Genetically predicted endogenous sex hormone levels with risk of eczema or dermatitis.

Background and objectives: Growing evidence suggests that endogenous sex hormones (ESH) are associated with the risk of eczema or dermatitis. However, the causal relationship is not yet clear. This study aims to examine the potential effects of ESH (sex hormone-binding globulin levels, estradiol levels, total testosterone levels) on the risk of eczema or dermatitis using a two-sample Mendelian randomization (MR) study.

Methods: Genetic instruments from the largest available genome-wide association study (GWAS) for sex hormone-binding globulin levels, estradiol levels, and total testosterone levels were utilized to investigate the relationships between ESH and eczema or dermatitis. A set of complementary approaches was conducted to assess horizontal pleiotropy and potential caveats associated with this MR study.

Results: The MR analysis suggested that higher sex hormone-binding globulin levels are associated with an increased risk of eczema or dermatitis (MR-Egger: odds ratio [OR] = 1.003, 95% confidence interval [CI]:1.001-1.005, P = 0.007; weighted median: OR = 1.003, 95CI%:1.000-1.005, P = 0.023). Additionally, a suggestive association was observed between total testosterone levels and an increased risk of eczema or dermatitis (inverse variance weighted: OR = 1.005, 95CI%: 1.001-1.010, P = 0.024). However, the results showed no causal effects of estradiol levels on eczema or dermatitis. The accuracy and robustness of these findings were confirmed through sensitivity analyses.

Conclusions: This MR study supports a causal effect of SHBG sex hormone-binding globulin and TT levels on the risk of eczema or dermatitis, whereas estradiol appears to have no effect. These findings suggest that endogenous sex hormones may serve as potential biomarkers for eczema or dermatitis, which could be relevant to population groups beyond those of Europe.