DIENESTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIENESTROL (DIENESTROL).
Synthetic nonsteroidal estrogen that binds to estrogen receptors, activating transcription of estrogen-responsive genes, leading to effects similar to endogenous estrogens.
| Metabolism | Primarily hepatic metabolism via CYP3A4 and other enzymes; undergoes enterohepatic recirculation. |
| Excretion | Primarily renal (40-60% as glucuronide conjugates) and biliary/fecal (30-50% with enterohepatic recycling). |
| Half-life | Terminal elimination half-life is approximately 24-48 hours, longer with hepatic impairment. |
| Protein binding | 97-99% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | 0.7-1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 20-30% due to first-pass metabolism; Intravaginal: ~60-80%. |
| Onset of Action | Oral: 1-2 hours; Intravaginal: 2-4 hours. |
| Duration of Action | Oral: 4-6 days; Intravaginal: 5-7 days. |
0.1 to 0.5 mg orally once daily for estrogen replacement therapy; 0.5 to 1.0 mg orally once daily for prostatic carcinoma.
| Dosage form | CREAM |
| Renal impairment | No specific dose adjustment recommendations; use with caution in severe renal impairment. |
| Liver impairment | Contraindicated in severe hepatic disease; Child-Pugh A or B: use with caution, monitor hepatic function; Child-Pugh C: avoid use. |
| Pediatric use | Not indicated for use in pediatric patients for approved indications. |
| Geriatric use | Initiate at lower end of dosing range; monitor for thromboembolic events and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIENESTROL (DIENESTROL).
| Breastfeeding | Not recommended. Dienestrol is excreted in human milk; M/P ratio not established. Potential for estrogenic effects in nursing infant, including gynecomastia and vaginal bleeding. Lactation should be avoided or drug discontinued. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: Increased risk of female offspring developing clear cell adenocarcinoma of the vagina and cervix, vaginal adenosis, and cervical ectropion. Second and third trimesters: No additional specific malformation risk, but potential for urogenital tract abnormalities in female offspring, and possible increased risk of hypospadias in male offspring. Use contraindicated in pregnancy. |
■ FDA Black Box Warning
Estrogens have been reported to increase the risk of endometrial carcinoma. Close clinical surveillance of all women taking estrogens is important. Progestins may reduce this risk but are not proven.
| Serious Effects |
Known or suspected pregnancy, undiagnosed abnormal genital bleeding, known or suspected breast cancer (except appropriately selected cases), active thromboembolic disorders, history of thromboembolic disorders associated with estrogen use, known or suspected estrogen-dependent neoplasia.
| Precautions | Increased risk of endometrial cancer, thromboembolic disorders, cardiovascular events (e.g., stroke, MI), breast cancer, and gallbladder disease. Use lowest effective dose for shortest duration. Discontinue if jaundice or visual disturbances occur. |
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| Fetal Monitoring | Monitor for signs of fetal exposure: ultrasound for urogenital tract abnormalities if inadvertent exposure. No specific monitoring required if used appropriately; avoid pregnancy. In case of accidental pregnancy, refer for fetal evaluation. |
| Fertility Effects | May suppress ovulation and interfere with fertility due to estrogenic activity. Reversible upon discontinuation. |