Incidence of endometrial cancer among postmenopausal women using vaginal estrogen compared to estrogen and progestin combination hormone therapy

OBJECTIVE: To estimate the incidence of endometrial cancer in women who used low, moderate, or high-dose vaginal estrogen compared with women who used estrogen plus progestogen therapy (EPT). METHODS: This cohort study included postmenopausal women from the United States Healthcare Integrated Research Database (HIRD) and the Swedish National Registers. The index date was the date of treatment initiation between January 1, 2007 and December 31, 2021, in the HIRD or between July 1, 2007 and December 31, 2019, in Sweden. Participants had at least 1 year of baseline continuous health plan enrollment or 2 years of Swedish residency, and no history of hormone therapy use, hysterectomy, or endometrial cancer. Hazard ratios (HR) and confidence intervals were estimated using Cox proportional hazards models adjusted for demographic, comorbid, and prescription history. RESULTS: In the HIRD, the HR for endometrial cancer when comparing low-dose vaginal estrogen to EPT was 0.74 (0.45-1.22). In the Swedish Registers, this association was 1.34 (0.84-2.13). Moderate-dose vaginal estrogen initiation was positively associated with endometrial cancer compared with EPT in the HIRD (HR= 1.95 ;0.86-4.45) but not in Sweden (HR=1.15; 0.73-1.83). High-dose Premarin vaginal cream had an association of 0.84 (0.49-1.44) compared with EPT (HIRD). CONCLUSIONS: Rates of endometrial cancer among women using low and high-dose vaginal estrogens were comparable to rates among women using EPT.