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What if the Women’s Health Initiative had used transdermal estradiol and oral progesterone instead?

Simon, James A. MD, CCD, NCMP, IF, FACOG

doi: 10.1097/GME.0000000000000169
Personal Perspective

The author considers hypothetical comparisons between oral conjugated equine estrogens and transdermal estradiol and between oral medroxyprogesterone acetate and oral micronized progesterone for their effects on four primary outcomes of the Women’s Health Initiative (WHI): cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focuses on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of nonoral 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 is assessed or compared, the author uses statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputes those risks into the WHI primary outcomes.

From the Department of Obstetrics and Gynecology, George Washington University School of Medicine, Women’s Health & Research Consultants, Washington, DC.

Received December 8, 2012; revised and accepted October 23, 2013.

Funding/support: Medical writing and editorial support (by Dory Greene; Infor-Med LLC, Warren, NJ) and statistical analysis support (by Howard Hait, MS; Edenridge Associates LLC, Wilmington, DE) were funded by ASCEND Therapeutics (Herndon, VA) and BESINS Healthcare (Bangkok, Thailand).

Financial disclosure/conflicts of interest: J.A.S. has served (within the last year) or is currently serving as consultant to or on the advisory boards of Abbott Laboratories/AbbVie Inc (North Chicago, IL), Agile Therapeutics Inc (Princeton, NJ), Amgen Inc (Thousand Oaks, CA), Apotex Inc (Toronto, Canada), ASCEND Therapeutics, BioSante (Lincolnshire, IL), Depomed Inc (Menlo Park, CA), Everett Laboratories Inc (West Orange, NJ), Intimina by Lelo Inc (San Jose, CA), Lupin Pharmaceuticals (Baltimore, MD), TherapeuticsMD (Boca Raton, FL), Meda Pharmaceuticals Inc (Somerset, NJ), Merck and Co Inc (Whitehouse Station, NJ), Novartis Pharmaceuticals Corp (East Hanover, NJ), Noven Pharmaceuticals Inc (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Novogyne (East Hanover, NJ), Pfizer Inc (New York, NY), Shionogi Inc (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Slate Pharmaceuticals Inc (Durham, NC), Sprout Pharmaceuticals (Raleigh, NC), Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), Warner Chilcott (Rockaway, NJ), and Watson Pharmaceutical Inc (Corona, CA). He has received (within the last year) or is currently receiving grant/research support from Abbott Laboratories/AbbVie Inc, BioSante, EndoCeutics Inc (Quebec, Quebec), Novo Nordisk, Novogyne, Palatin Technologies (Cranbury, NJ), Teva Pharmaceutical Industries Ltd, and Warner Chilcott. He has also served or is currently serving on the speakers bureaus of Amgen Inc, Eisai Inc (Woodcliff Lake, NJ), Merck and Co Inc, Novartis (Basel, Switzerland), Noven Pharmaceuticals Inc, Novo Nordisk, Novogyne, Shionogi Inc, Teva Pharmaceutical Industries Ltd, and Warner Chilcott. J.A.S. was the chief medical officer for Sprout Pharmaceuticals within the last year.

Address correspondence to: James A. Simon, MD, CCD, NCMP, IF, FACOG, Women’s Health & Research Consultants, Suite 450, 1850 M Street, NW, Washington, DC 20036. E-mail:

© 2014 by The North American Menopause Society.