Prostaglandins for Controlling Mares' Estrous Cycles

Breeders always appreciate ways to help improve their mares' chances of becoming pregnant, and one way veterinarians can help is by administering prostaglandins. At the 2013 Society for Theriogenology Conference, held Aug. 7-10 in Louisville, Ky., Carlos R. F. Pinto, MedVet, PhD, Dipl. ACT, presented a lecture on using prostaglandin F2? (PGF) to control the mare's estrous cycle.

Pinto, an associate professor at the Ohio State University College of Veterinary Medicine, began by reviewing PGF and its effects on the mare's reproductive cycle. PGF administration during diestrus (when the mare is not in heat) induces luteolysis, or the degradation of the corpus luteum (the structure formed after the follicle releases the egg, or ovulates, and then produces progesterone). Following luteolysis, mares will return to an ovulatory estrus, Pinto said.

Following PGF administration, Pinto said, there is generally "distinct evidence" (determined by checking concentrations of blood progesterone) of luteolysis within 24 hours; complete luteolysis typically occurs by 48 hours. Overt signs of estrus generally appear in three to four days, although they can appear in as little as two or as long as six days post-administration, he said.

Clinical Applications

So how is PGF used in practice? There are several scenarios in which veterinarians might choose to implement PGF treatment:

  • "Short Cycling"—Veterinarians typically use PGF to "short cycle" mares, or begin their return to estrus sooner than if allowed to progress through their cycle naturally. Following administration, mares can come into estrus and ovulate in as little as two to five days, if a large follicle (35 millimeters or greater) is in the ovary when PGF is administered. For mares with a small follicle (less than 25 mm), it could take a week or longer to come into estrus. The average time for a mare to develop estrus is around four to six days, Pinto said. When using PGF to short cycle a mare, there are numerous administration protocols veterinarians can follow, depending on the circumstance. In some cases a single dose can induce luteolysis; other cases might require additional doses.
  • PGF in Postpartum Mares—Pinto said that when a mare has a dystocia (difficult birth) or retains her fetal membranes, breeders and veterinarians might opt not to breed her on the following foal heat so her uterus can recover from inflammation and potential infections. "In this scenario, instead of having horse owners waiting for mares to come into their second postpartum estrus, one strategy would be to treat mares with PGF approximately five to seven days after ovulation in the foal heat," effectively short cycling her back into estrus, Pinto said.
  • Prolonged Diestrus—Pinto said that veterinarians can administer a single dose of PGF to mares in a state of persistent diestrus—one lasting more than 16 days post-ovulation. This should prompt mares to return to estrus, he said.
  • Estrus Synchronization—Likely most useful in larger breeding operations, breeders can use PGF to synchronize mares' breeding cycles, Pinto said.

PGF Safety and Formulations

Pinto said PGF administration appears fairly safe for use in horses. Study results show that administering 20 to 40 times the recommended dose did not elicit any toxic effects, and even doses up to 800 mg did not prove fatal, although they did cause recumbency (which resolved in four to five hours following administration).

Pinto noted that 20-40% of mares exhibit side effects including sweating, restless behavior, diarrhea, or coliclike signs; a smaller percentage of mares might also exhibit ataxia (incoordination).

"It is important to note that the side effects are dose-dependent and typically subside within the first hour following PGF treatment," he stressed.

Veterinarians use several different PGF preparations to induce luteolysis, and Pinto reviewed the dosing regimens of two products.

Dinoprost tromethamine—This natural PGF analog (also known as PGF tromethamine salt) is the only PGF approved by the Food and Drug Administration (FDA) for equine use in the United States. Pinto said the labeled dose is 5 to 10 milligrams (mg) per mare, administered once. He noted that research indicates two 0.5 mg doses administered 24 hours apart can also induce luteolysis without the traditional side effects (including sweating and colicky behavior); however, a single 0.5 mg dose is not effective. Dinoprost tromethamine has a half-life (the time required for the drugs' blood concentration to be decreased by 50%) of about 25 minutes.

Pinto said dinoprost tromethamine's efficacy in inducing luteolysis depends on the dose, the number of treatments, and the stage of the mare's estrous cycle when administered. However, he said he believes the drug can be 100% effective if administered properly.

Cloprostenol—"In contrast to several other countries, cloprostenol formulations are not FDA-approved for use in horses in the United States," Pinto said. "Nevertheless, cloprostenol is widely used in the United States by equine practitioners, mainly because of its longer half-life (1 to 3 hours in other species) and association with lesser side effects than dinoprost tromethamine."

There are two different cloprostenol formulations available from the substance's two optically active isomers: d-cloprostenol and l-cloprostenol. The most common formula in the United States is the d,l cloprostenol mixture, which is administered at a rate of 200 to 500 micrograms (µg) per mare. In other countries, Pinto said, d-cloprostenol, is administered at even a lower rate than d,l cloprostenol.

"In a recent report, the bolus dose of 37.5 µg of d-cloprostenol was found to induce complete luteolysis similar to mares receiving 250 µg of a d,l cloprostenol preparation," he explained.

Pinto cautioned that some study results have shown that mares predisposed to ovulatory disorders could be at increased risk of developing side effects when treated with cloprostenol. Additionally, he said, research has shown that d-cloprostenol has the potential to be hypertensive (or cause high blood pressure) in rats, although researchers aren't sure if the same is true in horses.

"Overall, all types of cloprostenol are relatively safe and have less systemic side effects than natural prostaglandin," he concluded.

Take-Home Message

"PGF is a remarkable pharmacologic tool in reproductive management," Pinto said. Breeders and their veterinarians can administer this substance to induce estrus, increasing the likelihood of a mare getting in foal with no negative effects, he said.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.

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