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The effect of progesterone on endothelium-dependent and endothelium-independent vasodynamics in the human microcirculation


In an effort to determine the effect of progesterone on endothelium derived nitric oxide production and vascular smooth muscle sensitivity to nitric oxide, we coupled the iontophoretic delivery of acetylcholine and sodium nitroprusside to laser doppler flowmetric and photoplethysmographic assessments of microvasculature flux and distensibility, respectively, in the left forearm. Three study populations were tested : 23 healthy women (22.3+/-1.8 years old, mean +/- S.D.) with consistent menstrual cycles, 15 amenorrheic women (21.5+/-1.3 years old) on monophasic oral contraceptive therapy (0.15 mg of levonorgestrel and 0.03mg ethinyl estradiol), and 15 healthy men (22.1 +/- 3 years) prior to and during bio- identical progesterone treatment. In healthy women, we found that the microvasculature flux and distensibility follow a contrary pattern along the course of the menstrual cycle in that peak flux is attained during the early luteal phase, whereas peak distensibility is attained during the late follicular phase for both the endothelium dependent and independent responses. Further, blood pressure is lowest during the early luteal phase in healthy women. Amenorrheic women on oral contraceptive therapy attained their peak iontophoretic responses during the active phases of the therapy. Additionally, blood pressure decreased during the active phase of therapy. The administration of bio-identical progesterone in men served to significantly decrease blood pressure while increasing both endothelium dependent and independent iontophoretic responses. These results provide evidence for the vasoprotective effects of progesterone, and may reinforce the future use of progesterone therapy as a prophylactic or palliative treatment against the onset or progress of cardiovascular disease

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