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

Menopause. 2014 Jul;21(7):769-83. doi: 10.1097/GME.0000000000000169.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adult
  • Breast Neoplasms / chemically induced
  • Cardiovascular Diseases / chemically induced
  • Dose-Response Relationship, Drug
  • Estrogen Replacement Therapy / adverse effects
  • Estrogen Replacement Therapy / methods*
  • Female
  • Hot Flashes / drug therapy*
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects
  • Menopause
  • Middle Aged
  • Progesterone / administration & dosage*
  • Progesterone / adverse effects
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Venous Thromboembolism / chemically induced
  • Women's Health*


  • Progesterone
  • Medroxyprogesterone Acetate