However, other research indicates that the toxic effects of DES may simply be due to overactivation of the ERs. In contrast to estradiol, the hydroxyl groups of DES do not undergo oxidation into an estrone-like equivalent.The elimination half-life of DES is 24 hours. The metabolites of DES are excreted in urine and feces. Chemistry
DES belongs to the stilbestrol (4,4-dihydroxystilbene) group of compounds. It is a nonsteroidal open-ring analogue of the steroidal estrogen estradiol. DES can be prepared from anethole, which also happens to be weakly estrogenic. Anethole was demethylated to form anol and anol then spontaneously dimerized into dianol and hexestrol, with DES subsequently being synthesized via structural modification of hexestrol. As shown by X-ray crystallography, the molecular dimensions of DES are almost identical to those of estradiol, particularly in regards to the distance between the terminal hydroxyl groups. History
Synthesis
DES was first synthesized in early 1938 by Leon Golberg, then a graduate student of Sir Robert Robinson at the Dyson Perrins Laboratory at the University of Oxford. Golbergs research was based on work by Wilfrid Lawson at the Courtauld Institute of Biochemistry, (led by Sir Edward Charles Dodds at Middlesex Hospital Medical School now part of University College London). A report of its synthesis was published in Nature on 5 February 1938.DES research was funded by the UK Medical Research Council (MRC), which had a policy against patenting drugs discovered using public funds. Because it was not patented, DES was produced by more than 200 pharmaceutical and chemical companies worldwide.
However, similarly to the case of prostate cancer, arguments have been made for the use of bioidentical estrogens like estradiol instead of DES for breast cancer.Oral DES at 0.25 to 0.5 mg/day is effective in the treatment of hot flashes in men undergoing androgen deprivation therapy for prostate cancer.Although DES was used to support pregnancy, it was later found not to be effective for this use. Side effects
At more than 1 mg/day, DES is associated with high rates of side effects including nausea, vomiting, abdominal discomfort, headache, and bloating (incidence of 15–50%). Breast changes and feminization
The pigmentation of the breast areolae are often very dark and almost black with DES therapy. The pigmentation that occurs with synthetic estrogens such as DES is much greater than with natural estrogens such as estradiol. The mechanism of the difference is unknown. Progestogens like hydroxyprogesterone caproate have been reported to reduce the nipple hyperpigmentation induced by high-dose estrogen therapy.In men treated with it for prostate cancer, DES has been found to produce high rates of gynecomastia (breast development) of 41 to 77%. Blood clots and cardiovascular issues
In studies of DES as a form of high-dose estrogen therapy for men with prostate cancer, it has been associated with considerable cardiovascular morbidity and mortality. The risk is dose-dependent. A dosage of 5 mg/day DES has been associated with a 36% increase in non-cancer-related (mostly cardiovascular) deaths. In addition, there is an up to 15% incidence of venous thromboembolism.