Sex hormones play a key role in gender differences in asthma presentation among adults
Study Authors: Yueh-Ying Han, Erick Forno, et al.; Fernando Holguin
Target Audience and Goal Statement: Allergists, pulmonologists, endocrinologists, obesity specialists, obstetrician-gynecologists, family physicians, primary care physicians
The goal of this study was to examine the association between sex hormone levels and asthma in adults.
- What was the relationship between free testosterone and estradiol levels and asthma among adult participants in the U.S. National Health and Nutrition Examination Survey (NHANES)?
- Did obesity modify the estimated effects of sex hormones on asthma?
Study Synopsis and Perspective:
Nearly 6.1 million children and 20.4 million adults in the U.S. have asthma. Asthma tends to be more prevalent among boys than girls under age 18 years. However, among adults (≥18 years old), asthma prevalence is higher in women than men.
- In the first population-based study of sex hormone levels and asthma in adults, it was shown that elevated levels of free testosterone were significantly associated with reduced odds of asthma in women.
- Note that the study also suggests that obesity modifies the effects of sex hormones on asthma in adults.
Previous studies have shown that obesity can be both a risk factor and a disease modifier in asthma.
A cross-sectional study of U.S. NHANES participants suggested that circulating sex hormones (estradiol and free testosterone) play a key role in the widely recognized gender differences in asthma presentation among adults, according to Juan Celedón, MD, DrPH, of Children’s Hospital of Pittsburgh, and colleagues.
Additionally, obesity modified the effect of such hormones on asthma in women and men, they reported in the American Journal of Respiratory and Critical Care Medicine.
Their study consisted of 7,615 adults (3,953 men and 3,662 women), ages 18 to 79 years, who participated in the NHANES surveys from 2013-2014 and 2015-2016.
The overall prevalence of current asthma among participants was 9.0% (6.1% among men and 12.5% among women).
Overall, elevated levels of sex hormones appeared to reduce the likelihood of asthma. Free testosterone levels in the highest quartile versus the lowest quartile were associated with 44% lower odds of asthma in women. A similar trend was observed for obese women: 41% lower odds of asthma with levels of testosterone in the highest quartile compared with the lowest quartile.
Levels of estradiol in the highest quartile versus the lowest quartile in obese women were associated with 57% lower odds of asthma. Compared with the lowest quartile, estradiol levels in the second and third quartiles were also associated with decreased odds of asthma in these women.
For non-obese men, estradiol levels in the highest quartile versus the lowest quartile were associated with 56% lower odds of asthma.
There was no significant interaction between serum free testosterone or serum estradiol and eosinophilia on asthma in men or women (P>0.20 in all instances).
Endogenous and exogenous hormones were not estimated due to the small sample number of participants who reported current use of prescribed systemic steroids or any sex hormones (n=173), the researchers acknowledged. Because this was a cross-sectional analysis, they could not examine temporal relationships. In addition, no data on menopausal status were available. They also lacked data on several potential confounders, including insulin resistance, follicular phase of the menstrual cycle, and environmental exposure to endocrine disruptors. Other study limitations included the possibilities of selection and misclassification biases.
Source References: American Journal of Respiratory and Critical Care Medicine 2020; DOI: 10.1164/rccm.201905-0996OC
Editorial: American Journal of Respiratory and Critical Care Medicine 2020; DOI: 10.1164/rccm.201910-1923ED
Study Highlights and Explanation of Findings:
In the first population-based study of sex hormone levels and asthma in adults, it was shown that elevated levels of free testosterone were significantly associated with reduced odds of asthma in women. Elevated levels of free testosterone and estradiol were also significantly associated with reduced odds of asthma in obese women. In addition, estradiol levels in the highest quartile were significantly associated with decreased odds of asthma in non-obese men.
“Our study results suggest that the circulating sex hormones estradiol and free testosterone contribute to sex differences in asthma among adults,” Celedón said in a press release. “Furthermore, obesity appears to modify the effect of such hormones on asthma in women and men.”
“Testosterone, the predominant androgen in men, may protect against asthma in women through systemic and airway-specific anti-inflammatory effects,” the researchers wrote. Testosterone in men has also positively been associated with lung function and lower levels of C-reactive protein. Consistent with its potential beneficial effects against asthma, nebulized dehydroepiandrosterone-3-sulfate improved asthma control in adults with poorly controlled moderate to severe asthma on inhaled corticosteroids and long-acting beta-2-agonists.
Celedón and team did not find a significant interaction between estradiol levels and eosinophilia on current asthma, suggesting that estradiol might affect asthma through non-eosinophilic-mediated mechanisms.
In an accompanying editorial, Fernando Holguin, MD, of the University of Colorado at Denver, Anschutz Medical Campus, said that while prior epidemiological studies “have attributed changes in asthma-related outcomes to sex hormones only by proxy (i.e., puberty or menstrual period), the results from this study, by directly measuring serum levels, significantly strengthen causality.”
“Further, the association with testosterone, which had been largely overlooked in many prior asthma studies, potentially adds new insights into the pathophysiology of sex hormones and airway diseases,” he added.
Holguin noted that while sex hormone fluctuation suppression through hormone replacement therapy (HRT) would seem to be a logical treatment for reducing asthma risk or improving asthma outcomes in adults, “this has not been consistently shown, and in fact, some longitudinal studies have shown that HRT actually increases the odds of developing this disease.”
“Several factors, such as the type and timing of HRT, the type of study design, and individual characteristics (obese vs nonobese) may potentially explain the variability in response to this treatment,” he wrote. “It may also imply, however, that we do not fully understand how variations in sex hormone levels affect asthma, and therefore, we do not know in whom HRT could be useful.”Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
American Journal of Respiratory and Critical Care Medicine
American Journal of Respiratory and Critical Care Medicine
Source Reference: Boyles S “Elevated Testosterone May Lower Asthma Risk in Women” 2020.