Pharmacology and pharmacokinetics of estrogens

Abstract

The primary source of estrogen, ovarian 17 beta-estradiol, is normally converted to estrone and estriol, both of which are metabolized to their sulfate and glucuronide forms, as well as oxidated to nonestrogens. In postmenopausal women, the primary sources of estrogen are nonovarian, including the production of androstenedione from the adrenal cortex and its metabolism to estrone by the liver, adipose tissue, skeletal muscle, kidney, brain, and hair follicles. Estrogen circulates bound to sex hormone-binding globulin and albumin. The sulfate form may be a storage form of this hormone and is freely converted back to estrone and estriol. The glucuronide and sulfate forms have limited cell penetration; they are excreted mainly in the kidney, with little tubular reabsorption. Several theories have been advanced to explain the effects of estrogens on the basis of their receptors. A consideration of pharmacologic and pharmacokinetic characteristics reveals specific advantages and disadvantages of the preparations currently available for estrogen replacement therapy. Oral agents have the disadvantage of being subject to a considerable first-pass hepatic effect, resulting in their conversion to estriol, oxidation to nonestrogens, and conjugation to sulfate and glucuronide salts. These preparations can also be associated with poor patient compliance, as can injectable, topical, or suppository preparations. On the other hand, transdermal patches are not subject to a first-pass hepatic effect, provide relatively uniform serum levels, and may help alleviate the problem of noncompliance.