REN and hypertensive disorder: Although there are publications stating that estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin (21), estrogen is also shown to counterregulate the classic, pressor angiotensin-converting enzyme/Ang II/AT1R pathway, which is upregulated in males, thereby playing a protective role against HTN and end-organ damage in women (22, 23).