When the pandemic began, it was quickly noted that a disproportionate number of men were dying from it. Made sense, since women mount a stronger immune response than me with high-normal testosterone [T].
And then the Italian study came out in May (2020) [3]:
"Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections."
But now we find that low T increases covid risk:
"Among 90 men with COVID-19 who arrived to the Barnes Jewish Hospital in St Louis, Missouri from March to May 2020, 31 men presented with severe disease, another 35 developed severe disease 1-3 days into their hospital stay, and 24 had mild disease.
"Median testosterone levels upon admission were significantly lower among men who presented with severe COVID-19 (48 ng/dL) or who developed severe COVID-19 during hospitalization (65 ng/dL) compared with men who had mild disease (151 ng/dL), the investigators reported in JAMA Network Open. Median testosterone levels were lowest at day 3 (median 19 vs 111 ng/dL) and day 7 (median 20 vs 180 ng/dL) for men with severe COVID-19 vs mild illness.
"Day 3 total testosterone was 17 vs 104 ng/dL in men with and without ICU admission, 12 vs 60 ng/dL in men with and without ventilator use, and 15 vs 49 ng/dL among men who died and survived, respectively, the investigators reported.
"Overall, testosterone levels in the severe COVID-19 group showed recovery at day 14 (53 ng/dL) and day 28 (102 ng/dL). All of these levels were well within the reference range for low testosterone of less than 250 ng/dL.
"Men with severe COVID-19 had approximately 65% to 85% lower testosterone concentrations compared with men who had milder disease, independent of other known risk factors associated with severity of COVID-19, such as age, body mass index, comorbidities, smoking, and race, according to Dr Diwan’s team. Testosterone levels did not correlate with disease severity among the 62 women with COVID-19 who presented at the hospital.
"With respect to inflammatory markers, testosterone concentrations were inversely and significantly associated with interleukin 6, C-reactive protein, interleukin 1 receptor antagonist, hepatocyte growth factor, and interferon γ–inducible protein 10 in men. Estradiol and insulin-like growth factor 1 concentrations were not associated with COVID-19 severity in men.
“These data suggest caution should be practiced with approaches that antagonize testosterone signaling or supplement estrogen to treat men with severe COVID-19,” Dr Diwan and colleagues wrote. "
Perhaps castrate T due to ADT is a special subset of castrate T men?
Yes, they had lower testosterone at baseline tests already in hospital for COVID. So it may have been a marker for general frailty and aging which made them vulnerable for more severe disease. Hard to extrapolate to ADT or to how developing COVID might have affected testosterone since that appears to have recovered along with the disease recovery.
Can we know if lower T contributes to more severe COVID versus the possibility that more severe COVID might contribute to lower serum levels of T?
As well as whether man had medically-induced low T or naturally low T, it would also be interesting to see T correlations with both chronological age and other age-related conditions, since lower T naturally comes with more advanced aging (along with decreasing muscle mass and bone density and increased inflammation, etc.)
"Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm."
Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection
Stefano Salciccia 1 , Francesco Del Giudice 2 , Michael L Eisenberg 3 , Claudio M Mastroianni 4 , Ettore De Berardinis 2 , Gian Piero Ricciuti 2 , Pietro Viscuso 2 , Antonella Zingaropoli 4 , Patrizia Pasculli 4 , Maria Rosa Ciardi 4 , Alessandro Sciarra 2 , Martina Maggi 2
Affiliations collapse
Affiliations
1 Department of Maternal-Infant and Urological Sciences, Prostate Cancer Unit, Sapienza Rome University, Policlinico Umberto I, Viale dell'Università, Rome, 00161, Italy.
2 Department of Maternal-Infant and Urological Sciences, Prostate Cancer Unit, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.
3 Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
4 Department of Public Health and Infectious Diseases, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.
The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 is causing a severe health emergency, and an individual's hormonal milieu may play an important role in both susceptibility to infection and severity of clinical course. We analyzed the role of testosterone in the immune response, and we hypothesized possible mechanisms to explain the high incidence of COVID-19 infection and a worse clinical course in elderly male patients. Testosterone may impair the immune response, and this effect could explain the greater susceptibility of men to infection. Transmembrane serine protease 2 (TMPRSS2) plays a crucial role in the entry of the virus into the respiratory epithelial cells, leading to COVID-19 disease. It is crucial to emphasize that testosterone levels and chemical castration (e.g. by androgen deprivation therapy for prostate cancer) may have contrasting roles in the phases of COVID-19 infection. Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm. If testosterone levels play these different roles, it is necessary to carefully identify patients for any indicated testosterone manipulation.
Keywords: COVID-19; SARS-CoV2; androgen deprivation therapy; hypogonadism; immune response; male serum testosterone; sex differences; testosterone replacement therapy.
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