JOURNAL ARTICLE
REVIEW
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Are all estrogens created equal? A review of oral vs. transdermal therapy.

BACKGROUND: To compare oral and transdermal delivery systems in domains of lipid effects; cardiovascular, inflammatory, and thrombotic effects; effect on insulin-like growth factor, insulin resistance, and metabolic syndrome; sexual effects; metabolic effects including weight; and effects on target organs bone, breast, and uterus.

METHODS: Review of the literature 1990-2010. Studies selected on basis of applicability, quality of data, and relationship to topic.

RESULTS: Data applicable to the comparisons of oral versus transdermal delivery systems for postmenopausal estrogen therapy were utilized to perform a review and formulate conclusions.

CONCLUSIONS: Significant differences appear to exist between oral and transdermal estrogens in terms of hormonal bioavailability and metabolism, with implications for clinical efficacy, potential side effects, and risk profile of different hormone therapy options, but neither results nor study designs are uniform. Bypassing hepatic metabolism appears to result in more stable serum estradiol levels without supraphysiologic concentrations in the liver. By avoiding first-pass metabolism, transdermal hormone therapy may have less pronounced effects on hepatic protein synthesis, such as inflammatory markers, markers of coagulation and fibrinolysis, and steroid binding proteins, while oral hormone therapy has more pronounced hyper-coagulant effects and increases synthesis of C-reactive protein and fibrinolytic markers. Both oral and transdermal delivery systems have beneficial effects on high-density lipoprotein cholesterol to low-density lipoprotein cholesterol ratios (oral>transdermal), while the transdermal system has more favorable effects on triglycerides. Incidence of metabolic syndrome and weight gain appears to be slightly lower with a transdermal delivery system. Oral estrogen's significant increase in hepatic sex hormone binding globulin production lowers testosterone availability compared with transdermal delivery, with clinically relevant effects on sexual vigor.

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