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All Studies   Meta Analysis    Recent:   

Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy

Bennani et al., Annals of Oncology, doi:10.1016/j.annonc.2020.08.2095
Aug 2020  
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Mortality 95% Improvement Relative Risk ICU admission -119% Hospitalization 25% Severe case 8% Antiandrogens  Bennani et al.  Prophylaxis Is prophylaxis with antiandrogens beneficial for COVID-19? Retrospective 118 patients in Italy Higher ICU admission with antiandrogens (not stat. sig., p=0.4) c19early.org Bennani et al., Annals of Oncology, Aug 2020 Favorsvarious Favorscontrol 0 0.5 1 1.5 2+
7th treatment shown to reduce risk in September 2020
 
*, now with p = 0.000000056 from 49 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,500+ studies for 81 treatments. c19early.org
Retrospective 118 prostate cancer patients, 4 on androgren deprivation therapy, not showing significant differences (as expected with only 4 patients in the treatment group).
risk of death, 94.9% lower, RR 0.05, p = 1.00, treatment 0 of 4 (0.0%), control 18 of 114 (15.8%), NNT 6.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 119.2% higher, RR 2.19, p = 0.40, treatment 1 of 4 (25.0%), control 13 of 114 (11.4%).
risk of hospitalization, 25.0% lower, RR 0.75, p = 0.60, treatment 2 of 4 (50.0%), control 76 of 114 (66.7%), NNT 6.0.
risk of severe case, 8.1% lower, RR 0.92, p = 1.00, treatment 1 of 4 (25.0%), control 31 of 114 (27.2%), NNT 46.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bennani et al., 17 Aug 2020, retrospective, Italy, peer-reviewed, 2 authors.
This PaperAntiandrogensAll
Abstract: Annals of Oncology Letters to the Editor number 176045], Prostate Cancer Foundation [grant number 19CHAL08]; and Italian Association for Cancer Research Investigator Grant [grant number 22030]. DISCLOSURE The authors have declared no conflicts of interest. REFERENCES 1. Delanghe JR, De Buzyere ML, De Bruyne S, Van Criekinge W, Speeckaert MM. The potential influence of human Y-chromosome haplogroup on COVID-19 prevalence and mortality. Ann Oncol. 2020;31(11):1582-1584. 2. Jin J-M, Bai P, He W, et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health. 2020;8:152. 3. Maan AA, Eales J, Akbarov A, et al. The Y chromosome: a blueprint for men’s health? Eur J Hum Genet. 2017;25(11):1181-1188. 4. McCoy J, Wambier CG, Vano-Galvan S, et al. Racial variations in COVID19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020;19(7): 1542-1543. 5. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. 6. Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging. 2020;12(11):1008710098. Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy Cellular transmembrane-serine-protease-2 (TMPRSS2), first cloned in 1997, has been intermittently the subject of intensive medical research, starting with the discovery of its role in recurrent TMPRSS2/ETS fusions and prostate cancer pathogenesis. TMPRSS2 protein was subsequently shown to proteolytically activate human respiratory tract viruses including influenza A, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Following the emergence of SARS-CoV-2 underlying the current coronavirus disease 2019 (COVID-19) pandemic, eyes naturally turned to the androgen-regulated TMPRSS2 gene for SARS-CoV-2 lung tropism, mortality rates, and gender bias. A study by Montopoli et al. in the Annals of Oncology reported findings congruent with the prevailing notion that high SARS-CoV-2 infection rates and disease severity in men may be the result of high androgen-driven TMPRSS2 expression in the lungs. The authors posit that since TMPRSS2 is under positive transcriptional control by the androgen receptor (AR), reduction of TMPRSS2 expression following androgen deprivation therapy (ADT) in prostate cancer patients would be expected to correlate with reduced SARS-CoV-2 incidence, and in case of Volume 31 - Issue 11 - 2020 infection, with lesser disease severity.1 While fewer prostate cancer patients undergoing ADT contracted the virus, androgen suppression did not lessen disease severity (Table 1). Several findings indicate that TMPRSS2 is unlikely to play a major role in SARS-CoV-2 lung pathology in men (and women): first, modulation of SARS-CoV-2 by TMPRSS2 has so far been observed only in TMPRSS2 protein overexpression experiments and no patient data to this effect are available. Moreover, while high TMPRSS2 mRNA levels have been documented in the human lung,2 AR and TMPRSS2 proteins do not appear to be highly expressed in the lungs.2,3 This indicates that androgens do not..
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