Normal testosterone levels in men might be protective against severe COVID-19, a retrospective cohort study suggested.
Among 723 men with a mean age of 55, those who had hypogonadism had a higher risk of hospitalization for COVID-19 versus men with eugonadism (OR 2.4, 95% CI 1.4-4.4, P<0.003), reported Sandeep Dhindsa, MD, of St. Louis University School of Medicine in Missouri, and colleagues.
Of these men, 45% with hypogonadism were hospitalized with COVID-19 versus only 12% with eugonadism, the group noted in JAMA Network Open.
“Our study brings forth another impact of low testosterone: decreased ability to overcome an illness such as COVID-19,” Dhindsa told MedPage Today.
However, testosterone therapy did appear to offset this risk. Men receiving this therapy had a similar risk of hospitalization as men with normal levels (OR 1.3, 95% CI 0.7-2.3, P=0.35).
One caveat, though, was that if men were receiving an inadequate dose of testosterone therapy and unable to reach normal levels, they still had a higher likelihood of hospitalization compared with men who had normal levels while receiving therapy (multivariable adjusted OR 3.5, 95% CI 1.5-8.6, P=0.003).
“Since men are more likely than women to require hospitalization from COVID-19, it has been assumed that testosterone is the reason for that increased risk,” Dhindsa noted. “However, we know that not all men have the same testosterone levels.”
He added that it was “clear early in the pandemic that elderly and obese men are more likely to get sick enough from COVID to require hospitalization” — two male populations that tend to have lower testosterone levels compared with younger or normal weight men, which is what led the researchers to believe that low testosterone was not in fact protective against COVID, contrary to popular belief.
“The fact that testosterone treatment lowered the risk further solidified our finding that low testosterone should be considered a risk factor for hospitalization from COVID,” he pointed out.
Despite this finding, Dhindsa said that it’s too early to recommend testosterone treatment as a primary prevention for hospitalization from acute illnesses, but did suggest that future studies look into this possibility.
The study’s findings build upon prior research led by Dhindsa, which found that men with severe COVID illness tended to have significantly lower testosterone levels at the time of diagnosis than men with mild cases: 151 ng/dL versus 53 ng/dL. This trend also held true throughout the course of COVID illness.
The current study was conducted at two large St. Louis-based healthcare systems. Among the 723 men included in the analysis, 116 were hypogonadal and 427 were eugonadal; 180 were receiving testosterone therapy. The researchers excluded men whose testosterone concentrations were only measured during illness.
Hypogonadism was classified as a total testosterone concentration below the lab-defined limit of normal, which ranged from 175 to 300 ng/dL. Adjustments were made for several potential confounders, including age, race and ethnicity, BMI, immunosuppression, and comorbidities.
Median testosterone levels for hypogonadal and eugonadal men were 131 ng/dL and 381 ng/dL, respectively.
Compared with eugonadal men, hypogonadal men tended to be older (62 vs 53), have a higher BMI (35 vs 33), have more comorbidities (2 vs 0), have diabetes (39% vs 21%), and be immunosuppressed ( 16% vs 6%).
Testosterone measurements among outpatients were typically spurred by symptoms indicating potential hypogonadism, the most common of which were fatigue, erectile dysfunction, decreased libido, gynecomastia, low mood, opiate use, pituitary adenoma, and obesity.
“Historically, the screening for hypogonadism and treatment of testosterone is dependent upon the presence of symptoms such as decreased sexual desire and low energy,” Dhindsa said. “However, studies over the last decade have demonstrated that low testosterone adversely impacts metabolic health — such as increased risk of diabetes — and testosterone treatment decreases that risk.”
Dhindsa and co-authors reported relationships with Bayer, Acerus Pharmaceuticals, Clarus Therapeutics, Pfizer, Elsevier, the National Institutes of Health, the Agency for Healthcare Research and Quality, Clario, and Dewpoint Therapeutics.