Estradiol-to-testosterone ratio versus testosterone in relation to thromboelastographic clot strength in men with type 2 diabetes: a secondary cross-sectional analysis
Year: 2026
Type: article
Abstract: Testosterone deficiency is common in men with type 2 diabetes mellitus (T2DM) and has been associated with a procoagulant thromboelastography (TEG) profile. Whether the estradiol-to-testosterone ratio (E2/T) provides information beyond testosterone alone is uncertain. We performed an exploratory secondary cross-sectional analysis of 92 hospitalized men with T2DM from a previously published single-center cohort. E2/T was calculated as estradiol (pmol/L) divided by total testosterone (nmol/L). TEG data were available for 84 participants. Routine TEG testing used a TCA-6000 analyzer with kaolin activation and citrated whole blood. E2/T was examined continuously after natural-log transformation and descriptively by tertiles. Spearman correlations and multivariable linear regression adjusted for age, body mass index, glycated hemoglobin, and fasting glucose were used. Sensitivity analyses used heteroscedasticity-consistent (HC3) standard errors, false-discovery-rate correction, alternative hormone models, exclusion of the maximum E2/T value, winsorization, Cook’s-distance screening, and leave-one-out refitting. Median E2/T was 10.92 (interquartile range 5.97–17.23). Across increasing tertiles, median TEG maximum amplitude (MA) increased from 59.4 to 62.4 and 65.9 mm ( P = 0.002). In the adjusted model, log E2/T was associated with MA (B = 2.85 mm, 95% CI 0.85–4.85; conventional P = 0.006; FDR-adjusted P = 0.024; HC3 P = 0.021). The estimate remained positive after excluding the maximum E2/T value (B = 3.40; HC3 P = 0.014), winsorization (B = 3.00; HC3 P = 0.017), exclusion of observations with Cook’s distance > 4/n (B = 3.29; HC3 P = 0.002), and every leave-one-out refit (B range 2.36–3.44; all HC3 P < 0.05). A testosterone-based model fit MA slightly better than the E2/T model (AIC 525.2 vs. 526.2). Higher E2/T was consistently associated with greater TEG clot strength in hospitalized men with T2DM, particularly MA, but the ratio did not outperform testosterone alone. E2/T should be viewed as a descriptive index of relative androgen-estrogen balance rather than an established independent thrombotic biomarker; the finding is hypothesis-generating and requires prospective confirmation.
Source: BMC Endocrine Disorders
Author: Xiao-Jun Chen
Institution: Shanghai Tenth People's Hospital
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W7208808182
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