Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy
Bennani et al.
, Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy
, Annals of Oncology, doi:10.1016/j.annonc.2020.08.2095
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.
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].
The authors have declared no conﬂicts of interest.
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.
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.
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):
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
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
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..
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC
provide treatment protocols.