- Research Article
- Open Access
Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis
Infectious Agents and Cancer volume 16, Article number: 66 (2021)
Previous studies hypothesized that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19.
We performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation in both models. In the first model we performed a pair-matched propensity score model between those under active and non-active use of ADT. To the second model we initially performed a multivariate backward elimination process to select variables to a final inverse-weight adjusted with double robust estimation model.
We analyzed 199 PC patients with COVID-19 that received ADT. In total, 52.3% (95/199) of our patients were less than 75 years old, 78.4% (156/199) were on active ADT, and most were using a GnRH analog (80.1%; 125/156). Most of patients were in palliative treatment (89.9%; 179/199). Also, 63.3% of our cohort died from COVID-19. Forty-eight patients under active ADT were pair matched against 48 controls (non-active ADT). All patients (199) were analyzed in the double robust model. ADT active use were not protective factor in both inverse-weight based propensity score (OR 0.70, 95% CI 0.38–1.31, P = 0.263), and pair-matched propensity score (OR 0.67, 95% CI 0.27–1.63, P = 0.374) models. We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT, with important reductions in the differences after the adjustments.
The active use of ADT was not associated with a reduced risk of death in patients with COVID-19.
The pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus has been a challenge to health systems worldwide . World Health Organization already recognized more than 5 million deaths . To date, limited drugs have proved survival benefits in clinical trials for coronavirus disease 2019 (COVID-19) . Recent trials demonstrated that COVID-19 vaccines offer great hope for the pandemic control [4,5,6], although the equitable distribution of vaccines and long term effects still`s a major concern . Strategies prioritizing multiple approaches are critical in the war against the COVID-19 pandemic and recent evidence demonstrate that they are associated with better clinical outcomes .
From the early studies of COVID-19, there has been a clear susceptibility of the male sex to increased severity and mortality . Recent reports have suggested that sex hormones play an important role in this finding . For instance, conditions associated with hyperandrogenic states, such as androgenic alopecia, were associated with severe presentations of COVID-19 [11, 12]. Mechanistically, in vitro studies demonstrated that androgen blockade could reduce the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors, resulting in reduced infectivity by the SARS-CoV2 virus [13, 14]. Currently, several trials are exploring androgen blockade as an alternative for the treatment and prevention of COVID-19 .
Prostate cancer (PC) represents a singular situation in COVID-19. TMPRSS2, a critical pathway to SARS-CoV2 infectivity, is also one of the most frequently mutated genes in PC. In theory, some investigators have pointed out that this could lead to an increased susceptibility to severe COVID-19 . At the same time, PC patients are submitted to long periods of androgen deprivation therapy (ADT) , which is considered safe and its use is adequate during pandemic, furthermore it could lead to reduced infectivity and severity of COVID-19 [18,19,20]. This hypothesis was initially tested in Italian populations, where PC patients in ADT presented lower infection rates compared to other cancer populations , although other studies reported different results . Herein, we investigated the influence of ADT in prostate cancer patients with COVID-19 on survival outcomes.
Materials and methods
To investigate the influence of ADT in PC patients with COVID-19, we performed a retrospective cohort study linking COVID-19 databases with outpatient treatment databases from the Brazilian Unified Health System. In Brazil, all cases of suspected flu-like syndrome requiring hospitalization should be notified to SIVEP (Flu Epidemiologic Surveillance Information System) according to federal law. Since the start of the pandemic, the Brazilian Ministry of Health has adopted the SIVEP to account for COVID-19 information. We chose to analyze only cases with a reported positive SARS-COV2 PCR test. Intending to improve data quality, we selected only patients with COVID-19 reported by oncologic or academic hospitals. We also excluded patients with outpatient treatment, puerperal and pregnant women, patients less than 18 years old, with missing information on sex and age, and those without defined outcomes (in course hospitalization). Hospital discharge and death were defined as possible outcomes.
The variables age, presence of comorbidities (heart disease, asthma, chronic lung disease, nephropathy, and neurologic disease), Brazilian region of residence (Southeast vs. non-Southeast), and clinical outcome were retrieved from SIVEP. Cancer information was not mandatory information in SIVEP; thus, we found this information through an active search of comorbidities reported in free space in the SIVEP form. We excluded patients without a reported X-ray or radiologic information, assuming that all patients should have performed at least one radiological assessment during the hospitalization. Afterwards, we defined missing comorbidity information as an absence.
