Diethylstilbestrol (DES) is a synthetic form of the hormone estrogen first manufactured in 1938. Physicians widely prescribed this nonsteroidal medication to pregnant women in the mid-20th century, believing it could prevent miscarriage and other pregnancy complications. This belief was later proven incorrect. The widespread use of DES created a large population of exposed individuals whose long-term health consequences continue to be studied.
Historical Use and Withdrawal
DES was most heavily prescribed to pregnant women in the United States between 1940 and 1971. The flawed medical theory was that DES could correct a natural estrogen deficiency causing pregnancy issues. During this period, an estimated five to ten million Americans were exposed to the drug, either by taking it or being exposed in utero.
The use of DES began to decline after 1953, when research indicated the drug was not effective in preventing miscarriages. It remained on the market until a landmark 1971 study definitively linked prenatal DES exposure to a rare form of cancer. Researchers found an association between DES and clear cell adenocarcinoma (CCA) of the vagina and cervix in young women who had been exposed before birth.
Following this discovery, the U.S. Food and Drug Administration (FDA) advised physicians to immediately stop prescribing DES to pregnant women. This action officially withdrew approval for its use during pregnancy due to lack of efficacy and evidence of harm. Although its use for pregnancy ended, DES continued to be used for other indications, such as treating breast and prostate cancer, for several more years.
Health Effects on Exposed Offspring
The most significant long-term effects of DES exposure manifest in the offspring exposed prenatally, known as DES Daughters and DES Sons. These effects often involve structural changes and functional issues within the reproductive systems that developed while the fetus was exposed to the synthetic hormone.
DES Daughters
DES Daughters face an elevated, though rare, lifetime risk of developing clear cell adenocarcinoma (CCA) of the vagina and cervix. This cancer typically appeared in young women and adolescents, with an estimated risk of approximately one case per 1,000 to 10,000 exposed individuals. The majority of DES Daughters also experience non-cancerous structural changes in their reproductive organs. These abnormalities include a T-shaped uterus, which is a misshapen uterine cavity, and structural changes to the cervix.
These anatomical changes can lead to functional problems, most notably in pregnancy outcomes. DES Daughters have an increased risk of poor outcomes, including spontaneous abortion, ectopic pregnancy, and preterm delivery. They also face an increased risk of infertility, often due to issues with the fallopian tubes or uterus stemming from the abnormal development caused by DES.
DES Daughters may also face a slightly increased risk of breast cancer later in life. Studies suggest they have nearly twice the risk of developing breast cancer after the age of 40 compared to unexposed women. Beyond reproductive health, DES Daughters also have more than twice the risk of experiencing early menopause, defined as menopause beginning before age 45.
DES Sons
For DES Sons, the long-term effects primarily involve non-cancerous abnormalities of the male reproductive system. The most common finding is an increased occurrence of epididymal cysts, which are fluid-filled sacs on the epididymis. Other potential abnormalities include cryptorchidism (undescended testicles) and smaller than average testicles.
While these genital abnormalities are documented, DES Sons do not appear to have a higher overall risk of infertility. Some evidence suggests a slight increase in abnormal semen quality or changes in sperm morphology. The association between DES exposure and the risk of testicular cancer remains controversial.
Maternal Health Risks
The women who ingested DES during their pregnancies (DES Mothers) face distinct long-term health consequences. The most significant established risk is a modest increase in the likelihood of developing breast cancer compared to unexposed women. This elevated risk becomes more pronounced as the mothers age. The increase in breast cancer mortality observed in this population suggests the elevated incidence is a genuine biological effect.
Current Screening and Medical Management
Individuals who know or suspect they were exposed to DES in utero must inform their healthcare providers to ensure appropriate management. Since no medical test confirms past exposure, establishing the connection often requires reviewing historical obstetric or medical records. This disclosure allows providers to tailor screening protocols to address the specific long-term risks associated with the drug.
DES Daughters require specialized gynecological screening that goes beyond routine Pap smears. An annual pelvic examination is recommended, including careful palpation of the entire vaginal wall and cervix to detect subtle clear cell adenocarcinoma tumors. Cytological testing should collect cell samples from both the cervix and the entire length of the vagina.
Follow-up with colposcopy may be used to investigate any abnormal findings. Regular breast cancer screening is also important, particularly as these women reach age 40, to monitor for their elevated risk. For DES Sons, the primary recommendation involves regular self-examination of the testicles and periodic physical examinations by a healthcare provider.