Transdermal estrogen replacement therapy decreases sympathetic activity inpostmenopausal women

Background-Menopause heralds a dramatic increase in incident hypertension, suggesting a protective effect of estrogen on blood pressure (SP). In femal e rats, estrogen has been shown to decrease sympathetic nerve discharge (SN D) and BP. SND, however, has not been recorded during estrogen replacement therapy (ERT) in humans. Methods and Results-In 12 normotensive postmenopausal women, we conducted a randomized crossover placebo-controlled study to test whether chronic ERT caused a sustained decrease in SND and BP. Twenty-four-hour ambulatory BP, SND, and arterial baroreflex sensitivity were measured before and after 8 w eeks of transdermal estradiol (200 mug/d), oral conjugated estrogens (0.625 mg/d), or placebo. To test the acute effects of estrogen on SND, additiona l studies were performed in the same women receiving intravenous conjugated estrogens or sublingual estradiol. After 8 weeks of transdermal ERT, the b asal rate of SND decreased by 30% (from 40+/-4 to 27+/-4 bursts per minute, P=0.0001) and ambulatory diastolic BP fell by 5+/-2 mm HE (P=0.0003). In c ontrast, SND and BP were unaffected either by 8 weeks of oral ERT or by acu te estrogen administration. Neither transdermal nor oral ERT had any effect s on baroreflex sensitivity. Conclusions-In normotensive postmenopausal women, chronic transdermal ERT d ecreases SND without augmenting arterial baroreflexes and causes a small bu t statistically significant decrease in ambulatory BP. Sympathetic inhibiti on is evident only with chronic rather than acute estrogen administration, implying a genomic mechanism of action. Because the effects of transdermal ERT are larger than those of oral ERT, the route of administration may be a n important consideration in optimizing the beneficial effects of ERT on BP and overall cardiovascular health.