Some antiepileptic drugs, namely phenytoin, phenobarbital, carbamazepine, oxcarbazepine, and eslicarbazepine, are known to decrease free testosterone androgen levels in males and can cause potential side effects due to hypogonadism . Future studies should deepen our understanding of TRTs’ effects on MS in men with testosterone deficiency and those with normal levels along with optimizing therapeutic strategies across a broader spectrum of demyelinating diseases. This data highlights the potential protective effects of androgens in demyelinating disorders. Recently, the non-genomic effects of testosterone on behavior bypassing the nuclear receptors have attracted the interest of researchers. Reduction to dihydrotestosterone by 5-alpha reductase increases the androgen activity; conversion to estradiol by aromatase converts the androgen to estrogen activity. Numerous relevant studies on rodents and a few on humans focusing on specific behavioral and cognitive parameters have been published. Testosterone influences the brain via organizational and activational effects. The decline of androgen levels in elderly men and its clinical and therapeutic implications. The testosterone metabolite, dihydrotestosterone, which cannot be metabolized to estradiol did not showed this effect (Bimonte-Nelson et al., 2003). In aged rats, an important experiment showed that the positive effect was found only when testosterone was administered. Animal experiments help us to uncover the molecular and physiological mechanisms behind the phenotype correlations seen in human studies. Testosterone in this case worsened the verbal memory (Moller et al., 2010). However, the interaction between testosterone and mental rotation tests is bidirectional. This seems to be true both for actual testosterone (Moffat and Hampson, 1996) and for prenatal testosterone (Grimshaw et al., 1995). 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). In a study analyzing the effects of a single testosterone injection on elderly men the treatment caused a worsening of verbal memory (Wolf et al., 2000). This might be related to the tasks used, as the testosterone levels in men are related to the learning strategies, especially for spatial memory (Choi and Silverman, 2002). In young women, a single dose of testosterone improved spatial memory (Postma et al., 2000). Numerous clinical studies in postmenopausal women and men in the andropause showed improvements of learning and memory after testosterone supplementation. Spatial cognitive abilities as well as general cognition and memory decline with aging together with the testosterone levels. In depressive disorders with decreased libido and low testosterone, the androgen hormone replacement therapy was at least as effective as serotonin reuptake transporters (Kranz et al., 2014). Indeed, these studies were not triggered by the lone fact of testosterone decline and sex difference in prevalence of depressive disorders. Another advantage of animal experiments is the possibility to surgically localize the administration of testosterone into specific brain structures, which is ethically not possible in humans. But whether the potential is used depends on other factors including environment and timing and form of learning. However, in male deer mice it has been shown that aging but not testosterone affects memory (Perrot-Sinal et al., 1998). This indicates that the effect of testosterone on memory is mediated by estradiol and the effect of aromatase which converts testosterone to estradiol.
