STILBESTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STILBESTROL (STILBESTROL).
Synthetic nonsteroidal estrogen that acts by binding to estrogen receptors (ERα and ERβ), leading to translocation to the nucleus, modulation of gene transcription, and promotion of estrogenic effects in target tissues.
| Metabolism | Primarily metabolized in the liver via glucuronidation and sulfation; undergoes enterohepatic recirculation. Major metabolites include diethylstilbestrol glucuronide and sulfate conjugates. |
| Excretion | Renal excretion of glucuronide and sulfate conjugates accounts for approximately 60-80% of an administered dose; biliary/fecal excretion accounts for 15-30%; less than 5% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 24-48 hours, with a prolonged phase due to enterohepatic recirculation; requires dosing adjustment in hepatic impairment. |
| Protein binding | Approximately 90-95% bound, primarily to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Vd is approximately 2-4 L/kg, indicating extensive tissue distribution; concentrates in breast, uterine, and adipose tissues. |
| Bioavailability | Oral: 40-60% due to first-pass metabolism; Intramuscular: 100%; Topical: 5-15% for systemic absorption. |
| Onset of Action | Oral: 1-2 hours for estrogenic effects; Intramuscular: 30-60 minutes; Topical: 1-3 hours for local effects. |
| Duration of Action | Oral: 2-4 hours for single dose, but effects persist for 12-24 hours due to metabolite activity; Intramuscular: 2-3 days; Topical: 6-12 hours. |
| Molecular Weight | 268.35 |
0.5 to 2 mg orally once daily; or 25 mg intramuscularly once daily for 5 days; for prostate cancer: 1 to 3 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (GFR < 30 mL/min) due to potential fluid retention. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for use in children due to risk of premature epiphyseal closure and other adverse effects. |
| Geriatric use | Initiate at lowest effective dose; monitor for thromboembolic events, cardiovascular effects, and electrolyte imbalances. |
| 1st trimester | Contraindicated: high risk of vaginal adenosis and clear cell adenocarcinoma in female offspring; also associated with increased risk of spontaneous abortion and congenital anomalies. |
| 2nd trimester | Contraindicated: continued risk of serious adverse effects on fetal development, including genitourinary tract abnormalities. |
| 3rd trimester | Contraindicated: risk of vaginal adenosis and clear cell carcinoma persists; also linked to premature birth and other adverse outcomes. |
Clinical note
Comprehensive clinical and safety monograph for STILBESTROL (STILBESTROL).
| Placental transfer | Diethylstilbestrol crosses the placenta readily and accumulates in fetal tissues, particularly the genital tract. Documented to cause transplacental carcinogenesis. |
| Breastfeeding | Diethylstilbestrol (DES) is excreted into breast milk in small amounts. Potential for estrogenic effects in the infant, including gynecomastia and vaginal adenosis. Avoid use during breastfeeding due to possible long-term carcinogenic effects. |
■ FDA Black Box Warning
Estrogens have been reported to increase the risk of endometrial carcinoma in postmenopausal women. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding. There is no evidence that estrogens are effective for nervous symptoms or depression during menopause, and they should not be used to treat such conditions.
| Serious Effects |
PregnancyBreastfeedingEstrogen-dependent neoplasia (e.g., breast cancer, endometrial cancer)Undiagnosed abnormal genital bleedingActive thromboembolic disordersHistory of thromboembolic disorders associated with estrogen useKnown hypersensitivity to DES
| Precautions | Increased risk of endometrial cancer, Increased risk of thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism), Increased risk of cardiovascular events (e.g., stroke, myocardial infarction), Known or suspected pregnancy should be ruled out before initiation; contraindicated in pregnancy due to risk of fetal harm (DES syndrome), Caution in patients with hepatic impairment or active liver disease, May exacerbate angioedema in patients with hereditary angioedema, May cause fluid retention, which can worsen conditions such as asthma, epilepsy, migraine, cardiac, or renal dysfunction, Should not be used for prevention of cardiovascular disease or dementia |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Diethylstilbestrol (DES) exposure increases risk of vaginal adenosis, clear cell adenocarcinoma, and structural genital tract anomalies in female offspring, and epididymal cysts, hypotrophic testes, and infertility in male offspring. Second and third trimesters: Associated with increased risk of spontaneous abortion, preterm delivery, and fetal death. DES is contraindicated in pregnancy. |
| Fetal Monitoring | If inadvertent exposure occurs, monitor female offspring for vaginal adenosis and clear cell carcinoma (screening starting at menarche or age 14). Monitor male offspring for genital tract abnormalities and fertility issues. For maternal use during pregnancy, monitor for signs of preterm labor and fetal distress. |
| Fertility Effects | In females: DES exposure in utero can lead to infertility, menstrual irregularities, and poor pregnancy outcomes. In males: In utero exposure may cause oligospermia and reduced fertility. In adults, DES used historically as a high-dose estrogen for prostate cancer; can cause gynecomastia and sexual dysfunction. |
| Food/Dietary | Grapefruit and grapefruit juice may increase systemic exposure to STILBESTROL (CYP3A4 inhibition). Avoid concurrent consumption. No other significant food-drug interactions reported. Take with food to reduce gastrointestinal upset. Alcohol may exacerbate estrogen-related side effects (e.g., nausea, dizziness). |
| Clinical Pearls | STILBESTROL (diethylstilbestrol) is a synthetic nonsteroidal estrogen used historically for miscarriage prevention and advanced prostate cancer. It is rarely used today due to carcinogenic risks (clear-cell adenocarcinoma in female offspring, vaginal adenosis, breast cancer). Contraindicated in pregnancy (DES-exposed daughters have increased cancer risk). For prostate cancer, monitor for cardiovascular events (thromboembolism, stroke) and gynecomastia. Avoid concurrent use with strong CYP3A4 inducers/inhibitors. Baseline and periodic liver function tests, blood glucose, and serum calcium recommended. |
| Patient Advice | STILBESTROL is a synthetic estrogen with serious risks including cancer; use only under strict medical supervision. · Never use during pregnancy; it can cause severe birth defects and increase cancer risk in female offspring. · Report any new or unusual vaginal bleeding, lumps, or pelvic pain immediately. · Men taking for prostate cancer: monitor for signs of blood clots (leg pain, chest pain, sudden shortness of breath) and breast tenderness or enlargement. · Avoid alcohol and grapefruit products while on this medication. · Do not take any herbal supplements, especially St. John's Wort, without consulting your doctor. · Take with food to reduce nausea; if you miss a dose, do not double the next dose. · Keep all follow-up appointments for blood tests and cancer screenings. |