Diethylstilbestrol (DES) is a synthetic form of the hormone estrogen, first created in 1938 as the first non-steroidal estrogen compound. This medication was widely adopted in the mid-20th century. Unlike natural estrogens, DES was highly active when taken orally, making it a convenient and inexpensive treatment option for various conditions before its severe long-term consequences were fully understood.
Historical Applications and Timeline of DES
DES was introduced into medical practice in the late 1930s and was commonly prescribed to pregnant women between 1940 and 1971. Physicians believed the drug could reduce the risk of pregnancy complications, including miscarriage, premature labor, and stillbirth. Millions of women received the drug under the mistaken belief that it was an effective pregnancy support treatment.
The drug was also used for non-pregnancy related issues, such as relieving menopausal symptoms and treating painful menstrual periods. It was utilized to suppress lactation after childbirth and, at higher doses, was prescribed as an emergency contraceptive pill. However, studies as early as the 1950s suggested that DES was not effective in preventing miscarriages.
Current Regulatory Status and Usage
The pivotal regulatory shift occurred in 1971 after a study linked prenatal DES exposure to clear cell adenocarcinoma (CCA), a rare vaginal and cervical cancer, in young women. The U.S. Food and Drug Administration (FDA) issued a warning and withdrew approval for DES to be prescribed during pregnancy. This marked the end of its use in the United States, though it was administered in some other countries until the early 1980s.
Today, DES is no longer prescribed for use in pregnancy, and its overall use in human medicine is rare and highly restricted. It is occasionally used in specific cancer treatments, such as for advanced prostate cancer and, less often, for advanced breast cancer in postmenopausal women. For prostate cancer, the typical daily dosage is 1 to 3 milligrams. However, even in oncology, its use has largely been supplanted by newer hormonal therapies with fewer cardiovascular side effects.
The drug was historically used in veterinary medicine to promote growth in livestock, but this application was banned in U.S. food-producing animals due to concerns about trace amounts of the hormone in meat. While technically approved for certain non-reproductive cancers, its widespread use is a practice of the past. DES remains classified as a known human carcinogen, reinforcing strict regulatory limits on its application.
Long-Term Health Consequences of Exposure
The long-term health consequences of DES exposure affect three generations: mothers, daughters, and sons. Women who took DES during pregnancy, known as DES Mothers, face a slightly elevated risk of developing breast cancer compared to women who were not exposed.
For DES Daughters, who were exposed in utero, the health risks are more pronounced and involve the reproductive tract. They have a 40-fold increased risk of developing clear cell adenocarcinoma of the vagina or cervix, though the overall risk remains low (approximately 1 in 1,000 exposed women). Daughters also face a higher incidence of reproductive tract abnormalities, such as T-shaped uteruses. These structural changes contribute to increased risks for infertility, ectopic pregnancy (3 to 5 times higher risk), and premature delivery.
DES Sons, exposed in the womb, also exhibit potential reproductive issues, mainly involving genital abnormalities. These issues include a higher rate of non-cancerous epididymal cysts (growths on the tube behind the testicle). There is also an elevated risk for genital malformations such as cryptorchidism (undescended testicles) and hypospadias (misplaced urethral opening). While the association with testicular cancer is not definitively established, some research suggests a doubled risk ratio.