DEPO-ESTRADIOL
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Estradiol is an estrogen hormone that binds to estrogen receptors (ERα and ERβ) in target tissues, modulating gene transcription and exerting effects such as proliferation of endometrial tissue, regulation of gonadotropin secretion (negative feedback on FSH and LH), and maintenance of secondary sexual characteristics.
| Metabolism | Primarily hepatic metabolism via cytochrome P450 enzymes, mainly CYP3A4 and CYP1A2, to estrone and estriol. Undergoes enterohepatic recirculation and conjugation (glucuronidation and sulfation). Metabolites are excreted primarily in urine. |
| Excretion | Estradiol is extensively metabolized in the liver, with conjugated metabolites (glucuronides and sulfates) primarily excreted in urine (about 90%) and feces (about 10%). Less than 5% is excreted unchanged. |
| Half-life | The terminal elimination half-life of estradiol after intramuscular injection of Depo-Estradiol is approximately 5-9 days, reflecting slow release from the depot and prolonged systemic exposure. |
| Protein binding | Approximately 98-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | The volume of distribution is approximately 1.1 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Intramuscular administration provides 100% bioavailability due to complete absorption from the injection site. |
| Onset of Action | After intramuscular injection, clinical effects (e.g., relief of menopausal symptoms) are typically observed within 2-4 hours. |
| Duration of Action | Duration of action after a single intramuscular dose is approximately 3-4 weeks, due to sustained release from the injection site and enterohepatic recirculation. |
| Molecular Weight | 272.38 |
1 to 5 mg intramuscularly every 3 to 4 weeks for estrogen replacement therapy.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment. |
| Liver impairment | Contraindicated in severe hepatic disease; for Child-Pugh A or B, initiate at lowest dose and titrate cautiously. |
| Pediatric use | Not indicated for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lowest effective dose; monitor for thromboembolic events and estrogen-sensitive malignancies. |
| 1st trimester | Estradiol is contraindicated in pregnancy. Use during first trimester is associated with a risk of fetal harm, including congenital anomalies such as cardiovascular and limb defects. Estrogens can increase the risk of vaginal adenosis and cervical cancer in female offspring. Depo-Estradiol should not be used during the first trimester of pregnancy. |
| 2nd trimester | Estradiol is contraindicated in pregnancy. Use during the second trimester is not recommended due to potential adverse effects on fetal development, including genital abnormalities and potential long-term reproductive effects. There is no indication for use during pregnancy. |
| 3rd trimester | Estradiol is contraindicated in pregnancy. Use during the third trimester may cause fetal harm, including potential effects on fetal growth and development. Estrogens can delay parturition and have been associated with increased risk of postpartum complications. Avoid use in third trimester. |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
■ FDA Black Box Warning
Estrogens increase the risk of endometrial cancer in postmenopausal women with an intact uterus. Estrogens should not be used to prevent cardiovascular disease or dementia. The Women's Health Initiative (WHI) substudy reported increased risks of stroke, deep vein thrombosis, pulmonary embolism, and myocardial infarction in postmenopausal women (50-79 years of age) treated with conjugated estrogens. The WHI Memory Study (WHIMS) reported increased risk of probable dementia in postmenopausal women over 65 years of age treated with conjugated estrogens.
| Common Effects | osteoporosis prevention |
| Serious Effects |
Known or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancerKnown or suspected estrogen-dependent neoplasiaActive deep vein thrombosis, pulmonary embolism, or history of these conditionsActive arterial thromboembolic disease (e.g., stroke, myocardial infarction) or history of these conditionsKnown hypersensitivity to estradiol or any component of the formulationHepatic impairment or disease (if liver function tests are not normal)Known thrombophilic disorders (e.g., protein C, protein S, or antithrombin deficiency)
| Precautions |
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| Placental transfer | Estradiol readily crosses the placenta and is transferred to the fetus. Animal studies have shown transplacental passage, and in humans, estradiol levels in fetal circulation are comparable to maternal levels. This transfer can lead to fetal exposure and potential adverse effects. |
| Breastfeeding | Estradiol is excreted into human breast milk in small amounts. The American Academy of Pediatrics considers estradiol compatible with breastfeeding, but caution is advised as estrogens may reduce milk production and alter milk composition. Use only if clearly needed and monitor infant for adverse effects such as jaundice or breast enlargement. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| Teratogenic Risk | Estradiol is contraindicated in pregnancy. First trimester exposure is associated with a potential risk of congenital anomalies, including cardiovascular and limb defects, based on observational studies. Second and third trimester exposure may lead to urogenital tract abnormalities in female offspring and potential long-term reproductive effects. Use during pregnancy has been linked to an increased risk of vaginal adenocarcinoma in female offspring (in utero DES exposure, a related estrogen). Animal studies show embryotoxicity and teratogenicity at clinically relevant doses. |
| Fetal Monitoring | If inadvertent exposure during pregnancy occurs, monitor fetal development via high-resolution ultrasound and echocardiography. Monitor maternal blood pressure, glucose, and lipid profiles. Assess for signs of thromboembolism, especially if coexisting risk factors. Serial growth scans in later pregnancy if continued exposure. |
| Fertility Effects | Estradiol may impair fertility by suppressing gonadotropins and ovulation at high doses. It is used in some assisted reproductive protocols but can also disrupt natural menstrual cycles. Reversible upon discontinuation. Chronic use may delay return to fertility. |
| Cardiovascular disorders (e.g., stroke, MI, thromboembolism), malignancy (endometrial, breast), dementia, gallbladder disease, hypercalcemia, visual abnormalities, fluid retention, elevated blood pressure, hypertriglyceridemia, hypothyroidism, hereditary angioedema, exacerbation of endometriosis, and pregnancy (category X). Monitor for signs of thrombosis, abnormal uterine bleeding, and hepatic impairment. |
| Food/Dietary | Grapefruit juice may inhibit CYP3A4 metabolism of estradiol, leading to increased serum levels and risk of adverse effects. Avoid excessive grapefruit consumption. No other significant food interactions known. Take with food if gastrointestinal upset occurs. |
| Clinical Pearls | Administer by deep IM injection only, not IV or subcutaneously. Rotate injection sites (gluteal, deltoid). Use a 21-22 gauge needle; aspirate to avoid intravascular injection. Do not use in pregnancy or undiagnosed abnormal genital bleeding. Monitor for thromboembolic events, hypertension, hypertriglyceridemia, and endometrial cancer risk. For cyclic regimen, start day 5 of menstrual cycle; for continuous, administer every 28 days. Can cause local injection site reactions, including sterile abscess. In patients with intact uterus, use with progestin to reduce endometrial hyperplasia risk. |
| Patient Advice | This medication is a form of estrogen given as an injection to manage menopausal symptoms or low estrogen levels. · It is typically injected into a muscle (buttock or thigh) by a healthcare provider every 4 weeks. · Do not use if pregnant, breastfeeding, or have a history of blood clots, breast cancer, or liver disease. · Report any signs of blood clots: leg pain/swelling, chest pain, sudden shortness of breath, or vision changes. · Smoking while using this drug increases risk of serious cardiovascular side effects, especially if over 35 years old. · Use the lowest effective dose for the shortest duration possible. · If you have a uterus, you may need to take a progestin to prevent uterine cancer. · Common side effects include injection site pain, breast tenderness, headache, and nausea. · Avoid grapefruit juice which can increase estrogen levels and side effects. · Do not drive after injection if you feel dizziness or drowsiness. |