The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in 2019, leading to the COVID-19 pandemic. In order for SARS-CoV-2 to infect a host cell, both ACE-2 (angiotensin converting enzyme 2) and TMPRSS2 (transmembrane protease serine 2) receptors must be present.¹ ACE-2 and TMPRSS2 are both expressed in the male reproductive tract, and since the pandemic started, this has led to several questions surrounding the effects of COVID-19 on men’s health. In this review, we will highlight the effects of COVID-19 on male reproductive and sexual medicine.

Studies evaluating testosterone levels in men with COVID-19 have had mixed results; however, testosterone tends to be low after an infection and rises in the recovery phase of the illness.² Hypogonadism is an independent predictor for developing COVID-19 and is associated with worse outcomes after an infection.^2,3 Salonia et al performed a retrospective cohort study highlighting that men admitted to the hospital with COVID-19 were 6 times more likely to have hypogonadal levels of testosterone compared to a matched healthy population.³ Furthermore, they identified that men who had significantly lower levels of testosterone had worse outcomes, such as intensive care unit admission and death. Long-term studies are needed for a more comprehensive understanding of the effect of COVID-19 on androgen levels in men.

Most studies that have examined semen for the presence of SARS-CoV-2 have not identified viral particles within the seminal fluid, making it unlikely that COVID-19 is sexually transmitted. However, several studies have shown a decrease in sperm concentration after COVID-19 in the short term, but this improves over time.⁴ This transient effect on semen parameters is seen with other febrile illnesses as well, and it remains unclear whether SARS-CoV-2 is directly gonadotoxic despite some reports showing damage to testicular architecture.

Several studies have identified an association with COVID-19 and erectile dysfunction (ED).⁵ A retrospective review using the TriNetx research network found that men with COVID-19 were observed to have ED with an odds ratio 20% higher than men who were never infected (OR 1.2, 95% CI 1.004-1.248, P = .04). Additionally, it was found that ED was more prevalent in men who had COVID-19 (28% vs 9.33%) and that viral infections were an independent predictor of ED (OR 5.27, 95% CI 1.49-20.09).⁵ Mechanisms of why SARS-CoV-2 leads to ED that have been proposed include vasculogenic, neurogenic, endocrinologic, and psychogenic causes.

Studies have shown that SARS-CoV-2 reaches high levels in the male genitourinary tract. Animal model research by Madden et al showed increased positron emission tomography–CT signal in the male genitourinary tract of animal subjects at varying time points postinfection, implying potential pathologic sites of viral replication.⁶ Replication by itself does not completely account for some of the known structural-physiologic changes that accompany ED. At its base level, ED often stems from dysfunction of the vascular endothelium. Hence, the induced hyperinflammatory response resulting from COVID-19 and consequent cytokine release-TNF-α, IL-6, and IL-1beta are thought to precipitate endothelial dysfunction in erectile tissue leading to ED.⁷ With transmission electron microscopy, Kresch and colleagues were able to demonstrate decreased endothelial progenitor cells, a diminished expression of endothelial nitric oxide synthetase, as well as intact viral particles in the corporal tissue harvested during prosthetic placement long after the initial infection.⁸ Despite small sample sizes, these results suggest a multifaceted pathogenesis of COVID-19–related ED and potential mechanistic explanations for prior retrospective data.

The pandemic has also brought about an increase in sales of medications for the treatment of ED. Data on the sales of phosphodiesterase-5 inhibitors including sildenafil, tadalafil, vardenafil, and avanafil were obtained from IQVIA from 2018 to 2020. After the first 2 months of the pandemic, the trend in sales significantly increased (coefficient for trend change =920,947, P < .001). Sales of these drugs were 67% higher during the pandemic when compared to before the pandemic was declared in the United States (February 2020), representing sustained growth.⁹ While this may represent a culmination of the aforementioned organic factors, other etiologies of ED may be of equal importance as well. The psychosocial strain of a global pandemic cannot be overstated. Reduced social contact and increased isolation, increased stress and anxiety, and even increased pornography usage have all been linked to the pandemic and are all factors contributing to psychogenic ED as well as other ejaculatory and sexual disorders.¹⁰

COVID-19 has both a direct and indirect effect on male reproductive and sexual function. SARS-CoV-2 can potentially affect vascular, nervous, and endocrine systems in men, leading to reproductive and sexual dysfunction. The psychogenic effects of the pandemic have been paramount, and it is important to evaluate mental well-being for men presenting with these complaints. It is evident that COVID-19 remains a multifactorial andrological concern. The medical community must remain vigilant in evaluating and managing these patients and continue to provide high level research in the area.