•Prospective, double-blind, randomized pilot study.•Compares efficacy of oxytocin and promestriene in Genitourinary Menopause Syndrome.•The two medications improved the three domains of the FSFI scales scores evaluated.•Both medications showed an increase in the thickness of the vaginal epithelium (p < 0.05).•Oxytocin and promestriene were both effective in Genitourinary Menopause Syndrome.