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Biological Effects of Estradiol-17β in Postmenopausal Women: Oral Versus percutaneous Administration

Department of Reproductive Endocrinology Hopital Necker,75015 Paris, France
Department of Nutrition and Laboratoire d'Hemostase Hotel-Dieu 75004 Paris, France
Department of Medicine Broussais, 75014 Paris, France
Laboratoire D'Hormonologie INSERM U33 Hopital Du Kremlin-Bicetre, 94270 Paris, France

Address correspondence and reprint requests to R.Sitruk-Ware,Department of Reproductive Endocrinology, Hopital Necker, 149 ruede Sèvres, 75015 Paris, France.

To determine whether the route of administration or the type of estrogen used in estrogen replacement therapy (ERT) is more important in avoiding effects on hepatic function,24 postmenopausal women were studied before and at the end of 2 months of oral or percutaneous administration of the same estrogen, estradiol-17β (E₂). The treatments studied were oral micronized E₂, 2 mg/day (9 women); oral E₂ valerate, 2 mg/day (5 women), and percutaneous E₂, 3 mg/day (10 women). Specific plasma biological and biochemical markers of estrogenic action were evaluated, namely, E₂, estrone (E₁), LH, FSH, sex steroid binding protein (SBP), renin substrate, antithrombin activity,and lipoproteins (high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein triglycerides).Both oral and percutaneous administration of E₂ increased plasma E₂ levels up to midfollicular values and decreased LH and FSH levels into the same range. Oral administration of E₂ led to substantial increases in plasma Elf SBP, renin substrate, and VLDL levels, whereas AT decreased significantly. Percutaneous administration of E₂ led to a physiological plasma E₁/E₂ ratio and did not induce any change in hepatic proteins.

These data suggest that the route of administration of E₂ determines the biochemical response to ERT in postmenopausal women. SBP is the most sensitive marker of the liver action of estrogen, and triglycerides also are simple and useful markers for this effect. Percutaneous E₂ therapy is an effective method of ERT, and has no measurable effects on hepatic markers of estrogen action.

Received March 11, 1985.

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