ESTRADIOL CYPIONATE
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Estradiol cypionate is a synthetic ester of estradiol, a form of estrogen. It binds to estrogen receptors (ERα and ERβ) in target tissues, modulating gene expression and leading to effects such as development of female secondary sexual characteristics, regulation of menstrual cycle, and maintenance of reproductive tissues. It also has effects on bone density, lipid metabolism, and coagulation factors.
| Metabolism | Estradiol cypionate is hydrolyzed in the liver to estradiol, which is then metabolized primarily via cytochrome P450 3A4 (CYP3A4) to estrone and estriol, and undergoes conjugation (glucuronidation and sulfation). |
| Excretion | Primarily renal (approximately 90% as glucuronide and sulfate conjugates; less than 5% as unchanged drug). Biliary/fecal elimination accounts for about 10%. |
| Half-life | Terminal elimination half-life is approximately 7–9 days following intramuscular injection, reflecting prolonged absorption from the oil depot. |
| Protein binding | Approximately 98–99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Not well established for estradiol cypionate; estradiol Vd is approximately 1–2 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Intramuscular: ~100% bioavailability due to complete absorption; oral not available for this ester. |
| Onset of Action | Intramuscular: Clinical effects (e.g., estrogenic response) typically observed within 1–3 days. |
| Duration of Action | Intramuscular: Duration approximately 3–4 weeks after a single injection due to slow release from the oil depot. |
| Molecular Weight | 396.56 |
1-5 mg intramuscularly every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for renal impairment. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). In mild to moderate impairment, use with caution and consider dose reduction. |
| Pediatric use | Not recommended for use in pediatric patients for hormone therapy; if used, dose is individualized based on weight and clinical response. |
| Geriatric use | Use lowest effective dose due to increased risk of cardiovascular and thromboembolic events; monitor closely. |
| 1st trimester | Contraindicated in pregnancy; estrogens are associated with fetal harm, including congenital anomalies. Use only if clearly needed and no safer alternative. |
| 2nd trimester | Contraindicated; risk of fetal harm persists. Avoid use during pregnancy. |
| 3rd trimester | Contraindicated; estrogens can cause fetal harm and should not be used during pregnancy. |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Placental transfer | Estradiol crosses the placenta readily; clinically significant transfer occurs. |
| Breastfeeding |
■ 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 increase. Use lowest effective dose and shortest duration consistent with treatment goals.
| Common Effects | osteoporosis prevention |
| Serious Effects |
PregnancyHistory of or known breast cancerKnown or suspected estrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingActive or past history of thromboembolic disordersLiver disease or impaired liver functionKnown hypersensitivity to estradiol cypionate or any component
| Precautions | Cardiovascular disorders: increased risk of stroke, DVT, PE, MI, Malignancy: endometrial cancer risk with unopposed estrogen, breast cancer risk, Dementia: increased risk of probable dementia in women over 65, Gallbladder disease, Hypertriglyceridemia, Fluid retention, Hypocalcemia in hypoparathyroidism, Ocular abnormalities: retinal thrombosis, Hereditary angioedema exacerbation, Exacerbation of other conditions: asthma, diabetes, epilepsy, migraine, SLE, hepatic hemangiomas, Impact on laboratory tests: thyroid function, coagulation factors, etc. |
Loading safety data…
| Estradiol cypionate is excreted in human breast milk in low concentrations. Potential for adverse effects in nursing infant; caution advised. Use only if benefits outweigh risks. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Estradiol cypionate is contraindicated in pregnancy. First trimester: Associated with congenital anomalies including cardiovascular and limb defects. Second and third trimesters: Potential for genitourinary tract abnormalities, feminization of male fetuses. No safe dose established. |
| Fetal Monitoring | Monitor maternal blood pressure, glucose, lipid profile, and signs of thromboembolism. Fetal ultrasound for anatomical development and growth restriction. |
| Fertility Effects | Suppresses ovulation and may impair fertility. Used as a contraceptive in some formulations. Reversible upon discontinuation. |
| Food/Dietary | No significant food interactions. Grapefruit juice may increase estrogen levels but is not a major concern with injectable route. Maintain adequate calcium and vitamin D intake for bone health. |
| Clinical Pearls | Estradiol cypionate is a long-acting estradiol ester used in hormone therapy. IM injection avoids first-pass metabolism. Monitor for thromboembolic events, especially in smokers or those with obesity. Not for use in pregnancy (Category X). Use with progestin in women with intact uterus to prevent endometrial hyperplasia. Onset of action is 1-2 days, duration 2-3 weeks. |
| Patient Advice | This medication is a form of estrogen given as an injection every 2-4 weeks. · Do not use if you are pregnant, breastfeeding, or have a history of blood clots or breast cancer. · Report any signs of blood clots (leg pain, sudden shortness of breath, chest pain) or stroke (sudden severe headache, vision changes, slurred speech). · Use in women with a uterus requires a progestin to reduce risk of uterine cancer. · Cigarette smoking increases risk of serious cardiovascular side effects; avoid smoking. · Common side effects include nausea, breast tenderness, and bloating; usually improve over time. |