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We demonstrated in a previous cross-sectional study that arterial compliance is elevated in postmenopausal women taking estrogen-containing hormonal therapy, which may partially account for the reduction in cardiovascular risk observed.To investigate the effects of withdrawal and recommencement of hormonal therapy, each for 4 weeks, on arterial compliance.Seventeen postmenopausal women [aged 56 ± 4 years (mean ± SD)] taking long-term hormonal therapy (+HT group) were studied at baseline, 4 weeks after withdrawal of hormonal therapy and again 4 weeks after recommencement. Systemic arterial compliance (SAC), pulse wave velocity (PWV) in the aorto-femoral and femoral-dorsalis pedis regions, and hemodynamic variables were measured at baseline, and at the end of each study intervention. As a time-control, seventeen postmenopausal women (aged 63 ± 7 years) not taking hormonal therapy (−HT group) were also investigated.SAC significantly decreased from 0.47 ± 0.06 to 0.40 ± 0.05 arbitrary compliance units (mean ± SEM; P < 0.05) after 4 weeks withdrawal from hormonal therapy. PWV in the femoral-dorsalis pedis region was elevated significantly by the withdrawal of hormonal therapy (8.4 ± 0.4 to 9.4 ± 0.5 m/s; P < 0.05), but PWV in the aortofemoral region did not change. After therapy had been recommenced for 4 weeks, SAC and PWV in the femoral-dorsalis pedis region were restored to baseline values. The −HT group showed no difference in SAC or PWV, and mean arterial pressure did not change in either group throughout the study period.These data suggest that hormonal modulation of distal arterial vascular tone may account for short-term changes in arterial compliance associated with estrogen-containing hormonal therapy.