BackgroundEstrogen therapy and penile inversion vaginoplasty (PIV) are necessary, life-saving interventions for many transfeminine patients. Patients undergoing PIV are generally at low baseline risk for venous thromboembolism (VTE) based on Caprini Score. Estrogen therapy may increase VTE risk in surgical patients, but its cessation may be psychiatrically dysphoric for transfeminine patients. AimThis study examines whether perioperative estrogen cessation impacts VTE risk in patients undergoing PIV. MethodsThis was a pre-post study of patients undergoing PIV. From 2014 through 2018, all patients stopped estrogen therapy for 2 weeks before surgery and resumed 1 week postoperatively (group 1). Starting in 2019, all patients continued estrogen therapy perioperatively, with dose reductions for those whose dose was >6 mg/day (group 2). OutcomesThe primary outcome was 90-day VTE rate. Results178 patients were included in the study, with 117 in group 1 and 61 in group 2. Median Caprini Score was 4 in group 1 (interquartile range: 3–6) and 3 in group 2 (interquartile range: 3–4) (P = .011). Complications per patient were higher in group 1 (2.2 vs 0.9, P < .001), with a longer follow-up (14.1 vs 10.2 months, P < .001). Rates of 90-day VTE were not different between groups (0.0% vs 1.6%, P = .166). Clinical ImplicationsPatients undergoing PIV are generally at low risk for VTE, based on 2005 Caprini Scores. This study provides preliminary evidence that perioperative estrogen therapy continuation does not appear to substantially increase VTE risk in transfeminine patients undergoing PIV with low Caprini Scores, although more investigation is needed to establish true safety. Strengths & LimitationsStrengths include the pre-post design and single-surgeon experience, high proportion of patients with 90-day follow-up, and relatively large series to understand baseline VTE risk by Caprini Score in a PIV population. The main weakness of this study is its limited power to measure true differences in VTE risk based on estrogen continuation. ConclusionsThis study suggests that perioperative estrogen continuation may be safe for patients undergoing PIV, the overwhelming majority of whom are at low baseline VTE risk. However, clinicians should weigh the magnitude of the risks and benefits of estrogen cessation on a case-by-case basis.Nolan IT, Haley C, Morrison SD, et al. Estrogen Continuation and Venous Thromboembolism in Penile Inversion Vaginoplasty. J Sex Med 2021;18:193–200.