Association of Testosterone-to-estradiol Ratio with Inflammation and Clinical Outcomes among Postmenopausal HFpEF

OBJECTIVE: Sex hormones is linked to the inflammatory and diastolic dysfunction. The testosterone-to-estradiol ratio (T/E2) may better capture the relative androgenic-to-estrogenic balance more comprehensively. We investigated whether T/E2 is associated with systemic inflammation, diastolic dysfunction, and short-term outcomes in postmenopausal women with HFpEF. METHODS: This single-center prospective cohort included 184 postmenopausal women with HFpEF and followed up for 12 months. Sex hormones were measured by chemiluminescent immunoassays. Associations of T/E2 with inflammatory biomarkers, echocardiographic indices, 12-month NT-proBNP and clinical outcomes were evaluated using correlation, multivariable linear regression, and logistic regression analyses. RESULTS: Median testosterone and estradiol concentrations were 14.61 ng/dL and 18.60 pg/mL, respectively. Higher T/E2 was independently associated with lower hs-CRP (β = -0.353, P < 0.001), NLR (β = -0.162, P = 0.015), IL-6 (β = -0.166, P = 0.005), and E/e' (β = -0.073, P = 0.032), but not with D-dimer, LAD or 12-month NT-proBNP (β = 0.065, 95% CI -0.115 to 0.245; P = 0.481). The 12-month composite clinical endpoint occurred in 54 participants (29.3%). Higher T/E2 was associated with lower odds of the composite endpoint (OR = 0.653, 95% CI 0.450-0.949; P = 0.025), mainly reflecting heart failure hospitalization (OR = 0.618, 95% CI 0.417-0.915; P = 0.016). CONCLUSIONS: In postmenopausal women with HFpEF, lower T/E2 is associated with greater systemic inflammation, worse diastolic hemodynamics, and higher odds of short-term clinical event. These findings suggest that T/E2 may serve as a candidate endocrine-inflammatory marker for HFpEF phenotyping in postmenopausal women.