DELESTROGEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DELESTROGEN (DELESTROGEN).
Estradiol, the active component, binds to estrogen receptors (ERα and ERβ) in target tissues, modulating gene transcription and exerting estrogenic effects on the reproductive, cardiovascular, skeletal, and central nervous systems.
| Metabolism | Estradiol is metabolized primarily in the liver via phase I hydroxylation by CYP3A4 and CYP1A2, followed by conjugation (glucuronidation and sulfation) to inactive metabolites (e.g., estrone, estriol, conjugates). Enterohepatic recirculation occurs. |
| Excretion | Renal (primarily as glucuronide and sulfate conjugates, ~50-80%), fecal (~10-20%) |
| Half-life | Terminal elimination half-life: ~12-24 hours; clinical context: prolonged with hepatic impairment, steady-state achieved within ~5-7 days of daily IM dosing |
| Protein binding | ~98-99% bound primarily to sex hormone-binding globulin (SHBG) and albumin |
| Volume of Distribution | Approximately 1-2 L/kg; indicates widespread distribution into tissues, including fat and reproductive organs |
| Bioavailability | IM (estradiol valerate): 100% (prodrug rapidly hydrolyzed to estradiol); Oral estradiol: variable ~5-10% due to first-pass metabolism |
| Onset of Action | IM injection: estradiol valerate, onset of estrogenic effects within a few hours; typical clinical response (e.g., vasomotor symptom relief) within 1-2 weeks |
| Duration of Action | IM injection: approximately 2-3 weeks for estradiol valerate; duration sufficient for once-monthly dosing in hormone therapy |
| Molecular Weight | 272.38 |
10-20 mg intramuscularly every 4 weeks for estrogen replacement therapy.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment due to potential fluid retention. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). In mild to moderate impairment (Child-Pugh A or B), use lowest effective dose and monitor liver function. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Use lowest effective dose due to increased risk of thromboembolic events, cardiovascular disorders, and malignancy. Not recommended for prevention of dementia. |
| 1st trimester | Estradiol is contraindicated in pregnancy. Use in first trimester is associated with fetal harm, including congenital anomalies such as cardiovascular and limb defects. Estrogens are not indicated for use during pregnancy. |
| 2nd trimester | Estradiol is contraindicated in pregnancy. Avoid use during second trimester due to risk of fetal harm. |
| 3rd trimester | Estradiol is contraindicated in pregnancy. Use in third trimester may cause urogenital tract abnormalities and delayed fetal development. |
Clinical note
Comprehensive clinical and safety monograph for DELESTROGEN (DELESTROGEN).
| Placental transfer | Estradiol crosses the placenta readily, with fetal-to-maternal serum concentration ratios reported as 0.5-1.0. Placental transfer is significant, and exposure may cause fetal harm. |
| Breastfeeding | Estradiol is excreted in human milk and may reduce milk production and quality. Breastfeeding is generally not recommended during estradiol therapy. If used, monitor for potential adverse effects in the infant, such as jaundice and breast enlargement. |
■ FDA Black Box Warning
Estrogens should not be used to prevent cardiovascular disease or dementia. Increased risk of endometrial cancer, stroke, deep vein thrombosis, pulmonary embolism, and myocardial infarction. Breast cancer risk may be increased with combined estrogen-progestin therapy. Use lowest effective dose for shortest duration.
| Serious Effects |
PregnancyBreastfeeding (relative, but often listed as absolute in labeling)Undiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasia (e.g., breast cancer, endometrial cancer)Active venous thromboembolism or history of thrombosisLiver disease or impaired hepatic functionHypersensitivity to estradiol or any component of the formulation
| Precautions | Cardiovascular disorders (stroke, DVT, PE, MI), malignancy (endometrial, breast, ovarian), dementia, gallbladder disease, hypercalcemia, visual abnormalities, fluid retention, hereditary angioedema, hypertriglyceridemia, hypothyroidism, exacerbation of asthma, diabetes, epilepsy, migraine, porphyria, SLE, hepatic hemangiomas, and severe hepatic impairment. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 |
| Teratogenic Risk | Delestrogen (estradiol valerate) is contraindicated in pregnancy. First trimester: associated with increased risk of congenital anomalies including cardiovascular and limb defects. Second and third trimesters: risk of urogenital abnormalities in female fetuses, vaginal adenosis, and cervical dysplasia. Fetal exposure may lead to reproductive tract abnormalities and increased lifetime cancer risk. |
| Fetal Monitoring | Monitor maternal blood pressure, hepatic function, and signs of thromboembolism. Fetal monitoring includes ultrasound for growth and development if inadvertent exposure occurs. Assess for signs of androgenization in female fetuses. |
| Fertility Effects | Delestrogen suppresses gonadotropin secretion, inhibiting ovulation and spermatogenesis. Reversible effect: fertility returns upon discontinuation. Chronic use may lead to endometrial atrophy, reducing implantation potential. |
| Grapefruit juice may increase estradiol levels and should be avoided or limited. No other significant food interactions are known, but maintaining a healthy diet low in saturated fats is advised to reduce cardiovascular risk. |
| Clinical Pearls | Delestrogen (estradiol valerate) is an oil-based IM injection; ensure deep intramuscular administration into the gluteal muscle and avoid intravascular injection. Rotate injection sites to prevent lipodystrophy. Monitor for thrombophlebitis, hypertension, and glucose intolerance. Use with caution in patients with estrogen-dependent tumors or history of thromboembolism. |
| Patient Advice | This medication is given as an injection into a muscle, usually by a healthcare provider. · Report any signs of blood clots (chest pain, shortness of breath, leg swelling, sudden headache or vision changes) immediately. · Do not smoke while using this drug, as smoking increases risk of serious cardiovascular side effects. · Inform your doctor if you have a history of breast cancer, blood clots, liver disease, or unexplained vaginal bleeding. · Regular check-ups including blood pressure, mammograms, and pelvic exams are recommended. |