| Many studies have investigated the benefits of androgen therapy and neurosteroids
in aging men, while concerns remain about the potential associations of exogenous
steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is
neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are
mediated primarily through conversion of a small amount of testosterone to estradiol by the
catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies
suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone,
either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between
pharmacologic androgen use and the incidence of IS are questionable, because a significant
portion of testosterone is converted to DHT. There is also insufficient evidence to reject a
causal relationship between the pro-testosterone adrenal androgens and incidence of IS.
Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial
symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria
for androgen therapy for cerebrovascular complications are unclear. Confounding variables,
including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to
be considered. Information extracted from pharmacogenetic testing may aid in expounding
the protective–destructive properties of neurosteroids, as well as the prognosis of androgen
therapy, in particular their cerebrovascular outcomes. This investigative review article
addresses relevant findings of the clinical and experimental investigations of androgen
therapy, emphasizes the significance of genetic testing of androgen responsiveness towards
individualized therapy in post-IS injuries as well as identifying pertinent questions. |