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Review
. 2025 Aug 28.
doi: 10.1007/s00266-025-05179-y. Online ahead of print.

Targeted Nipple-Areola Complex (NAC) Reinnervation (TNR): A Systematic Review and Meta-Analysis

Antoinette T Nguyen  1 , Rebeka A Dejenie  2 , Rena A Li  3 , Marco F Ellis  3 , Robert D Galiano  4
Affiliations
Review

Targeted Nipple-Areola Complex (NAC) Reinnervation (TNR): A Systematic Review and Meta-Analysis

Antoinette T Nguyen et al. Aesthetic Plast Surg. .

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, I2 = 67.78%; MD: - 1.73, 95% CI: - 1.91 to - 1.56, p < 0.0001, I2 = 0%; MD: - 1.59, 95% CI: - 1.81 to - 1.37, p < 0.0001, I2 = 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 .

Keywords: Gender-affirming surgery; Mastectomy; Meta-analysis; Nipple-areola complex; Systematic review; Targeted nipple reinnervation.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethics Approval and Consent to Participate This article does not contain any studies with human participants or animals performed by any of the authors. Consent for Publication: For this type of study, informed consent is not required.

References

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