The Double Edge Sword of Testosterone's Role in the COVID-19 Pandemic
by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
For a number of years, researchers have been trying to understand why COVID-19 patients are disproportionately male. Their research has shown that sex hormones play a role in this disparity.
It has become increasingly clear that low testosterone levels are associated with worse outcomes. This is not surprising given that testosterone has a known negative effect on the immune system and a host’s ability to fight off infections.
Sex Bias in COVID-19
Sex bias has been a frequent theme in COVID-19 clinical research, with studies reporting that men are more likely to have severe disease and death from COVID-19 than women. The male sex bias is a prominent feature of most COVID-19 pandemics, including SARS-CoV-2, and is largely attributed to a biological difference in the response to SARS-CoV-2 infection between the two sexes.
Sex is a complex and often multi-layered factor that influences many aspects of health and illness, from sex-related behaviours to socioeconomic status. Therefore, it is critical to understand and address sex biases in biomedical research and clinical practice to maximize equity across the COVID-19 pandemic.
In one paper, researchers aim to illustrate the role of sex in COVID-19 using computational models based on data from sex-dis-aggregated global observational studies. The research team developed and tested a causal model for the relationship between sex and COVID-19 severity in which we incorporate the known confounding and mediating factors derived from gender-related COVID-19 research.
The model consists of three metrics (Total Effect, Natural Direct Effect, and Indirect Effect) that indicate the difference in probability of a COVID-19 severe disease case from a normal condition for men and women. The values are expressed as a percentage of the normal probability in the presence of all other conditions, i.e. a positive value indicates that Sex = Male is associated with higher probability of severe COVID-19 disease than Sex = Female and a negative value implies a COVID-19 severity bias for women.
These metrics are then used to calculate regression based estimates for the mediation analysis. Using these estimates, the team can then calculate Confidence Intervals for the mediation analysis metrics (NDE, TE, NIE) in a synthetic dataset to show the impact of Sex on COVID-19 severity by evaluating different biological (BioVar) and Lifestyle variables.
The researcher's found that male patients were more sensitive to the SARS-CoV-2 pathogen than female patients and had a poorer T cell response during SARS-CoV-2 infection. Additionally, male patients showed significantly higher levels of innate immune cytokines, whereas female patients had lower levels of these cytokines. They also identified a negative correlation between the T cell response and age in male patients, whereas the opposite was true in female patients. These findings suggest a possible mechanism for the sex biases observed in SARS-CoV-2 infection and offer a basis for developing sex-dependent approaches to prevention, care, and therapy of COVID-19 patients.
Testosterone’s Role in COVID-19
Testosterone is a male sex hormone that is essential for the development of male sexual organs, such as the penis and prostate. It is also needed for sperm production. It is produced mainly in the testes of men, and in smaller amounts in women. In men, the brain’s hypothalamus and pituitary gland tell the testes how much testosterone to make.
When someone is born with low levels of testosterone, it can cause problems in fetal development and sexual development during childhood or puberty. This condition is called androgen insensitivity syndrome (AIS). It causes the body to not produce normal male characteristics, such as facial hair and a deep voice, and it often leads to infertility during adulthood.
In men, testosterone is produced primarily in the testes, but also in small amounts in the adrenal glands. It is released into the bloodstream and transported in a number of different forms, including a large amount that is bound to a protein in the blood called sex hormone binding globulin (SHBG).
SHBG-bound testosterone is thought to regulate the production of sperm by the Leydig cells and Sertoli cells in the testes. It is also involved in sex hormone production by the gonads, the ovaries and the placenta in women.
Another important role of testosterone in the human body is regulating a man’s sense of well-being and energy. If a man’s testosterone is too low, it can result in changes in his mood and sleep patterns. It may also make him feel less confident, and he may become depressed or irritable.
These symptoms can affect a person’s daily life and work. They can also affect his ability to care for others.
There is growing evidence that testosterone affects the immune system, and this is a possible reason why COVID-19 can spread so easily. It appears that SARS-CoV-2 mutates in response to testosterone, increasing its ability to invade the immune system and cause infection.
To help keep your immune system strong, it is important to follow some simple tips. Get enough rest, eat healthy foods, drink plenty of fluids and exercise. Using a virus-killing hand sanitizer can also be helpful.
Testosterone’s Treatment in COVID-19
Throughout the pandemic, doctors have seen that men tend to fare worse than women in COVID-19 hospitalizations and deaths. This sex bias is thought to be due to the hormonal difference between males and females, which makes them more susceptible to severe disease.
Since testosterone is a natural male hormone, researchers have been interested in whether it may play a role in this phenomenon. They have found that testosterone is a powerful anti-inflammatory and immune-modulatory substance that plays an important role in the body’s ability to mount an anti-viral response.
Testosterone’s physiology is complicated, and it can affect a number of different organ systems. In particular, it can influence a number of immune cells, including T lymphocytes and classical monocytes. It also affects a number of other metabolic processes, including glucose metabolism.
The SARS-CoV-2 virus has been shown to disrupt the production of testosterone by ACE2-expressing testicular cells, mainly Leydig cells. This may lead to a decrease in circulating LH and adrostenedione levels.
As it has been demonstrated that testosterone deficiency is a significant risk factor for COVID-19, researchers have explored the possibility of using testosterone to treat the infection. They have found that testosterone therapy significantly reduces the likelihood of hospitalization and death from COVID-19.
Another study, which was published in the Journal of Clinical Endocrinology & Metabolism, has shown that testosterone replacement therapy can be effective in treating men with low levels of this hormone. It has also been shown to be safe and effective for reducing the risk of diabetes in men with hypogonadism.
In fact, research shows that testosterone can be an effective treatment for a variety of other diseases, including lung cancer and prostate cancer. It can also help prevent the onset of these conditions in patients with low levels of this hormone.
A trial is being conducted at University of California, Los Angeles, where researcher Matthew Rettig is directing a study to see if androgen-suppressing drug degarelix could prevent hospitalizations from COVID-19. This randomized, placebo-controlled trial is testing a single injection that virtually zeroes out testosterone levels within 3 days. The drugs, which are similar to surgical castration, are being tested on 200 veterans with COVID-19 in Los Angeles, Seattle and New York City.
As testosterone levels decline, morbidity and mortality increase with severe illness from COVID-19. This is partly because low testosterone can lead to dangerous inflammatory responses and exacerbate lung damage, respiratory muscle catabolism and thrombin induced death (TLD) , which are all risk factors for hospitalization or death from COVID-19.
Whether or not testosterone has a direct effect on COVID-19 infection is unclear and could depend on the immune system's response to the virus. However, it is known that testosterone suppresses the immune system and can help prevent inflammatory cytokines from increasing, which is why testosterone replacement therapy is recommended for men with low testosterone after Covid-19 infection.
It is thought that this effect of testosterone on the immune system may be mediated by correlated changes in glucocorticoid levels, which can also affect immunity and infection risk. This is a common theory of testosterone-parasite associations and could explain the link between high testosterone levels and increased parasite exposure, as well as why women who have polycystic ovary syndrome with higher SexHs are more susceptible to infection and poorer outcomes than women with lower SexHs.
This is a complicated relationship between testosterone, the immune system and parasites. There are many reasons why the obligate trade-off between sexual signalling and immunity might not apply to all parasites and even to different components of the immune system, but there is considerable evidence that testosterone does have indirect effects on host behaviour that enhance or reduce the presence of parasites.