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

Authors: Yueh-Ying Han, PhD, Erick Forno, MD, Juan C. Celedón, MD, DrPH

We found that elevated serum levels of free testosterone are associated with lower odds of

current asthma in women. Given evidence of an interaction between obesity and sex hormone

levels on asthma risk, as well as prior knowledge of obesity effects on both hormone levels and

asthma, we repeated the analysis after stratification by obesity. In this analysis, elevated serum

levels of both free testosterone and estradiol were associated with lower odds of current asthma

in obese women, and an elevated serum estradiol level was associated with lower odds of current

asthma in non-obese men. Our findings suggest that circulating sex hormones (estradiol and free

testosterone) play a role in sex differences in asthma among adults, and further suggest that

obesity modifies the effect of such hormones on asthma in women and men.

 

Asthma affects more than 300 million people worldwide, including approximately 6.1 million

children and 20.4 million adults in the United States (U.S.)(1). The burden of asthma varies by

age group and sex throughout the lifespan (2). In the U.S, the prevalence of asthma is higher in

boys (9.2%) than in girls (7.4%) among individuals younger than 18 years, but such prevalence

is higher in women (10.4%) than in men (6.2%) among individuals 18 years and older. Similarly,

mortality from asthma is higher in boys than in girls during childhood and adolescence, yet

asthma-related mortality is higher in women than in men during adulthood (3).

Many epidemiologic studies have reported sex-specific differences in asthma and asthma

outcomes (4-6). Compared with girls, boys are more likely to have asthma, asthma symptoms,

and allergic sensitization, and to use medications for asthma. After puberty, there is a sex shift in

asthma prevalence, such that asthma becomes more common and severe or difficult to treat in

women than in men (7, 8).

Sex differences in asthma may be partly explained by changes in the levels of sex hormones

during the life course (9, 10). A recent systematic review and meta-analysis of 57 studies (51

observational and 6 experimental) examined asthma in relation to menstruation, menopause,

hormonal contraceptives, and hormonal replacement therapy (HRT) in women. In that study,

irregular menstruation, menopause onset, and current HRT were each associated with increased

risk of current asthma. Moreover, past HRT, ever HRT, current HRT, and current estrogen-only

HRT were each associated with new-onset asthma (10). In a cross-sectional study of children

(ages 6 to 18 years) with asthma (enriched for severe disease), serum levels of sex steroid

hormones (estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate [DHEA-S, a

non-virilizing hormonal derivative of testosterone without untoward side effects on girls]) were

measured in 45 boys and 23 girls. In that study, DHEA-S was inversely associated with asthma

symptoms but positively associated with FEV1 and FVC in boys, while estradiol level was

negatively associated with FEV1 and FVC in girls (11). Androgens such as testosterone may

reduce innate and adaptive immune responses, while estrogen and progesterone may enhance Thelper

cell type 2 (Th2) allergic airway inflammation (12).

Given a plausible role of sex steroid hormones in sex-specific differences in asthma, we

examined the relation between serum levels of two such hormones (free testosterone and

estradiol) and asthma among adult participants in the U.S. National Health and Nutrition

Examination Survey (NHANES). Because of the known link between obesity and sex hormone

levels (4, 13), we also examined whether obesity modifies the estimated effects of sex hormones

on asthma. Some of the results of this study have been previously reported in an abstract (14).

 

Cognitive Ability Testosterone