Charles Dodds (1899–1973), Charles Huggins (1901–1997)
Estrone and other estrogenic compounds were isolated from human and horse urine during the 1930s and were used to relieve symptoms of menopause. These natural products had limited effectiveness when given orally, however, so they had to be injected. Moreover, their extraction from urine or the laboratory synthesis of such complex molecules was expensive. These problems were solved in 1938 when, in the laboratory of the British biochemist Charles Dodds at Oxford University, diethylstilbestrol (DES, stilbestrol) was synthesized.
DES had a simple nonsteroid chemical structure, was inexpensive to manufacture, and was very active when taken by mouth. Highly effective for the treatment of menopause, it was approved for this use in 1941 and for other estrogen-deficiency disorders in subsequent years. In 1947, its uses were extended to prevent complications of pregnancy—in particular, miscarriages—for which it was widely prescribed.
Later clinical studies failed to support claims of its effectiveness in preventing miscarriages. Moreover, women who used DES during pregnancy had a greater likelihood of developing breast cancer. Far more ominously, a 1971 report provided strong evidence that DES use was associated with vaginal cell cancer in girls and young women whose mothers had taken the drug during pregnancy. That year, the FDA withdrew their approval of DES to prevent miscarriages and emphasized that it should not be given during pregnancy.
Despite its link to breast and vaginal cancers, DES continues to be used for the treatment of prostate cancer. During the late 1930s, Charles Huggins at the University of Chicago noted that castration shrunk prostate tumors in dogs and that DES shut down the production of testosterone, producing a chemical castration. From these observations and subsequent studies involving breast cancer, Huggins postulated that certain cancers required hormones to grow and survive—a finding that spearheaded the development of certain classes of anticancer drugs and that earned him the 1966 Nobel Prize in Physiology or Medicine.
SEE ALSO Estrone and Estrogen (1929), Testosterone (1935), Premarin (1941), Tamoxifen (1973), 17P/ Progesterone Injections and Gel (2003).
Prostate cancer is the third deadliest cancer in men of all ages and the most common cause of death from cancer in men over seventy-five years of age.