To obtain oncological information about the COVID-19 cases, we performed a linkage between SIVEP, SIA (Outpatient Information System), and SIH (Hospitalization Information System) databases. In Brazil, all outpatient treatments performed in the Unified Health System are registered in SIA. This system was initially created for reimbursement, but also contains information about clinical stage, primary site, line of treatment, and the scheme of treatment performed. SIH is similar to SIA, but includes information about in-hospital treatments, and also accounts for information in the diagnosis, procedures performed during hospitalization, outcomes, and some epidemiological information. As SIVEP is a primary dataset of hospitalized patients, those patients treated in Brazilian Unified Health System are in SIH as well. We performed the first linkage between SIVEP and SIH to improve the overall pool of variables to matching (adding zip postal code, and orchiectomies performed). The second linkage was performed between SIVEP/SIH and SIA. We used the second linkage to extract the oncological variables and ADT types. The linkages were deterministic and involved the variables birth date, sex, available dates (hospitalization, discharge, and admission to intensive care units), institution of code, city of residence, and zip code. After every phase of the linkage, the investigator assessed false matches confronting the available information (i.e.: primary site described in SIVEP against described in SIA). The SIA and SIH were limited to treatments performed between January 2018 and the last available dataset (ends of 2020). Finally, we select patients that have performed ADT to PC treatment. This methodology was previously described in another work by our group .
The SIVEP variables were considered positive if reported, otherwise, they were considered negative. Age was categorized as above or below 75 years, based on the overall median of the selected cohort. We defined those patients that used invasive mechanical ventilation as a critical presentation. Patients were also grouped according to the use or not of GnRH analogs, the line of treatment (palliative and non-palliative), and active or inactive use of ADT based on the past 2 months. Orchiectomy was considered an active treatment.
In the statistical analysis, we first compared the distribution of variables between survival and non-survival and then assessed them using an Exact Fisher test. Then, we performed a multivariate logistic regression model, with backward elimination, selecting variables with a minimum significance of 0.10.
To specifically test the effect of the active (versus non-active) use of ADT, we applied two propensity score models. In the first model, we used a pair matching process with a 1:1 ratio, with all variables used. We accessed this result with a conditional logistic regression between the paired groups.
In the second propensity score model, we performed a double robust estimation with the inverse weighting of the propensity score. In this model, we used all variables for the propensity score estimation, but only variables selected in the first logistic regression with backward elimination (performed before the first propensity score) were selected for outcome-based statistics. This model was assessed with a Wald test [24,25,26].
All values with a statistical significance superior to P < 0.05 were accepted. The work was performed in the software SAS Institute Inc., Cary, NC, USA. The project was submitted and approved by our institutional ethics (Comitê de Ética em Pesquisa (CEP) da Universidade Estadual de Campinas) commitment and the consent form was waived.
As of 26 April 2021, there were 1,850,626 cases of flu-like reported in SIVEP, and 762,316 with a positive RT-PCR test for SARS-COV2. After exclusions, we identified that 199 patients had performed ADT for prostate cancer treatment. Figure 1 summarizes the data flow-chart. As shown in Table 1, most of our patients were younger than 75 years old (52.3%; 104/199) and were from the Southeast region of Brazil (60.8%; 121/199). Heart disease was the most commonly reported comorbidity (40.7%; 81/199), followed by diabetes (24.6%; 49/199). 78.4% (156/199) were actively using ADT at the moment of the COVID-19 infection. LHRH analog was present in most of current ADT use (80.1%; 125/156). The majority were in the palliative line of treatment (89.9%; 179/199).
Overall, 66.3% (132/199) of our cohort died. In our univariate logistic regression, no variable was associated with mortality. In the first multivariate logistic regression analysis, the active use of ADT (OR 0.63, CI 95% 0.29–1.37, P = 0.241) remained without association to survival.
In the propensity score-based pair matching, we found that active use of ADT was not associated to mortality (OR 0.67, 95% CI 0.27–1.63, P = 0.374). Figure 2 shows the cumulative incidence of deaths of prostate cancer patients with COVID-19 according to the use of ADT after pair matching. Of note, in the propensity score analysis, we observed a significant imbalance between the variables before starting the adjustments (Additional file 1: Table S1, Additional file 2: Fig. S1, Additional file 3: Fig. S2). Even with a reduction of 84.5%, our matching algorithm presented difficulty to balance some variables (i.e., Critical Presentation).
In our second propensity score model, using double robust estimation with inverse weight, we confirmed the previous findings that current ADT (OR 0.70 95% CI 0.38–1.31, P = 0.263) was not associated to survival outcomes, Fig. 3. After inverse weigh adjustment, we also found that southeast region was a protective factor (OR 0.30 95% CI 0.15–0.61, P = 0.001), Table 2. Additional file 4: Figure S3 presents the distribution of weights between the analyzed groups.
