STILBETIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).
Diethylstilbestrol (STILBETIN) is a nonsteroidal estrogen that binds to estrogen receptors, activating estrogen-responsive genes, leading to increased synthesis of proteins involved in growth and differentiation of female reproductive tissues.
| Metabolism | Hepatic metabolism via hydroxylation and glucuronide conjugation; undergoes enterohepatic recirculation. |
| Excretion | Primarily renal as glucuronide and sulfate conjugates; approximately 50-80% of a parenteral dose excreted in urine within 24 hours; 10-20% via bile into feces. |
| Half-life | Terminal elimination half-life is approximately 1-2 hours (range 1-3 h) for estradiol; clinical relevance: requires multiple daily dosing (e.g., 3-4 times/day) for sustained effect. |
| Protein binding | ~98% bound primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Vd approximately 0.5-1 L/kg (estradiol); distributes widely into tissues with high lipid content. |
| Bioavailability | Oral: very low (<5%) due to extensive first-pass hepatic metabolism; parenteral (IV/IM): 100% (by definition). |
| Onset of Action | Intravenous: 5-10 min; oral: 1-2 h (following absorption and hepatic metabolism to active estrogen). |
| Duration of Action | Duration of estrogenic effects is 4-6 hours for IV; oral effects persist 6-8 hours; clinical note: effects wane quickly, necessitating frequent dosing. |
| Molecular Weight | 268.35 |
25 mg orally 3 times daily for 5 days; repeat if necessary after 1 month.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate impairment. For severe impairment (GFR <30 mL/min), use with caution and consider reducing dose by 50%. |
| Liver impairment | Contraindicated in Child-Pugh class C cirrhosis. For Child-Pugh class A or B, reduce dose by 50% and monitor liver function. |
| Pediatric use | Weight-based dosing: 0.5 mg/kg/day orally divided every 8 hours for 5 days; maximum 25 mg per dose. |
| Geriatric use | Start at lowest effective dose (e.g., 12.5 mg 3 times daily) and titrate cautiously due to increased risk of adverse effects; monitor renal function. |
| 1st trimester | Contraindicated. Associated with increased risk of vaginal adenosis and clear cell adenocarcinoma in female offspring. |
| 2nd trimester | Contraindicated. Risk of fetal harm; may cause genitourinary tract abnormalities. |
| 3rd trimester | Contraindicated. Potential for fetal harm; use only if clearly needed for life-threatening conditions. |
Clinical note
Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).
| Placental transfer | Crosses placenta; diethylstilbestrol (STILBETIN) is a well-documented transplacental carcinogen. |
| Breastfeeding | Excreted into breast milk; due to potential for serious adverse reactions in nursing infants, use is contraindicated. |
| Lactation Rating |
■ FDA Black Box Warning
There is an increased risk of endometrial cancer in postmenopausal women using estrogens. STILBETIN is contraindicated in women with known or suspected pregnancy due to risk of vaginal adenosis and clear cell adenocarcinoma in female offspring exposed in utero.
| Serious Effects |
PregnancyBreastfeedingKnown or suspected estrogen-dependent neoplasiaActive thromboembolic disordersHypersensitivity to diethylstilbestrol
| Precautions | Increased risk of thromboembolic events, stroke, myocardial infarction, and pulmonary embolism; increased risk of endometrial cancer; caution in patients with cardiovascular disease, hepatic impairment, or history of thromboembolic disorders; may exacerbate fluid retention and hypertension. |
| Food/Dietary | Grapefruit and grapefruit juice may increase diethylstilbestrol levels. Avoid alcohol as it may increase estrogen levels. Calcium-rich foods may reduce absorption; separate by 2 hours. |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | STILBETIN (diethylstilbestrol) is a known transplacental carcinogen and teratogen. First trimester exposure causes vaginal clear cell adenocarcinoma in female offspring (0.1-0.4%) and genital tract malformations. Second/third trimester exposure risks preterm labor, fetal demasculinization in males, and Mullerian anomalies. Contraindicated in pregnancy. |
| Fetal Monitoring | Maternal: baseline and periodic hepatic function, renal function, serum electrolytes, and endometrial evaluation. Fetal: serial ultrasound for growth and anatomy if inadvertent exposure. Long-term follow-up of offspring for vaginal adenosis and clear cell adenocarcinoma. |
| Fertility Effects | STILBETIN may impair fertility in both sexes. In females: anovulation, menstrual irregularities, and reduced ovarian reserve. In males: oligospermia, testicular hypotrophy. Long-term use increases risk of endometriosis and uterine fibroids. |
| Clinical Pearls | STILBETIN (diethylstilbestrol) is a nonsteroidal estrogen used historically for pregnancy support but now contraindicated due to teratogenicity and increased cancer risk. Monitor for thromboembolic events, vaginal adenocarcinoma in offspring. Use only in select cases like prostate cancer or lactation suppression. |
| Patient Advice | This medication is a synthetic estrogen with serious risks including cancer and blood clots. · It must not be used during pregnancy as it causes severe birth defects. · Report any unusual vaginal bleeding, breast lumps, or leg swelling immediately. · Regular gynecologic exams are required due to increased cancer risk. · Do not take with other hormonal medications without consulting your doctor. |