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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STILBESTROL (STILBESTROL).
| Breastfeeding | Diethylstilbestrol is excreted in breast milk; M/P ratio not reported. Suppresses lactation due to estrogenic effects. Breastfeeding is not recommended due to potential adverse effects on the infant. |
| 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. |
■ 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 |
["Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected estrogen-dependent neoplasia (e.g., breast cancer, endometrial cancer) except in appropriately selected patients for palliative treatment","Active thromboembolic disorders or history of thrombophlebitis","Severe hepatic impairment or acute liver disease","Hypersensitivity to diethylstilbestrol or any component of the formulation"]
| 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"] |
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| 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. |