Venous thromboembolism and cardiovascular disease complications in menopausal women using transdermal versus oral estrogen therapy

Menopause. 2016 Jun;23(6):600-10. doi: 10.1097/GME.0000000000000590.


Objective: To evaluate the risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) complications, and assess healthcare costs in menopausal women using an estradiol transdermal system versus oral estrogen therapy (ET).

Methods: Health insurance claims from 60 self-insured US companies from 1999 to 2011 were analyzed. Women at least 50 years of age, newly initiated on transdermal or oral ET, were included. Cohorts were matched 1:1 based on exact factors and propensity score-matching methods. The incidence rate ratios (IRRs) of CVD complications, as well as VTE and other CVD events separately, were assessed through conditional Poisson models. Cohorts were also compared for healthcare costs using linear regression models to assess per-patient per-month cost differences. Confidence intervals (CIs) and P values were determined using a nonparametric method for cost outcomes.

Results: From each cohort, 2,551 users were matched to form the study population. A total of 274 transdermal ET users developed CVD complications compared with 316 women in the oral ET cohort (adjusted IRR 0.81; 95% CI, 0.67-0.99). Transdermal ET users also incurred lower adjusted all-cause and VTE/CVD-related healthcare costs relative to oral ET users (all-cause per-patient per-month cost difference [95% CI] = $41 [-34; 137], P = 0.342).

Conclusions: This large matched-cohort study based on real-world data suggests that women receiving transdermal ET have significantly lower incidences of CVD events compared with those receiving oral ET, and that they also incur lower healthcare costs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous*
  • Administration, Oral*
  • Cardiovascular Diseases / epidemiology*
  • Cohort Studies
  • Estradiol / administration & dosage
  • Estrogen Replacement Therapy / adverse effects
  • Estrogen Replacement Therapy / economics
  • Estrogen Replacement Therapy / methods
  • Estrogens / administration & dosage*
  • Estrogens / adverse effects
  • Female
  • Health Care Costs
  • Humans
  • Insurance Claim Reporting
  • Menopause*
  • Middle Aged
  • Retrospective Studies
  • Venous Thromboembolism / epidemiology*


  • Estrogens
  • Estradiol