The Effect of Estrogen Replacement Therapy on Plasma Nitric Oxide and Endothelin-1 Levels in Postmenopausal Women

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Abstract
Estrogen replacement therapy (ERT) in postmenopausal women decreases cardiac mortality and improves endothelial function. The endothelium regulates vascular tone and growth by releasing such factors as nitric oxide and endothelin-1. To determine whether ERT alters the balance between the total oxidized products of nitric oxide and endothelin-1. Single-arm, before–after clinical trial. Outpatient clinical research center of an academic medical center. 15 postmenopausal women. Treatment with 17β-estradiol for 6 months and a 10-day course of methoxyprogesterone every 3 months. Plasma nitric oxide and endothelin-1 levels were measured at baseline and after 6 months of ERT. The mean baseline nitric oxide level was 27.5 nmol/mL (range, 20.3 to 34.8 nmol/mL) and increased by a mean of 7.2 nmol/mL (range, 0.2 to 14.1 nmol/mL) (P = 0.04). The mean baseline plasma endothelin-1 level was 16.4 pg/mL (range, 12.0 to 20.8 pg/mL) and decreased by a mean of 3.9 pg/mL (range, 0.4 to 7.8 pg/mL) (P = 0.04). The mean baseline ratio of nitric oxide to endothelin-1 was 2.0 (range, 1.3 to 2.8) and increased by 1.2 (range, 0.1 to 2.2) (P = 0.03). ERT results in an increased ratio of nitric oxide to endothelin-1. This may be one mechanism by which ERT provides cardiovascular benefit.

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