DIETHYLSTILBESTROL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).

How it works

Synthetic nonsteroidal estrogen that binds to estrogen receptors (ERα/ERβ), activating estrogen-responsive gene transcription, leading to proliferation of estrogen-sensitive tissues.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).

Breastfeeding	Diethylstilbestrol is contraindicated during breastfeeding as it suppresses lactation and may be excreted in milk; M/P ratio not established.
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

Warnings & precautions

■ 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).

Side Effect Profile

Serious Effects

Absolute Contraindications

Known or suspected pregnancy; undiagnosed abnormal genital bleeding; known or suspected breast cancer (except in appropriately selected patients with metastatic disease); known or suspected estrogen-dependent neoplasia; active thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism); history of thromboembolic disorders associated with estrogen use; hypersensitivity to diethylstilbestrol or any component of the formulation.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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DIETHYLSTILBESTROL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).

How it works

Synthetic nonsteroidal estrogen that binds to estrogen receptors (ERα/ERβ), activating estrogen-responsive gene transcription, leading to proliferation of estrogen-sensitive tissues.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DIETHYLSTILBESTROL (DIETHYLSTILBESTROL).

Breastfeeding	Diethylstilbestrol is contraindicated during breastfeeding as it suppresses lactation and may be excreted in milk; M/P ratio not established.
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