STILBETIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).

Breastfeeding	STILBETIN is excreted in human milk; M/P ratio approximately 1.0. Potential for serious adverse effects in nursing infant. Breastfeeding not recommended due to estrogen exposure and long-term carcinogenic risk.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known or suspected pregnancy; known or suspected breast cancer (except in selected metastatic cases); known or suspected estrogen-dependent neoplasia; active thromboembolic disorders or history of such; undiagnosed abnormal genital bleeding; known hypersensitivity to diethylstilbestrol.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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STILBETIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for STILBETIN (STILBETIN).

Breastfeeding	STILBETIN is excreted in human milk; M/P ratio approximately 1.0. Potential for serious adverse effects in nursing infant. Breastfeeding not recommended due to estrogen exposure and long-term carcinogenic risk.
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.