Due to the long periods of ADT, PC patients represent a powerful model with which to study sex hormone suppression in patients with COVID-19. In our dataset, we found that the active use of ADT was not associated with lower COVID-19 mortality. The seminal work of Montopoli et al.  reported that PC patients using ADT had a 4 times lower risk of COVID-19 infection than others with PC. Although the work suggests a protective role of ADT in COVID-19 infection, the authors did not evaluate the impact of ADT in survival or disease severity. The present data did not support the protective effect of ADT to an inpatient scenario, since ADT use was not associated with favorable COVID-19 prognosis.
In vitro models demonstrated that there is an intrinsic relationship between androgen receptors and the expression of ACE2 and TMPRSS2 proteins, a critical pathway to COVID-19 infection [13, 14]. Both TMPRSS2 and ACE2 are indispensable to SARS-COV2 infection [27,28,29]. Interestingly, the TMPRSS2:ERG fusion gene is a common PC driver mutation in PC [30, 31], which represents a possible bridge between the two entities . Indeed, Qiao et al. showed that androgen receptor blockade could not only reduce the expression of ACE2 and TMPRSS2 in a murine model but also reduce the in vitro infectivity rate of COVID-19 . There are several clinical trials ongoing exploring ADT and TMPRSS2 blockers (Camostat and Nafamostat) in the treatment of COVID-19 . In contrast to the preclinical findings Caffo et al.  did not observe reduced mortality associated with ADT in patients with metastatic castration-resistant PC (mCRPC). Accordingly, we did not observe that the line of treatment was not statistically associated with survival, although the subgroup of mCRPC was under-represented in our cohort.
Previous studies have demonstrated a strong association between sex hormones [33, 34], GnRH , and the immune system. Clinical models demonstrated that lymphocytes express the GnRH receptors and can interact with its feedbacks loops [36,37,38]. We cannot rule out the possibility that GnRH analogs could down-regulate hyper-inflammatory states of COVID-19. GnRH analogs already were used to treat other hyper-inflammatory conditions . In our cohort, the absolute number of patients using a GnRH analog limited our ability of analyze this variable in a stable model. Thus, we do not discard the possibility of a protective effect of GnRH analogs against COVID-19.
Of note, oncological cohorts of PC did not present survival outcomes data of COVID-19 according to the use of ADT. Lee et al. . did not report prostate cancer to be a protective factor against COVID-19, although the ADT per se was not evaluated in their analysis. On the other hand, the CCC19 group reported that the recent use of cancer hormone therapy was a protective factor , but the authors did not investigate the ADT itself. In our cohort, we noted a significant imbalance between the groups of prostate cancer patients in active ADT versus those in non-active ADT. Therefore, we recommend caution when evaluating ADT in observational studies. Even, using more robust propensity score-based models it was difficult to adjust all the imbalances between the groups. Importantly, the OR, independent of the statistical method used, remained not statistically significant. Consistent with our data, a recent metanalysis showed that patients receiving ADT did not have a reduced COVID-19 infection risk as well as COVID-19 hospitalization risk, ICU admission, and Mortality risk .
In general, the Brazilian SIVEP cohort presents a higher mortality [43, 44]. We believe that this finding represents the overall severity of Brazilian COVID-19 patient’s hospitalizations, as discussed elsewhere . Allied to this, PC is a condition of elderly patients, with an established high risk of COVID-19 infection due to the high prevalence of comorbidities in this group of patients . Although we believe that our statistical methods, using propensity score approaches, could improve our quality of analysis, important limitations of our work are the retrospective design and the inherent risk of bias in the data generation process. We also used a deterministic linkage process based on cancer treatment; thus, we do not discard the possibility of selection bias that prioritizes selection of those in active treatment.
Our study indicates that PC patients in active ADT does not have lower mortality from COVID-19.
Availability of data and materials
The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.
Woolf SH, Chapman DA, Lee JH. COVID-19 as the leading cause of death in the United States. JAMA. 2020;325:123–4.
World Health Organization COVID-19 [Internet]. [cited 2021 November 05]. Available from: https://covid19.who.int
Angriman F, Ferreyro BL, Burry L, Fan E, Ferguson ND, Husain S, et al. Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context. Lancet Respir Med. 2021. https://doi.org/10.1016/S2213-2600(21)00139-9.
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020;397:99–111.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15. https://doi.org/10.1056/NEJMoa2034577.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2035389.
Burki T. Equitable distribution of COVID-19 vaccines. Lancet Infect Dis. 2021;21(1):33–4.
