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. |
| Molecular Weight | 266.33 |
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 | DIENESTROL is contraindicated in the first trimester due to risk of fetal harm, including congenital anomalies such as cardiovascular and urogenital defects. Estrogens have been associated with an increased risk of fetal abnormalities. |
| 2nd trimester | DIENESTROL should be avoided in the second trimester as it may cause adverse fetal effects, including potential for future reproductive tract abnormalities in female offspring (e.g., vaginal adenosis, clear cell adenocarcinoma). |
| 3rd trimester | DIENESTROL is contraindicated in the third trimester due to risk of delayed fetal bone maturation, feminization of male fetuses, and potential for neonatal withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for DIENESTROL (DIENESTROL).
| Placental transfer | DIENESTROL crosses the placenta readily, with fetal plasma levels approximately 5-10% of maternal levels. Studies in animals have demonstrated fetal exposure and associated adverse effects. |
| Breastfeeding |
■ 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 |
Pregnancy (known or suspected)Undiagnosed abnormal genital bleedingKnown or suspected breast cancer (except in certain metastatic cases)Known or suspected estrogen-dependent neoplasiaActive thromboembolic disorders or history of suchKnown hypersensitivity to dienestrol or any componentHepatic impairment (porphyria, acute liver disease)
| 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. |
| Food/Dietary | None reported specifically for dienestrol. Grapefruit juice may theoretically increase estrogen levels via CYP3A4 inhibition, but data are lacking for topical use. No dietary restrictions required. |
Loading safety data…
| DIENESTROL is excreted into human breast milk and may reduce milk production. The American Academy of Pediatrics considers estrogens to be compatible with breastfeeding, but caution is advised due to potential for infant estrogen exposure. Use only if clearly needed and monitor infant for unusual vaginal bleeding or feminization. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Dienestrol is a synthetic nonsteroidal estrogen used topically for atrophic vaginitis. Due to systemic absorption, it shares the same risks as systemic estrogens, including thromboembolism and endometrial cancer. Avoid use in patients with undiagnosed vaginal bleeding, active thromboembolic disorders, or known/suspected estrogen-dependent neoplasia. Topical application may still cause endometrial hyperplasia; adding a progestin is not required for topical use, but monitor for uterine bleeding. Consider limiting duration of use to the shortest effective time. |
| Patient Advice | Apply the cream exactly as prescribed, usually once daily for 2 weeks, then reduce to 2–3 times per week. · Wash hands thoroughly before and after application. · Do not use more than prescribed or for longer than advised. · Report any unusual vaginal bleeding, pain, or discharge. · Inform your doctor if you have a history of blood clots, stroke, heart attack, or breast cancer. · Avoid use during pregnancy or breastfeeding. · Store at room temperature away from moisture and heat. |