Testosterone replacement therapy in Parkinson’s disease a narrative review of current evidence

Abstract Testosterone is a steroid hormone primarily produced by the male gonads. It performs several critical physiological functions, such as maintaining sexual health and promoting the development of muscle mass and bone density. Additionally, testosterone plays a vital role in regulating various bodily systems, including the cardiovascular system, metabolic processes, liver function, the immune system, and the central nervous system. During the aging process, the natural production of testosterone naturally declines, resulting in diverse physiological changes. In the central nervous system (CNS), low testosterone levels are linked to increased vulnerability of the substantia nigra and a heightened risk of developing Parkinson’s disease (PD). In addition, some evidence indicates that testosterone treatment may have adverse effects based on the neurological setting and the initiation of hormone administration. This narrative review examines the current evidence from preclinical and clinical studies on the effects of testosterone treatment in parkinsonian models and patients affected by Parkinson’s disease, emphasizing the potential benefits, the risks dependent on the temporal context regarding the initiation of treatment, and its limitations that currently prevent the recommendation of clinical treatment protocols.