Cognition and depression effects of androgen receptor axis-targeted drugs in men with prostate cancer: A systematic review

Batra, Anupam; Marchioni, Michele; Hashmi, Ardeshir Z.; Lonergan, Peter E.; Morgans, Alicia K.; Nead, Kevin T.; Nguyen, Paul L.; Winquist, Eric; Chin, Joseph L.

doi:10.1016/j.jgo.2020.11.002

Cited by 18 publications

(25 citation statements)

References 66 publications

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“…Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function Three prior studies 12,13,30 have examined objective cognitive function with at least 1 agent in the mCRPC setting. 8 In a single-arm study, Gotto et al 30 reported a small change in MoCA in men taking abiraterone (mean difference, <1 point) after 12, 24, 48, and 72 weeks of treatment. A study by Khalaf et al 12 examined the proportion of men who developed an abnormal MoCA score (<26 of 30) during treatment with abiraterone or enzalutamide and found no difference (47% vs 54%, P = .40).…”

Section: Jama Network Open | Oncologymentioning

confidence: 99%

“…6 Older patients receiving oncologic therapies are at even greater risk for cognitive decline for multiple reasons, particularly comorbidity and medication effects. 2 Although numerous studies 7 have examined the cognitive adverse effects of ADT, few studies 8 have examined other treatments for advanced prostate cancer. Previous studies 8,9 have reported broad associations between chemotherapy and cognitive decline (known as chemo brain), but studies specific to docetaxel and prostate cancer could not be found.…”

Section: Introductionmentioning

confidence: 99%

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Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer

et al. 2021

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IMPORTANCE Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. OBJECTIVE To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. DESIGN, SETTING, AND PARTICIPANTS A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were

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Section: Jama Network Open | Oncologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer

et al. 2021

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“…A recent systematic review examined existing studies investigating the association of second-generation AAs with depression. 7 The authors found that no prior studies have examined the association of second-generation AAs with a clinical diagnosis of depression. Prior studies were limited to those examining the association of second-generation AAs with patient well-being questionnaires and research-based depression inventories such as the Functional Assessment Cancer Therapy–Prostate emotional well-being subscale.…”

Section: Discussionmentioning

confidence: 99%

“… 6 This increased potency may carry a greater risk of adverse effects related to blocking and suppressing testosterone. 7 …”

Section: Introductionmentioning

confidence: 99%

Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer

et al. 2021

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Key Points Question Are second-generation antiandrogens (AAs) associated with increased risk of depression among older men diagnosed with prostate cancer? Findings In this cohort study of 30 069 men aged 66 years and older, there was a statistically significant 2-fold increase in depression among patients treated with second-generation AA compared with traditional forms of hormone therapy (HT) and no HT. Meaning These findings suggest that use of second-generation AAs is associated with a clinically significant increased risk of depression when compared with traditional HT alone or no HT.

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“…Interestingly, neuronal activity also regulates aromatase activity and estrogen synthesis in the CNS of birds and rodents. 62 , 63 However, the role of androgens 64 , 65 and estrogens 66–68 in human cognition is still controversial. Nevertheless, some single-nucleotide CYP19A1 polymorphisms are associated with decreased performance in memory tests in women 69 and aromatase inhibitors used for cancer treatment have a negative impact on cognition in some patients, 70 with subtle effects on hippocampal-dependent verbal and visual memory.…”

Section: Physiological and Pathophysiological Function Of Brain Aromatasementioning

confidence: 99%

Aromatase in the Human Brain

Azcoitia

Méndez

Garcia-Segura

2021

Androgens: Clinical Research and Therapeutics

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The aromatase cytochrome P450 (P450arom) enzyme, or estrogen synthase, which is coded by the CYP19A1 gene, is widely expressed in a subpopulation of excitatory and inhibitory neurons, astrocytes, and other cell types in the human brain. Experimental studies in laboratory animals indicate a prominent role of brain aromatization of androgens to estrogens in regulating different brain functions. However, the consequences of aromatase expression in the human brain remain poorly understood. Here, we summarize the current knowledge about aromatase expression in the human brain, abundant in the thalamus, amygdala, hypothalamus, cortex, and hippocampus and discuss its role in the regulation of sensory integration, body homeostasis, social behavior, cognition, language, and integrative functions. Since brain aromatase is affected by neurodegenerative conditions and may participate in sex-specific manifestations of autism spectrum disorders, major depressive disorder, multiple sclerosis, stroke, and Alzheimer's disease, we discuss future avenues for research and potential clinical and therapeutic implications of the expression of aromatase in the human brain.

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Cognition and depression effects of androgen receptor axis-targeted drugs in men with prostate cancer: A systematic review

Cited by 18 publications

References 66 publications

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer

Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer

Aromatase in the Human Brain

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