Postoperative Estradiol Levels Associate With Development of Primary Graft Dysfunction in Lung Transplantation Patients

Abstract

Primary graft dysfunction (PGD) frequently complicates lung transplantation in the immediate postoperative period. Both female gender and estradiol modulate the body’s response to injury and may influence the rate of alveolar fluid clearance. We hypothesized that female gender and higher estradiol levels would be associated with a lower risk of PGD after lung transplantation. We measured plasma estradiol levels pre-operatively, 6 hours postoperatively and 24 hours postoperatively in a cohort of 111 lung transplant recipients at two institutions. The mean age was 57 years (+/− 12.5) and 52% were female. The median postoperative estradiol level was 63.9 pg/ml (IQR 28.8–154.3) in men and 65.1 pg/ml (IQR 28.4–217.2) in females. Contrary to our hypothesis, higher estradiol levels at 24 hours were associated with an increased risk of PGD at 72 hours in males (p=0.001). This association was preserved when accounting for other factors known to be associated with PGD. However, there was no relationship between gender and risk of PGD or between estradiol levels and PGD in females. These findings suggest that there may be different biologic effects of estrogens in males and females and highlight the importance of considering gender differences in future studies of PGD.

Lung transplantation and gender effects on survival of recipients with cystic fibrosis

“…[33] Thus, the complex interplay of hormonal factors observed pre-transplant, could perpetuate post-LT, preventing CF female recipients from gaining the edge noted by females in the overall ISHLT population. Based on the results of our study, it does not appear that the rates of chronic rejection differ between the genders at ten years but we do not know if longer follow-up may produce different results.…”

Phenotypic Plasticity, CYP19A1 Pleiotropy, and Maladaptive Selection in Developmental Disorders

“…Circulating serum estradiol demonstrates wide ranging effects throughout the body and directly regulates the inflammatory response in all tissues (Bastarache et al, 2012; Bechlioulis et al, 2012; Chakrabarti & Davidge, 2013; Douin-Echinard et al, 2011; Sophonsritsuk et al, 2013; Zierau, Zenclussen, & Jensen, 2012) and is linked to autoimmunity in males (Becker, 2012). The inflammatory cascade is a system of feed-forward and feedback loops, and metabolites of these processes directly regulate gene expression in cells that reside within entirely different tissues, such as the gastrointestinal (GI) tract (Ahlquist et al, 1982; Grossman, Brazier, & Lechago, 1981; Strober & Fuss, 2011; Whittle, 1981).…”