Introduction: Little is known regarding the molecular changes in genital skin after initiation of gender-affirming hormone therapy or gonadectomy, which is of particular interest given the use of this tissue as full-thickness skin graft in creating the neovagina in vaginoplasty. In order to learn anatomic and microscopic details of the skin, we set out to characterize androgen and estrogen receptor (AR and ER) prevalence in a cohort of patients undergoing gender affirming vaginoplasty or vulvoplasty (GAV). Methods: Retrospective review of 48 patients who underwent GAV was performed (Table 1). Immunohistochemistry (IHC) was performed on scrotal skin collected at time of surgery. AR and ER percent expression determined by IHC was categorized into absent ( <0.3%), weak (0.3-0.5) moderate (0.5-0.8), and strong expression (>0.8). Univariate and multivariate analyses were performed. Results: Patients with history of prior orchiectomy had statistically lower ER and AR percent expression (Table 2). No preoperative characteristics differed between the prior orchiectomy group and the remainder of the cohort. On average, orchiectomy was performed 2.7 years before GAV (range 1-7, SD 1.8). Several patients (30/48) within the cohort had absent expression of AR in the scrotal skin. Conclusions: Patients with history of prior orchiectomy had lower ER and AR present on IHC of scrotal skin. It remains unclear if HRT or orchiectomy was responsible. Given the absence of AR expression in the cohort, we plan to re-assess a new cohort of patients as formalin fixation may limit IHC assessment. While pre-HRT and pre-orchiectomy skin samples were unavailable in our study, this work lends itself to investigate the result of hormone changes on genital skin. Further, these insights may aid in treating genital skin changes in the post-operative transgender population. SOURCE OF Funding: None