ESTRADIOL CYPIONATE
Chemistry - Estradiol is a naturally occurring steroidal estrogen. Estradiol cypionate is produced by esterifying estradiol with cyclopentanepropionic acid, and occurs as a white to practically white, crystalline powder. It is either odorless or may have a slight odor and has a melting range of 149-153°C. Less than 0.1 mg/ml is soluble in water and 25 mg/ml is soluble in alcohol. Estradiol cypionate is sparingly soluble in vegetable oils.
Commercially available injectable solutions of estradiol cypionate are sterile solutions in a vegetable oil (usually cottonseed oil); they may contain chlorobutanol as a preservative.
It is not recommended to mix estradiol cypionate with other medications.
Estrogens have effects on the skeletal system. They increase calcium deposition, accelerate epiphyseal closure and increase bone formation. Estrogens have a slight anabolic effect and can increase sodium and water retention.
Estrogens affect the release of gonadotropins from the pituitary gland. This can cause inhibition of lactation, inhibition of ovulation and inhibition of androgen secretion.
Uses, Indications - For mares, indications for the use of estradiol include, induction of estrus during the non-breeding or breeding seasons and to enhance the mare's uterine defense mechanism. Estradiol cypionate has also been used as an abortifacient agent (see warnings below) in cattle, cats and dogs.
One product (ECP® ¯ Upjohn) approved for use in breeding cattle, indications listed in its package insert for use in bovine medicine include:
To correct anestrus (absence of heat period) in the absence of follicular cysts in some cases.
To treat cattle having persistent corpus luteum due to certain causes.
To expel purulent material from the uterus in pyometra of cows.
To stimulate uterine expulsion of retained placentas and mummified fetuses.
Contraindications/Precautions - Estradiol is contraindicated during pregnancy. It has beendemonstrated to cause fetal malformations of the genitourinary system and to induce bone marrowdepression in the fetus.
In cases of prolonged corpus luteum in cows, thorough uterine exam should be completed todetermine if endometritis or a fetus is present
In cat le, prolonged estrus, genital irritation, decreased milk flow, precocious development andfollicular cysts may develop after estrogen therapy. These effects may be secondary to overdosageand dosage adjustment may reduce or eliminate them.
Overdosage - No reports of inadvertent acute overdosage in veterinary patients was located; see
Adverse Effects above.
Other known enzyme inducers (e.g., phenobarbital, phenylbutazone, etc.), may have a similareffect, but clinical significance is unclear.
Enhanced glucocorticoid effects may result if estrogens are used concomitantly with corticosteroid agents. It has been postulated that estrogens may either alter the protein binding of corticosteroids and/or decrease their metabolism. Corticosteroid dosage adjustment may be necessary when estrogen therapy is either started or discontinued.
Oral anticoagulant activity may be decreased if estrogens are administered concurrently.
Increases in anticoagulant dosage may be necessary if adding estrogens.
Drug/Laboratory Interactions - Estrogens in combination with progestins (e.g., oral contraceptives) have been demonstrated in humans to increase thyroxine-binding globulin (TBG) withresultant increases in total circulating thyroid hormone. Decrease T3 resin uptake also occurs, butfree T4 levels are unaltered. It is unclear if estradiol affects these laboratory tests.
Storage, Stability, Compatibility
Estradiol cypionate should be stored in light-resistant containers at temperatures of less than 40°C, preferably at room temperature (15-30°C); avoid freezing.Commercially available injectable solutions of estradiol cypionate are sterile solutions in a vegetable oil (usually cottonseed oil); they may contain chlorobutanol as a preservative.
It is not recommended to mix estradiol cypionate with other medications.
Pharmacology - ESTRADIOL CYPIONATE
The most active endogenous estrogen, estradiol possesses the pharmacologic profile expected of the estrogen class. Estrogens are necessary for the normal growth and development of the female sex organs and in some species contribute to the development and maintenance of secondary female sex characteristics. Estrogens cause increased cell height and secretions of the cervical mucosa, thickening of the vaginal mucosa, endometrial proliferation and increased uterine tone.Estrogens have effects on the skeletal system. They increase calcium deposition, accelerate epiphyseal closure and increase bone formation. Estrogens have a slight anabolic effect and can increase sodium and water retention.
Estrogens affect the release of gonadotropins from the pituitary gland. This can cause inhibition of lactation, inhibition of ovulation and inhibition of androgen secretion.
Uses, Indications - For mares, indications for the use of estradiol include, induction of estrus during the non-breeding or breeding seasons and to enhance the mare's uterine defense mechanism. Estradiol cypionate has also been used as an abortifacient agent (see warnings below) in cattle, cats and dogs.
One product (ECP® ¯ Upjohn) approved for use in breeding cattle, indications listed in its package insert for use in bovine medicine include:
To correct anestrus (absence of heat period) in the absence of follicular cysts in some cases.
To treat cattle having persistent corpus luteum due to certain causes.
To expel purulent material from the uterus in pyometra of cows.
To stimulate uterine expulsion of retained placentas and mummified fetuses.
Pharmacokinetics - ESTRADIOL CYPIONATE
No specific information was located regarding the pharmacokinetics ofestradiol in veterinary species. In humans, estrogen in oil solutions after IM administration areabsorbed promptly and absorption continues over several days. Esterified estrogens (e.g., estradiolcypionate) have delayed absorption after IM administration. Estrogens are distributed throughoutthe body and accumulate in adipose tissue. Elimination of the steroidal estrogens occurs principallyby hepatic metabolism. Estrogens and their metabolites are primarily excreted in the urine, but arealso excreted into the bile, where most is reabsorbed from the GI.Contraindications/Precautions - Estradiol is contraindicated during pregnancy. It has beendemonstrated to cause fetal malformations of the genitourinary system and to induce bone marrowdepression in the fetus.
In cases of prolonged corpus luteum in cows, thorough uterine exam should be completed todetermine if endometritis or a fetus is present
Adverse Effects, Warnings
Estrogens have been associated with severe adverse reactions insmall animals; see the Adverse Effects section in the DES monograph (prior to this one) for moreinformation.In cat le, prolonged estrus, genital irritation, decreased milk flow, precocious development andfollicular cysts may develop after estrogen therapy. These effects may be secondary to overdosageand dosage adjustment may reduce or eliminate them.
Overdosage - No reports of inadvertent acute overdosage in veterinary patients was located; see
Adverse Effects above.
Drug Interactions
Rifampin may decrease estrogen activity if administered concomitantly. Thisis presumably due to microsmal enzyme induction with resultant increase in estrogen metabolism.Other known enzyme inducers (e.g., phenobarbital, phenylbutazone, etc.), may have a similareffect, but clinical significance is unclear.
Enhanced glucocorticoid effects may result if estrogens are used concomitantly with corticosteroid agents. It has been postulated that estrogens may either alter the protein binding of corticosteroids and/or decrease their metabolism. Corticosteroid dosage adjustment may be necessary when estrogen therapy is either started or discontinued.
Oral anticoagulant activity may be decreased if estrogens are administered concurrently.
Increases in anticoagulant dosage may be necessary if adding estrogens.
Drug/Laboratory Interactions - Estrogens in combination with progestins (e.g., oral contraceptives) have been demonstrated in humans to increase thyroxine-binding globulin (TBG) withresultant increases in total circulating thyroid hormone. Decrease T3 resin uptake also occurs, butfree T4 levels are unaltered. It is unclear if estradiol affects these laboratory tests.