Elevated Testosterone Is Associated with Decreased Likelihood of Current Asthma Regardless of Sex

Abstract

Background: Asthma prevalence decreases post-puberty in males. Testosterone inhibits airway smooth muscle contraction and attenuates type 2 inflammation.Objective: To investigate the relationship between serum testosterone and current asthma prevalence and lung function in a nationally-representative dataset.Methods: Serum testosterone and self-reported physician-diagnosed current asthma were obtained from 7,584 participants ages 6-80 years from the cross-sectional 2011-2012 National Health and Nutrition Examination Survey (NHANES). We used logistic regression to test associations between testosterone and current asthma, adjusting for demographics and stratifying by sex and age; linear regression to evaluate correlations between testosterone and lung function among asthmatic patients; and interaction terms to test for effect modification by blood eosinophils and FeNO.Results: Serum testosterone inversely associated with odds of current asthma in both men and women but this association was nonlinear. Similar protective effect sizes were observed for both sexes after log 2 -transformation of serum testosterone. For every 1-unit increase in log 2 testosterone, the odds of current asthma decreased by 11% in men and 10% in women, although the association was statistically significant in women only among those ≥12 years old after multiple imputation. Serum testosterone did not associate with current asthma prevalence among those <12 years old.

Targeting androgen signaling in ILC2s protects from IL-33–driven lung inflammation, independently of KLRG1

“…53 Indeed, increased levels of androgens have been associated with asthma protection in many recent studies. [54][55][56] Moreover, pharmacological and genetic studies support a protective action of androgens. [57][58][59] Supplementation with the androgen dehydroepiandrosterone (DHEA) -which can be metabolized into testosterone, the precursor of DHT, by the dehydrogenase encoded by the HSD3B1 gene -is beneficial in mild to moderate asthma.…”

Androgen receptor activation alleviates airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma

“…However, the specific role of AR activation in airway physiology is limited. Considering the clinical and epidemiological evidence suggesting intrinsic sex differences in asthma pathophysiology, with men showing lower prevalence and severity of asthma compared with women (61,64,72,73) and the direct correlation of serum androgen levels with reduced asthma symptoms (27,28), warrants for studies on understanding the broad role of androgens in the airways, especially in the context of asthma.…”

“…The prevalence and severity of asthma remains constant (low compared with females) in men postpuberty, where circulating androgens are at their highest levels (11,25,27). However, this trend is reversed in aged men showing increased severity of asthma symptoms with declined serum testosterone levels, which suggest a potential beneficial role of androgens in asthma (25,27,28). Interestingly, few studies also suggest a beneficial role for androgens in asthmatic women (29).…”

Sex and gender in asthma

“…Additionally, decreasing testosterone levels in men older than 45 years was associated with increased asthma prevalence [82]. Participants with asthma aged 6-80 years old from the National Health and Nutrition Examination Survey (n=7584), it was found that in both men and women greater than 12 years old, increased serum testosterone was associated with decreased asthma prevalence in a dose-dependent manner and was associated with increased FEV 1 [83]. In another large cross-sectional study of 256 219 adults aged 40-69 years old in the United Kingdom, increased free testosterone levels were significantly associated with decreased symptoms of asthma, decreased hospitalisations due to asthma in women, and decreased FEV 1 and FVC in men [4].…”