To determine if reproductive hormones played a role at physiological levels on vascular resistance of uterine arteries, we studied young women having inactive ovaries who received exogenous estradiol (E2) and progesterone (P). Six women, ages 27 to 36 with absent or nonfunctioning ovaries, received transdermal E2 and vaginal P after a 28-day replacement regimen duplicating E2 and P levels seen in the menstrual cycle. Vascular resistance of uterine arteries was evaluated before treatment (baseline), on days 13 to 14 and on days 26 to 27, using transvaginal pulsed Doppler combined with real-time imaging. Doppler waveforms were analyzed by the pulsatility index (PI). Baseline evaluation showed narrow systolic Doppler flow waves with a PI of 5.2 +/- 0.4, mean +/- SEM. On cycle day 13, Doppler waveforms showed a marked broadening with uninterrupted diastolic flow indicative of a profound decrease in vascular resistance. This was reflected by a significant decrease in PI to 1.3 +/- 0.3, mean +/- SEM. Doppler measurements made on days 26 to 27 showed no significant change. Our results indicate that at physiological levels, E2 affects vascular resistance of uterine arteries. This represents a new parameter of estrogen action, readily measurable by a noninvasive technique that, in the future, may help for assessing the efficacy of various estrogenic treatments.