Gabriele S. Merki-Feld, MD; Paul J. Keller, MD
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Merki-Feld G., Keller P.; Decrease in Endothelin-1 Plasma Levels during the Menstrual Cycle and after Ethinylestradiol Treatment. Ann Intern Med. 1999;131:394. doi: 10.7326/0003-4819-131-5-199909070-00019
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Published: Ann Intern Med. 1999;131(5):394.
TO THE EDITOR:
The endothelium regulates vascular tone and growth by releasing factors such as endothelin-1 and nitric oxide (1). Impaired endothelial function and elevated levels of endothelin-1 contribute substantially to cardiovascular disorders (2-4). Oral contraceptives containing ethinylestradiol are associated with an increased cardiovascular risk (5). It is not known whether this risk is caused by changes in endothelium-derived factors.
We investigated whether 7-day therapy with ethinylestradiol, 50 µg/d, causes changes in the potent vasoconstrictor endothelin-1. Participants were 10 healthy premenopausal women (mean age, 32.4 years). Three fasting blood samples for the measurements of endothelin-1, progesterone, and estradiol levels were taken during the pretreatment cycle as follows: sample 1, cycle days 2 through 4; sample 2, 7 days after sample 1; sample 3, cycle days 20 through 24. To correspond with the pretreatment cycle, the blood samples during the treatment cycle were taken at cycle days 2 through 4 (before treatment) and 7 days after the first sample (after treatment). During the pretreatment cycle, endothelin-1 levels decreased significantly (from 3.89 ng/L to 2.93 ng/L; P < 0.04) whereas estradiol levels increased (Figure). Ethinylestradiol treatment led to a significant decrease in endothelin-1 levels compared with baseline levels during the treatment cycle (from 2.94 ng/L to 2.26 ng/L; P < 0.03) and compared with all measurements during the pretreatment cycle.
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