Erik Reiche, MD
Postdoctorate research fellow
Erik Reiche MD; Yu Tan PhD; Patrick R Keller MD; Matthew R Louis MD; Vance Soares MS; Calvin R Schuster BA; Tingying Lu BS; Vanessa Mroueh MD; Jessica Mroueh MD; Devin Coon MD MSE
Devin Coon MD MSE
Research Category: Women's Health, Sex-Differences and Gender Biology
Background: Wound healing problems are a major cause of morbidity for gender-affirming surgery (GAS) patients. Prior studies have shown sex differences in wound healing may exist. We hypothesized exogenous testosterone supplementation may impair post-GAS wound healing and developed a novel model to investigate this phenomenon.
Methods: Mice were randomized based on hormone regimen and gonadectomy (OVX). Gonadectomy or sham occurred on POD0 and mice were assigned to no-T (-T), mono- or bi-weekly (T/2T) testosterone groups. Dorsal splinted wounding occurred on POD14 and harvest on POD21. Serum T levels were quantified with mass-spectrometry. Wound tissue underwent analysis with planimetry, qPCR, ELISA and immunofluorescence.
Results: Mean testosterone trough levels for bi-weekly regimen were higher compared to mono-weekly (397ng/dL vs. 272ng/dL; p=.027). At POD5, 2T injections led to 24.9% and 24.7% increases in mean wound size relative to SHAM and OVX/-T, respectively (p=.004; .001). Wounds in OVX/+2T mice demonstrated increased gene expression for inflammatory cytokines (i.e., TNFa,VEGFa,TGFb1,MIF,Col-1,Col-3,aSMA) and macrophage marker F4/80 (p<.05). ELISA confirmed elevated wound TNFα levels (p<.05). Quantitative multiplex immunofluorescence with F4/80/NOS2/ARG1 showed significant increases in macrophage prevalence in OVX/+2T (p<.05).
Conclusions: We developed a novel model of the GAS hormonal milieu to study effects of exogenous testosterone on wound healing.
Background: Wound healing problems are a major cause of dissatisfaction for gender-affirming-surgery(GAS) patients. Prior studies have shown sex differences in wound healing may exist. We hypothesized exogenous testosterone supplementation may impair post-GAS wound healing and developed a novel mice model to investigate this phenomenon.
Methods: Our team allocated mice into experimental groups. Given that estrogens positively improve wound healing, most mice underwent ovariectomy surgeries. To mimic a gender-affirming-surgery patient, some mice received exogenous T-supplementation once/twice a week (T/2T Groups). All mice were wounded on day 14 and wound tissue was harvested for analysis on day 21.
Results: Mice from the experimental groups that received exogenous testosterone therapy had higher testosterone levels. On the fifth day after wounding, animals with T-therapy had bigger, less healed wounds when compared to mice without T-therapy. Wound tissue analysis of the T-treated group showed significant inflammation markers and differences in the cellular concentration.
Conclusions: The most common reason for re-operation after chest masculinization surgery is ugly scarring and hormones may play a role. Since this animal model recreates the hormone environment of a typical gender-affirming-surgery patient, it may help understand better how testosterone affects wound healing and thus significantly improve the quality-of-care surgeons can provide.