St. Louis, MO—Almost since the beginning of the COVID-19 pandemic, it appeared that men generally were more likely to have a severe infection and unfavorable outcomes than women.

A new study in the Journal of the American Medical Associate Network Open pointed out, however, that it is unclear if the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh).

The study team sought to compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh. These researchers conducted a cohort study in two large academic health systems in St. Louis, Missouri, including 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021.

The participants had a mean age of 55 years and a mean BMI of 33.5. In terms of gonadal status, 116 men had hypogonadism, 427 had eugonadism, and 180 were receiving TTh. For purposes of the study, hypogonadism was defined as a total testosterone concentration below the limit of normal provided by the laboratory (which varied from 175-300 ng/dL [to convert to nanomoles per liter, multiply by 0.0347]). The primary outcome was defined as the rate of hospitalization for COVID-19.

The results indicated that men with hypogonadism were more likely than men with eugonadism to be hospitalized with COVID-19 (52 of 116 [45%] vs. 53 of 427 [12%]; P <.001). After multivariable adjustment, men with hypogonadism continued to have higher odds than men with eugonadism of being hospitalized (odds ratio [OR], 2.4; 95% CI, 1.4-4.4; P <.003).

While men receiving TTh had a similar risk of hospitalization as men with eugonadism (OR, 1.3; 95% CI, 0.7-2.3; P = .35), those whose TTh supplementation was inadequate—defined as subnormal testosterone concentrations while receiving TTh—also had higher odds of hospitalization compared with men who had normal testosterone concentrations while receiving TTh (multivariable-adjusted OR, 3.5; 95% CI, 1.5-8.6; P = .003).

“This study suggests that men with hypogonadism were more likely to be hospitalized after COVID-19 infection compared with those with eugonadism, independent of other known risk factors,” the researchers concluded. “This increased risk was not observed among men receiving adequate TTh. Screening and appropriate therapy for hypogonadism need to be evaluated as a strategy to prevent severe COVID-19 outcomes among men.”

Because patients hospitalized for COVID-19 are more likely to be men than women, the authors pointed out, “Therefore, it was presumed that testosterone is a risk factor for severe COVID-19 and that estrogen may be protective against COVID-19. However, not all men have similar testosterone concentrations. Men’s testosterone concentrations decrease continuously by 1% to 2% per year, starting after the third decade of life.”

The article added that obesity, metabolic syndrome, and chronic illnesses, such as type 2 diabetes, kidney insufficiency, and chronic lung disease are linked with lower serum testosterone concentrations among men, adding, “Thus, aging and the presence of comorbid conditions, which are risk factors for hospitalization for COVID-19, are also associated with hypogonadism, which raises the question of whether hypogonadism is a risk factor for COVID-19–related hospitalization among men.”

The St. Louis University School of Medicine–led authors suggested that the findings go against common misconceptions about men and COVID-19, explaining, “We found that men with hypogonadism were 2.4 times more likely than men with eugonadism to be hospitalized if they contracted COVID-19. This increased risk was independent of other factors that increase the risk of hospitalization for COVID-19, such as advanced age, comorbid conditions, and immunosuppression. This finding contrasts with a widely held notion that men are more likely than women to be admitted owing to COVID-19 because they have higher concentrations of circulating testosterone. On the contrary, our data suggest that male hypogonadism is a risk factor for hospitalization for COVID-19.”

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