Exogenous estradiol increases cardiovagal baroreflex sensitivity during a hypertensive stimulus in premenopausal...

Women have a greater reduction in cardiovagal baroreflex sensitivity (CVBRS) as they age which contributes to an elevated cardiovascular disease risk. One potential contributor to the attenuated CVBRS may be reductions in estrogen. Therefore, we tested the hypothesis that isolated estradiol (E₂) and combined E₂ and progesterone (P₄) would increase CVBRS to the same extent. To examine the acute effects of E₂ and P₄ on CVBRS in healthy premenopausal women, we used a gonadotropin-releasing hormone antagonist to suppress endogenous sex hormones. We tested 29 young adult women over 10-12 days of hormone manipulation. After 4 days of hormone suppression, participants were given either 0.1-0.2 mg transdermal estradiol (E₂) or 200 mg oral micronized progesterone (P₄) per day. Following 3-4 days of isolated hormones, combined hormones (200 mg of progesterone and 0.1-0.2 mg estradiol) were administered. CVBRS was assessed during a modified Oxford protocol approximately 4 days following each change in hormones. Overall CVBRS was determined as the slope of the response between the R-R interval and systolic blood pressure. CVBRS slope during the hypotensive (sodium nitroprusside) and hypertensive (phenylephrine) phases of the modified Oxford were also assessed. There was no change in the overall R-R interval or hypotensive CVBRS during any of the hormone trials. Interestingly, the E₂ group's CVBRS increased in response to the hypertensive stimulus, whereas the P₄ group had no change. These data suggest that estradiol alone augments CVBRS to a hypertensive stimulus, but progesterone alone and combined E₂ and P₄ do not change CVBRS.NEW & NOTEWORTHY Attenuated cardiovagal baroreflex sensitivity is associated with cardiovascular disease. Female sex hormones have a significant impact on the development of cardiovascular disease across the lifespan. Using an experimental model of hormone suppression and add-back, estradiol add-back alone increased cardiovagal baroreflex sensitivity to a hypertensive stimulus unlike the other hormone manipulation conditions. These data suggest that estradiol alone plays a significant role in cardiovagal baroreflex sensitivity and reductions may contribute to potential cardiovascular disease development.