Effects of estrogen replacement therapy on natriuretic peptides and blood pressure

Estrogen replacement therapy (ERT) has been reported to affect blood pressure. Since natriuretic peptides have natriuretic and vasodilatory activity and also inhibit the renin-angiotensin-aldosterone system and lower blood pressure, it was hypothesized that the changes in blood pressure effected by ERT might be mediated via changes in natriuretic peptides.

Fifty-eight postmenopausal hysterectomized women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate 2 mg/day or transdermal estradiol gel containing 1 mg estradiol/day for 6 months. Blood pressure was measured by using an automatic, oscillometric device. Plasma atrial natriuretic peptide (ANP), N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP), aldosterone, and renin were determined by radioimmunoassay.

The mean decrease in diastolic blood pressure was -6 mmHg both in the peroral group (n = 26) (P = 0.002) and in the gel group (n = 27) (P = 0.001), and the corresponding decreases in systolic blood pressure were -4 mmHg (P = 0.070) and -7 mmHg (P = 0.028) in the sitting position. Plasma NT-proANP rose from 212 to 264 pmol/l (P = 0.001) on peroral ERT and from 240 to 292 pmol/l (P = 0.008) on transdermal ERT. No significant changes were observed in the plasma ANP, BNP, aldosterone, and renin levels.

Both peroral and transdermal ERT result in elevated plasma levels of NT-proANP, indicating an activation of the natriuretic peptide system. This could explain, at least in part, the lowering of blood pressure during ERT.