Estrogens chlorotrianisene

Clomiphene citrate, a partial estrogen agonist, is closely related to the estrogen chlorotrianisene (Figure 40-3). This compound is well absorbed when taken orally. It has a half-life of 5-7 days and is excreted primarily in the urine. It exhibits significant protein binding and enterohepatic circulation and is distributed to adipose tissues. 

Estrogens, estrone (28.1.9), estradiol (28.1.17), ethynylestradiol (28.1.26), diethylstilbe-strol (28.1.33), and chlorotrianisene (30.5.2), are used for palliative treatment of postmenopausal breast cancer, prostate cancer, and breast cancer in men. It is highly probable that the mechanism of action is similar to the mechanism of action of androgens. 

In addition to estrogen agonists based on steroid structures, a variety of nonsteroidal estrogens have also been synthesized and used clinically dienestrol (5.30), diethyl-stilbestrol (5.31), benzestrol (5.32), hexestrol (5.33), methestrol (5.34), methallenestril (5.35), and chlorotrianisene (5.36). 

In addition to the steroidal estrogens, a variety of nonsteroidal compounds with estrogenic activity have been synthesized and used clinically. These include dienestrol, diethylstilbestrol, benzestrol, hexestrol, methestrol, methallenestril, and chlorotrianisene (Figure 40-3). 

Chlorotrianisene does not bind in vitro to the uterine estrogen receptor but has potent estrogenic and antiestrogenic actions in vivo, suggesting that it is a prodrug. Its antiestrogenic activity has been proposed to be due to a reactive intermediate (1). 

Clinically important, potentially hazardous interactions with amphotericin B, chlorotrianisene, colestyramine, diuretics, estrogens, furosemide, insulin, live vaccines, methotrexate, oral contraceptives, pancuronium, phenobarbital, rifampicin... 

Chlorotrianisene is a nonsteroidal synthetic estrogen that is used in postpartum breast engorgement (12 mg 4 times/day for 7 days), vasomotor symptoms associated with menopause (12 mg/day cyclically for 30 days), atrophic vaginitis and Kraurosis vulvae (12 mg/day cyclically for 60 days), female hypogonadism (12 mg/day cyclically for 21 days), and inoperable prostate carcinoma (12 mg/day given chronically) (see also Figure 28). 

Diestriol, diethylstilbestrol (DES), benestriol, methestrol, hexestrol and chlorotrianisene are all nonsteroidal estrogenic drugs. 

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