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1.
ESMO Open ; 7(2): 100448, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763725

ABSTRACT

BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cognitive decline, but results are conflicting. This study describes changes in cognitive performance in patients with prostate cancer, according to ADT, during the first year after prostate cancer diagnosis. PATIENTS AND METHODS: Patients with prostate cancer treated at the Portuguese Institute of Oncology of Porto (n = 366) were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after 1 year. All baseline evaluations were performed before the coronavirus disease 2019 (COVID-19) pandemic and 69.7% of the 1-year assessments were completed after the first lockdown. Cognitive decline was defined as the decrease in MoCA from baseline to the 1-year evaluation below 1.5 standard deviations of the distribution of changes in the whole cohort. Participants scoring below age- and education-specific normative reference values in the MoCA were considered to have cognitive impairment. Age- and education-adjusted odds ratios (aORs) were computed for the association between ADT and cognitive outcomes. RESULTS: Mean MoCA scores increased from baseline to the 1-year evaluation (22.3 versus 22.8, P < 0.001). Cognitive decline was more frequent in the ADT group, and even more after the onset of the COVID-19 pandemic (aOR 6.81 versus 1.93, P for interaction = 0.233). The 1-year cumulative incidence of cognitive impairment was 6.9% (9.1% before and 3.7% after the pandemic onset), which was higher among patients receiving ADT, but only after the pandemic (aOR 5.53 versus 0.49, P for interaction = 0.044). CONCLUSIONS: ADT was associated with worse cognitive performance of patients with prostate cancer, mostly among those evaluated after the first COVID-19 lockdown.


Subject(s)
COVID-19 , Cognitive Dysfunction , Prostatic Neoplasms , Androgen Antagonists/adverse effects , Androgens , Cognitive Dysfunction/complications , Cognitive Dysfunction/etiology , Communicable Disease Control , Humans , Male , Neon , Pandemics , Prospective Studies , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
2.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1686174

ABSTRACT

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
3.
JAMA Netw Open ; 4(11): e2134330, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1513769

ABSTRACT

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.


Subject(s)
Androgen Antagonists/adverse effects , COVID-19/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/mortality , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , Cohort Studies , Humans , Male , Middle Aged , Prostatic Neoplasms/epidemiology , Risk Factors , Tennessee/epidemiology
4.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1484899

ABSTRACT

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
5.
Urol J ; 18(6): 577-584, 2021 Jul 24.
Article in English | MEDLINE | ID: covidwho-1323503

ABSTRACT

PURPOSE: Transmembrane serine protease 2 (TMPRSS2) facilitates SARS-CoV-2 cellular entry. Androgens regulate this protein and may increase the risk of COVID-19. Therefore, androgen deprivation therapy (ADT) may protect patients with prostate cancer from SARS-CoV-2 infection or decrease the severity of the disease. Therefore, we conducted a meta-analysis to study the effect of androgen deprivation therapy (ADT) on COVID-19 in patients with prostate cancer. METHODS: We systematically searched PubMed, Embase, Scopus, and Cochrane databases. All records underwent a two-step screening process to identify the eligible studies. The registered PROSPERO number of this study was CRD42021228398. We evaluated the effect of ADT on the risk of infection, hospitalization, ICU admission, and mortality. RESULTS: Six studies met inclusion criteria and were evaluated in this study. We performed meta-analysis on four eligible studies. The overall incidence of COVID-19 was 2.65% among patients with prostate cancer receiving ADT. COVID-19 mortality rate was about 22.7% in ADT (+) patients. ADT did not decrease the risk of any of the major outcomes; infection risk (OR= 0.63, 95% CI= 0.27- 1.48, P = 0.29), hospitalization rate (OR= 0.51, 95% CI= 0.10- 2.53, P = 0.41), ICU admission (OR= 1.11, 95% CI= 0.43- 2.90, P = 0.82), and mortality risk (OR= 1.21, 95% CI= 0.34- 4.32, P = 0.77). CONCLUSION: We did not observe a protective effect on the risk of infection, hospitalization, ICU admission, and mortality in patients receiving ADT; therefore, it should not be considered as a prophylactic or treatment for COVID-19. On the other hand, ADT did not increase the mortality and morbidity of COVID-19 and should be considered a safe treatment for patients with prostate cancer during the pandemic. Further studies are necessary to confirm our findings.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists/adverse effects , Androgens , Humans , Male , Prostatic Neoplasms/drug therapy , SARS-CoV-2
8.
Prog Urol ; 31(5): 243-244, 2021 04.
Article in French | MEDLINE | ID: covidwho-1038161
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