Estradiol Cypionate in Oil (Canada)

Company: P.V.L.

DIN: 00345318

Active Ingredient(s): The sterile solution is available in 4 mg/mL concentration in cottonseed oil containing 5 mg anhydrous chlorobutanol (chloral deriv.), as a preservative.

Estradiol Cypionate in Oil Indications

ESTRADIOL CYPIONATE has a wide range of usefulness in veterinary practice as it offers all of the functional activity of natural estrogenic substances with prolonged action.

The indications in animal medicine include the following:

1. To correct anestrus (absence of heat period) in the absence of follicular cysts.

2. To treat cattle having a persistent corpus luteum.

3. To expel purulent material from the uterus in pyometra of cows.

4. As replacement therapy in spayed female dogs, particularly to treat those with urinary incontinence.

5. To stimulate uterine expulsion of retained placentas and mummified fetuses.

6. To prevent implantation of the fertilized ova in the mismated bitch.

Clinical evidence indicates value as palliative treatment for benign anal tumors in aged male dogs.

Pharmacology

The product is the oil-soluble 17β-cyclopentylpropionate ester of “alpha” estradiol. It provides estradiol-17β, believed to be the most potent of the naturally occurring estrogens, in the form of the cyclopentylpropionate ester, a highly fat-soluble derivative with profound estrogenic effects.

Comparative studies have demonstrated that estradiol cypionate produces estrogenic effects which are qualitatively the same as those produced by other estradiol esters. Estrus is usually induced in the majority of animals following injection of the preparation. Estrus may be maintained for variable periods, depending upon the status of the animal at the time of injection.

Dosage and Administration

ESTRADIOL CYPIONATE sterile solution is for intramuscular injection only. Recommended average doses are as follows and may be repeated, if necessary, in one (1) week.

Do not overdose.

Contraindication(s): As with all products of this nature, a complete examination to determine the status of the reproductive tract should be undertaken prior to administration of the drug. Pregnancy may be the prime reason for either anestrus or the persistence of the corpus luteum. Since pregnancy may be terminated by estrogens, estradiol cypionate is contraindicated where a desired pregnancy exists.

Caution(s): For veterinary use only.

Administration of an estrogenic substance to an animal may result in the development of follicular cysts.²

In the case of prolonged persistence of the corpus luteum, a thorough examination should also be made of the uterus to determine the presence of an endometritis or a fetus. The use of the appropriate antimicrobial agents, in addition to estradiol cypionate should be considered if endometritis exists.

In the absence of normally developing follicles on the ovaries, estrus may be produced, but ovulation may not accompany estrus. Because it is impossible to determine exactly if and when ovulation may occur in treated females during an induced heat period, it may help to have the female bred frequently throughout the induced heat periods in order to improve the possibility of conception.

Repeat breeding will improve the chance of conception only if ovulation occurs. In the case of bitches, the prolonged action of estradiol cypionate may, in some instances, interfere with nidation.

When used in mismated bitches, injection should be made as soon as possible after mismating. After nidation of the fertilized ova has taken place, the regimen is ineffective.

Side Effects

Prolonged estrus, precocious development, genital irritation, follicular cysts, and a reduction of milk flow may occur following estrogen therapy, frequently as a result of overdosage. If any of these phenomena are observed, the dosage should be reduced accordingly.

Estrogens used in the canine in large doses may produce a gradual anaemia and a profound leukocytosis which is followed by leukopaenia. Thrombocytopaenia may result with a concomitant alteration in the clotting mechanisms. If marked overdosage occurs, it would be prudent to consider periodic hematology and supportive therapy as deemed necessary.¹ Further estrogen therapy should not be undertaken.

Discussion: Anestrus in conjunction with a persistent corpus luteum probably reflects some interference with normal function of the uterine endometrium. As indicated earlier, pregnancy must be considered as a cause of the persistence of the corpus luteum. Prolonged maintenance of the corpus luteum has also occurred following hysterectomy or the experimental induction of endometritis.^5-6 It is doubtful that corpora lutea are retained indefinitely in cattle with normal uterine function.^4-6 It has been demonstrated that estrogens will cause regression of the corpus luteum in cycling, pregnant, or hysterectomized cattle.⁷ In the absence of a pregnancy or a detectable uterine malfunction, repeated rectal palpations will be required to establish a diagnosis of persistent corpus luteum. Although estrogens may produce luteal regression, consideration of proper uterine treatment should also be given.

The proper diagnosis of anestrus without frequent rectal palpation is difficult since normal ovarian cycles can occur without accompanying estrus. It has been reported that such “silent heat” is more frequent at the first post-partum estrus.⁴

Regression of the corpus luteum following estrogen treatment and noticed in cattle may not be noticed in all species; for example, in swine, a persistent corpus luteum may be a sequel of estrogen therapy.⁸

Trial Data: Recent research findings indicate the necessity for a reappraisal of the causes and effects of anestrus in cattle.

Two recent reports have suggested that frequently cows with a follicular cyst may be more inclined to be anestrual than nymphomaniac.^3-4 Many cows will recover spontaneously from anestrus (if due to follicular cysts) if less than 60 days post-parturient.⁴ In cases of anestrus due to follicular cysts, estrogens are not usually indicated.

Frequently, anestrus or follicular cysts have developed in association with a marked loss in body condition due to disease or high milk production.⁴

References

Available upon request.

Presentation: 100 mL vials.

CPN: 12030180