DIETHYLSTILBESTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).
Synthetic nonsteroidal estrogen that binds to estrogen receptors (ERα/ERβ), activating estrogen-responsive gene transcription, leading to proliferation of estrogen-sensitive tissues.
| Metabolism | Primarily hepatic via hydroxylation and conjugation (glucuronidation and sulfation); undergoes enterohepatic recirculation; metabolized by CYP3A4 and other P450 enzymes. |
| Excretion | Primarily renal (90% as glucuronide and sulfate conjugates), with less than 5% excreted unchanged in urine; biliary/fecal elimination accounts for about 10%. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 20-30 hours) in adults; prolonged in hepatic impairment. |
| Protein binding | High (>95%), primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Approximately 10 L/kg, indicating extensive tissue distribution with sequestration in fat and reproductive tissues. |
| Bioavailability | Oral: ~40-60% due to first-pass metabolism; Intramuscular: near 100%. |
| Onset of Action | Oral: 1-2 hours for estrogenic effects; Intramuscular: 30-60 minutes. |
| Duration of Action | Oral: 12-24 hours; Intramuscular: 1-3 days; effects persist longer due to enterohepatic recirculation. |
| Molecular Weight | 268.35 |
0.5-2 mg orally once daily for palliative treatment of advanced prostate cancer; 5-15 mg orally once daily for prevention of postpartum breast engorgement.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment; careful monitoring recommended in significant renal impairment. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for pediatric use due to carcinogenic risk. |
| Geriatric use | Start at lowest effective dose; monitor for fluid retention, thromboembolism, and cardiovascular adverse effects. |
| 1st trimester | Contraindicated: risk of severe teratogenicity including vaginal adenosis, clear cell adenocarcinoma, and congenital abnormalities. |
| 2nd trimester | Contraindicated: associated with increased risk of spontaneous abortion, fetal death, and adverse effects on fetal development. |
| 3rd trimester | Contraindicated: linked to premature delivery, neonatal complications, and long-term reproductive tract abnormalities. |
Clinical note
Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).
| Placental transfer | Readily crosses the placenta; documented in human studies with significant fetal exposure. |
| Breastfeeding | Excreted into breast milk; may cause adverse effects in nursing infants including estrogenic effects. Use is not recommended. |
■ FDA Black Box Warning
Boxed Warning: Increased risk of endometrial carcinoma in postmenopausal women using unopposed estrogens; increased risk of thromboembolic disorders (e.g., pulmonary embolism, stroke, myocardial infarction); contraindicated in pregnancy due to risk of vaginal adenosis and clear cell adenocarcinoma in female offspring (DES daughters).
| Serious Effects |
Breast cancerEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingActive thromboembolic disordersKnown or suspected pregnancyLactationHistory of deep vein thrombosis or pulmonary embolism
| Precautions | Increased risk of endometrial cancer; increased risk of thromboembolic events; breast cancer risk; gallbladder disease; hypertension; hypercalcemia; fluid retention; exacerbation of endometriosis; hepatic hemangiomas; hereditary angioedema; migraine; monitoring of blood pressure, glucose, calcium, and endometrial biopsy. |
| Food/Dietary | Grapefruit juice may increase estrogen levels and risk of side effects; avoid concurrent intake. High-fat meals can increase absorption; take with food to reduce gastrointestinal upset. No specific dietary restrictions beyond maintaining a balanced diet to manage weight and blood pressure. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | First trimester: High risk of vaginal adenosis and clear cell adenocarcinoma in female offspring, and genitourinary tract anomalies in male offspring. Second trimester: Continued risk of similar anomalies. Third trimester: Risk of preterm labor and fetal distress. |
| Fetal Monitoring | Monitor fetal growth and amniotic fluid volume via ultrasound; assess for signs of preterm labor; periodic cervical exams. |
| Fertility Effects | In females: Can cause menstrual irregularities and anovulation; possible impaired fertility. In males: May affect sperm production and quality. |
| Clinical Pearls | Diethylstilbestrol (DES) is a synthetic nonsteroidal estrogen historically used for miscarriage prevention and menopausal symptoms; banned in pregnancy due to transplacental carcinogenesis (vaginal clear cell adenocarcinoma in female offspring, genitourinary anomalies in males). Monitor for thromboembolism, hypertension, and endometrial cancer. Use is now rare, restricted to certain advanced prostate cancer or transgender hormone therapy under strict protocols. Do not use in pregnancy, history of thromboembolism, or estrogen-sensitive malignancies. |
| Patient Advice | This medication is a form of estrogen; discuss any history of blood clots, stroke, heart attack, or cancer with your doctor. · Do not use this medication if you are pregnant, planning to become pregnant, or breastfeeding due to serious risks to the fetus. · Report sudden chest pain, shortness of breath, leg pain or swelling, severe headache, vision changes, or unusual vaginal bleeding immediately. · Avoid smoking while taking this medication, as it increases the risk of serious blood clots. · Regular monitoring of blood pressure, blood sugar, and pelvic exams is required during therapy. |