Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women

Background Oral estrogen replacement therapy (ERT) is known to stimulate the synthesis of angiotensinogen. The effects of such therapy on renin, ACE, and aldosterone are less clear. This seems noteworthy, however, since further activation of the system could be disadvantageous to postmenopausal women who replace estrogen in the context of heart failure, coronary artery disease, or hypertension. Methods and Results Estrogen status and components of the renin-angiotensin system were examined in a population-based sample of postmenopausal women and age-matched men. Renin was quantified immunoradiometrically, ie, independent of substrate abundance; aldosterone, angiotensinogen, and ACE activity were determined by standard methods. Renin levels were lower in women with ERT (n=107; 12.0+/-0.7 mU/L) compared with women without ERT (n=223; 16.6+/-0.9 mU/L; P=.001) or men (n=342, 20.5+/-1.5 mU/L, P<.0001). In contrast, angiotensinogen was higher in women with ERT (1.36+/-0.08 mg/L) compared with women without ERT (1.03+/-0.02 mg/L; P<.0001) or compared with men (0.97+/-0.01 mg/L; P<.001). Renin suppression was seen with either oral or transdermal estrogen replacement (-30% and -31%, respectively; both P<.001). In contrast, the increase of angiotensinogen was limited to women taking oral estrogens (+58%, P<.001). Multivariate analysis revealed that these estrogen effects were independent of age, body mass index, blood pressure, and/or antihypertensive medication. Finally, only marginal differences between groups were observed for serum ACE activity and aldosterone. Conclusions Aside from a well-documented induction of angiotensinogen, ERT is related to a substantial suppression of renin, a phenomenon that might have received little attention because of widely used indirect measurements of the hormone.