A Comparative Observational Study Evaluating the Incidence Rate of Endometrial Cancer in Women aged 50 Years and Over Who Use Low dose Vaginal Estrogen Unopposed by a Progestogen: A Post-authorization Safety Study in the United States and Sweden (Low dose vaginal estrogen and endometrial cancer)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Premarin, Estring, Oestring, Vagifem, Yuvafem, Imvexxy
• Anatomical Therapeutic Chemical (ATC) code:
  (G03CA03) estradiol

  estradiol
• Medical condition to be studied:
  Endometrial cancer metastatic

  Endometrial cancer recurrent

  Endometrial cancer stage 0

  Endometrial cancer stage I

  Endometrial cancer stage II

  Endometrial cancer stage III

  Endometrial cancer stage IV

  Endometrial cancer

Population studied

• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  152941

Study design details

• Main study objective:
  Estimate and compare IR of endometrial cancer in postmenopausal women aged >50 years with a uterus regardless of prior hormone therapy (any estrogen, progestin, E+P HT or opposed estrogen hormone therapy) in the following groups: a. New users of LDVE vs. non-users of vaginal estrogen b. New users of MDVE vs. non-users of vaginal estrogen c. New users of HDVC vs. non-users of vaginal estrogen
• Outcomes:
  The endpoint is the occurrence of endometrial cancer. In the United States, the cases of endometrial cancer will be identified using a validated algorithm in the United States and using the Swedish Cancer Register in Sweden.
• Data analysis plan:
  Propensity score matching will be applied to each cohort pair (comparison) with a 1:4 exposed:comparator matching ratio. Propensity scores will be estimated separately for each comparison, using logistic regression and a set of baseline covariates. Descriptive statistics and all additional analyses will be performed on the PS-matched cohorts. Baseline characteristics will be compared across the study cohorts to assess comparability. The IR of endometrial cancer and 95% confidence intervals (CIs) will be computed for each study cohort. Adjusted hazard ratios (HRs) will be calculated using Cox proportional hazards models to compare the hazard of endometrial cancer between 1) unopposed LDVE and non-users, 2) unopposed MDVE and non-users, 3) unopposed HDVC with non-users (US only).