Sensory outcomes after targeted nipple-areola complex reinnervation: A systematic review and meta-analysis

Targeted nipple-areola complex (NAC) reinnervation (TNR) aims to restore nipple sensation after gender-affirming (GA) chest surgery and oncologic mastectomy; however, the outcomes have not been systematically synthesized.

We performed a PRISMA systematic review (PROSPERO CRD420250653209; March 20, 2025) of the PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov databases. Two independent reviewers performed screening and data extraction. Risk of bias was assessed using ROBINS-I. Random-effects meta-analysis pooled postoperative Semmes-Weinstein (SW) monofilament thresholds as mean differences (TNR minus control) at the longest comparable follow-up. Included studies were observational (prospective and retrospective cohorts and case series).

Ten studies were included (4 GA; 6 oncologic/prophylactic), representing 281 unique patients. The meta-analysis included three comparative cohorts. TNR was associated with improved nipple sensation (-1.40 SW units; 95% CI -1.95, -0.86; I² 58.1%). In a GA subgroup (2 studies), the pooled effect was similar (-1.54; 95% CI -2.28, -0.80; I² 74.9%). Single-arm studies reported recovery of protective sensation after TNR. In the largest comparative cohort with multidimensional quantitative sensory testing, NAC cold detection differed by 11.1 °C (95% CI 7.6, 14.6), and NAC 2-point discrimination was present in 40% of TNR patients versus 0% of controls. In a nipple erection substudy, nipple erection was reported in 73% (16/22) of TNR nipples versus 39% (7/18) of controls.

TNR was associated with improved postoperative NAC sensory outcomes, but the available evidence was observational and subject to moderate-to-serious risk of bias. Larger prospective multicenter studies with standardized sensory testing, longer follow-up, and validated patient-reported outcomes are needed.