Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions

Sex steroids are commonly known for their contribution to phenotypic as well as biological reproductive sex differences mediated through classical regulation of neuroendocrine loops. However, sex steroids also have considerable impact on physiological function of non-reproductive tissues including the cerebrovasculature. Preclinical studies have shown that endogenous and exogenous administration of sex steroids significantly influences both cerebrovascular tone and brain function under normal conditions and following a pathological insult (e.g., middle cerebral artery occlusion). However, the precise mechanism(s) of how sex steroids modulate vasomotor responses and/or neurological outcomes in vivo is difficult to define since evidence based on both clinical and experimental studies has been shown to be dependent upon several variables including dose, duration of administration, presence of underlying pathologies, species, and sex. While progesterone, testosterone (TEST), and dihydrotestosterone (DHT) have all been investigated for their impact on the cerebral circulation, the effects of 17β-estradiol (E2) have been best characterized. Since recent reviews have highlighted studies reporting the actions of E2 on cerebral vascular function and health, only key points are included in this review. Conversely, less is known about the effect of androgens on the blood vessel wall, particularly in the cerebral circulation. The few studies that do address a role for androgen's modulation of cerebrovascular function under normal and pathophysiological conditions provide confounding evidence for either beneficial or detrimental effects. Therefore, the focus of this review is to highlight mechanisms associated with TEST, DHT, and its recently recognized androgen metabolite (3β-diol) on cerebrovascular function during healthy and diseased states.