Study: Elevated Sex Hormone-Binding Globulin Protects Against Asthma

Ryan Arathimos, PhD

It has long been observed that asthma prevalence is higher in males during childhood and higher in females during adolescence and adulthood, but evidence linking shifting sex hormones to this difference has been unreliable until now.

Using observational evidence, a new study suggests that elevated sex hormone-binding globulin (SHBG)—a glycoprotein that transports and regulates both testosterone and estrogen— seems to act as a safeguard against asthma.

The findings could be significant, as SHBG is present in about 9.7% of adult women who have asthma and 5.4% of adult men with asthma, according the Asthma and Allergy Foundation of American (AAFA).

Investigators retrieved data for this study from the Avon Longitudinal Study of Parents and Children (ALSPAC), the Trans-National Asthma Genetics Consortium (TAGC) genome-wide association (GWAS) of asthma, and the UK Biobank.

From ALSPAC, SHBG and total testosterone (TT) was measured in 512 males at 9, 11, 13, 15, and 17 years. ALSPAC mothers collected information on asthma symptoms through questionnaires at ages 10, 13.1, and 13.8 years of age and by study subjects at ages 16 and 22 years. Two-sample Mendelian randomization (MR) was utilized to evaluate genetic evidence of SHBG and asthma.

Investigators then meta-analyzed the MR results intersecting data from the UK Biobank and TAGC. Of the 500,000 subjects from the UK Biobank, 38,337 asthma cases and 296,245 controls were left after genotype-related exclusions and quality control were performed. TAGC identified 673 genome-wide single nucleotide polymorphisms (SNP) from 19,954 asthma cases and 107,715 controls from 56 studies.

While observational evidence showed a mild association between increased testosterone and improved asthma symptoms, there was not a strong indication that this was linked to SHBG.

But genetic evidence using two-sample MR showed that increased SHBG was protective for asthma at 0.86 (95% CI: 0.74 - 1.00) for the inverse-variance weighted approach and 0.83 (95% CI: 0.72 - 0.96) for the weighted median estimator. The protective effect was most pronounced in females.

However, it is still unclear exactly how sex hormones impact asthma and by what means treatment therapies might help manage the condition.

“To further explore the associations we found, it may be possible to use the recent release of data in the UK Biobank study that includes SHGB, testosterone, and estrogen measured in blood samples of participants to disentangle which sex hormone, or combination thereof, is having the effect on asthma,” lead investigator Ryan Arathimos, PhD, of the University of Bristol, told MD Magazine®.

The study, “Genetic and observational evidence supports a causal role of sex hormones on the development of asthma”, was published online in Thorax.