The effects of different types and doses of oestrogen replacement therapy on clinic and ambulatory blood pressure and the renin-angiotensin system innormotensive postmenopausal women

Objective The effect on blood pressure of oral 'replacement' doses of exoge nous oestrogen may depend on the type and dose of oestrogen administered. T his study was designed to compare with placebo the effect of once daily tre atment with a 'natural' oestrogen, piperazine oestrone sulphate, in two dif ferent doses and a semisynthetic oestrogen, ethinyloestradiol, on clinic an d ambulatory blood pressure and the renin-angiotensin system in postmenopau sal women. Design and methods Twenty-four normotensive postmenopausal women (median ag e 54 years, range 47-60 years) participated in the study which used a doubl e-blind crossover design. For each subject there were four randomized treat ment phases, each lasting 4 weeks. The separate treatments administered onc e daily were 0.625 mg oestrone sulphate, 2.5 mg oestrone sulphate, 0.02 mg ethinyloestradiol and matching placebo. Clinic blood pressure, heart rate a nd weight were measured weekly with the mean values of weeks three and four of each phase used for analysis. Ambulatory blood pressure and biochemical measurements were performed in the final week of each phase. Results Twenty-four subjects entered and 22 completed the randomized phases of the study. Compared with the placebo phase, end-of-phase mean clinic di astolic blood pressure was reduced in subjects taking the semisynthetic oes trogen (P < 0.01) but was unchanged in those taking the 'low' and 'high' do se natural oestrogen. Mean clinic systolic blood pressure was also unchange d by any of the oestrogen treatments. Ambulatory night-time systolic, diast olic and mean arterial blood pressures were reduced with the low-dose natur al and semisynthetic oestrogen treatments compared with placebo (P < 0.01), whereas there was no significant effect of the oestrogen treatments on amb ulatory daytime blood pressures. A reduction in clinic and ambulatory heart rate was observed with the high-dose oestrone and semisynthetic oestrogen treatments. There was a dose-dependent increase in plasma renin substrate a nd decrease in plasma renin concentration with all active treatments; howev er, there was no change in plasma renin activity or plasma aldosterone conc entration. Conclusion In normotensive postmenopausal women, replacement doses of natur al and semisynthetic oestrogen reduce night-time ambulatory blood pressure with either no change or a small reduction in clinic blood pressure. Reduct ion in blood pressure is not explained by reduced activity of the renin-ang iotensin system but could have a component of reduced central sympathetic d rive consistent with the decreased heart rate. J Hypertens 1999, 17:405-411 (C) Lippincott Williams & Wilkins.