Khalifa SAM, Mohamed BS, Elashal MH, Du M, Guo Z, Zhao C, et al. Comprehensive overview on multiple strategies fighting covid-19. Int J Environ Res Public Health. 2020;17(16):1–13.
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20. https://doi.org/10.1056/NEJMoa2002032.
Seeland U, Coluzzi F, Simmaco M, Mura C, Bourne PE, Heiland M, et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med. 2020;18(1):1–9.
Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, et al. A preliminary observation: male pattern hair loss among hospitalized COVID-19 patients in Spain—A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol [Internet]. 2020;19(7):1545–7. https://doi.org/10.1111/jocd.13443.
Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83(1):308–9.
Qiao Y, Wang X, Mannan R, Pitchiaya S, Zhang Y, Wotring JW, et al. Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Proc Natl Acad Sci. 2021;118(1): e2021450118. https://doi.org/10.1073/pnas.2021450118.
Samuel RM, Majd H, Richter MN, Ghazizadeh Z, Zekavat SM, Navickas A, et al. Androgen signaling regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men. Cell Stem Cell. 2020;27(6):876-889.e12. https://doi.org/10.1016/j.stem.2020.11.009.
Cattrini C, Bersanelli M, Latocca MM, Conte B, Vallome G, Boccardo F. Sex hormones and hormone therapy during COVID-19 pandemic: implications for patients with cancer. Cancers (Basel). 2020;12(8):2325.
Dai Y-J, Zhang W-N, Wang W-D, He S-Y, Liang C-C, Wang D-W. Comprehensive analysis of two potential novel SARS-CoV-2 entries, TMPRSS2 and IFITM3, in healthy individuals and cancer patients. Int J Biol Sci. 2020;16(15):3028–36.
Litwin MS, Tan H-J. The diagnosis and treatment of prostate cancer. JAMA. 2017;317(24):2532.
Pradhan A, Olsson PE. Sex differences in severity and mortality from COVID-19: are males more vulnerable? Biol Sex Differ. 2020;11(1):1–11.
Bahmad HF, Abou-Kheir W. Crosstalk between COVID-19 and prostate cancer. Prostate Cancer Prostatic Dis. 2020;23(4):561–3. https://doi.org/10.1038/s41391-020-0262-y.
Chakravarty D, Nair SS, Hammouda N, Ratnani P, Gharib Y, Wagaskar V, et al. Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer. Commun Biol. 2020;3(1):1–12. https://doi.org/10.1038/s42003-020-1088-9.
Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020;31(8):1040–5.
Klein EA, Li J, Milinovich A, Schold JD, Sharifi N, Kattan MW, et al. Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2. J Urol. 2020. https://doi.org/10.1097/JU.0000000000001338.
Duarte MBO, Leal F, Argenton JLP, Carvalheira JBC. Outcomes of COVID-19 patients under cytotoxic cancer chemotherapy in Brazil. Cancers (Basel). 2020;12(12):3490.
Tran L, Yiannoutsos C, Wools-Kaloustian K, Siika A, Van Der Laan M, Petersen M. Double robust efficient estimators of longitudinal treatment effects: comparative performance in simulations and a case study. Int J Biostat. 2019. https://doi.org/10.1515/ijb-2017-0054.
Nguyen TL, Collins GS, Spence J, Devereaux PJ, Daurès JP, Landais P, et al. Comparison of the ability of double-robust estimators to correct bias in propensity score matching analysis. A Monte Carlo simulation study. Pharmacoepidemiol Drug Saf. 2017;26(12):1513–9.
Luque-Fernandez MA, Belot A, Valeri L, Cerulli G, Maringe C, Rachet B. Data-adaptive estimation for double-robust methods in population-based cancer epidemiology: risk differences for lung cancer mortality by emergency presentation. Am J Epidemiol. 2018;187(4):871–8.
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 (Albany NY). 2020;12(11):10087–98.
Hou Y, Zhao J, Martin W, Kallianpur A, Chung MK, Jehi L, et al. New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Med. 2020;18(1):216. https://doi.org/10.1186/s12916-020-01673-z.
Zipeto D, da Palmeira JF, Argañaraz GA, Argañaraz ER. ACE2/ADAM17/TMPRSS2 interplay may be the main risk factor for COVID-19. Front Immunol. 2020;11:1–10.
Wang Z, Wang Y, Zhang J, Hu Q, Zhi F, Zhang S, et al. Significance of the TMPRSS2: ERG gene fusion in prostate cancer. Mol Med Rep. 2017;16(4):5450–8.
