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The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.

The long-term effect of percutaneous and oral estrogen replacement therapy on blood pressure, plasma renin substrate, and serum estrogens was examined in a 2 year placebo-controlled study with 110 early postmenopausal women. The women were allocated to four treatment groups: (1) oral cyclical combination of 2 mg estradiol valerate and cyproterone acetate, (2) oral placebo, (3) percutaneous 17 beta-estradiol, supplemented by 200 mg oral progesterone during the second year, or (4) percutaneous placebo cream. Systolic and diastolic blood pressure remained unchanged in both hormone treatment groups, whereas the diastolic blood pressure tended to increase in both placebo groups. Plasma renin substrate increased during oral treatment with estradiol, but remained unchanged with percutaneous estradiol. No correlation was found between blood pressure and plasma renin substrate. During percutaneous administration of estradiol, the serum concentrations of estrone and estradiol continued to rise after 3 months and reached a plateau at 6 months of therapy. Serum estrone but not estradiol showed the same pattern during oral estradiol therapy. No further changes in any of the measured variables were observed in the women treated with percutaneous estradiol after addition of cyclical oral progesterone. We conclude that both oral and percutaneous treatment with estradiol may provide protection against the age-related increase in diastolic blood pressure observed in early postmenopausal women, and that the metabolic steady state is not attained until after 3 months of estradiol therapy.