Low testosterone levels in men with symptomatic COVID-19 were associated with a greater risk of severe illness or death, according to Italian researchers.

Their case-control study found that, among men admitted to the emergency department of a Milan Hospital during the first wave of the pandemic, the lower the level of testosterone the higher the likelihood they would need intensive care, intubation, and long hospital stays.

In addition, after accounting for disease severity, low testosterone was associated with a 33% higher risk of death, reported Paolo Capogrosso, MD, of Università Vita-Salute San Raffaele in Milan, Italy, during a presentation at the European Association of Urology virtual annual congress.

The more severe the illness, the lower the average testosterone level:

• Mildly symptomatic and discharged home (3.9 nmol/L)
• Admitted into the internal medicine unit (3.0 nmol/L)
• Admitted to the ICU (1.0 nmol/L)
• Deceased because of COVID-19 (0.7 nmol/L)

“This study outlines that testosterone levels in men with COVID-19 deserve clinical attention, although it remains to be established whether testosterone is simply a marker of health or measuring it may help to target a very high-risk population, while establishing counteractive therapeutic measures,” Capogrosso concluded at the session.

Which came first — the low testosterone levels or COVID-19 — wasn’t clear from these data, said the study’s senior author, Andrea Salonia, MD, of University Vita-Salute San Raffaele and a urologist at the IRCCS Ospedale San Raffaele, in a release accompanying the study.

“Testosterone does play a role in protecting men from disease,” he said. “However, it’s also possible that the virus itself is able to induce an acute reduction in testosterone levels, which then predisposes these men to a worse outcome. We’re now following up these patients over a longer time period, to see how their hormone levels change over time, so we can try and answer these questions.”

This was one of several studies that has showed an association between low testosterone and COVID-19 severity. In a small, single-center study published last month in JAMA Network Open, men with severe COVID-19 had significantly lower levels of testosterone than men with mild cases (53 vs 151 ng/dL).

And last year a study in The Aging Male found that, among 221 men hospitalized with COVID-19, low serum total testosterone levels at baseline significantly increased the risk of ICU admission and mortality.

Capogrosso’s study included 286 patients with symptomatic COVID-19 admitted to the emergency department who were compared with a cohort of 281 healthy men as well as 24 men with asymptomatic COVID-19.

The patients with COVID-19 were categorized into four groups according to disease severity: mildly symptomatic and discharged home, admitted into the internal medicine unit, admitted to the ICU, and deceased because of COVID-19.

All patients in the study were checked for levels of male hormones, including testosterone, which was considered low if less than 9.2 nmol/L (hypogonadism).

Nine out of every 10 symptomatic COVID-19 patients (89.8%) had hypogonadism compared with 14.9% of healthy controls and 33% of men with asymptomatic COVID-19. Mean total testosterone levels were significantly lower in patients with symptomatic COVID-19 (2.5 nmol/L) compared with healthy patients (10.4 nmol/L) and men with asymptomatic COVID-19 (11.8 nmol/L).

In logistic regression analyses, a lower testosterone level was associated with a lower likelihood of survival (OR 0.66, 95% 0.45-0.98) after accounting for the critical illness score, Capogrosso and his colleagues reported.

The investigators scored health-related comorbidities with the Charlson Comorbidity Index and calculated a composite risk score in order to estimate the risk of men with COVID-19 developing critical illness.