VAG-4602: Vaginal estradiol tablets (Vagifem®) and endometrial cancer risk in the treatment of postmenopausal vaginal atrophy: A register-based cohort study in postmenopausal women

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Vagifem, Other LDVE product
• Medical condition to be studied:
  Atrophic vulvovaginitis

Population studied

• Age groups:
  Adults (46 to < 65 years)

  Adults (65 to < 75 years)
• Estimated number of subjects:
  500000

Study design details

• Main study objective:
  The aim of this study is to evaluate whether exposure to Vagifem® increases the rate of endometrial cancer in postmenopausal women.
• Outcomes:
  he primary objective is to investigate the hypothesis that there is no difference in risk of endometrial cancer between women using low dose vaginal estrogens (LDVE) (split into Vagifem® and other LDVE products) and women using no hormone replacement therapy to manage symptoms related to the postmenopausal phase. The secondary objective is to compare the rate of endometrial cancer for women exposed to Vagifem® 10 mcg and 25 mcg, respectively, with women that have been exposed to systemic cyclic HRT (defined as estrogen taken daily and progestogen taken in a cyclic pattern for 10 to 14 days of the month) or oral, transdermal and opposed injectable systemic HRT products.
• Data analysis plan:
  The main statistical analysis will compare patients initiating LDVE (new users), split into Vagifem® and other LDVE, in the study period in a 1:2 ratio with non-users, in an intention to treat fashion, i.e. the patient will be considered at risk after initiation of treatment regardless of treatment discontinuation. Propensity score matching methods will be employed involving the available risk factors, including previous use of HRT. The IR and the 95% confidence intervals will be presented both for the exposure groups and the comparator group. Hazard Ratio and 95% confidence interval will be estimated using a Cox proportion hazard rate model. For the secondary objective, the same methods will be used, with users of systemic cyclic HRT and oral, transdermal and opposed injectable systemic HRT products in the comparator group rather than non-users. A range of sensitivity analyses will be performed.