Sex steroid hormones and asthma in males: a state-of-the-art review

Introduction: The incidence, prevalence, and disease prognosis of asthma differ between males and females throughout the life course. However, the underlying mechanisms are not known. Sex hormones might have a potential role in asthma pathogenesis. But most studies on the role of sex hormones in asthma have focused on females, with a paucity of evidence in males. Areas covered: This paper provides a comprehensive review of the state-of-the-art on sex steroids in asthma, focusing on males, covering mechanistic, clinical, and epidemiological studies. Literature search was conducted in PubMed in September 2024. Expert opinion: Androgen signaling has a protective role in asthma by reducing airway smooth muscle (ASM) contractility and decreasing airway inflammation. In contrast, estrogens appear to promote type 2 (T2) airway inflammation, while the effect on ASM remains controversial. To date, suggested mechanisms have not fully clarify the underlying pathways through which sex steroids modulate ASM and T2 inflammation in asthma. The balance between androgen and estrogen signaling might also play a role. While epidemiological studies support a protective role for androgens, the evidence on onset of puberty and asthma is inconclusive. Larger longitudinal population samples and stratification based on age and obesity are needed to resolve these questions.