Abstract
BACKGROUND: Loss of nipple-areola complex (NAC) sensation following mastectomy is a significant concern in both gender-affirming and oncologic breast surgery. Targeted nipple-areola complex reinnervation (TNR) has emerged as a technique to improve sensory outcomes by restoring nerve connections to the NAC. This study systematically reviews the literature and conducts a meta-analysis to evaluate the efficacy of TNR in both gender-affirming mastectomy and oncologic breast reconstruction. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, and Scopus were searched for studies reporting NAC neurotization outcomes. Studies were included if they assessed sensory recovery following TNR in gender-affirming mastectomy or oncologic breast reconstruction. A random-effects meta-analysis was performed on four studies reporting monofilament thresholds, with separate meta-analyses conducted for areola sensation and peripheral breast sensation. Heterogeneity between studies was assessed. RESULTS: Twelve studies encompassing 342 participants (195 with TNR, 147 controls) were included. Meta-analysis of TNR in gender-affirming mastectomy patients demonstrated significantly improved NAC, areola, and peripheral breast skin sensation compared to controls (MD: - 1.73, 95% CI: - 2.15 to - 1.32, p < 0.0001, I(2) = 67.78%; MD: - 1.73, 95% CI: - 1.91 to - 1.56, p < 0.0001, I(2) = 0%; MD: - 1.59, 95% CI: - 1.81 to - 1.37, p < 0.0001, I(2) = 0% respectively). Comparisons between gender-affirming and oncologic mastectomy cohorts indicated earlier and more consistent sensory recovery in gender-affirming procedures, likely due to proactive neurotization techniques. CONCLUSION: TNR significantly enhances NAC sensation in both gender-affirming and oncologic mastectomy patients. Gender-affirming cases demonstrate earlier and more predictable recovery, whereas oncologic reconstruction studies show more variable outcomes. Further research is needed to standardize neurotization techniques and evaluate long-term sensory restoration. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .