ObjectiveTo compare carotid vascular resistance in long-term estrogen users with that of age-matched nonusers.MethodsPairwise comparisons between 18 long-term users of 17β-estradiol (E2) implants (mean age 67.8 years, mean duration of treatment 18.8 years, range 5.8–33.9 years) and 18 age-matched (± 2 years) nonusers. We used color Doppler ultrasound to assess pulsatility index (PI) and resistance index (RI) in common, external, and internal carotid arteries.ResultsEstrogen users compared with age-matched non-users had significantly lower mean values for common carotid RI, −4%; −0.04 (95% confidence interval [CI] −0.07, −0.03,P= .036) and marginally significant for PI, −12%; −0.25 (95% CI −0.54, 0.04,P= .087). Differences in external and internal carotids were smaller and insignificant. Age was a determinant of internal carotid vascular resistance in estrogen users and nonusers. Increasing pairwise differences in external carotid vascular resistance with advancing age (r= 0.55;P= .02), with magnitudes of mean group differences indicate a modest but true effect of long-term estrogen therapy on vascular resistance in common carotids, less in external, and negligible in internal carotid arteries. The study had an 80% power to detect a 10% mean difference (0.08 units) in common carotid RI at the 5% level. The standard deviation was considerably lower for estimates of RI than for PI.ConclusionLong-term estrogen therapy was associated with minor reduction of vascular resistance in common carotid, less in external, and negligible in internal carotid arteries. Effects on carotid vascular resistance do not seem to be a major mechanism in the long-term protective effect of estrogen therapy on cardiovascular risk.