Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

Abstract

Since its discovery, several chemical modifications in the testosterone molecule have been done by pharmaceutical industry in order to improve its pharmacological effects, resulting in the creation of anabolic steroids (AS). Despite the therapeutic benefits, AS abuse has spread among elite and recreational athletes in the search for improvements on physical appearance and physical performance. Illicit use of anabolic AS has been correlated with several adverse effects, such as cardiovascular, endocrine, reproductive, and neurobehavioral dysfunctions. Recently, declines on cognitive and mnemonic performance have been demonstrated clinically and experimentally. Experimental studies have demonstrated that these neurological dysfunctions are correlated to spread neuronal apoptosis throughout important areas of the central nervous system (CNS), such as hippocampus and cortex. Several pathophysiological mechanisms have been linked to the AS-induced neurotoxicity, including redox imbalance and recruitment of pro-apoptotic downstream pathways. Furthermore, exposure to AS has arisen as a potential risk factor to the development of Alzheimer's disease. Altogether, these evidences imply that AS abuse per se induces neurodegeneration and can aggravate the prognosis of neurodegenerative diseases.

Misadventures in Toxicology: Concentration Matters for Testosterone-Induced Neurotoxicity

“…While beyond the scope of this opinion paper, it is worth noting that several groups have reported findings indicating that AAS users may suffer from brain alterations and cognitive dysfunction [ 19 , 72 , 73 , 74 , 75 ]. However, these study designs generally do not allow for a causal relationship to be established.…”

“…While TRT is generally considered to be a rather safe practice, there are of course risks for adverse effects (e.g., erythrocytosis and acne) as with any pharmacotherapy [ 13 , 14 , 15 , 16 , 17 ]. While the adverse effects of testosterone—and in a broader sense, all anabolic-androgenic steroids—are fairly well described, more recent attention has been devoted to potential neurological side effects [ 18 , 19 ]. While short-term alterations in psychiatric and cognitive variables have been noted with acute administration in men, these changes are primarily thought to involve neurochemical changes or alterations in signaling pathways leading to temporary alterations in function rather than permanent neurological changes [ 20 , 21 , 22 , 23 , 24 ].…”

“…Relatedly, it has also been proposed that testosterone, especially in the “high normal” and “supraphysiological” range, may cause neurotoxicity, resulting in an increased risk for neurodegenerative diseases (e.g., Parkinson’s, Alzheimer’s, Huntington’s) or at the very least general cognitive decline, especially with chronic use, noting that these, like many of the adverse effects of androgens in general are dose and duration dependent [ 18 , 19 , 25 , 26 , 27 , 28 ]. Such a hypothesis requires a more extensive examination into the evidence cited for such claims.…”