Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women

Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):e164-7. doi: 10.1161/01.ATV.0000140198.16664.8e. Epub 2004 Jul 29.


Objectives: Previous studies indicated that oral estrogen increased C-reactive protein by a first-pass hepatic effect. In this study, we determine whether the route of estrogen administration influences serum amyloid A (SAA), another acute-phase protein produced by the liver, and the SAA content of the high-density lipoprotein (HDL-SAA) in postmenopausal women.

Methods and results: In 29 postmenopausal women without coronary heart disease, we conducted a randomized crossover placebo-controlled study to compare effects of transdermal versus oral estrogen on SAA and HDL-SAA. SAA, apolipoprotein A-I, HDL, and HDL-SAA were measured before and after 8 weeks of transdermal estradiol (100 microg per day), oral-conjugated estrogens (0.625 mg per day), or placebo. We found that oral estrogen significantly increased levels of SAA, HDL, and HDL-SAA, whereas transdermal estrogen reduced both SAA and HDL-SAA but had no effect on HDL in the same women.

Conclusions: Oral estrogen increased SAA and altered HDL composition to contain a higher level of SAA by a first-pass hepatic mechanism. Because elevated SAA levels predict adverse prognosis in healthy postmenopausal women, and elevated HDL-SAA levels have been shown to interfere with HDL function, the route of administration may be an important consideration in minimizing side effects of estrogen replacement therapy on cardiovascular outcomes.

Publication types

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

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Cross-Over Studies
  • Estrogens / administration & dosage*
  • Estrogens / pharmacology*
  • Female
  • Humans
  • Lipoproteins, HDL / blood*
  • Middle Aged
  • Postmenopause / physiology*
  • Serum Amyloid A Protein / metabolism*


  • Estrogens
  • Lipoproteins, HDL
  • Serum Amyloid A Protein