Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice.

Objectives: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17β-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens.
Study Design: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records.
Main Outcome Measures: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA.
Results: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92).
Conclusions: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.
Competing Interests: Declaration of competing interest N. Panay has lectured and acted in an advisory capacity for a number of pharma companies, including Theramex. R.E. Nappi has lectured and acted in an advisory/consultant capacity for a number of pharma companies, including Theramex. P. Stute has been a consultant with honorarium for Theramex. S. Palacios has been a consultant with honorarium for Theramex and has lectured and acted in and advisory/consultant capacity for other pharma companies. T. Paszkowski has been a consultant with honorarium for Theramex and received honoraria as consultant/member of advisory boards/lecturer from a number of pharma companies, including Theramex. R. Kagan has been an Advisor/Consultant with honorarium and has lectured for a number of pharma companies, including TherapeuticsMD. D. F. Archer has been a consultant with honorarium for a number of pharma companies, including TherapeuticsMD. J. Heroux is an employee and the owner of Heroux Consulting, which received research funding for the conduct of the current study. M. Boolell is an employee of and stockholder in Theramex.
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