The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage.

The steroid hormone, oestradiol, has pleiotropic functions. The protective effects of oestradiol are attributed to its anti-inflammatory, antioxidant, anti-atherogenic, anti-apoptotic, vasodilatory activities and regulation of micro RNA. Oestradiol upregulates endothelial nitric oxide synthase gene expression and increases the production of nitric oxide, an important vasodilator. It suppresses the renin-angiotensin system and monitors haemodynamic stress. The hormone maintains the integrity of blood vessels by reducing oxidative stress while upregulating the expression of antioxidant enzymes and prevents vascular inflammation by regulating pro- and anti-inflammatory cytokines. Aneurysmal subarachnoid haemorrhage (aSAH) occurring as a consequence of the rupture of an intracranial aneurysm is a devastating cerebrovascular event, representing 5-7% of all strokes. Postmenopausal women are more susceptible to aSAH compared to men in the same age group. This gender disparity has been attributed to reduced levels of the vascular protective hormone oestradiol following menopause. This review is focused on the protective role of oestradiol on vasculature and how the drop in oestradiol levels after menopause dramatically increases the incidence of aSAH in women. During menopause, oestradiol deficiency may affect vascular integrity causing dysregulation of vascular homeostasis by affecting the renin-angiotensin-aldosterone system (RAAS) and inflammatory and apoptotic cascades, resulting in the weakening of the cerebral arterial wall and potentially to development of an aneurysm and its rupture. In view of the role of oestradiol in maintaining vascular integrity, treatments involving hormone replacement could be a promising approach in postmenopausal women who are at risk of developing or rupturing an intracranial aneurysm.