BACKGROUND: Several anatomical and functional changes occur during menopause and lead to female sexual dysfunction (FSD). The use of energy-based devices to improve women's sexual health brings an innovative scenario. AIM: To evaluate the effect of non-invasive radiofrequency (RF) treatment compared to vaginal estrogen therapy (E) and vaginal moisturizer (M) in postmenopausal women with FSD. MATERIALS & METHODS: Thirty-two sexually active postmenopausal women aged 45-75 years were enrolled in a single center randomized controlled trial with three intervention arms: non-invasive RF, vaginal estrogen (E), or vaginal moisturizer (M) treatment. Assessments at baseline, and 4 months were conducted using the Female Sexual Function Index (FSFI). The primary outcome of this RCT was an assessment of the effect of RF on FSD compared to that of E and M. RESULTS: According to the total FSFI score, 100 % of participants in the RF and E arms and 90 % in the M arm had sexual problems at the baseline. The mean age of the participants was 58+/-5.3, 57.9+/-6.3, and 59.6+/-6.0 years in the RF, E, and M arms, respectively (p = 0.741). After 4 months of follow-up, FSD had ameliorated by 146.1 % in the RF arm (improvement of 17.32 points in the total FSFI score), with no significant improvement in the other arms (p = 0.009). We observed improvements in sexual desire (1.32 points in the partial FSFI score), arousal (2.37 points in the partial FSFI score), and orgasm (2.8 points in the partial FSFI score) only in the RF arm (p = 0.004, p <
0.001, and p <
0.001, respectively). CLINICAL IMPLICATIONS: The use of an energy-based device independently of hormonal therapy to improve female SF is very promising. Our findings may contribute to treatment decisions when there is failure of vaginal estrogen therapy, a need for a combination of treatments, or a patient preference for the use of energy-based devices, in postmenopausal women with FSD. CONCLUSION: Non-invasive RF treatment for FSD showed superior efficacy compared to vaginal estrogen therapy and vaginal moisturizer after 4 months of follow-up. Further studies with longer follow-up periods are needed to corroborate these findings and evaluate the long-term effects of non-invasive RF therapy on sexual function.