Estrone sulfate

Overview

E1S itself is biologically inactive, with less than 1% of the relative binding affinity of estradiol for the ERα and ERβ, but it can be converted by steroid sulfatase (also called estrogen sulfatase) into estrone, which is an estrogen. Simultaneously, estrogen sulfotransferases convert estrone to E1S, resulting in an equilibrium between the two steroids in various tissues. E1S is thought to serve as a long-lasting reservoir for estrone and estradiol in the body. In addition to its biological role, as the sodium salt, sodium estrone sulfate, E1S is the primary active estrogen in conjugated equine estrogens (Premarin) and esterified estrogens. Aside from its presence in these estrogen formulations, E2S is not available as a commercial pharmaceutical drug. However, it is available as estropipate (piperazine estrone sulfate), a salt of E1S and piperazine.

When exogenous estradiol is administered orally, it is subject to extensive first-pass metabolism (95%) in the intestines and liver. A single administered dose of estradiol is absorbed 15% as estrone, 25% as estrone sulfate, 25% as estradiol glucuronide, and 25% as estrone glucuronide. Formation of estrogen glucuronide conjugates is particularly important with oral estradiol as the percentage of estrogen glucuronide conjugates in circulation is much higher with oral ingestion than with parenteral estradiol. Estrone glucuronide can be reconverted back into estradiol, and a large circulating pool of estrogen glucuronide and sulfate conjugates serves as a long-lasting reservoir of estradiol that effectively extends its terminal half-life of oral estradiol. In demonstration of the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol, the terminal half-life of oral estradiol is 13 to 20 hours whereas with intravenous injection its terminal half-life is only about 1 to 2 hours.