What is the relationship between ADT and COVID-19 mortality?

In the early days of the COVID-19 pandemic, it became clear from data out of Italy that more men than women were dying of the disease. Many of us began speculating that maybe androgen deprivation could improve the survival of men infected with COVID-19…or perhaps reduce their risk of getting the disease in the first place. In the last year and half, several researchers have speculated on this. The studies so far have had small sample sizes and have failed to reach consistent conclusions. Now, however, there is an impressively large retrospective study out of Sweden built upon data from over 5000 men on ADT. The authors soundly conclude that there is "no clear evidence in support of an effect of androgen deprivation therapy on COVID-19 mortality”.

The paper reviews the argument for why androgen suppression should reduce the risk of COVID-19 infection. But the authors don't have much to say about why ADT patients nevertheless do not have better COVID-19 survival. On this topic they have but a single sentence, where they suggest that "ADT could be detrimental in later stages of severe COVID-19 since it could exacerbate or activate an excessive and harmful inflammatory response."

There may, however, be a simpler explanation. ADT leads to sarcopenic obesity; i.e., loss of muscle mass, but a gain in body fat. A large amount of abdominal fat will push up against the diaphragm and impede breathing. Similarly, the diaphragm itself is a muscle. If it is losing mass and becoming weaker because of ADT, that may lead to less effective coughing, which is part of the body's natural defence against irritants in the lungs. Although this is speculative, it may indeed be true that androgens increase the chances of catching COVID-9, but ADT fails to help men overcome the infection because of the multiple ways that ADT can impair respiratory function.

We look forward to some rigorous data on ADT's impact on the morphology of the diaphragm as well as its impact on respiratory physiology.

To read the full paper, see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496782/

Reference:

Gedeborg R, Styrke J, Loeb S, Garmo H, Stattin P. Androgen deprivation therapy and excess mortality in men with prostate cancer during the initial phase of the COVID-19 pandemic. PLoS One. 2021 Oct 7;16(10):e0255966. doi: 10.1371/journal.pone.0255966. PMID: 34618806; PMCID: PMC8496782.