Testosterone and Covid-19: What's the link?

Take-home points

• COVID-19 can reduce testosterone levels and may take months to years of recovery in more severe cases.
• Scientists are unsure if low testosterone levels in men increase the risk and severity of infection.
• Speak to a healthcare professional if you are concerned about low testosterone levels.

Low testosterone and COVID-19

Male testosterone is produced almost entirely from the testis and is necessary to live healthily. This hormone upholds fertility, sex drive, strength and muscle mass. The normal testosterone range in adult men is between 300 and 1,000 ng/dL. Most men will fall within this bracket. Any less and the Endocrine Society suggest that healthcare professionals should consider a diagnosis for hypogonadism.¹

Coronavirus Disease‐19 (COVID‐19) is an infection caused by severe acute respiratory syndrome‐coronaviruses‐2 (SARS‐CoV‐2), a highly pathogenic and transmissible virus. Most cases of COVID‐19 have mild to moderate symptoms (cough, fever, myalgias, and headache) but severe complications are possible, including death. As of early 2023, according to the World Health Organisation, there have been over half a billion cases of COVID-19 and nearing 10 million related deaths.²

What is the link between low testosterone and COVID-19?

Although testosterone and COVID-19 sound unrelated, researchers continue to debate the relationship between the two. An early observation during the pandemic was that low testosterone levels at the time of hospitalisation predict the most severe clinical outcomes such as ICU admission and death.³ However, at the same time, women were at lower risk of COVID-19 despite having far less testosterone than men. With these observations seemingly contradicting each other, scientists called for robust studies to uncover two relationships: testosterone’s impact on COVID-19, and COVID-19’s impact on testosterone. 

Years later, strong data has generated more certainty about the latter relationship. Circulating testosterone levels can meaningfully decrease after COVID-19 infection, with a slow and perhaps incomplete recovery of pre-disease testosterone levels over time.^4,5 One research group showed that over 50% of men hospitalised from COVID‐19 still had low testosterone levels up to 7 months of recovery.⁵ This figure reduces to around 30% of hospitalised men after 12 months of recovery.⁶

We do not expect such drastic consequences in men not hospitalised by the virus. Still, the severity of infection does not seem to impact the presence of COVID-19 in male genital tract samples.⁴ Mechanistic studies demonstrate that SARS‐CoV‐2 enters the uro‐genital system and may eventually damage the cells (Leydig cells) that produce testosterone.^7,8 Experiencing a milder form of the disease likely does not change that fact.

What is still debated, however, is how much the drop in testosterone is responsible for worse clinical outcomes. Is testosterone involved in protecting against the disease, or does it merely mark the severity of illness? Currently, there is only weak evidence suggesting that testosterone replacement therapy influences the severity of COVID-19 outcomes.⁹

Unanswered questions: What we still do not know about testosterone and COVID-19

Because COVID-19 can acutely reduce testosterone levels, it's challenging to know whether low testosterone increases the risk of infection. Just because men in hospital with COVID-19 likely have low testosterone does not mean sufficient testosterone would have kept the disease at bay. It's possible that testosterone levels were normal before infection and sank lower post-infection. Unfortunately, almost all the studies to date have only measured testosterone levels after infection, not before, creating a knowledge gap that needs exploring.

Adding to the challenge is the fact that numerous comorbidities cause reductions in testosterone levels. We have expanded on this in previous articles. Therefore, even if research found that men with lower testosterone were more likely to be infected by COVID-19, the researchers would have to consider if the comorbidities or testosterone itself (or both) is to blame. Future research can hopefully respond to these question marks directly.

Treating low testosterone after COVID-19

Although research is not conclusive, from a safety-first perspective it's important to maintain healthy testosterone levels. We cannot overstate the importance of living a healthy lifestyle (eating well, keeping active, sleeping sufficiently, and restricting alcohol and smoking) free of chronic diseases, and considering standard treatment protocols such as testosterone replacement therapy if diagnosed with a testosterone deficiency. 

If you are concerned about low testosterone levels or suspect that COVID-19 may have reduced your testosterone levels, we recommend talking to a healthcare professional. Important COVID-19 advice and services can be found on the National Health Service (NHS) website.

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References

1. Bhasin S et al. J Clin Endocrinol Metab 2006;91(6):1995–2010.
2. Website Source: https://covid19.who.int/table.
3. Lanser L et al. Front Endocrinol (Lausanne) 2021;12:694083.
4. Corona G et al. J Endocrinol Invest 2022;45(12):2207–2219.
5. Salonia A et al. Andrology 2022;10(1):34–41.
6. Salonia A et al. Andrology 2023;11(1): 17–23.
7. Nie X et al. Cell 2021;184(3):775-791.e14.
8. Yang M et al. Eur Urol Focus 2020;6(5):1124–1129.
9. Rambhatla et al. J Sex Med 2021;18(1):215–218.