Sympathetic transduction to blood pressure in early-menopausal females

Introduction: Early menopause (EM; before age 46yrs) increases cardiovascular disease (CVD) risk by 20-40% compared to menopause completion at a typical age (>46yrs), though the mechanisms through which this occurs are unclear. We compared resting muscle sympathetic nerve activity (MSNA) and sympathetic transduction to blood pressure (BP) in midlife females with EM and premenopausal females (PRE). We hypothesized that EM would show higher MSNA and transduction, indicating early autonomic dysregulation. Methods: Twenty-two females (EM: 8; PRE: 14) completed an in-laboratory testing session consisting of 10min supine rest, beat-to-beat BP, heart rate (HR), MSNA were recorded; and blood was drawn for sex hormone levels. Premenopausal participants were studied during the early follicular phase. Weighted sympathetic baroreflex sensitivity (sBRS) was calculated using a custom Excel binning method. Burst-triggered, signal-averaged sympathetic transduction to diastolic BP (DBP) was calculated across 10 cardiac cycles after each MSNA burst. Transduction after non-burst cycles was also assessed. Independent t-tests and two-way repeated-measures ANOVA were used to compare resting autonomic and cardiovascular measures between EM and PRE. Results: Results are presented as mean+SD. EM were older than PRE (EM: 45+2; PRE: 41+4yrs, p0.05 for all. Both HR (69+12 vs. 55+6bpm; p=0.02) and MSNA burst frequency (25+4 vs. 19+8bursts/min; p=0.03) were higher in EM than PRE. While groups were similar in overall sympathetic transduction to DBP (time*group: p=0.08; group: p=0.09), following cardiac cycles without MSNA bursts, EM had larger reductions in DBP compared to PRE (time*group: p=0.03; group: p=0.04). When adjusting for T/E2 ratio, but not age, group differences were eliminated for nonburst transduction. Conclusions: Overall, EM exhibit elevated resting MSNA and HR with greater DBP reductions following cardiac cycles without MSNA bursts, despite similar overall sympathetic transduction to DBP. This altered sympathetic transduction, however, was dependent on hormone ratio, suggesting a link between menopause and autonomic BP dysregulation. Although age differences did not appear to statistically impact our primary analyses and all females were below the age of 50, further investigation is warranted to understand how age and hormone deficiency interact to influence sympathetic transduction to BP in females. Funding This work was supported by NIH R21 AG080503 (MKR), K01 AG064038 (MKR) and 1F32HL160012 (EJL) and by the Clinical Translational Sciences Activities NIH UL1TR002494. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.