Impact of Testosterone on Alzheimer’s Disease

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.

The Role of Testosterone in the Elderly: What Do We Know?

“…Conversely, in a smaller study involving 296 older men by Schneider et al, testosterone has been shown to increase the risk of panic and phobic anxiety in patients with a genetically determined long CAG repeat polymorphism of the androgen receptor [ 137 ]. Regarding the effects of androgens in the elderly, it has been reported that low testosterone serum levels are independently associated with incident dementia and Alzheimer’s disease, confirmed by an increased incidence of those conditions in ADT patients [ 147 , 148 ]. Conversely, further evidence is required to enlighten the relation between testosterone and Parkinson’s disease, considering the neuroprotective effects of 5-alfa reductase inhibitors in animal models [ 149 ].…”

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“…Pathologies or symptoms related to AD usually occur before and/or concomitantly with the onset of symptoms, such as memory loss. Multiple factors are associated with AD, including hypertension, diabetes, hypercholesterolemia, obesity, and depression [ 1 ], as well as sex hormones [ 11 ] and hyperhomocysteinemia [ 12 ], all of them linked in some way to Cu and S disturbances.…”

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“…For instance, androgen deprivation therapy (ADT) is known to increase the risk of bone fracture [ 26 ], diabetes [ 27 , 28 ], and cardiovascular disease [ 29 , 30 ], although there are some ways to mitigate these concerns [ 31 ]. Since testosterone has a neuro-protective effect including the improvement of energy metabolism and reduction of oxidative stress in neurons [ 32 ], ADT may deteriorate cognitive function [ 33 ] and may increase the risk of dementia as well [ 34 ]. Low serum testosterone level also correlates positively with lean body mass, which can be calculated by subtracting the weight of all the fat from the total weight of the body [ 35 ].…”