Context: Symptoms of vulvo-vaginal atrophy/genito-urinary syndrome of menopause (VVA/GSM) are common in breast cancer survivors (BCS), as a consequence of cancer and its treatment. They influence many dimensions of well-being and are often overlooked and not fully addressed in clinical practice. Sexual function is strongly affected and a multitude of factors may contribute to sexual distress both in natural menopausal women (NMW) and in BCS. Objectives: to relate sexual function and distress to the severity of objective signs and subjective symptoms of VVA/GSM in NMW and BCS. Methods: NMW (n=33) and BCS (n=30) complaining of moderate/severe VVA symptoms (dryness and others) filled in: 1) Female Sexual Function Index (FSFI); 2) (Female Sexual Distress Scale-Revised (FSDS-R); 3) Hospital Anxiety and Depression Scale (HADS); 4) Women’s Health Questionnaire (WHQ); 5) Vulvovaginal Symptoms Questionnaire (VSQ). Maturation Index (MI) and the Vaginal Health Index (VHI) were performed. Results: Mean age was 56.0±5.4 yrs in NPW and 48.9±8.7 yrs in BCS (p <.001) and the median age at menopause was 49 (95%CI: 48-50) and 44 yrs (95%CI: 41-45.8), respectively (p <.001). VHI was significantly lower in BCS (10.9±2.8 vs 13.3±3.3) as compared with NMW (p <.003) and a significant higher number of BCS [n=27, 90% vs NMW n=21, 63.6% (c2:5.9; p=.014)] scored <15 (VHI cut-off score). Almost the totality of BCS had <5% superficial cells [median 0 (95%CI: 0-0) vs 5 (95%CI: 0-10), p <.001)]. VVA symptoms reported by BCS and NMW were superimposable, as well as the emotional, social and sexual impact. Sexual behaviour was the only WHQ dimension scoring differently in BCS vs NMW (p=.002). Sexual function was lower in BCS in respect with NMW (p <.005). Median sexual distress was higher in BCS (p <.001), as well as mean HADS score (p <.02). Sexual function was significantly lower (p=.004) and distress higher (p=.006) in women with severe VVA (VHI<15) and with <5% superficial cells (p=.05, for both). The best model to predict a better BCS sexual function includes a VHI score> 14 (3; p=.006) and a lower HADS score (-2.8; p=.01). HADS score is the only predictor of sexual distress (2.8; p=.009) in BCS, whereas VSQ total score (2.5; p=.02) is the only predictor of sexual distress in NMW. Conclusions: This study showed that the objective condition of VVA/GSM and the subjective impairment of sexual function are more severe in BCS in comparison with NMW.