Introduction Both estradiol and misoprostol have been used for complete visualization of the transformation zone (TZ) in colposcopy. However, no consensus has been reached on the priority of one medication over the other. This study aimed to compare the efficacy of estradiol and misoprostol for complete visualization of TZ in colposcopy of premenopausal and postmenopausal women.

Methods In this clinical trial, 78 patients with unsatisfactory colposcopy were randomly divided into three groups using a block randomization software package. Group 1 (n=25) received 25 µg of vaginal estradiol for 14 days prior to colposcopy. Group 2 (n=27) received 400 µg of misoprostol 12 h prior to colposcopy. Group 3 (n=26) served as the control group and did not receive any medication. TZ visibility, age, BMI, history of vaginal delivery or sexually transmitted diseases or human papillomavirus (HPV) and drug-related side effects were compared among the three groups and also between premenopausal and postmenopausal women. Data were analyzed using analysis of variance (ANOVA), Kruskal-Wallis, Chi-square, and Fisher’s exact tests.

Results The percentage of complete TZ visualization was 72%, 55.6%, and 26.9% in the estradiol, misoprostol, and control groups, respectively (P=0.005). These values were 70%, 33.3%, and 0%, respectively, in postmenopausal women (P=0.043) and 60%, 72.7%, and 33.3%, respectively, in premenopausal women (P=0.152). With regard to drug-related side effects, there was no statistically significant difference between the three groups (P=0.374).

Conclusion/Implications Estradiol was significantly superior to misoprostol for complete visualization of TZ, particularly in postmenopausal women, with no difference in side effects.