The effectiveness of 12.5 and 25 micrograms 17β‐estradiol vaginal gel for postmenopausal vaginal atrophy: A randomized non‐inferiority trial

Abstract Objective To compare the effectiveness of two dosages (12.5 and 25 μg) of 17β‐estradiol vaginal gel for treating postmenopausal vaginal atrophy. Methods A randomized non‐inferiority trial was conducted in the Gynecologic Endocrinology and Menopause Clinic of a university hospital from June 2022 to February 2023. A total of 80 postmenopausal women were randomly assigned to receive a 12.5 μg (half‐dose) or 25 μg (full‐dose) 17β‐estradiol vaginal gel daily for 14 days, followed by twice‐weekly for 10 weeks. Efficacy outcomes were vaginal maturation value (VMV), vaginal health index (VHI), vaginal pH, most bothersome symptoms (MBSs), and female sexual function index (FSFI). Safety outcomes were endometrial thickness, serum estradiol level, and adverse events. All study outcomes were evaluated at three time points: baseline, week 4, and week 12. Results At week 12, both the half‐dose and full‐dose groups displayed a significant improvement in the VMV, with median (25th–75th percentile) of 67.3 (59.1–72.9) and 71.8 (60.3–79.5), respectively. While the full‐dose group exhibited slightly greater improvement in VMV, the difference was not statistically significant. The upper bound of the 95% confidence interval (CI) for the median difference in VMV was below the predefined non‐inferiority margin of 15 (4.5, 95% CI: −0.5, 10.0; P = 0.082). Additionally, both groups demonstrated significant improvements from baseline in all efficacy outcomes without any safety concerns. Conclusion Both 12.5 and 25 μg doses of 17β‐estradiol vaginal gel are safe and effectively improve vaginal atrophy in postmenopausal women. The non‐inferiority of the half‐dose to the full‐dose suggests its potential as a cost‐effective treatment option with comparable benefits.