Respiratory
Free testosterone, estradiol, and asthma endotypes in Puerto Rican youth Yueh-Ying Han* Yueh-Ying Han Franziska J. Rosser Glorisa Canino Juan C. Celedón
Background: Sex hormones may explain age- and sex-related differences in asthma. We examined whether free testosterone or estradiol level was associated with asthma endotypes in Puerto Rican youth, a group with high asthma burden.
Methods: We analyzed data from 320 Puerto Ricans aged 10-20 years with (cases) and without (controls) asthma in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study (EVA-PR) and 334 Puerto Ricans aged 6-14 years in the Puerto Rican Genetics of Asthma and Lifestyle study (PR-GOAL). Using nasal epithelial transcriptomic profiles, EVA-PR participants with asthma were classified as having T2-high, T17-high, or T2-low/T17-low endotypes, and a machine learning approach based on blood eosinophils, total IgE, and atopy was used to predict T2-high asthma in PR-GOAL cases. Serum total testosterone, estradiol, sex hormone binding globulin (SHBG), and progesterone were measured, and free testosterone levels were calculated using testosterone and SHBG. Multinomial regression was used for the multivariable analysis of free testosterone, estradiol and asthma endotypes (with controls as the reference group), separately by sex.
Results: In the multivariable analysis in EVA-PR, 1-unit increment in free testosterone was associated with 1.08 times increased odds (95% confidence interval [CI]=1.03 to 1.15) of T17-high asthma in females. In males, 1-unit increment in estradiol was associated with 1.03 increased odds (95% CI=1.01 to 1.06) of T2-high asthma. Similarly, in PR-GOAL 1-unit increment in free testosterone was associated with 1.05 times increased odds of T2-low asthma in females. In males, 1-unit increment in estradiol was associated with 1.08 times increased odds of T2-high asthma.
Conclusions: In Puerto Rican youth, free testosterone was positively associated with T17-high asthma in females, and estradiol was positively associated with T2-high asthma in males. Sex hormones may influence asthma via T2 and non-T2 immune pathways.