The drug used to bring mares into heat for breeding might be just as effective at keeping them out of heat when given at different doses, according to Austrian researchers.

Deslorelin, in the form of a slow-release implant, successfully keeps pony mares from having estrus behavior and coming into heat, said Christine Aurich, DVM, PhD, head of the Graf Lehndorff Institute, in Neustadt, Germany, and professor of artificial insemination and embryo transfer in the Vetmeduni veterinary school Department for Small Animals and Horses, in Vienna, Austria.

It’s the same pharmaceutical product as that used in the commercial drug Ovuplant, which stimulates ovulation within 48 hours for well-timed breeding, she said. But when veterinarians administer deslorelin at different doses over different periods, it can have opposite effects.

“Deslorelin is a GnRH agonist, which means it’s a drug that stimulates pituitary secretion and synthesis of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) gonadotrophins,” Aurich said. “In mares, LH stimulates ovulation and luteal function (creating a good environment for the embryo).”

Treating mares with deslorelin in relatively low doses over a short time induces ovulation, Aurich explained. “But if deslorelin is given as a slow-release implant, this will result in a short stimulation of pituitary hormone release that is followed by downregulation of the pituitary receptors for GnRH (where deslorelin will also bind),” she said. “The pituitary gland will then no longer release LH and FSH, which is associated which a cessation of ovarian function.”

Two Skipped Cycles After a Single Injection

In their study, Aurich and her fellow researchers treated 11 Shetland pony mares with two doses of slow-release deslorelin implants and five Shetland mares with a low dose of deslorelin in an injectable formulation as a control. They found the higher dose of 9.4 milligrams withheld estrus for up to two heat cycles, with ovulation occurring between 38 and 82 days in that group of mares. The lower dose of 4.7 milligrams resulted in the mares skipping, on average, one heat cycle, with ovulations occurring between 25 and 40 days post-injection. The scientists also noted an absence of behavioral signs of estrus during most of the suppression period.

However, estrus control relied on the mare being in a post-ovulatory phase at the time of the injection, Aurich added. That’s determined by the presence of the corpus luteum, the structure that creates progesterone after ovulation. In the mares that didn’t have a corpus luteum (because they were entering a pre-ovulatory phase of their cycles), the deslorelin implants seemed to trigger ovulation; they all ovulated within nine days, with normal estrus behavior, regardless of the dose they received.

By comparison, the group of control mares (receiving the low dose in short release) came into heat between 13 and 29 days later, she said.

Ovuplant-Treated Mares Sometimes Have Delays in Next Ovulation

Researchers initially suspected deslorelin might work both ways (stimulating as well as suppressing ovulation) when they noticed mares on Ovuplant who didn’t get pregnant sometimes came back into heat as many as 10 days later than they should have, Aurich said. This spurred them to start testing various alternatives of dosing and release timing to find a combination that would purposefully suppress ovulation instead of stimulating it.

Aurich’s group wasn’t convinced it would work, however, because deslorelin wasn’t effective in suppressing reproductive activity in males of some species, including horses, said Aurich. Deslorelin affects GnRH regulation in both sexes of animals, and it’s been used for several years to temporarily “chemically castrate” male dogs. She said it doesn’t successfully stop the testicles from functioning in either bulls or stallions, though. However, it does seem to delay ovulation in female cattle, so researchers hoped it might also work in female horses.

Safer and More Reversible than Altrenogest, but Expensive

Slow-dose deslorelin shows promise as a safe and effective alternative to other methods of controlling estrus in performance mares, said Aurich. Altrenogest (Regumate), for example, potentially exposes the handler to long-term fertility and health complications. Handlers must give altrenogest daily, which exposes them to more frequent contact with the drug. Meanwhile, GnRH immunization (Equity), which might also result in transient suppression of ovarian function, has an unpredictable time of action (between four months and more than two years) and can cause injection site inflammation.

“The treatment with deslorelin, however, is very safe and has no side effects, and the effect on the ovaries is transient and fully reversible, meaning there are no long-term effects on ovulation or fertility to be expected,” said Aurich.

However, a downside is its expense, she added. Researchers are also unsure how much individual variation occurs, and research is still underway.

“Treatment of mares with deslorelin implants may be considered for management of problems associated with estrus behavior, but it is expensive, and there are large individual variations with regard to the time period during which ovulation is inhibited,” she said.

Although the study was performed on Shetland mares, slow-release deslorelin implants should also be effective on larger horses with appropriate doses, Aurich said.