Dr Erik Sören Halvard Hansen

A Danish registry study has found testosterone therapy was linked to lower use of inhaled corticosteroids in men with COPD, but it did not reduce exacerbation rates.

Dr Erik Sören Halvard Hansen, a respiratory physician at Copenhagen University Hospital-Hvidovre, and colleagues analysed prescription data for 858 men who were using inhaled corticosteroids when they started systemic testosterone therapy between 1995 and 2022. Each man acted as his own control, with his inhaler use and exacerbations compared before and after starting testosterone.

Writing in in Respiratory Medicine [link here], the researchers said the study was prompted by growing evidence that sex hormones influenced airway disease. They noted asthma became more common and more severe in women after puberty, and observational studies had linked higher natural testosterone levels with lower asthma risk and better lung function.

What the study found

• Inhaled corticosteroid use stayed stable for 18 months after starting testosterone, then fell during months 18 to 24, dropping by an average of 54 micrograms of budesonide equivalent per day (P=0.03)
• The fall was steepest in men with COPD, down 106 micrograms per day during months 18 to 24 (P=0.03). Men with asthma alone showed no significant change
• Men with primary hypogonadism also cut their inhaled corticosteroid use, by 125 micrograms per day (P=0.03)
• Exacerbation rates did not change significantly, though the researchers noted a non-significant rise of 0.7 exacerbations per year (P=0.13)
• Men over 45 used more reliever medication after starting testosterone, with 111 extra doses every six months (P=0.009). Younger men showed no such increase
• Outcomes did not differ by blood eosinophil count, suggesting any effect was not confined to eosinophilic disease

Dr Hansen and colleagues said it remained unclear whether the lower steroid use reflected a true biological effect of testosterone or simply a delay in stepping down maintenance treatment. They noted that testosterone has been shown in experimental studies to dampen both type 2 and non-type 2 inflammation involved in airway disease.

On the rise in reliever use among older men, the authors suggested this likely reflected who gets prescribed testosterone rather than a direct drug effect. They said testosterone tends to be prescribed to older men with declining physical function, so the increase may reflect underlying frailty rather than the treatment itself.

The authors cautioned that the study was observational, relied on prescription records, and used broad inclusion criteria. More than 60% of participants did not carry a formal asthma or COPD diagnosis in the registry.

They concluded that the findings pointed to a “complex and potentially heterogeneous” relationship between testosterone and airway disease, and called for prospective studies to test whether testosterone has a therapeutic role in obstructive airway disease.