The Influence of Sex Hormones on Coagulation and Inflammation in the Trauma Patient

Abstract

Recent clinical studies have shown a sex dimorphism of morbidity and mortality due to shock, trauma, and sepsis, with females tolerating these insults better than males. Experimental animal studies have suggested that sex hormones have a pivotal role in this dimorphism. In the present investigation, a prospective cohort study at a university level-1 trauma center was conducted to evaluate the association between sex hormones and alterations in coagulation and inflammation. Patients with an admission to the intensive care unit, injury severity score (ISS) greater than 4, and obtainable consent were included in the study. In addition to routine clinical laboratories and patient outcomes, plasma TNF-[alpha], IL-6, IL-8, estradiol, progesterone, and testosterone were measured. Sixty-two patients (71% men, 29% women) met criteria for entry. Mean age was 42 +/- 17 years, and mean ISS was 23 +/- 13, with no statistical difference in age or ISS between sexes. Estradiol levels were positively correlated with ISS (P < 0.05) and negatively correlated with TNF-[alpha] (P < 0.01). Initial estradiol levels were higher in patients who developed an infection (P < 0.05). Testosterone was negatively correlated with age (P < 0.01) and was higher in patients who developed acute respiratory distress syndrome (P < 0.05) and in patients who did not survive (P < 0.05). The estradiol-to-progesterone ratio (E2-Pr) was higher in the survivors (P < 0.05). The E2-Pr had positive correlations with fibrinogen levels, rate of fibrin deposition and cross-linking, and overall clot strength (P < 0.05). Estradiol-to-progesterone ratio was negatively correlated with partial thromboplastin times (P < 0.01). In men, the E2-Pr was also negatively correlated with the time to onset of clot formation (P = 0.03). Sex hormone levels (or their ratios) were not correlated to platelet count or international normalized ratios. These findings provide evidence that sex hormone levels in the early posttraumatic period are significantly associated with alterations in the hemostatic and inflammatory response to trauma.

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

“…In the network, b-estradiol had multiple predicted interactions with proteins such as TNF-a, p38 MAPK, IL-6, IL-1b, annexin proteins, and serum acute phase reactants, among others. Although the role of sex-related hormones in the pathogenesis of ARDS is unknown, clinical studies suggest that women have better outcomes in sepsis and ARDS (24,26). These clinical observations are supported by animal studies showing that estrogen suppresses lung inflammation by modulating pro-inflammatory cytokines and vascular cell adhesion molecules (24,25,(27)(28)(29).…”

“…Although the role of sex-related hormones in the pathogenesis of ARDS is unknown, clinical studies suggest that women have better outcomes in sepsis and ARDS (24,26). These clinical observations are supported by animal studies showing that estrogen suppresses lung inflammation by modulating pro-inflammatory cytokines and vascular cell adhesion molecules (24,25,(27)(28)(29). Although the precise mechanism by which sex hormones influence the systemic inflammatory response is unknown, the network analysis in this study suggests that b-estradiol may dampen the lung inflammation of patients with ARDS by modulating the effects of pro-inflammatory cytokines, such as TNF-a, IL-1b, and IL-6.…”

The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone

“…However, female gender has been found to bestow better outcomes after trauma, with associated superior post traumatic fibrinogen concentrations [60]. In fact, the therapeutic administration of estrogen in the setting of orthotopic liver transplantation resulted in decreased transfusion requirements for fresh-27 frozen plasma, red blood cells, and platelets [61].…”

“…Plasma fibrinolytic potential of tissue factor induced clots, lysed by exogenous tissue plasminogen activator (tPA) [23][24][25] were determined for control plasma and plasma with different concentrations of 17β-estradiol (30,60,140, 220, 300 pg/ml and 1ng/ml) and progesterone (30, 60, …”

Hormonal status in protracted critical illness and in-hospital mortality

“…Despite these limitations, our study remains original, as we have assessed the relationships between various hormones and mortality at the postacute phase of critical illness in a patient cohort that is relatively large in comparison with other similar studies. It has to be noted that hormones were not chosen at random, but rather because they might affect outcomes, including even gonadotropic hormones [3,38]. …”