Major adverse cardiovascular events risk in menopausal women treated with oral estradiol/micronized progesterone versus conjugated estrogens/medroxyprogesterone: a claims data analysis in the USA

Objective: Using real-world data, the current study compared the risk of major adverse cardiovascular events (MACE) between two regulated combined oral hormonal products that are currently available to women in the USA: body-identical oral 17β-estradiol/micronized progesterone (E2/P4) and conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA). Methods: Women aged ≥40 years treated with E2/P4 or CEE/MPA were selected from a US claims database (April 2019–June 2021). The E2/P4 or CEE/MPA cohorts were defined based on the first dispensation of E2/P4 or CEE/MPA (index) as prescribed in the real world. Women with pre-index MACE hospitalization were excluded. Confounding was controlled via inverse probability of treatment (IPT) weighting. MACE risk was compared between the IPT-weighted cohorts using Cox and Poisson/negative binomial regression models. Results: The E2/P4 and CEE/MPA cohorts included 6520 and 29,426 women respectively (mean follow-up 1.2 and 1.4 years). In the IPT-weighted analyses, MACE rates were 23.5 versus 85.4 per 10,000 women-years among women treated with E2/P4 and CEE/MPA (IPT-weighted incidence rate ratio [IRR] 0.28, 95% confidence interval [CI] 0.17 − 0.45; IPT-weighted hazard ratio [HR] 0.37, 95% CI 0.27 − 0.50). Conclusions: Real-world evidence suggests that the MACE risk is significantly lower among women treated with E2/P4 compared to CEE/MPA.