Sex hormones and the total testosterone: estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men

Abstract

Background: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. Objectives: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. Materials and methods: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. Results: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 μg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). Discussion and conclusion: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.