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.