation rates among individuals treated with ICS who initiate systemic androgen treatment. Methods We conducted a nationwide, population-based register study comprising individuals treated with inhaled corticosteroid who initiated systemic testosterone (ATC G03B) between 1995 and 2022. Primary outcomes were changes in daily doses of inhaled corticosteroids, use of reliever medication, and exacerbation rates (defined as oral corticosteroid courses ≥125 mg or hospital admissions with obstructive airway disease). Outcomes were compared before and after androgen initiation using a within-subject design. Results A total of 858 male individuals on ICS (mean age 51 years) initiated testosterone therapy and were included. Their ICS dose was stable for the first 18 months after starting testosterone but decreased during months 18–24 (mean reduction 54 μg; SE 19; P = 0.03). SABA use increased among those >45 years (mean increase 111 puffs; SE 34; P = 0.009). Exacerbation rates did not change. Conclusion Systemic testosterone treatment was associated with a reduction in ICS use after 18–24 months of therapy whereas use of SABA increased among older adults. These findings indicate a complex, age-dependent relationship between testosterone therapy and airway symptoms.
Plain Language Summary
Asthma is more common and more severe in women than men after puberty, which has led researchers to suspect that the male sex hormone testosterone may play a protective role in the lungs. While observational studies have linked higher testosterone levels to better lung function and fewer asthma attacks, the real-world effect of testosterone treatment on asthma and other obstructive lung diseases had not been well studied. In this nationwide Danish cohort study, we investigated what happens to inhaler use and flare-up rates when patients with obstructive lung disease start systemic testosterone therapy. We identified 858 male patients on inhaled corticosteroids (the standard preventer inhaler) who began testosterone treatment between 1995 and 2022. We tracked their inhaler use and exacerbation rates before and after starting testosterone. Their preventer inhaler dose remained stable for the first 18 months, but then decreased meaningfully in months 18–24. However, use of short-acting relief inhalers increased among patients older than 45, and overall flare-up rates did not change. Our findings suggest that testosterone therapy has a complex, age-dependent relationship with lung disease — reducing the need for preventer medication after prolonged use, but potentially increasing reliance on reliever inhalers in older adults. These results call for further research before testosterone can be considered a treatment strategy for respiratory conditions.