Ko CJ, Huang CC, Lin HY, Juan CP, Lan SW, Shyu HY, et al. Androgen-induced TMPRSS2 activates matriptase and promotes extracellular matrix degradation, prostate cancer cell invasion, tumor growth, and metastasis. Cancer Res. 2015;75(14):2949–60.
Caffo O, Gasparro D, Di Lorenzo G, Volta AD, Guglielmini P, Zucali P, et al. Incidence and outcomes of severe acute respiratory syndrome coronavirus 2 infection in patients with metastatic castration-resistant prostate cancer. Eur J Cancer. 2020;140:140–6. https://doi.org/10.1016/j.ejca.2020.09.018.
Roved J, Westerdahl H, Hasselquist D. Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav. 2017;88:95–105. https://doi.org/10.1016/j.yhbeh.2016.11.017.
Özdemir BC, Dotto GP. Sex hormones and anticancer immunity. Clin Cancer Res. 2019;25(15):4603–10.
Chen H-F, Jeung E-B, Stephenson M, Leung PCK. Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor γ-chain messenger ribonucleic acids that are regulated by GnRH in vitro 1. J Clin Endocrinol Metab. 1999;84(2):743–50. https://doi.org/10.1210/jcem.84.2.5440.
Chen H, Jeung E, Stephenson M, Leung PCK. Ribonucleic acids that are regulated by GnRH in vitro. Endocrinol Metab. 1999;84(2):743–50.
Min JY, Park MH, Lee JK, Kim HJ, Park YK. Gonadotropin-releasing hormone modulates immune system function via the nuclear factor-κB pathway in murine Raw264.7 macrophages. NeuroImmunoModulation. 2009;16(3):177–84.
Sung N, Salazar García MD, Dambaeva S, Beaman KD, Gilman-Sachs A, Kwak-Kim J. Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes. Am J Reprod Immunol. 2016;76(1):50–8.
Kåss A, Hollan I, Fagerland MW, Gulseth HC, Torjesen PA, Førre ØT. Rapid anti-inflammatory effects of gonadotropin-releasing hormone antagonism in rheumatoid arthritis patients with high gonadotropin levels in the AGRA trial. PLoS ONE. 2015;10(10):e0139439. https://doi.org/10.1371/journal.pone.0139439.
Lee LYW, Cazier J-B, Starkey T, Briggs SEW, Arnold R, Bisht V, et al. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study. Lancet Oncol. 2020;2045(20):1–8.
Wise-Draper TM, Desai A, Elkrief A, Rini BI, Flora DB, Bowles DW, et al. LBA71 systemic cancer treatment-related outcomes in patients with SARS-CoV-2 infection: A CCC19 registry analysis. Ann Oncol. 2020;31:S1201–2.
Karimi A, Nowroozi A, Alilou S, Amini E. Effects of androgen deprivation therapy on COVID-19 in patients with prostate cancer: a systematic review and meta-analysis. Urol J. 2021. https://doi.org/10.22037/uj.v18i.6691.
Baqui P, Bica I, Marra V, Ercole A, van der Schaar M. Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study. Lancet Glob Heal. 2020;8(8):e1018–26. https://doi.org/10.1016/S2214-109X(20)30285-0.
Ranzani OT, Bastos LSL, Gelli JGM, Marchesi JF, Baião F, Hamacher S, et al. Characterisation of the first 250000 hospital admissions for COVID-19 in Brazil: a retrospective analysis of nationwide data. Lancet Respir Med. 2021;2600(20):1–12.
Salciccia S, Del Giudice F, Eisenberg ML, Mastroianni CM, De Berardinis E, Ricciuti GP, et al. Androgen-deprivation therapy and SARS-Cov-2 infection: the potential double-face role of testosterone. Ther Adv Endocrinol Metab. 2020;11:204201882096901. https://doi.org/10.1177/2042018820969019.
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. Supplemental Table 1. Baseline variables of active and non-active androgen deprivation therapy groups and standardized mean differences after propensity score-based pair matching.
. Figure S1. Standardized mean difference. The mean difference represents the difference between propensity score inside the variable before and after pair matching.
. Figure S2. Cumulative distribution of logit propensity score. The graphs summarize the cumulative distribution of logit propensity score, as well as the difference between active and non-active groups before and after matching.
. Figure S3. Density of propensity score distribution. The figure summarizes the distribution of propensity score applied in the double robust estimation model according to the use of androgen deprivation therapy (ADT).
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Duarte, M.B.O., Leal, F., Argenton, J.L.P. et al. Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis. Infect Agents Cancer 16, 66 (2021). https://doi.org/10.1186/s13027-021-00406-y
- Androgen antagonists
- Androgen receptor antagonists
- Antineoplastic agents