Effect of estrogen replacement therapy on sympathetic activity in postmenopausal women.

Sympathetic Activity in Postmenopausal Women To the Editor: Two recent articles in Circulation described modulations of sympathetic nerve activity to the muscle vascular bed in postmenopausal women on long-term estrogen replacement therapy (ERT). Vongpatanasin et al1 reported a decrease in resting muscle sympathetic nerve activity (MSNA) after transdermal but not oral estrogen administration. Furthermore, the diastolic blood pressure was significantly decreased after transdermal ERT. The authors concluded that the decrease in blood pressure was induced by a fall in MSNA to the muscle vascular bed. These data confirm and extend the results of a recent study that administered 2-day transdermal ERT to postmenopausal women and measured MSNA to the muscle vascular bed in the superficial peroneal nerve using a placebo-controlled, within-subject crossover design.2 In this study, resting MSNA decreased from 37.1 3.1 to 30.1 3.1 bursts/min by the second day of estrogen treatment. Vongpatanasin and colleagues1 show that this effect is sustained for a treatment period of 8 weeks. In the short-term study by Weitz et al,2 however, the identical decrease in MSNA was not accompanied by a fall in blood pressure. This finding casts doubt on the hypothesis that the decrease in blood pressure is the consequence of reduced sympathetic tone to the muscle vascular bed. Rather, other mechanisms, such as direct vascular effects, could account for the blood pressure–lowering effects of transdermal ERT after prolonged treatment. This effect, however, must be combined with an influence on baroreflex function in postmenopausal women, because otherwise a decrease in blood pressure would have resulted in an increase in MSNA. In fact, the effects of estrogens on baroreflex regulation have been repeatedly demonstrated, most recently in the study by Hunt et al3 in postmenopausal women in the same issue of Circulation. However, in premenopausal women, an increased suppression of MSNA in response to an elevation of blood pressure has also been observed during phases of high estrogen levels during the menstrual cycle,4 although neither study showed any change in blood pressure. Thus, these studies indicate that estrogens lower the centrally regulated baroreflex set point in normotensive postmenopausal women. This effect might explain the adaptive changes in MSNA in relation to the prevailing blood pressure, but they do not seem to explain the blood pressure decrease in the study of Vongpatanasin et al.1