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

Patricia J.M. Best, MD; Peter B. Berger, MD; Virginia M. Miller, PhD; and Amir Lerman, MD
[+] Article, Author, and Disclosure Information

From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Grant Support: By grants HL07111-21D and HL51736 from the National Institutes of Health, the Miami Heart Research Institute, the Rappaport Program in Vascular Biology, and the Mayo Foundation. Requests for Reprints: Amir Lerman, MD, Department of Internal Medicine and Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Current Author Addresses: Drs. Best, Berger, and Lerman: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;128(4):285-288. doi:10.7326/0003-4819-128-4-199802150-00006
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Background: 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.

Objective: To determine whether ERT alters the balance between the total oxidized products of nitric oxide and endothelin-1.

Design: Single-arm, before–after clinical trial.

Setting: Outpatient clinical research center of an academic medical center.

Patients: 15 postmenopausal women.

Intervention: Treatment with 17β-estradiol for 6 months and a 10-day course of methoxyprogesterone every 3 months.

Measurements: Plasma nitric oxide and endothelin-1 levels were measured at baseline and after 6 months of ERT.

Results: 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).

Conclusion: ERT results in an increased ratio of nitric oxide to endothelin-1. This may be one mechanism by which ERT provides cardiovascular benefit.


Grahic Jump Location
Figure 1.
Individual patient data on plasma oxidized products of nitric oxide (left) and endothelin-1 (right) before and after 6 months of estrogen replacement therapy in 15 postmenopausal women.

The dashed lines represent mean changes.

Grahic Jump Location




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