Journal of Applied Physiology · Nov 7, 2026

Hormone Replacement Therapy and Cerebral Hemodynamics in Postmenopausal Women: A Systematic Review and Meta-Analysis

By Vetter E, Vittalam K, Winter S et al.

Background: Hormone replacement therapy (HRT) has well-established effects on systemic vascular function in postmenopausal women, but its effects on cerebral hemodynamics remain poorly understood. This systematic review and meta-analysis evaluated the effects of HRT on ultrasound-based measures of cerebral hemodynamics. We hypothesized that HRT would be associated with reduced pulsatility index (PI), with stronger effects for estrogen-only formulations. Methods: Embase, PubMed, Web of Science, and CENTRAL were searched following PRISMA guidelines (January 25, 2026). Studies reporting PI, resistive index (RI), and cerebral blood velocity (CBV) in postmenopausal women using HRT were included. Risk of bias was assessed using validated tools. Multilevel meta-analytic models using restricted maximum likelihood accounted for dependency among effect sizes. Separate models examined between-group and within-individual comparisons. Moderator analyses examined hormone formulation and administration route. Results: Thirty-eight studies (27 meta-analyzed) were included. HRT was associated with lower PI versus controls, with a pooled mean difference of -0.051, 95% CI [-0.089, -0.012], p=0.009, k=31. Within-individual analyses demonstrated a reduction in PI over time, with a pooled mean change of -0.049, 95% CI [-0.081, -0.015], p=0.004, k=55. RI and CBV were not significantly altered (RI: p=0.74, CBV: p=0.54). Estrogen-only regimens were associated with greater reductions in PI than estrogen plus progestin or tibolone, while route of administration demonstrated no consistent effects. Between-study heterogeneity was substantial. Discussion: HRT was associated with reduced cerebrovascular pulsatility, suggesting a physiological effect on cerebral circulation. However, substantial heterogeneity across studies limits conclusions regarding factors that may modify this response.

doi.org/10.1152/japplphysiol.90127.2026PubMed 42997989Interventions