The Rise and Fall of a 'Miracle' Drug
Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen, was first synthesized in 1938 [1.2.5]. It was marketed heavily and prescribed to millions of pregnant women from the 1940s through 1971, based on the incorrect belief that it could prevent miscarriages and other pregnancy complications [1.4.1, 1.4.5]. At its peak, it was considered a revolutionary treatment. However, studies in the 1950s began to show it was ineffective for this purpose, and some even indicated it led to higher rates of miscarriage and premature births [1.4.4].
The true turning point came in 1971 when researchers discovered a shocking link between in-utero DES exposure and a rare form of vaginal and cervical cancer called clear-cell adenocarcinoma (CCA) in the daughters of women who had taken the drug [1.4.1, 1.5.3]. This discovery led the U.S. Food and Drug Administration (FDA) to issue a warning to physicians, advising them to stop prescribing DES to pregnant women [1.4.2, 1.5.3]. The drug was banned for use as a growth promoter in livestock in 1979 [1.3.3]. The legacy of DES is often called a "medical tragedy" or a "biological time bomb" due to the multigenerational health consequences that continue to be studied today [1.2.2].
The Lingering Health Consequences of DES Exposure
The health implications of DES have extended far beyond its initial discovery. The individuals exposed are categorized by their relationship to the drug:
- DES Mothers: The women who were prescribed DES during pregnancy have a slightly increased risk of developing breast cancer [1.6.1, 1.10.3].
- DES Daughters: Women exposed in the womb face a wide range of health issues. They have a 40-fold increased risk of developing CCA, though the cancer itself remains rare (affecting about 1 in 1,000 DES daughters) [1.5.3, 1.6.3]. They also have an increased risk of breast cancer after age 40, reproductive problems (infertility, ectopic pregnancy, premature delivery), and structural abnormalities of the reproductive tract, such as a T-shaped uterus [1.5.1, 1.6.3, 1.6.4, 1.6.5]. Other potential risks include early menopause, cardiovascular issues, and high cholesterol [1.6.3].
- DES Sons: Men exposed in the womb have an increased risk of non-cancerous epididymal cysts and other genital abnormalities like undescended testicles [1.6.3, 1.6.4]. The link to testicular cancer remains unclear, though some studies suggest a possible increased risk [1.6.4, 1.5.5].
- DES Grandchildren (Third Generation): Research into the third generation is ongoing. Some studies suggest potential effects like a higher risk of birth defects (including hypospadias in grandsons), delayed menstruation, menstrual irregularity, and possibly infertility in granddaughters [1.2.1, 1.6.3, 1.10.4]. The data is still emerging, and these associations are based on small numbers, requiring further study [1.6.3].
Current Medical Applications: A Limited and Cautious Role
Despite its widespread ban for use in pregnancy, the answer to 'Is diethylstilbestrol still used today?' is a qualified yes. Its use is now extremely limited to specific oncological contexts where its hormonal effects can be beneficial. The primary modern application is as a palliative or second-line hormonal therapy for advanced, castration-resistant prostate cancer (CRPC) [1.2.2, 1.7.5].
In this setting, DES works by suppressing the production of testosterone, which fuels the growth of most prostate cancers [1.7.5]. It can be effective even after other hormonal therapies have failed [1.7.2]. However, due to significant risks, particularly cardiovascular side effects like blood clots and an increased risk of death from cardiovascular events, its use is approached with caution [1.5.1, 1.3.2]. Low doses (e.g., 1 mg daily) are used to minimize these risks, and patients may be given anticoagulants as a preventive measure [1.7.1, 1.7.2]. Gynecomastia (breast enlargement in men) is another common side effect [1.5.2, 1.7.1].
DES has also been used occasionally to treat breast cancer in postmenopausal women, though it is not a first-line treatment [1.3.4, 1.8.3]. In veterinary medicine, it is sometimes prescribed to treat urinary incontinence in spayed female dogs [1.2.1, 1.5.4]. It is no longer commercially available in the U.S. for human use and must be specially prepared by a compounding pharmacy [1.7.1, 1.5.4].
Comparison of DES Usage: Past vs. Present
| Feature | Historical Use (1940s-1971) | Current Use (Today) |
|---|---|---|
| Primary Indication | Prevention of miscarriage and pregnancy complications [1.4.1, 1.4.5] | Palliative treatment for advanced prostate cancer [1.7.5] |
| Other Indications | Menopausal symptoms, postpartum lactation suppression, acne, postcoital contraception [1.2.5] | Occasionally for advanced breast cancer in postmenopausal women; urinary incontinence in dogs [1.3.4, 1.5.4] |
| Patient Population | Millions of pregnant women [1.2.1] | Men with castration-resistant prostate cancer [1.7.1] |
| Dosage | Highly variable, often high doses [1.3.4] | Low, carefully monitored doses (e.g., 1-3mg/day) [1.7.1, 1.7.2] |
| Known Risks | Initially thought to be safe; later linked to transgenerational cancer and reproductive harm [1.4.1, 1.5.3] | High risk of cardiovascular events (thrombosis, heart failure) and gynecomastia [1.5.1, 1.7.1] |
| Regulatory Status | FDA-approved for pregnancy support until 1971 [1.4.4, 1.10.2] | Use in pregnancy banned; not commercially available in the U.S. for humans, must be compounded [1.4.1, 1.7.1] |
Conclusion
Diethylstilbestrol is a powerful example of a medication that went from widespread acceptance to near-total prohibition due to devastating, long-term side effects. It is no longer used to support pregnancy and is banned in many countries for most human applications [1.3.4]. Today, its role is confined to a small, specific niche in oncology—primarily as a last-resort treatment for advanced prostate cancer, where its benefits in slowing the cancer may outweigh its considerable risks [1.7.2, 1.7.5]. The story of DES serves as a crucial lesson in pharmacology about the importance of rigorous, long-term drug testing and the potential for unforeseen, multigenerational consequences.
For more information, consult the National Cancer Institute's Fact Sheet on DES.
