Reversible Parkinson's Dementia Associated with Withdrawal of Androgen‐Deprivation Therapy for Prostate Cancer

Abbate, Carlo; Caputo, Ludovica; Damanti, Sarah; Zappa, Carlo; Nicolini, Paola; Rossi, Paolo; Arosio, Beatrice; Mari, Daniela; Riz, Milena A. De; Dormia, G; Trimarchi, Pietro Davide; Morello, Elisabetta; Monfardini, S.

doi:10.1111/jgs.14417

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…The impact of androgen deficits in increasing PD risk onset or exacerbating the incidence and/or severity of nonmotor and extrapyramidal symptoms was also observed in men affected by prostate cancer and subjected to androgen deprivation therapy [ 176 , 177 ]. In these patients, the withdrawal of anticancer therapy reversed the cognitive and motor deficits [ 178 ]. However, the androgen protective role in neurodegenerative conditions is still a matter of debate as other studies did not detect a clear association between androgen deprivation therapy and PD [ 179 ].…”

Section: Androgens and Neurodegenerative Diseasesmentioning

confidence: 99%

Androgen Therapy in Neurodegenerative Diseases

Bianchi¹,

Rizzi

Bresciani

et al. 2020

Journal of the Endocrine Society

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Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are characterized by the loss of neurons, as well as neuronal function in multiple regions of the central- and peripheral- nervous system. Several studies in animal models have shown that androgens have neuroprotective effects in the brain and stimulate axonal regeneration. The presence of neuronal androgen receptors (AR) in the peripheral and central nervous system (CNS) suggests that androgen therapy might be useful in the treatment of neurodegenerative diseases. To illustrate, androgen therapy reduced inflammation, amyloid-β (Aβ) deposition, and cognitive impairment in AD patients. As well, improvements in re-myelination in multiple sclerosis have been reported; by comparison, only variable results are observed in androgen treatment of PD. In ALS, androgen administration stimulated motoneuron recovery from progressive damage and regenerated both axons and dendrites. Only a few clinical studies are available in human subjects despite the safety and low cost of androgen therapy. Clinical evaluations of the effects of androgen therapy of these devastating diseases using large populations of patients are strongly needed.

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Section: Androgens and Neurodegenerative Diseasesmentioning

confidence: 99%

Androgen Therapy in Neurodegenerative Diseases

Bianchi¹,

Rizzi

Bresciani

et al. 2020

Journal of the Endocrine Society

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“…Cerebellar dysfunction may lead to various impairments, including depression, schizophrenia, autism spectrum disorder, dysmetria, Parkinson's disease, and Alzheimer's disease (Hampson & Blatt, 2015; Hoxha et al., 2018; Parker et al., 2014; Schmahmann, 2004; Solstrand Dahlberg et al., 2020). On the other hand, the depletion of both serum and brain androgen levels or antiandrogens therapy, especially in the male, may be associated with a higher risk of cognitive decline, senescence, Parkinson's disease, and Alzheimer's disease (Abbate et al., 2016; Drummond et al., 2009; Jayadevappa et al., 2019; Mitchell et al., 2006; Nead et al., 2016; Okun et al., 2004; Verdile et al., 2015). Perhaps, despite the intricate androgen interacting with the brain, the action of androgens in modulating cerebellar function could have a central role in their comprehensive regulation of behavior and could be essential for psychomotor balance.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Panichi

Dieni

Sullivan

et al. 2022

J of Comparative Neurology

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Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

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“…In addition to the adverse effects of ADT mentioned above, other psychological effects include, difficulties in multiple sexual domains, emotional lability, cognitive disturbances, reversible Parkinson's dementia, anxiety, and an increase in the risk for depression of up to 41%; these symptoms are significantly associated with alcohol consumption and smoking (92)(93)(94)(95). Similarly, couples can also suffer emotional consequences related to the effects of ADT, with exercise being a useful intervention for the dyad (96).…”

Section: Mental Health and Pcamentioning

confidence: 99%

Impact of lifestyle in prostate cancer patients. What should we do?

et al. 2022

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Objective: This review aimed to analyze interventions raised within primary and tertiary prevention concerning the disease's incidence, progression, and recurrence of Prostate Cancer (PCa). Priority was given to the multidisciplinary approach of PCa patients with an emphasis on modifiable risk factors. Materials and Methods: We conducted a comprehensive literature review in the following databases: Embase, Central, and Medline. We included the most recent evidence assessing cohort studies, case-control studies, clinical trials, and systematic reviews published in the last five years. We only included studies in adults and in vitro or cell culture studies. The review was limited to English and Spanish articles. Results: Preventive interventions at all levels are the cornerstone of adherence to disease treatment and progression avoidance. The relationship in terms of healthy lifestyles is related to greater survival. The risk of developing cancer is associated to different eating habits, determined by geographic variations, possibly related to different genetic susceptibilities. Discussion: PCa is the second most common cancer in men, representing a leading cause of death among men in Latin America. Prevention strategies and healthy lifestyles are associated with higher survival rates in PCa patients. Also, screening for anxiety and the presence of symptoms related to mood disorders is essential in the patient's follow-up concerning their perception of the condition.

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Reversible Parkinson's Dementia Associated with Withdrawal of Androgen‐Deprivation Therapy for Prostate Cancer

Cited by 4 publications

References 11 publications

Androgen Therapy in Neurodegenerative Diseases

Androgen Therapy in Neurodegenerative Diseases

Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Impact of lifestyle in prostate cancer patients. What should we do?

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