ABSTRACT

Background: There is a great need for non-estrogenic treatment of vulvovaginal atrophy (VVA) symptoms affecting sexual function and quality of life. Women with breast cancer on anti-estrogenic therapy are particularly vulnerable and in need of help. The primary aim of this proof-of-concept trial was to evaluate the efficacy of vaginal tamoxifen in reducing the most troublesome VVA symptom.
Methods: In this randomized, double blind, placebo-controlled study, 115 postmenopausal women, with or without breast cancer, were randomized to 20 mg vaginal tamoxifen once weekly or placebo (1:1). Follow-up after one and three-months of treatment, included self-reported VVA symptoms on the Endocrine Symptom Subscale of FACT-B, and gynecologic exams for VVA score and measurement of vaginal pH and endometrial thickness.
Findings: After three months, 37 (68.6 %) of women on vaginal tamoxifen reported their most troublesome VVA symptom to be mild or not present at all, whereas corresponding number in the placebo group was 5 (9.1 %), p <0.001. Expressed as odds, women on vaginal tamoxifen were more likely to report no or minor symptoms after three-months, OR 21.76 (95 % CI 7.36 – 64.3). The improvement in self-reported outcomes was accompanied by improvements in VVA scores and vaginal pH, p < 0.001.
Interpretation: This study has demonstrated that more than two-thirds of the women on vaginal tamoxifen improved in their most troublesome VVA symptom. This is likely due to a tamoxifen-induced estrogen agonistic effects in vagina in a low-estrogen environment. While findings are promising, further studies on improved vaginal administration and endometrial safety concerns are needed