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Review
. 2022 Apr;40(2):243-256.
doi: 10.5534/wjmh.210175. Epub 2022 Jan 2.

Impact of Testosterone on Alzheimer's Disease

Vittorio Emanuele Bianchi  1
Affiliations
Review

Impact of Testosterone on Alzheimer's Disease

Vittorio Emanuele Bianchi. World J Mens Health. 2022 Apr.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease responsible for almost half of all dementia cases in the world and progressively increasing. The etiopathology includes heritability, genetic factors, aging, nutrition, but sex hormones play a relevant role. Animal models demonstrated that testosterone (T) exerted a neuroprotective effect reducing the production of amyloid-beta (Aβ), improving synaptic signaling, and counteracting neuronal death. This study aims to evaluate the impact of T deprivation and T administration in humans on the onset of dementia and AD. A search was conducted on MEDLINE and Scopus for the "androgen deprivation therapy" and "testosterone therapy" with "dementia" and "Alzheimer's." Studies lasting twenty years with low risk of bias, randomized clinical trial, and case-controlled studies were considered. Twelve articles on the effect of androgen deprivation therapy (ADT) and AD and seventeen on T therapy and AD were retrieved. Men with prostate cancer under ADT showed a higher incidence of dementia and AD. The effect of T administration in hypogonadal men with AD and cognitive impairment has evidenced some positive results. The majority of studies showed the T administration improved memory and cognition in AD while others did not find any benefit. Although some biases in the studies are evident, T therapy for AD patients may represent an essential clinical therapy to reduce dementia incidence and AD progression. However, more specific case-controlled trials on the effect of androgens therapy in men and women to reducing the onset of AD are necessary.

Keywords: Alzheimer disease; Amyloid beta-peptides; Dementia; Estradiol; Neuroprotection; Testosterone.

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1. Testosterone, the effect of α-reductase, is reduced to DHT, the strongest non-aromatizable androgen. DHT is then in Androstenediol from which metabolites 3α- and 3β-diol have a weak effect on AR while are more active on Erα and Erβ. 3α-diol activates GABA-receptors which regulate anxiety, depression and seizure. Testosterone is also aromatized in 17β-estradiol which, activating Erα and β, stimulates mitochondrial function, neurotransmission, and anti-inflammatory effect with consequent improved cognition. DHT and DHEAS activate the NMDA receptors which regulate memory, learning impairment, and psychosis. DHT: dihydrotestosterone, NMDA: N-methyl-d-aspartate, AR: androgen receptor.
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