Estradiol elimination

A solution of 1.5 grams of 17a-ethynyl estradiol in 50 cc of absolute ethanol is added slowly to a mixture of 3 grams of cyclopentyl bromide and 2 grams of potassium carbonate. This mixture is heated to reflux and stirred for 3 hours, then filtered. Most of the alcohol is eliminated by distillation and the resulting solution diluted with water, and cooled in an ice-bath. The product which precipitates Is collected by filtration, washed and dried. After recrystallization from methanol the 3-cyclopentyl ether of 17a-ethynyl estradiol shows a melting point of 107° to 108°C. 

Estramustine, an oral drug, also inhibits microtubule assembly and has weak estrogenic activity at the estradiol hormone receptors of the cell. Approximately 75% of a dose of estramustine is absorbed.15 The terminal half-life ranges between 20 to 24 hours, with nonrenal excretion as the major route of elimination. This drug is used primarily for the treatment of prostate cancer, but its use is limited by the side effects, which include nausea and vomiting, diarrhea, thromboembolic events, and gynecomastia. 

The natural hormones are unsuitable for oral application because they are subject to presystemic hepatic elimination. Estradiol is converted via estrone to estriol by conjugation, all three can be rendered water soluble and amenable to renal excretion. The major metabolite of progesterone is pregnandiol, which is also conjugated and eliminated renally. 

Estrogens - Ethinyl estradiol is rapidly absorbed with peak concentrations attained in 1 to 2 hours. It undergoes considerable first-pass elimination. Mestranol is demethylated to ethinyl estradiol. Ethinyl estradiol is approximately 97% to 98% bound to plasma albumin. Half-life varies from 6 to 20 hours. It is excreted in bile and urine as conjugates, and undergoes some enterohepatic recirculation. 

In vitro data show that both etonogestrel and ethinyl estradiol are metabolized in liver microsomes by the cytochrome P450 3A4 isoenzyme. Etonogestrel and ethinyl estradiol are primarily eliminated in urine, bile, and feces. 

The first human experience with a 17(3-estradiol-eluting stent was recently published (35). The Estrogen and Stents to Eliminate Restenosis (EASTER) trial was a single-center feasibility study testing l7(3-estradiol-eluting BiodivYsio stents in 30 patients with de novo coronary lesions. The purpose of the EASTER study was to evaluate the feasibility of 17(3-estra-diol-eluting stents to inhibit restenosis in humans. 

Six month angiography after 17 -estradiol-eluting stent implantation in circumflex artery demonstrates late loss of only 0.13 mm. Abbreviations EASTER, estrogen and stents to eliminate restenosis FU, follow-up. 

Lee YJ, Kusuhara H, Sugiyama Y. Do multidrug resistance-associated protein-1 and -2 play any role in the elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione across the blood-cerebrospinal fluid barrier J Pharm Sci 2004 93 99-107. 

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