LUTREPULSE (GONADORELIN ACETATE)

Gonadorelin is recommended for the treatment of reproductive disorders associated with ovarian cysts and for, improvement of fertility in cows and the induction of ovulation in rabbits.

Therapeutic Class:

Reproductive Hormone (Systemic Drug)

General Notes:

• Human glycoprotein hormone that mimics luteinizing hormone; used for a variety of theriogenology conditions in many species.
• Only for parenteral administration.
• Contraindications: Androgen-responsive neoplasias, hypersensitivity to the drug.
• Adverse effects (rare): Anaphylactic reaction.1

Indications/Symptoms:

The veterinary FDA-approved product is labelled for “parenteral use in cows for the treatment of nymphomania (frequent or constant heat) due to cystic ovaries” and “as an aid in improving spawning function in male and female brood finfish.” 1 It has been used for other purposes in several species; refer to the Dosages section for more information.

Species:

Commonly used for used for a variety of theriogenology conditions in cattle, horses, dogs, cats, swine, sheep, goats and other species. 1

Pharmacology:

Chorionic gonadotropin (hCG) mimics the effects of luteinizing hormone (LH). In males, hCG stimulates the differentiation of testicular interstitial (Leydig) cells and produces androgens. The hormonal treatment of cryptorchidism with hCG is controversial in humans and domestic animals. 1

In females, hCG is primarily used as an ovulation-inducing agent (extra-label). In the bitch, administration of hCG induces estrogen secretion during anestrus and can, therefore, be used to identify spayed bitches with ovarian remnants. 2

Pharmacokinetics:

hCG is destroyed in the GI tract after oral administration, so it must be administered parenterally. After IM injection, peak plasma levels occur in about 6 hours. hCG is distributed primarily to the ovaries in females and to the testes in males, but some may also be distributed to the proximal tubules in the renal cortex. hCG is eliminated from the blood in a biphasic manner. The initial elimination half-life in humans is about 11 hours, and the terminal half-life is approximately 23 hours. 1

Contraindications / Precautions:

No labeled contraindications for veterinary patients were noted, but the above human contraindications should be used as guidelines. Antibody production to this hormone has been reported after repetitive use; however, despite this effect, pharmacologic activity (induction of ovulation) is expected to remain unaltered. 1

Adverse Effects:

hCG may cause abortion in mares before the 35th day of pregnancy, possibly because of increased estrogen levels. Potentially, hypersensitivity reactions are possible with this agent. Anaphylactic reactions are rare, and several practitioners have anecdotally reported mares showing transient hives and respiratory distress immediately following hCG administration. Problems associated with using hCG in dogs for estrus induction include the unpredictability of response, the potential for allergic reactions, and premature luteal failure. 3

Drug Interactions:

No interactions have been reported with hCG.

Other Warnings:

In humans, the FDA categorizes this drug as category X for use during pregnancy. Studies in animals or humans demonstrate fetal abnormalities or adverse reactions; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible benefit. In humans, hCG and its metabolites have been found in maternal milk.4 There are no similar studies with animals reported following the administration of hCG.1

Dosages:

Dogs – Cryptorchidism or increased libido in male dogs (extra-label): 25 – 500 Units IM 2 times per week for 4-6 weeks.

hCG Challenge test to determine if testicular tissue remains in castrated male dogs (extra-label): Note: Contact your laboratory for specific recommendations for testing. Various protocols exist, including taking a sample for resting testosterone level. Administer 44 micrograms/kg hCG IM and take a 4-hour post sample.

hCG Challenge test to identify the presence of ovarian tissue in intact bitches or those with ovarian remnants (extra-label): Administer 200 – 300 Units hCG IV and take a blood sample before and 90 minutes after treatment. Submit plasma samples for determination of estradiol concentrations.

Produce luteinization of a follicular cyst (extra-label): 500 – 1000 Units IM; repeat in 48 hours or every 24 hours for 3 days. 1

Induction of estrus in bitches (extra-label): 500 Units hCG IM once. (de Sousa Oliveira 2009). In one study, an injection of 5 mL of PG 600® induced proestrus in 17 of 19 bitches and caused ovulation in 8 of 19; the pregnancy rate was not reported. 5

Cats – hCG Challenge test to determine if testicular tissue remains in castrated male cats (extra-label): Note: Contact your laboratory for specific recommendations for testing. Various protocols exist, including taking baseline serum testosterone samples, administering 250 Units IM, and taking the second sample 4-hours later.1

hCG Challenge test to identify the presence of ovarian tissue in queens suspected to have ovarian remnants after being presumably spayed (extra-label): Administer 500 Units hCG IM between 1 and 3 days following the onset of estrous behaviour, and take a blood sample before hCG administration and 7 days later. Submit plasma samples for determination of progesterone concentrations. 6

Infertility, reduced libido, cryptorchidism in male cats (extra-label): 50 – 100 Units repeated if necessary. 7

Induction of ovulation in female cats (extra-label): 500 Units IM on day 1 or days 1 and 2 of estrus. Alternatively, 250 Units IM on days 2 and 3 of estrus, coupled with mating 3 times per day at 3-hour intervals for the first 3 days of estrus. 8

Birds – Reduce feather plucking (especially in female birds; extra-label): Dosage is empirical; 500 – 1,000 Units/kg IM. If no response in 3 days, repeat. If no response after the second injection, unlikely to be of benefit at any dose. If feather plucking is reduced, repeat after 4-6 weeks. A major drawback is that, with repeated usage, the time between treatments is reduced.9

Fish – Improve spawning function in male and female brood finfish (labelled dose): Administer IM just ventral to the dorsal fin for 1 to 3 injections.10

Horses – Induction of ovulation (extra-label in the US): Administer 1,500 – 3,000 Units hCG IV to mares in estrus with >30 mm follicle. Ovulation is expected to occur within 48 hours of administration.11

hCG Challenge test to determine if testicular tissue remains in a gelding (extra-label): Note: Contact your laboratory for specific recommendations for testing. Various protocols exist, including taking baseline serum testosterone samples, administering 6000 Units IV, and taking samples 20 minutes, 1 hour, and 2 hours later. 11

Cattle – Treatment of ovarian cysts (labeled dose): The reconstituted contents of 1 vial (10,000 Units; 10 mL) should be administered as a single, deep intramuscular injection. Dosage may be repeated in 14 days if the animal’s behaviour or rectal examination of the ovaries indicates the necessity for retreatment.10 Induction of ovulation (extra-label in the US): Intramuscular administration of only 1,500 or 2,000 Units will induce ovulation in cows subjected to estrus synchronization protocols.1

Swine – Induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts over five and one-half months of age and weighing at least 85 kg (187 lb) or in healthy sows at weaning experiencing delayed return to estrus. Sows should be injected at weaning during periods of delayed return to estrus.1

Sheep – Induction of estrus (extra-label in US): 400 – 800 Units hCG IM or SC in the anterior half of the neck.1

Goats – Induction of estrus (extra-label in US): 200 – 600 Units hCG IM or SC in the anterior half of the neck.1