Sex Steroid Hormones and Asthma in a Nationwide Study of U.S. Adults

Abstract

Rationale: Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear.Objectives: To examine sex hormone levels and asthma in adults.Methods: Cross-sectional study of serum levels of free testosterone and estradiol and current asthma in 7,615 adults (3,953 men and 3,662 women) aged 18-79 years who participated in the 2013-2014 and 2015-2016 U.S. National Health and Nutrition Examination Survey. Logistic regression was used for the multivariable analysis of sex hormones and current asthma, which was conducted separately in women and men.Measurements and Main Results: Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women (odds ratio [OR] for the fourth quartile [Q4] vs. Q1, 0.56; 95% confidence interval [CI], 0.39-0.80). Given an interaction between obesity and sex hormones on current asthma, we stratified the analysis by obesity. In this analysis, elevated free testosterone (OR for Q4 vs. Q1, 0.59; 95% CI, 0.37-0.91) and estradiol (OR for Q4 vs. Q1, 0.43; 95% CI, 0.23-0.78) levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men (OR for Q4 vs. Q1, 0.44; 95% CI, 0.21-0.90).Conclusions: Our findings suggest that sex hormones play a role in known sex differences in asthma in adults. Moreover, our results suggest that obesity modifies the effects of sex hormones on asthma in adults.

Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults

“…In mouse models, DHT downregulated Th2 inflammation in the lung, but ARs enhanced such inflammation by upregulating M2 macrophage polarisation that induces eosinophil recruitment. 29 In our previous analysis in NHANES, in which there were both a LLOD and a broader range of serum estradiol levels than those in the current study, 10 we found no significant association between serum estradiol and asthma in our main analysis. Although our current finding of an association between a detectable serum estradiol and asthma and reduced FEV 1 /FVC in women, and reduced lung function measures (FEV 1 , FVC…”

“…In our previous analysis of adults (ages 18 to 79 years) who participated in the US National Health and Nutrition Examination Survey (NHANES), we reported that higher levels of serum-free testosterone were associated with lower odds of current asthma in women but not in men. 10 Our finding of a significant inverse association between a high serumfree testosterone level and asthma among men in the current analysis is thus novel and likely due to greater statistical power, due to a much larger sample size in the UKB than in NHANES. 10 Alternatively, these results and our finding of no interaction between obesity and free testosterone in women with asthma in the UKB cohort could be explained by differences in the age range of participants in NHANES versus those in the UKB.…”

“…10 Our finding of a significant inverse association between a high serumfree testosterone level and asthma among men in the current analysis is thus novel and likely due to greater statistical power, due to a much larger sample size in the UKB than in NHANES. 10 Alternatively, these results and our finding of no interaction between obesity and free testosterone in women with asthma in the UKB cohort could be explained by differences in the age range of participants in NHANES versus those in the UKB. Consistent with our current results, a human phase II clinical trial reported that nebulised dehydroepiandrosterone-3-sulphate (DHEAS) improved asthma control and symptoms in adults with poorly controlled moderate-to-severe asthma on inhaled corticosteroids and long-acting ß 2 -agonists.…”

“…8 9 In a study of 7615 adults aged 18 to 79 years in the USA, we previously reported that a high serum testosterone level was associated with lower odds of current asthma in women (n=3662) but not in men (n=3953), a finding that could be explained by limited statistical power for the analysis in men (due to lower asthma prevalence in men than in women). 10 Given a potential protective role of testosterone against asthma and our prior negative results for asthma in a relatively small sample of US men, 10 we examined the relation between serum-free testosterone and asthma, current wheeze, asthma hospitalisations and lung function in an analysis of 256 419 British adults aged 40 to 69 years.…”

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

“…On the other hand, high concentrations of testosterone and cyclic AMP in sputum of asthmatic women during the luteal phase of the menstrual cycle were thought to play a role in premenstrual exacerbations (43). The idea that sex hormones may be a causal factor in asthma was significantly strengthened by a recent study of 7,615 adults that quantified serum sex hormones and asthma outcomes (44). That study showed that low testosterone in both women and men was associated with an increased incidence of asthma.…”