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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:e164.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Contrasting Effects of Oral Versus Transdermal Estrogen on Serum Amyloid A (SAA) and High-Density Lipoprotein–SAA in Postmenopausal Women

Aamer Abbas; Paul J. Fadel; Zhongyun Wang; Debbie Arbique; Ishwarlal Jialal; Wanpen Vongpatanasin

From the Department of Internal Medicine, University of Texas, Dallas.

Correspondence to Wanpen Vongpatanasin, MD, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, J4.134, Dallas, TX 75390-8586. E-mail wanpen.vongpatanasin{at}utsouthwestern.edu

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 µg 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.

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. 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 administration route may be an important consideration in minimizing side effects of estrogen replacement therapy on cardiovascular outcomes.

Key Words: hormones • inflammation • serum amyloid A • menopause • HDL

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