Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein

Thromb Haemost. 2003 Jul;90(1):124-31.


C-reactive protein (CRP) is one of the main independent predictors of cardiovascular events. Oral post-menopausal estrogen replacement therapy (ERT) increases CRP levels, but the effect of transdermal ERT is not well documented. CRP, interleukine-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated in a randomised study of 196 healthy postmenopausal women, who were allocated to receive continuous oral estradiol-1beta, (n=63) or transdermal estradiol-1beta, (n=68) both combined with micronised progesterone, or place-bo (n=65). Oral estrogen increased CRP levels compared with both placebo (p=0.010) and transdermal estrogen (p=0.004) at 6 months. There was no significant effect of transdermal estrogen on CRP levels compared with placebo (p=0.997). No significant difference was found in the median changes for IL-6 and TNF-alpha between the three treatment groups. In conclusion, transdermal estrogen has no significant effect on CRP levels at 6 months, but CRP concentrations increased significantly with oral estrogen although no changes in cytokine levels were detected. The clinical relevance of these effects remains to be determined.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adult
  • Aged
  • C-Reactive Protein / analysis
  • C-Reactive Protein / biosynthesis*
  • Coronary Disease / blood
  • Coronary Disease / chemically induced
  • Coronary Disease / prevention & control*
  • Double-Blind Method
  • Estradiol / administration & dosage*
  • Estradiol / adverse effects
  • Estradiol / pharmacology
  • Female
  • Follow-Up Studies
  • Hormone Replacement Therapy / adverse effects
  • Hormone Replacement Therapy / methods*
  • Humans
  • Interleukin-6 / blood
  • Middle Aged
  • Postmenopause
  • Progesterone / administration & dosage
  • Thrombophilia / blood
  • Thrombophilia / chemically induced
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Progesterone
  • Estradiol
  • C-Reactive Protein