Estrogens mestranol

Estrogens Mestranol i /0H Oral contraceptive - Effluents <1-8 ng L 1 [30] Degraded in aerobic... 

Clinical trials of these orally active progestins showed that they were effective as contraceptives with a success rate that exceeded 99%. These compounds were then marketed as obtained from the reaction sequence after appropriate purification. As the analytical methodology improved it became apparent that a small amount of an impurity was present in all active samples. An examination of the reaction scheme allowed ready identification of that by-product. Any unreduced estradiol methyl ether (13-1) will go to estrone methyl ether on oxidation this will then afford the potent orally active estrogen mestranol (9-1) on ethynylation. Subsequent... 

As far as the estrogens are concerned, the original estrogen, mestranol, was abruptly replaced by ethinylestradiol in most or all products after a wide-scale panic relating to the thrombosis issue in 1969. The motive lay entirely in the fact that the ethinylestradiol was about twice as... 

Another semisynthetic estrogen, mestranol, is the 3-O-methyl ether of EE (Fig. 46.6). Mestranol is a prodrug and, following oral administration, is rapidly metabolized to EE via hepatic O-demethylation. Mestranol and EE are used primarily in OC formulations (19). 

So it was in the 1980s, and so it might well have remained, but for one element the expiry of patents. The estrogen mestranol enjoyed no patent protection, but... 

Mestranol an estrogenic component of oral contraceptive drugs... 

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. 

Reaction of estrone with a metal acetylide affords 17a-ethynyl-173-hydroxy-estradiol (etbynylestradiol, 30a EE). This compound is equipotent with estradiol by subcutaneous administration, but it is 15 to 20 times as active when administered orally. Ethynylation of the methyl ether of estradiol analogously affords mestranol (30b), It should be noted that the same factors apply in these reactions as in previously discussed reductions at 17 almost the sole products of these reactions are those which result from attack of reagent from the least hindered a side of the steroid. Ethynylestradiol and mestranol are of special commercial significance since the majority of the oral contraceptives now on sale incorporate one or the other of the compounds as the estrogenic component. 

Two synthetic estrogens are used in hormonal contraceptives in the United States, ethinyl estradiol (EE) and mestranol. Mestranol must be converted to EE in the liver to be active. It is approximately 50% less potent than EE. Most combined oral contraceptives (OCs) contain estrogen at doses of 20 to 50 meg of EE daily. The contraceptive ring produces one-half the serum concentration of EE derived from a 30-mcg OC. 

In activated sludge, the synthetic estrogens ethynylestradiol and mestranol have been shown to remain stable and intact over 5 days, while progestogens are already up to more than 50% disintegrated after 48 h [32]. 

Estrogens Estradiol Estriol Estrone Ethynylestradiol Mestranol Contraceptive... 

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. 

Combined oral contraceptives contain one of the synthetic estrogens ethinylestradiol or mestranol. 

Synthetic steroid hormones retain the common steroid nucleus, but they may contain novel substituents that affect their pharmacological activity. The two most widely used synthetic steroid estrogens are ethinyl estradiol (Estinyl) and mestranol, found in oral contraceptives. Synthetic steroids containing an ethinyl substitution are metabolized more slowly. Thus, these synthetic steroid hormones have better oral absorption properties and extended biological half-lives than the natural estrogens. 

Approximately 50% of a dose of mestranol is de-methylated to form ethinyl estradiol. Ethinyl estradiol also can be deethinylated. Subsequently, the metabolism of these two synthetic estrogens proceeds by means of the same pathways as the natural steroid hormones. The principal metabolites of mestranol and ethinyl estradiol are hydroxylated derivatives that are conjugated with either glucuronic acid or sulfate. The synthetic steroid estrogens, in contrast to the natural estrogens, are excreted primarily in the feces. 

Today, a variety of therapeutic estrogens are produced semisynthetically from estrogen intermediates synthesized from diosgenin and other natural precursors. Two semisynthetic, orally active estrogens are ethinyl estradiol (5.27) and its 3-methyl ether (5.28, mestranol). Both of these are used in oral contraceptives (see section 5.8.3). Quinestrol (5.29) is another semisynthetic estrogen. The most important property of the semisynthetic estrogens is their increased oral effectiveness. 

Estrogen/progestogen combinations, oral conjugated estrogens/ medroxyprogesterone ethinyl estradiol/norethindrone acetate mestranol/norethindrone... 

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