Chlorotrianisene

Chlorotrianisene (INN, USAN, BAN; brand names Tace, Estregur, Anisene, Clorotrisin, Merbentyl, Triagen, many others; also known as CTA; tri-p-anisylchloroethylene, TACE, or tris(p-methoxyphenyl)chloroethylene) is a synthetic, non-steroidal estrogen of the triphenylethylene group that was formerly used for the treatment of menopausal symptoms, estrogen deficiency, and prostate cancer before being discontinued. It was approved in the United States as TACE in 1952, and was introduced throughout Europe subsequently. CTA was the first estrogenic compound of the triphenylethylene series to be introduced.

CTA was derived from estrobin (DBE), a derivative of the very weakly estrogenic compound triphenylethylene (TPE), which in turn was derived from structural modification of diethylstilbestrol (DES). CTA is a relatively weak estrogen, with about one-eighth the potency of DES. However, it is highly lipophilic and is stored in fat tissue for prolonged periods of time, with its slow release from fat resulting in a very long duration of action. CTA itself is inactive; it behaves as a prodrug to a weak estrogen that is formed as a metabolite via degradation of CTA in the liver. As such, the potency of CTA is reduced if it is given parenterally instead of orally.

Although it is referred to as a weak estrogen and was used solely as an estrogen in clinical practice, CTA is actually a partial agonist of the estrogen receptor. As such, it is a selective estrogen receptor modulator (SERM), with predominantly estrogenic but also antiestrogenic effects, and was arguably the first SERM to ever be introduced. CTA can antagonize estradiol at the level of the hypothalamus, resulting in disinhibition of the hypothalamic-pituitary-gonadal axis and an increase in estrogen levels. Clomifene and tamoxifen were both derived from CTA via structural modification, and are much weaker partial agonists than CTA and hence much more antiestrogenic in comparison. As an example, chlorotrianisene produces gynecomastia in men, albeit reportedly to a lesser extent than other estrogens, while clomifene and tamoxifen do not and can actually be used to treat gynecomastia.