Comparison of estradiol hemihydrate 10 µg vaginal tablets versus estradiol hemihydrate 10 µg vaginal gel in postmenopausal women with vaginal atrophy: a randomized crossover study.

AIM: This randomized crossover study evaluated the 12 week efficacy of a 10 µg estradiol hemihydrate vaginal tablet versus a vaginal gel (available at Siriraj Hospital, Thailand) in postmenopausal women with vaginal atrophy. Secondary endpoints included the most bothersome symptom, vaginal health index (VHI), vaginal pH, female sexual function index, serum estradiol, endometrial thickness, ease of use, comfort, and satisfaction. METHODS: Ninety participants were randomized to receive either the 10 µg estradiol tablet or the gel daily for 2 weeks, followed by twice-weekly application for 10 weeks. Afterward, they switched to the alternate treatment for another 12 weeks using the same dosing regimen. Assessments of VHI, pH, vaginal maturation value (VMV), female sexual function index, endometrial thickness, and estradiol levels were conducted at baseline, 12 weeks, and 24 weeks. RESULTS: Eighty-five participants completed the study. At 12 weeks (intention-to-treat analysis), the gel significantly increased VMV compared with the tablet (60.16 ± 12.00 vs 51.62 ± 23.77; P = 0.035; 95% CI 0.54 to 16.46), although the 95% CI included the noninferiority margin of 15. Per-protocol analysis showed no significant difference between groups. VHI improved, and pH decreased more markedly with the gel at 12 weeks. By 24 weeks, there were no significant between-group differences in VMV, pH, or most bothersome symptom. Acceptability was high for both treatments, although 55.3% of participants indicated a preference for continued gel use. CONCLUSIONS: Noninferiority of the 10 µg estradiol hemihydrate tablet relative to the gel could not be established. However, both treatments exhibited clinical benefits and high patient satisfaction, providing valuable insights for therapeutic decision-making in postmenopausal vaginal atrophy.