Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors.

Abstract

OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment. RESULT(S): In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.