Antiandrogens for COVID-19: real-time analysis of all 10 studies

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data

Welén et al., European Urology, doi:10.1016/j.eururo.2021.12.013 (Peer Reviewed)

Very small late stage RCT with 10 control patients and 29 enzalutamide patients, showing mixed results. Discharge and hospitalization time favored the control group, while viral load reduction was better with treatment on days 4&6 (day 4 ΔCt −5.6 p = 0.084), and the only death occurred in the control group. 27% of enzalutamide patients had diabetes compared to 0% of the control group.

Retrospective 7,894 COVID+ prostate cancer patients, analyzing patients on antiandrogen treatment, ADT, and ADT + abiraterone acetate or enzalutamide, showing mixed results and higher mortality for ADT + abiraterone acetate or enzalutamide.

In Vitro HBEC study showing no significant differences (p = 0.084).

The supplementary data is not currently available. NCT04475601.

risk of death, 79.6% lower, RR 0.20, p = 0.26, treatment 0 of 29 (0.0%), control 1 of 10 (10.0%), NNT 10.0, relative risk is not 0 because of continuity correction due to zero events, RCT result.

risk of mechanical ventilation, 31.0% lower, RR 0.69, p = 1.00, treatment 2 of 29 (6.9%), control 1 of 10 (10.0%), NNT 32, RCT result.

risk of no hospital discharge, 132.6% higher, RR 2.33, p = 0.03, treatment 29, control 10, RCT result.

hospitalization time, 50.0% higher, relative time 1.50, p = 0.01, treatment 29, control 10.

risk of death, 2.0% lower, RR 0.98, p = 0.94, treatment 21 of 358 (5.9%), control 167 of 4,980 (3.4%), adjusted, retrospective study, antiandrogen treatment.

risk of death, 11.0% lower, RR 0.89, p = 0.66, treatment 20 of 334 (6.0%), control 167 of 4,980 (3.4%), adjusted, retrospective study, ADT.

risk of death, 151.0% higher, RR 2.51, p < 0.001, treatment 24 of 152 (15.8%), control 167 of 4,980 (3.4%), adjusted, retrospective study, ADT and abiraterone acetate or enzalutamide.

risk of ICU admission, 28.0% higher, RR 1.28, p = 0.28, treatment 24 of 358 (6.7%), control 216 of 4,980 (4.3%), adjusted, retrospective study, antiandrogen treatment.

risk of ICU admission, 13.0% lower, RR 0.87, p = 0.62, treatment 16 of 334 (4.8%), control 216 of 4,980 (4.3%), adjusted, retrospective study, ADT.

risk of ICU admission, 21.0% lower, RR 0.79, p = 0.60, treatment 6 of 152 (3.9%), control 216 of 4,980 (4.3%), NNT 256, adjusted, retrospective study, ADT and abiraterone acetate or enzalutamide.

risk of hospitalization, 23.0% higher, RR 1.23, p = 0.09, treatment 126 of 358 (35.2%), control 1,108 of 4,980 (22.2%), adjusted, retrospective study, antiandrogen treatment.

risk of hospitalization, 24.0% higher, RR 1.24, p = 0.09, treatment 126 of 334 (37.7%), control 1,108 of 4,980 (22.2%), adjusted, retrospective study, ADT.

risk of hospitalization, 40.0% higher, RR 1.40, p = 0.06, treatment 66 of 152 (43.4%), control 1,108 of 4,980 (22.2%), adjusted, retrospective study, ADT and abiraterone acetate or enzalutamide.

Welén et al., 12/14/2021, Randomized Controlled Trial, Sweden, Europe, peer-reviewed, 27 authors, average treatment delay 9.5 days.

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

Leach et al., Nature Communications, doi:10.1038/s41467-021-24342-y (Peer Reviewed)

In Vitro and animal study showing that the antiandrogen enzalutamide reduces TMPRSS2 levels in human lung cells and in mouse lungs.

Leach et al., 7/1/2021, peer-reviewed, 10 authors.

Do Anti-androgens Have Potential as Therapeutics for COVID-19?

Mauvais-Jarvis et al., Endocrinology, doi:10.1210/endocr/bqab114 (Review) (Peer Reviewed)

Review of research related to the potential benefits of anti-androgrens for COVID-19.

Mauvais-Jarvis et al., 6/5/2021, peer-reviewed, 1 author.

Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial – Biochemical)

Cadegiani et al., Cureus, doi:10.7759/cureus.13047 (Peer Reviewed)

RCT 130 outpatients in Brazil, 54 treated with dutasteride, showing faster recovery with treatment. All patients received nitazoxanide. There were no hospitalizations, mechanical ventilation, or deaths. Some percentages for viral clearance in Table 3 do not match the group sizes, and a third-party analysis suggests possible randomization failure [1]. 34110420.2.0000.0008.

[1] steamtraen.blogspot.com/2021/10/applying-john-carlisles-table-1.html

risk of no recovery, 62.0% lower, RR 0.38, p = 0.009, treatment 7 of 44 (15.9%), control 18 of 43 (41.9%), NNT 3.9.

recovery time, 43.6% lower, relative time 0.56, p < 0.001, treatment 44, control 43, all symptoms.

recovery time, 40.2% lower, relative time 0.60, p < 0.001, treatment 44, control 43, all symptoms except loss of smell or taste.

Excluded in after exclusion results of meta analysis: potential randomization failure based on a third-party analysis.

Cadegiani et al., 2/1/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 4 authors.

