The risk of dementia with the use of 5 alpha reductase inhibitors

Welk, Blayne; McArthur, Eric; Ordon, Michael; Morrow, Sarah A.; Hayward, Jade; Dixon, Stephanie N.

doi:10.1016/j.jns.2017.05.064

Cited by 18 publications

(14 citation statements)

References 8 publications

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“…The CNS is an important target for sexual steroids such as androgens (5). Testosterone (T) is the main circulating androgen in men, and in addition to sexual functions, this hormone and its main metabolite, dihydrotestosterone (DHT), regulate diverse functions in the brain such as neuronal differentiation and brain masculinization (6), emotional states, impulsive and aggressive behavior, learning and memory (7, 8). Rapid modulation of dendritic spines induced by hippocampal T and DHT are essential in synaptic plasticity (9).…”

Section: Introductionmentioning

confidence: 99%

Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation

et al. 2019

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Glioblastomas (GBM) are the most frequent and aggressive human brain tumors due to their high capacity to migrate and invade normal brain tissue. Epidemiological data report that GBM occur in a greater proportion in men than in women (3:2), suggesting the participation of sex hormones in the development of these tumors. It has been reported an increase in testosterone (T) levels in patients with GBM. In addition, androgen receptor (AR) is overexpressed in human GBM, and genetic silencing of AR, and its pharmacological inhibition, induce GBM cell death in vivo and in vitro. However, the role of T in proliferation, migration and invasion in human GBM cell lines has not been evaluated. We observed that T increased the number of U87, U251, and D54 cells derived from human GBM due to an increase in cell proliferation. This induction was blocked with flutamide, an antagonist of AR. T also induced migration and invasion of GBM cells that flutamide partially blocked. These data suggest that T through AR contributes to the progression of GBM by promoting proliferation, migration, and invasion.

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Section: Introductionmentioning

confidence: 99%

Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation

et al. 2019

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“…They can reduce the level of DHT. The risk for dementia in patients on 5a reductase inhibitors is 2.18 and 1.52 times that of patients in the first and second years, respectively (24). This suggests that 5a reductase inhibitors may increase the risk of dementia by reducing the level of DHT.…”

Section: More Clinical Proof For Androgen Reduction and Cognitive Impmentioning

confidence: 99%

“…It has been shown that the decrease in TT and FT levels in plasma, which is independent of the relevant clinical and biochemical factors, is associated with an increased risk for dementia in older men (22), and the risk ratios of TT and FT for dementia were 1.14 and 1.18, respectively (23). Additionally, despite a lack of research on endogenous DHT, which can be converted from testosterone, and cognitive dysfunction, 5a reductase inhibitor-induced DHT deficiency has been shown to increase the risk of dementia in elderly men (24), suggesting that testosterone deficiency may lead to a lack of DHT, which is closely related to cognitive dysfunction. DHEA and its sulfated form (DHEA-S) are important neurosteroids that regulate brain development and function.…”

Section: Relationship Between Decreased Androgens and Impaired Cognitmentioning

confidence: 99%

An Updated Review: Androgens and Cognitive Impairment in Older Men

Cai

Liu

2020

Front. Endocrinol.

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“…In another study, the incidence of dementia was significantly increased in patients taking 5-ARIs. However, it has been reported that 5-ARIs and dementia are not causally linked because prolonged use reduced the risk of dementia [39].…”

Section: Injmentioning

confidence: 99%

Cognitive Function and Urologic Medications for Lower Urinary Tract Symptoms

2020

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Special considerations should be made when selecting medications for the treatment of lower urinary tract symptoms (LUTS) in older patients especially those over 65 years old. This review summarizes the relationship between current treatments for LUTS and cognitive impairment. Although the recently reported association between dementia and tamsulosin is debatable, the effects of α-blockers and pharmacokinetics are not reported in this context. Five-alpha reductase inhibitors appear to affect mood. However, the association between the development of dementia and cognitive impairment is unlikely. Anticholinergic agents, other than trospium, fesoterodine, and imdafenacin have a relatively high distribution in the central nervous system. In particular, oxybutynin is reported to cause cognitive impairment. Several animal studies on the blood-brain barrier permeability of oxybutynin support this. Therefore, care must be taken when they are used in older patients (65 years and older). Beta-3 agonists are an alternative to, or may be used in combination with, anticholinergic drugs for patients with an overactive bladder (OAB). Several phase 2 and 3 clinical studies report high tolerability and efficacy, making them relatively safe for OAB treatment. However, there is a possibility that cognitive function may be affected; thus, long-term study data are required. We have reviewed studies investigating the correlation of urologic medications with cognitive dysfunction and have provided an overview of drug selection, as well as other considerations in older patients (65 years and older) with LUTS. This narrative review has focused primarily on articles indexed in PubMed, Google Scholar, Scopus, and Embase databases. No formal search strategy was used, and no meta-analysis of data was performed.

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The risk of dementia with the use of 5 alpha reductase inhibitors

Cited by 18 publications

References 8 publications

Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation

Testosterone Promotes Glioblastoma Cell Proliferation, Migration, and Invasion Through Androgen Receptor Activation

An Updated Review: Androgens and Cognitive Impairment in Older Men

Cognitive Function and Urologic Medications for Lower Urinary Tract Symptoms

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