Effect of topical vaginal estrogen after radiotherapy for cervical cancer: a randomized, double-blind pilot trial.

OBJECTIVE

To evaluate the effect of topical vaginal estriol on vaginal epithelial maturation, quality of life, and sexual function in survivors of cervical cancer treated with pelvic radiotherapy.

METHODS

This was a randomized, double-blind, placebo-controlled pilot trial including patients aged 18 to 55 years with cervical cancer who had completed definitive radiation therapy. Participants were randomized 1:1 to receive vaginal estriol cream or placebo for 6 months. Assessments were performed at baseline and at 3 and 6 months thereafter, with histological assessments at baseline and 6 months after the interventions. The primary outcome was histological vaginal epithelial maturation. Secondary outcomes included pain during speculum examination, clinical vaginal atrophy, health-related quality of life (assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer Module, and sexual function, assessed using the Female Sexual Function Index).

RESULTS

Sixty patients were randomized from May 2024 to April 2025. Vaginal estriol did not significantly improve histological vaginal epithelial maturation compared with placebo at six months, although both groups showed progressive epithelial recovery over time. Pain during gynecological examination and clinical vaginal atrophy improved during follow-up in both study arms without significant between-group differences. Patients receiving estriol demonstrated higher absolute improvement over time in the lubrication, orgasm, and total Female Sexual Function Index domains. At 6 months, normal sexual function was observed in 25.9% of patients in the estriol and 18.5% in the placebo group, with no significant difference between groups (p = .745).

CONCLUSIONS

Topical vaginal estriol did not improve histological vaginal epithelial maturation compared with placebo. Greater absolute improvements in some patient-reported Female Sexual Function Index domains suggest a potential benefit of vaginal estriol for sexual function that this study may not have been powered to detect.