Estrone conjugates

Transdermai system In contrast to oral estradiol, the skin metabolizes estradiol via the transdermai system only to a small extent. Therefore, transdermai use produces therapeutic serum levels of estradiol with lower circulating levels of estrone and estrone conjugates, and requires smaller total doses. 

O Connor KA, Brindle E, Hohnan DJ> Klein NA, Soules MR, Campbell KL, et al. Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research. Clin Chem 2003 49 1139-48. 

Oral substance or estrogens aqueous suspension (primarily estrone) Conjugated estrogens (50-65% sodium estrone... 

The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). 

Iverson, S. L. Shen, L. Anlar, N. Bolton, J. L. Bioactivation of estrone and its catechol metabolites to quinoid-glutathione conjugates in rat liver microsomes. Chem. Res. Toxicol. 1996, 9, 492-A99. 

A similar transformation occurs as a critical step in the total synthesis of (+)-estrone by a Diels-Alder cycloaddition-cycloreversion pathway (Eq. 80).227 It is worth noting that in this reaction the conjugated double bond is stereoselectively reduced while both an isolated double bond and a ketone carbonyl are preserved. 

Conjugated equine estrogens are composed of estrone sulfate (50% to 60%) and other estrogens such as equilin and 17 a-dihydroequilin. 

In STP effluents, total extractable estrogens and conjugates have been detected at levels up to 1 /jg/L [9,11,26]. Despite the wide variability in terms of removal efficiency reported for different WWTPs, a general trend has been observed with respect to the identity of the compounds most frequently detected in WWTP effluents. Thus, of the various compounds most commonly monitored - namely, estradiol, its metabolites estriol and estrone, and the synthetic estrogen ethynylestradiol - estrone is the most ubiquitous both in WWTP effluents and in environmental waters in general, while the most potent estrogens estradiol and ethynylestradiol have only occasionally been detected [26,40-42]. As for the conjugates, the very few studies that have attempted their determination pointed out estrone sulfates as the most abundant, while glu-curonides are most often found below the limit of detection [26,36,38,39]. 

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. 

Conjugated equine estrogens (Premarin) are the most commonly used estrogens in the treatment of menopause-associated vasomotor symptoms and osteoporosis. Premarin is a mixture of estrogen sulfates, including estrone, equilin, and 17-(3-dihydroequilin. The sulfate derivatives are orally active and are cleaved within the body to yield the active, unconjugated estrogen. 

Pharmacokinetics Readily absorbed from the gastrointestinal (Gl) tract. Widely distributed. Protein binding 50%-80%. Rapidly metabolized in liver and Gl tract to estrone sulfate and conjugated and unconjugated metabolites. Excreted in urine and bile. Half-life Unknown. 

Natural estrogens are inactive orally due to rapid metabolism in liver. Synthetic estrogens are well absorbed after oral administration as well as by transdermal application. Estradiol is metabolized to estrone and estriol. All these are conjugated and excreted in urine and bile. Synthetic... 

Estradiol-17 derived from an implant is indistinguishable from the endogenous esfradiol-17 in the circulatory animal s system. Following administration of radiolabeled estradiol-17 to calves, radioactivity in urine was mainly due to estradiol-17, with much lower amounts of esfrone. Apart of the free forms, both compounds were present as conjugates as well. Radioactivity in feces was primarily due to estradiol-17 and to estradiol-17 and estrone, each compound occurring in the nonconjugated form (1). 

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