Elevated levels of serum testosterone appeared to be significantly associated with a reduced risk for asthma in women, and obesity modifies this risk, researchers reported.

Findings from the first population-based study of its kind suggest that sex hormones play a key role in the widely recognized gender differences in asthma presentation among adults.

In children and adolescents the prevalence of asthma is higher among boys than girls, but adult women have higher rates of asthma compared with men, noted Juan Celedón, MD, DrPH, of Children’s Hospital of Pittsburgh, and colleagues in the American Journal of Respiratory and Critical Care Medicine. Boys younger than 18 also have higher rates of asthma-related mortality than girls do, but in adulthood, asthma-related mortality is higher among women.

“The most obvious explanation for this is hormonal changes, but to our surprise there had not been a lot of research examining the objective management of hormones in asthma,” Celedón told MedPage Today.

The cross-sectional study showed that very elevated levels of free testosterone in women (fourth quartile vs first quartile) were associated with a lower risk of asthma (OR 0.56, 95% CI 0.39-0.80).

Among obese women, both elevated free testosterone (OR 0.59, 95% CI 0.37-0.91) and elevated estradiol (OR 0.43, 95% CI 0.23-0.78) were linked to lower asthma risk.

“We found an inverse association between the second and fourth quartiles of testosterone (but not the third quartile) and current asthma in all women and in obese women, suggesting a nonlinear relation,” the researchers wrote. “Testosterone, the predominant androgen in men, may protect against asthma in women through systemic and airway-specific anti-inflammatory effects.”

Study Details

The cross-sectional study included 7,615 adults (3,953 men and 3,662 women) from the ages of 18 and 79 who were enrolled in the 2013-2014 and 2015-2016 U.S. National Health and Nutrition Examination Surveys.

The researchers used logistic regression analysis to assess the impact of sex hormone levels on current asthma. The overall prevalence of current asthma among survey participants included in the study was 9.0% (6.1% among men and 12.5% among women).

In multivariate modeling that included serum levels of estradiol and free testosterone, women whose serum testosterone levels were in the second and fourth quartiles had 30% and 44% significantly lower odds of current asthma than those whose testosterone levels were in the first quartile, the team reported. “Among men, the magnitude of the estimated effect of serum testosterone, serum estradiol on current asthma was similar to that observed in female participants, but neither serum testosterone nor serum estradiol was significantly associated with current asthma.”

Celedón said this lack of association may indicate that the study was underpowered to show an association in men. Even though there were slightly more men in the study than women, higher numbers of men may have been needed because of the lower prevalence of asthma among adult men.

“It is conceivable that we would have seen a statistical difference with more men in the study,” he said, adding that larger, prospective studies are needed to better understand the relationship between sex hormones and asthma risk.

Other limitations cited by the researchers included the lack of data on potential confounders affecting sex hormone levels, including insulin resistance, the follicular phase of the menstrual cycle, and environmental exposure to endocrine disruptors.

Writing 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 continued. “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.”

The findings from Celedón and colleagues “should spearhead further longitudinal and intervention studies” examining sex hormones and asthma risk, Holguin concluded. “However, given its cross-sectional nature and the use of a self-referred asthma case definition, the findings should be interpreted with some caution.”

Last Updated January 17, 2020