Vibegron increased resting forearm vascular conductance in premenopausal (P=0.002) but not perimenopausal or postmenopausal females, with an age-associated decline stabilizing after 41.4 years.
RCT (n=23)
blinded
randomized
Does vibegron improve forearm vascular conductance across different stages of menopause in females?
β3-AR mediated vasodilation in females begins to decline prior to menopause onset, stabilizing after age 41.4.
valor p: p=0.025
Objective: Vascular β-adrenergic receptors (ARs) mediate vessel relaxation. Preclinical work demonstrates enhanced β3-AR–mediated vasodilation in females which is lost following ovariectomy. Unfortunately, ovariectomy (i.e., surgical menopause) fails to provide insight into the temporality of the menopausal transition which occurs in humans (i.e., perimenopause). We hypothesized β3-AR–mediated vasodilation declines progressively across stages of menopause. Methods: Twelve premenopausal (19-41 yr, 24±3 kg/m 2 ), five perimenopausal (42-51 yr, 24±3 kg/m 2 ) and six postmenopausal (57-70 yr, 23±3 kg/m 2 ) female participants completed two study visits randomized and blinded to oral placebo or vibegron (75mg; a β3-AR agonist). One hour following ingestion, forearm blood flow (FBF, venous occlusion plethysmography) and blood pressure (BP, finger photoplethysmography) were assessed during a 10-min quiet rest. FBF was normalized for mean BP (forearm vascular conductance, FVC). A two-way mixed effects ANOVA compared FVC across groups and treatments. A change-point analysis implemented via Markov chain Monte Carlo (MCMC) was applied to estimate the age-dependent change point and associated slope shift in ΔFVC (vibegron – placebo). Results: The effect of vibegron on FVC differed by group (group by treatment interaction, p=0.025); β3-AR–agonism increased resting FVC in premenopausal (p=0.002) but not perimenopausal (p=0.615) or postmenopausal (p=0.680) participants. There was a negative association between age and ΔFVC before 41.4 yr (ΔFVC: B=-0.0895±0.0440 mL/min/100 mmHg, P=0.042). Thereafter, significant associations between age and FVC were not observed (ΔFVC: B=0.0006±0.0361, P=0.987). Conclusion: β3-AR agonism increased FVC in pre- but not peri- or postmenopausal females, supporting an early decline in β-AR function across the menopause transition. Surprisingly, segmented regression analysis identified an age-associated decline in β3-AR mediated vasodilation until 41.4 yrs after which it stabilizes. These preliminary data are the first to show β-AR vasodilation in females begins to decline prior to menopause onset. Future analyses will investigate mechanisms responsible and explore strategies to restore vasodilatory responsiveness. Funding: AHA 909014 (DWJ), HL153523 (JKL), University of Missouri Research Council (NGB, BPB, JKL), APS SURF (VDV) 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.
Gonsalves et al. (Fri,) conducted a rct in Females across menopause stages (n=23). vibegron vs. oral placebo was evaluated on forearm vascular conductance (FVC) (p=0.025). Vibegron increased resting forearm vascular conductance in premenopausal (P=0.002) but not perimenopausal or postmenopausal females, with an age-associated decline stabilizing after 41.4 years.