5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia

McCoy et al., Journal of the European Academy of Dermatology and Venereology, doi:10.1111/jdv.17021 (Peer Reviewed)

Retrospective 48 androgenetic alopecia patients in Brazil treated with dutasteride, compared with 48 propensity score matched androgenetic alopecia patients not taking any 5ARis, showing a statistically significant reduction in the frequency of 20 of 29 COVID-19 symptoms with treatment.

McCoy et al., 11/2/2020, retrospective, Brazil, South America, peer-reviewed, 11 authors.

An open-label prospective observational study of antiandrogen and non-antiandrogen early pharmacological approaches in females with mild-to-moderate COVID-19. The Pre-AndroCoV Female Trial

Cadegiani et al., medRxiv, doi:10.1101/2020.10.05.20206870 (Preprint)

Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spiralactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.

recovery time, 76.7% lower, relative time 0.23, p = 0.006, treatment 8, control 262, excluding anosmia.

recovery time, 82.8% lower, relative time 0.17, p = 0.002, treatment 8, control 262, including anosmia.

time to viral-, 37.9% lower, relative time 0.62, p = 0.02, treatment 8, control 262.

Excluded in after exclusion results of meta analysis: significant unadjusted differences between groups.

Cadegiani et al., 10/6/2020, prospective, Brazil, South America, preprint, 4 authors.

Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men

Goren et al., Journal of the European Academy of Dermatology and Venereology, doi:10.1111/jdv.16953 (Peer Reviewed)

Prospective study of 77 men hospitalized with COVID-19, 12 taking antiandrogens (9 dutasteride, 2 ﬁnasteride, 1 spironolactone), showing lower ICU admission with treatment (statistically significant with age-matched controls only when excluding the spironolactone patient). NCT04368897.

risk of ICU admission, 81.0% lower, RR 0.19, p = 0.08, treatment 1 of 12 (8.3%), control 17 of 36 (47.2%), NNT 2.6, adjusted, age-matched controls.

risk of ICU admission, 86.0% lower, RR 0.14, p = 0.04, treatment 1 of 12 (8.3%), control 38 of 65 (58.5%), NNT 2.0, adjusted, all controls.

risk of death, 50.0% higher, RR 1.50, p = 1.00, treatment 1 of 12 (8.3%), control 2 of 36 (5.6%), age-matched controls.

risk of death, 35.4% higher, RR 1.35, p = 0.58, treatment 1 of 12 (8.3%), control 4 of 65 (6.2%), all controls.

Goren et al., 9/25/2020, prospective, Brazil, South America, peer-reviewed, 15 authors.

Impact of anti-androgen therapies on COVID-19 susceptibility: a case-control study in male population from two COVID-19 regional centers of Lombardy (Italy)

Lazzeri et al., medRxiv, doi:10.1101/2020.04.20.20068056 (Preprint)

Retrospective case-control study in Italy with 943 male COVID-19 patients, 45 on chronic 5ARI treatment (finasteride/dutasteride). There was significantly fewer COVID-19 patients >55 on 5ARI treatment compared to age-matched controls (5.57 vs. 8.14%, p=0.0083). The difference was greater for men aged >65 (7.14 vs. 12.31%, p=0.0001). There was no significant difference for ICU admission or death.

risk of death/ICU, 23.0% higher, RR 1.23, p = 0.33, multivariable, RR approximated with OR.

Lazzeri et al., 9/21/2020, retrospective, Italy, Europe, preprint, 11 authors.

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 (Peer Reviewed)

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.

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.

Bennani et al., 8/17/2020, retrospective, Italy, Europe, peer-reviewed, 2 authors.

Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign”

Wambier et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.05.079 (Peer Reviewed)

Analysis of 175 patients hospitalized with severe COVID-19, showing androgenetic alopecia (AGA) in 42% of women and 79% of men. Authors hypothesize that COVID-19 severity is androgen-mediated, and recommend study of antiandrogen treatments.

Wambier et al., 5/21/2020, peer-reviewed, 14 authors.

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)

Montopoli et al., Annals of Oncology, doi:10.1016/j.annonc.2020.04.479 (Peer Reviewed)

Retrospective 5,273 prostate cancer patients on androgen-deprivation therapy (ADT), and 37,161 not on ADT, showing lower risk of cases with treatment.

risk of severe case, 74.5% lower, RR 0.25, p = 0.01, treatment 1 of 5,273 (0.0%), control 31 of 37,161 (0.1%), NNT 1551, OR converted to RR.

risk of case, 75.3% lower, RR 0.25, p = 0.004, treatment 4 of 5,273 (0.1%), control 114 of 37,161 (0.3%), NNT 433, OR converted to RR.

Montopoli et al., 5/6/2020, retrospective, Italy, Europe, peer-reviewed, 12 authors.

Antiandrogens	(meta)	Metformin	(meta)
Aspirin	(meta)	Molnupiravir	(meta)
Bamlanivimab	(meta)	N-acetylcys..	(meta)
Bromhexine	(meta)	Nigella Sativa	(meta)
Budesonide	(meta)	Nitazoxanide	(meta)
Casirivimab/i..	(meta)	Paxlovid	(meta)
Colchicine	(meta)	Povidone-Iod..	(meta)
Conv. Plasma	(meta)	Probiotics	(meta)
Curcumin	(meta)	Proxalutamide	(meta)
Ensovibep	(meta)	Quercetin	(meta)
Favipiravir	(meta)	Remdesivir	(meta)
Fluvoxamine	(meta)	Sotrovimab	(meta)
Hydroxychlor..	(meta)	Vitamin A	(meta)
Iota-carragee..	(meta)	Vitamin C	(meta)
Ivermectin	(meta)	Vitamin D	(meta)
Melatonin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption