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In a recent publication, under the section heading ‘Personal Perspectives’, Dr James Simon considers hypothetical comparisons between oral conjugated equine estrogens (CEE) and transdermal estradiol and between oral medroxyprogesterone acetate (MPA) and oral micronized progesterone for their effects on four primary outcomes of the Women’s Health Initiative (WHI) [1]: cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focused on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of non-oral estrogen administration. After a brief review of the WHI and a survey of the relevant literature in which the safety of these various hormone therapies was assessed or compared, the author used statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputed those risks into the WHI primary outcomes.


  • Amos Pines
    Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Simon JA. What if the Womens Health Initiative had used transdermal estradiol and oral progesterone instead? Menopause 2014 Jan 6. Epub ahead of print
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