Effects of percutaneous estradiol and conjugated estrogens on the level of plasma proteins and triglycerides in postmenopausal women.

Percutaneous administration of estradiol (E2) is a new substitutive treatment for postmenopausal women. In order to compare hepatic action of percutaneous E2 with that of conjugated estrogens, 18 postmenopausal women were allocated at random to receive one of these two types of natural estrogens for 21 days. Eight patients (group I) received conjugated estrogens orally, 1.25 mg daily. Ten patients (group II) were told to apply percutaneous E2 ointment, 5 gm (i.e., 3 mg of E2), each evening on the abdominal skin. E2, estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), and several markers of estrogen action were evaluated before and after treatment. Both types of treatment were biologically effective, as indicated by the decrease in plasma gonadotropins and the increase in estrogen levels. However, conjugated estrogens produced a greater increase in E1 than in E2; hence, the E2/E1 ratio was 0.57 in group I, whereas it was approximately 1 in group II. Plasma renin substrate increased significantly (by 180%) in group I but not in group II. In the same way, conjugated estrogens produced a modest (12%) but significant decrease in antithrombin III, whereas there was no variation with percutaneous E2. Sex steroid-binding protein was the most sensitive parameter for the hepatic action of estrogen, and increased by 18.66% with percutaneous E2 and by 150% with conjugated estrogens. Plasma triglycerides tended to increase in group I and to decrease in group II, but not significantly. Therefore, percutaneous administration of of E2, in contrast to conjugated estrogens, can produce plasma levels of estrogens closer to those observed in the follicular phase and less alterations in protein synthesis. This lesser toxicity may be explained partially by the route of administration, since with percutaneous administration of E2, the steroid bypasses the liver.