Estradiol Cypionate
Estradiol cypionate is a long-acting, esterified derivative of the naturally occurring steroidal estrogen, estradiol. Historically, it was widely used as an abortifacient (mismating shot) in small animals. However, due to the severe and potentially fatal risk of **bone marrow suppression** (aplastic anemia) and the induction of **cystic endometrial hyperplasia/pyometra**, most theriogenologists no longer recommend its use in dogs and cats. Safer and more effective alternatives are now preferred. > **Clinical Pearl:** The FDA has strictly prohibited the use of estradiol cypionate in food-producing animals, making its administration or compounding for such species illegal.
Mechanism: Estradiol is the most active endogenous estrogen. It diffuses across the cell membrane and binds to specific intracellular **estrogen receptors (ERα and ERβ)**. The receptor-hormone complex translocates to the nucleus → binds to **estrogen response elements (EREs)** on DNA → modulates gene transcription. **Key systemic effects include:** * **Reproductive:** Stimulates normal growth and development of female sex organs, increases cervical mucosal secretions, thickens vaginal mucosa, and induces endometrial proliferation and uterine tone. * **Skeletal:** Increases calcium deposition, accelerates epiphyseal closure, and promotes bone formation. * **Endocrine:** Modulates pituitary gonadotropin release, which can inhibit lactation, ovulation, and androgen secretion.
Dosing by species
- Pregnancy avoidance after mismating · 250 micrograms/kg (0.25 mg/kg) IM once 6 days after coitus; or 0.25 mg/cat IM at 40 hours after coitus · IM · once · Rarely used for this indication today as there are safer, more effective treatments.
- Any · Illegal · The FDA has stated that the use of ECP in food-producing animals is illegal.
- To enhance estrus behavior and receptivity in ovariectomized mares · 5-10 mg (total dose) IM once · IM · once
- Treatment of mares with estrogen-responsive incontinence · 4-10 micrograms/kg estradiol cypionate IM daily for three days and then every other day · IM · daily then q48h · 3 days then ongoing · Some mares will improve, but does not 'cure'.
- Pregnancy avoidance after mismating · 44 micrograms/kg (0.044 mg/kg) IM once; during day 4 estrus to day 2 of diestrus · IM · once · Rarely used for this indication today as there are safer, more effective treatments. Toxic at >=100 micrograms/kg.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Pregnancy (teratogenic and causes fetal bone marrow depression)
- Food-producing animals (illegal per FDA)
- Ferrets (highly susceptible to severe bone marrow toxicity)
- Estrogen-responsive incontinence in small animals (safer alternatives like DES or estriol should be used)
Adverse effects
- Bone marrow toxicity (thrombocytopenia, leukopenia, fatal aplastic anemia)
- Cystic endometrial hyperplasia
- Pyometra
- Mammary neoplasia
- Feminization (in males)
- Prolonged estrus (in females)
- Genital irritation (cattle)
- Decreased milk flow (cattle)
- Follicular cysts (cattle)
Drug interactions
- Azole Antifungals (fluconazole, itraconazole, ketoconazole) · May increase estrogen levels due to CYP450 enzyme inhibition.
- Corticosteroids · Enhanced glucocorticoid effects; estrogens may alter protein binding or decrease metabolism of corticosteroids.
- Macrolide Antibiotics (erythromycin, clarithromycin) · May increase estrogen levels.
- Phenobarbital · May decrease estrogen activity via hepatic enzyme induction.
- Rifampin · May decrease estrogen activity via hepatic enzyme induction.
- St. John's Wort · May decrease estrogen activity.
- Warfarin · Oral anticoagulant activity may be decreased; dosage adjustments may be necessary.
Monitoring
- Packed Cell Volumes (PCV)
- White blood cell counts (CBC)
- Platelet counts (Baseline, one month after therapy, and repeated two months after cessation if abnormal)
- Liver function tests
Overdose
Acute overdosage reports in veterinary patients are rare, but chronic or high-dose exposure leads to severe adverse effects. **Overdose manifestations:** * **Small Animals:** Severe bone marrow depression (thrombocytopenia, leukopenia, aplastic anemia), cystic endometrial hyperplasia, and pyometra. * **Cattle:** Prolonged estrus, genital irritation, decreased milk flow, precocious development, and follicular cysts. Treatment is largely supportive. If bone marrow suppression occurs, aggressive supportive care (transfusions, broad-spectrum antibiotics) is required, though prognosis for aplastic anemia is poor.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.