People with androgen insensitivity syndrome may be more likely to develop asthma, a new study suggests. Researchers examined data on the prevalence of androgen insensitivity syndrome (AIS) and asthma in medical records for more than 76 million patients. Overall, the analysis included 310 patients with complete AIS and 670 patients with incomplete AIS. Compared to those without AIS, individuals with complete AIS (odds ratio 4.01) were significantly more likely to have asthma, the analysis found. However, those with incomplete AIS also had a significantly greater risk of asthma than people without AIS (OR 2.65). "We show that complete loss of androgen receptor and/or activity is strongly associated with having asthma, and that partial loss of androgen activity is also associated with having asthma, but not as strongly," said lead study author Dr. Benjamin Gaston, vice chair for translational research at the Riley Hospital for Children and Indiana University in Indianapolis. "These data are consistent with work showing that an enzyme that increases tissue androgens and is bad for you if you have prostate cancer - HSD31 - is good for you if you have asthma, and high androgen levels in the blood are associated with better lung function and asthma control," Dr. Gaston said by email. "Before the COVID pandemic, we didn't even know that there were androgen receptors in the human airway." When researchers excluded people with COPD and smokers, both complete AIS (OR 3.89) and incomplete AIS (OR 2.28) were still significantly associated with asthma. Asthma was still significantly associated with all AIS (OR 2.01) after adjusting for age, obesity, and nicotine dependence. Younger patients under 24 years old were significantly more likely to have asthma than older individuals (OR 3.35), the study also found. In a smaller validation cohort, researchers also compared 65 patients with complete and incomplete AIS to age-matched controls without this condition. In this analysis, AIS was associated with a significantly higher risk of asthma (OR 2.26). One limitation of the study is that researchers lacked detailed clinical information for individual patients, researchers note in JAMA Pediatrics. "It is still likely that other factors beyond receptor insensitivity are involved, since asthma in men is more common than receptor insensitivity," said Dr. Y.S. Prakash, chair of the Department of Physiology and Biomedical Engineering at the Mayo Clinic in Rochester, Minnesota. Even so, the study underlines the need for clinicians and researchers to pay attention to sex differences in asthma, and to think differently about the role of sex hormones when they see asthma in men vs. women, Dr. Prakash, who wasn't involved in the study, said by email. "Clinicians should always keep in mind about the complexity of asthma," said Dr. Mehmet Furkan Burak of Brigham and Women's Hospital and Harvard Medical School in Boston. "In addition to treating the allergic component of asthma, we should always address other metabolic problems of asthmatic patients such as hypogonadism, obesity and metabolic syndrome," Dr. Burak, who wasn't involved in the study, said by email. —Lisa Rapaport Source
