Low testosterone may impair immune response in men with COVID-19
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Low serum testosterone levels may predispose older men to worse COVID-19 outcomes and could explain the higher coronavirus case fatality rate among men compared with women, according to a literature review.
“To put it simply, men have a basal, biological predisposition to get sick from COVID-19, either from their higher plasma testosterone levels compared with women or from age-related low testosterone levels, which, being an important parameter of frailty, could result in severe and potentially fatal forms of COVID-19 infection among men,” Vito A. Giagulli, MD, PhD, head of the outpatient clinic for endocrinology and metabolic diseases at Conversano Hospital in Bari, Italy, told Healio.
Differences in outcomes
Data collected worldwide on COVID-19 cases reveal that men and women are equally likely to contract COVID-19, Giagulli said in an interview. Yet the number of patients hospitalized with COVID-19 complicated by severe clinical events, such as disseminated intravascular coagulation, venous thromboembolism, pulmonary distress, acute cardiovascular and renal injury, or sepsis and multi-organ failure, is statistically higher for men vs. women, he said.
“Upon closer inspection, we suspected that specific factors might cause a bias toward a poor prognosis in men affected by COVID-19, particularly by emphasizing the role of testosterone,” Giagulli said.
In a literature review published in Andrology, Giagulli and colleagues wrote that observational data show that patients with worse clinical progression — frequently older adults with one or more underlying chronic diseases — are more likely to have hypogonadism.
“Additionally, angiotensin-converting enzyme 2, or ACE2, which is essential for SARS-CoV-2 entry into host cells, is also expressed in the testes,” Giagulli said. “These results suggest that SARS-CoV-2 may infect testicles, potentially affecting testosterone secretion in younger patients, too. Therefore, as in the cases of older men or of those with dysmetabolic diseases like obesity, low serum testosterone level can predispose them to an impaired immune response ... leading to a worsening progression of SARS-CoV-2 infection in men.”
Giagulli said the hypothesis was recently demonstrated in a small, single-center study assessing 31 men with COVID-19 pneumonia admitted to a respiratory ICU in Italy. In the study, published in Andrology in May, researchers found that men with severe COVID-19 and overt hypogonadism were more likely to die compared with men with higher testosterone levels.
Research suggests that lower levels of plasma testosterone, which may be common among older men or men with obesity, as well as among men with other chronic diseases, could lead to systemic inflammation, impaired CV function, thromboembolism and worse COVID-19 outcomes, Giagulli said.
“Testosterone predisposes men to a less effective immune response against infectious agents, and male hypogonadism may trigger a detrimental cytokine dysfunction that might be responsible for poor prognoses in men with COVID-19,” he told Healio.
Research needed
Giagulli said the review suggests several strategies are needed to learn more about a connection between testosterone level and COVID-19 outcomes.
“First, basic research should aim to elucidate what role, if any, that androgen receptor plays in the facilitation of COVID-19 infection as well as on its severity,” Giagulli said. “Second, clinical research should be conducted to evaluate the pathophysiological role of the different hormonal milieu in COVID-19 infection for both sexes and whether COVID-19 infection facilitates the reduction of testosterone levels, since it can negatively affect testes causing overt hypogonadism. Consequently, different therapeutic approaches to COVID-19 infection might be carried out, based on the results of the aforementioned studies.”
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Vito A. Giagulli, MD, PhD, can be reached at Conversano Hospital, Clinic of Endocrinology and Metabolic Disease, Edmondo de Amicis 36, 70014 Conversano, Bari, Italy; email: vitogiagulli58@gmail.com.
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