Abstract PS1-05-26: Vaginal estrogen versus non-hormonal moisturizer for breast cancer survivors on aromatase inhibitor therapy: a randomized, controlled trial

Abstract Background: Among post-menopausal breast cancer survivors, more than 60% experience atrophic vaginitis, often resulting in impaired quality of life and sexual dysfunction. Nonetheless, vaginal dryness is commonly an unmet need among breast cancer survivors. While vaginal estrogen is a proven, effective treatment for atrophic vaginitis, it has not been adequately studied in Estrogen Receptor-positive (ER+) breast cancer survivors. Methods: In this randomized, controlled, unblinded clinical trial, we enrolled ER+ breast cancer survivors on adjuvant aromatase inhibitor (AI) therapy who were suffering from atrophic vaginitis. Women were assigned to receive either Replens® (a non-hormonal vaginal moisturizer) or vaginal estrogen. Based on patient preference, patients randomized to the estrogen arm chose between 6 months of Vagifem® vaginal tablets (10 mcg daily for the first 2 weeks, then twice a week thereafter) or Estring® vaginal ring (2 mg, placed every 3 months). We tested serum estradiol levels by tandem mass spectrometry (TMS) at several time points in the estrogen arm, and only at baseline & end of study in the Replens arm. Study duration was 24 weeks. The primary endpoint was vaginal dryness, as measured by a validated questionnaire. Secondary endpoints include sexual functioning, vaginal pH, and serum estradiol values. Results: Twenty-three patients were enrolled on the study, with 12 patients assigned to the Replens arm. Of the 11 patients assigned to the vaginal estrogen arm, 8 chose Estring and 3 chose Vagifem. The Vaginal Dryness scores (assessed on a scale from 0 to 4) in the estrogen arm improved by an average of 1.6 points, compared to 0.9 points in the Replens arm, which was a statistically significant improvement (p = 0.044). Similarly, there was a more significant reduction in vaginal pH in the vaginal estrogen arm as compared to the non-hormonal treatment, indicating return to healthier vaginal environment in the estrogen arm (p = 0.0286). We observed an improvement in patient-assessed dyspareunia, which was assessed on a scale from 0 to 10. Women on the estrogen arm saw an improvement of 4.8 points, whereas the women receiving nonhormonal treatment improved by an average of 1.7 points (p = 0.048). However, other sexual functioning parameters (libido, ability to achieve orgasm, sexual satisfaction, and relationship with partner) were not significantly different between the 2 groups. Serum estradiol levels remined low through the first 12 weeks in the estrogen arm and exceeded safety threshold (27 pg/mL at 2 weeks, or 12 pg/mL for the remainder of the study) for two of the 11 patients in the estrogen arm at 24 week. One of these patients was taking Vagifem, and her estradiol level rose to 21.8 pg/mL at 6 months. The other patient was using Estring, and her estradiol level increased to 16 pg/mL. Conclusions: Vaginal estrogen is a more effective treatment for vaginal dryness and dyspareunia compared to nonhormonal vaginal moisturizer. Serum estradiol levels remained low for 12 weeks, suggesting this duration of treatment may be considered in select patients. Some patients had an increase in estradiol level at 24 weeks, though its cause and clinical significance are uncertain. Further study is warranted as to why the serum estradiol rise occurred with a longer period of vaginal estrogen treatment. Citation Format: P. Niravath, M. Rimawi, A. Puri, K. Sun, H. Mai, S. Mathur, S. Hilsenbeck, D. Antosh, R. High, S. Hoopes, L. Langsjoen, A. Brock, J. Nangia, J. Chang, C. Osborne. Vaginal estrogen versus non-hormonal moisturizer for breast cancer survivors on aromatase inhibitor therapy: a randomized, controlled trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-05-26.