OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary
Abstract OBJECTIVE: This systematic review included clinical trials of Food and Drug Administration-approved vaginal estrogens. The primary objective of this systematic review was to examine the comparative safety of the Food and Drug Administration-approved vaginal estrogen preparations among postmenopausal women. METHODS: We performed a PubMed search of the primary literature from January 1, 1966 to July 16, 2019 for English-language clinical trials. Manual review of retrieved citations identified additional citations. RESULTS: Of 882 retrieved citations, 75 clinical trials met inclusion criteria. Maximum trial duration was 52 weeks. None of the trials predesignated breast or endometrial cancer, cardiovascular events, or venous thromboembolism as primary outcomes. Studies were not designed to rule out an increase in endometrial carcinoma risk with long-term use of vaginal estrogen. There were few head-to-head comparisons. Fifty trials examined serum sex steroid and gonadotrophin le