Low testosterone levels, a condition known as hypogonadism, can also have significant impacts on brain health and cognitive function. Although considerable attempts have been made to assess the effects of TRT in men and MCI, there is a notable lack of research on the role of androgens in the development of neurodegenerative disease in women or comparing these effects across genders. The following section highlights our current understanding of the role of androgens in certain CNS disorders and their potential therapeutic role across neurological domains. Injections, but there are indices that to study the effects of testosterone on brain functions, the steroid has to be injected directly into the target brain structure. Although the depressive disorder is more prevalent in females (Bebbington, 1996) when compared to males, the prevalence of depression in males increases with age (Khera, 2013) as plasma testosterone drops. Some of the animal experiments on testosterone and anxiety are summarized in Table 1. But in general, experiments on monkeys are more relevant to human behavior and, thus, this study must not be overseen. Its higher concentrations in men might be the reason for the sex differences in anxiety. Taken together, the results are consistent and despite differences in the methodology it seems clear that testosterone reduces anxiety in both genders. It is responsible for formation of external male genitalia in fetus, prostate growth, and plays a role in male pattern baldness. Testosterone is converted into dihydrotestosterone (DHT) by the action of 5-alpha reductase in the prostate and skin. Testosterone is the most potent androgen, produced primarily by the Leydig cells in the testis. Androstenedione acts as the precursor for both testosterone and estrogen. Androstenedione has moderate androgenic activity, is produced by adrenal glands and gonads, and is derived from DHEA. DHEAS is a weak androgen, produced in the adrenal glands that act as a DHEA reservoir. One of the primary mechanisms through which excessive testosterone can potentially damage the brain is through oxidative stress and neuroinflammation. It’s important to note that under normal circumstances, physiological levels of testosterone are not harmful to the brain. Now, let’s address the elephant in the room – the potential for testosterone to cause brain damage. It’s a reminder that our brains are influenced by a myriad of internal and external factors, with testosterone being just one piece of the puzzle. On the other hand, when levels go awry, it can potentially contribute to various forms of brain damage. On one hand, this hormone helps maintain cognitive sharpness, supports mood regulation, and even promotes neuroplasticity – the brain’s ability to form new neural connections. The menstrual cycle and thus the involvement of sex hormones, including testosterone, in spatial abilities was further confirmed by Pletzer et al. Several studies were performed using human volunteers for spatial tasks, memory as well as mood disorders/traits. When dihydrotestosterone—the androgen metabolite of testosterone was injected into the CA1 region of the hippocampus, spatial memory was improved (Babanejad et al., 2012). But in general, it is of importance to recognize the role of the target tissue that can convert testosterone to inducers of very different signaling pathways. In most target tissues, testosterone is converted into metabolites such as dihydrotestosterone—a more potent androgen receptor ligand. The effect of testosterone is influenced by several factors, but only some of them are known. In experiments, moderate, but not very low or very high doses of testosterone had some effect on behavioral measures such as memory (Spritzer et al., 2011). These pharmacological forms have, however, variable kinetics and might therefore have also variable effects, especially in the brain, where the kinetics is of special importance (Filova et al., 2012). It’s not just about bulging biceps and deep voices; this hormone has a profound impact on our brain’s structure and function. In conclusion, various neurological disorders exhibit male predominance, while some demonstrate reduced disease severity in men. The role of sex hormones in headache medicine is an emerging area of interest, though current literature largely focuses on female hormones and their association with migraines. These effects are also observed in women with catamenial epilepsy who experience decreased seizure frequency during the follicular phase of the menstrual cycle and improved seizure control in men who received testosterone supplements 64, 65. Androgens have antiseizure effects, which are further augmented when used with an aromatase inhibitor that decreases the conversion of androgen into the proconvulsant estradiol and increases levels of androgen .
