Faculty, Staff and Student Publications

Language

English

Publication Date

5-1-2026

Journal

Transfusion

DOI

10.1111/trf.70107

PMID

41700516

PMCID

PMC13184429

PubMedCentral® Posted Date

2-17-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products to mitigate endotheliopathy and coagulopathy.

Results: Literature suggests that the female sex, particularly the pre-menopausal age group, possesses an intrinsic advantage linked to circulating estradiol. Estrogen supplementation is noted to mitigate bleeding risks, as clinical reviews in surgical and critical care settings consistently demonstrated a reduction in transfusion requirements and improved hemostasis after administering conjugated estrogen. Current literature findings underscore the therapeutic utility of estrogen in targeting endotheliopathy and coagulopathy.

Conclusion: The evidence suggests that estrogen plays a critical, context-dependent role. One of the most compelling benefits is estrogen's capacity to maintain endothelial integrity, thereby correcting trauma-induced endotheliopathy. This mechanism, coupled with its inherent procoagulant effect, underlies the observed female survival advantage. Targeting this sex-based mechanism is a promising avenue to enhance trauma management. Future large-scale, randomized controlled trials are needed to validate the efficacy of direct estrogen supplementation and the strategic utilization of female-donated blood products in trauma resuscitation.

Keywords

Humans, Wounds and Injuries, Estrogens, Female, Blood Coagulation Disorders, Glycocalyx, Hemorrhage, Male, Animals

Published Open-Access

yes

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