The Safety of Local Hormonal Treatment for Vulvovaginal Atrophy in Women With Estrogen Receptor-positive Breast Cancer Who Are on Adjuvant Aromatase Inhibitor Therapy: Meta-analysis

Atrophic vaginitis is a relatively common adverse effect of aromatase inhibitors used as an adjunctive treatment for breast cancer. Vaginal estrogen therapy is a treatment option, but the safety of its use in estrogen receptor-positive breast cancer remains understudied. The aim of our study was to determine the safety of local hormonal treatment of vulvovaginal atrophy in women treated with aromatase inhibitors. Our meta-analysis was based on a systematic search of the literature and selection of high-quality evidence. The safety of local hormonal therapy of vaginal atrophy in women on aromatase inhibitors were summarized using calculators built by the authors; heterogeneity was assessed by the Cochrane Q test and I2 values. Several types of bias were assessed; publication bias was calculated by a funnel plot and the Egger regression. Eleven studies fulfilled the inclusion criteria for our study. After 8 weeks of local hormonal treatment, there was no change in the serum levels of luteinizing hormone and estradiol, whereas sex hormone binding globulins were low, and follicle stimulating hormone was almost doubled compared with the baseline. Adverse effect rates of vaginal discharge, facial hair growth, urinary tract or yeast infection, and vaginal or vulvar itching and/or irritation did not show significant changes in the sensitivity analysis, with exception of a single trial. Current evidence suggests that vaginal estrogen administration in postmenopausal women with a history of breast cancer is not associated with systemic absorption of sex hormones and may provide indirect evidence for the safety of their use.