OBJECTIVE: Depressed heart rate variability (HRV) reflects an imbalance of autonomic tone and independently predicts increased cardiovascular risk in patients with congestive heart failure or after acute myocardial infarction. While hormone replacement therapy (HRT) with estrogens beneficially modulates autonomic tone and blood pressure (BP) regulation in postmenopausal women, the impact of concomitant treatment with progestogens remains unclear. DESIGN: In this cross-sectional study, HRV and BP were examined in 62 healthy women (ages 48-71 years) using digital beat-to-beat interval recordings of heart rate and 24-hour ambulatory BP measurements. RESULTS: Demographic parameters did not differ among women without HRT (n = 23), on estrogen (n = 17; ERT), or on progestogen-estrogen containing HRT (n = 22; PERT). Total power of HRV was significantly lower, whereas mean heart rate (HR) was significantly higher among women on PERT group versus controls and ERT (total power: 1611 +/- 146 vs. 2497 +/- 308 and 2472 +/- 348 ms(2); heart rate: 80.7 +/- 1.2 vs. 75.0 +/- 1.4 and 74.0 +/- 2.2 bpm; p < 0.05). In addition, low-frequency power and time-dependent parameters of HRV were lower among women on PERT group versus controls and ERT (p < 0.05). ERT use was associated with reduced systolic and diastolic daytime BP, whereas no significant differences were evident PERT users compared with controls. CONCLUSIONS: Progestogen-containing replacement therapy was associated with increased HR and an attenuation of HRV in postmenopausal women. BP was lower in women on ERT, whereas this effect was offset in the PERT group. These observations could at least partially explain the ambiguous results of progestogen-containing HRT on cardiovascular risk in the Heart and Estrogen/Progestin Replacement Study (HERS).