Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women

Peripheral vascular responses to acute administration of natural progestero ne were studied in 12 postmenopausal women (mean +/- SD age 50.3 +/- 4.8 ye ars) with no evidence of cardiovascular disease. According to a randomized, double-blind protocol, all subjects were given natural progesterone as a v aginal cream, able to produce a rapid peak and decoy of plasma hormone conc entrations, or matched placebo, with crossover after a I-week washout perio d. Forearm blood flow and peak flaw after ischemic stress (ml/100 ml/min), local vascular resistance (mm Hg/ml/100 ml/min), venous volume (m1/100 mi), and venous compliance (m1/100 ml/mm Hg) were measured by strain-gauge veno us occlusion plethysmography at baseline and after progesterone or placebo administration. Plasma norepinephrine concentrations were determined by hig h-performance liquid chromatography with electrochemical detection. Progest erone sharply decreased forearm blood flow (p < 0.01) through an increase i n local vascular resistance (p < 0.01). Measures of venous function remaine d unchanged. Although the hormone increased circulating norepinephrine conc entrations (p < 0.05), there were no significant changes in mean arterial p ressure or heart rate. Furthermore, progesterone reduced the local vasodila tor capacity, shown by a decrease in forearm Delta flow (difference between peak flow and basal flow, p < 0.05). Compared with the well-known effect o f estrogen, progesterone exerted an opposite action on peripheral vascular responsiveness. Peripheral circulatory changes may be attributed to a direc t activity of progesterone on the arterial wall and may in part reflect a m odulation of the hormone on peripheral sympathetic tone. Consideration must be given to the hypothesis that the addition of may attenuate the benefici al effects of unopposed estrogen replacement therapy in postmenopausal wome n. (C) 1999 by Excerpta Medica, Inc.