What's New in Equine Estrus Manipulation

Current options for owners who want to control their mares’ heat cycles for breeding or performance reasons

Your mare comes equipped with the signals and structures necessary to reproduce. But nature doesn’t always have the most convenient timing. Like that time all the shipped semen went bad waiting for Ruby to ovulate. Or that embarrassing moment Ellie stopped in the middle of a dressage test and winked her vulva at a flashy Hanoverian stallion. Oh estrus.

All About Estrus

In the five to seven days before ovulating, mares go through estrus, says Christine Aurich, DVM, PhD, head of the Graf Lehndorff Institute for Equine Science, in Neustadt, Germany. During this time, the uterus is preparing to accept a pregnancy, and because semen can live several days inside the mare’s reproductive tract, she becomes “ready”—both physiologically and behaviorally—to receive a stallion.

Breeding centers must predict estrus accurately for well- timed mating or insemination, says Aurich. “With the help of induction of estrus and ovulation, breeding processes are much easier and, overall, fertility (conception rate) is much improved,” she says.

Likewise, success of assisted reproduction techniques such as intracytoplasmic sperm injection and embryo transfer require careful control of the estrous cycle to eliminate the complication of finding a recipient mare at the right stage of estrus, says Marco Antonio Alvarenga, PhD, of the Department of Animal Reproduction and Veterinary Radiology at Sao Paulo State University, in Botucatu, Brazil.

In performance mares owners might prefer to delay estrus to avoid its undesirable behavior aspects, says Robyn Ellerbrock, DVM, PhD, Dipl. ACT, assistant professor of theriogenology in the University of Georgia’s College of Veterinary Medicine, in Athens. “Manipulation is necessary in mares that become difficult to work with when in heat,” she says.

Changing the Hormone Balance

Manipulating estrus is essentially a game of altering hormonal balance to “trick” a mare’s reproductive system into staying longer in a nonestrous phase or to bring on estrus faster and shorten its duration, our sources say.

Delicate balances of primarily progesterone and estrogens induce the various phases of a mare’s estrous cycle, explains Aurich. Estrogen is the predominant hormone during estrus. In diestrus—the period between estrous cycles— progesterone takes the lead. It’s the “pro-gestation” hormone, meaning it promotes pregnancy by encouraging the uterus to accept and hold on to an embryo. Very basically, estrus makes a mare sexually excited, whereas progesterone keeps a mare calm and “maternal.”

Scientists have developed drugs to manipulate estrus, using equine hormones, hormones from other species, and synthetic variations of these hormones. They force a shift in the hormonal balance, changing the estrous cycle.

The reproductive system can also be “encouraged” to alter that balance without drugs, our sources say. By changing aspects of the mare’s environment—including her uterine environment—at different points in the estrous cycle, her body “believes” it needs to be releasing different proportions of hormones than it normally would.

Altrenogest: Still the Gold Standard for Performance Horses

Oral altrenogest (Regu-Mate) is today’s gold standard in estrus manipulation for performance horses in the U.S. and many other countries, says Ellerbrock. “This is the safest (for the mare) and most effective option, with the most predictable outcome,” she says. It’s also the only FDA-approved product for suppressing estrus, she adds.

Altrenogest is a synthetic hormone that shifts the hormone balance to become progesterone-dominant by interacting with the mare’s progesterone receptors, says Callum G. Donnelly, BVSc (Hons I), Dipl. ACT, ACVIM (LA), of the Finno Laboratory in the Department of Population Health and Reproduction at the University of California, Davis, School of Veterinary Medicine. Given orally as a liquid every day during the breeding season, altrenogest generally holds off estrus until about five days after treatment stops.

An injectable form reduces contamination risk for drug tests (more on this in a bit) but increases the risks of skin reactions, Ellerbrock says.

A new, though not yet FDA-approved, alternative is a long-term oxytocin injection, which is a “cheaper option that doesn’t risk hormonal exposure for the barn staff,” she explains, potentially interfere with a woman’s reproductive system if absorbed through the skin.

Oxytocin injections, given daily for a week, can cause cramping and don’t work in all mares. When they do, they can prolong diestrus by up to 60 days, says Donnelly.

The Anti-GnRH “Vaccine”

One way to control estrus is to render some of the mare’s hormones ineffective. That’s the principle of the anti-GnRH vaccine. The brain’s hypothalamus releases GnRH, signaling the mare’s reproductive system to cycle, says Aurich. The anti-GnRH vaccine stimulates the mare’s own antibodies to overact in response to GnRH, “killing” its action. The hypothalamus still sends out GnRH, but the reproductive organs no longer respond, and estrus doesn’t occur.

“It’s very effective,” Donnelly says. “But it comes with a huge downside in that mares might never cycle again.”

That could explain its lack of FDA approval, he says, though the drug is approved and in circulation in countries across Europe and South America.

While the vaccine might stop cycling, it might not change performance-related issues, says Alvarenga. 

What's New in Equine Estrus Manipulation

Novel Nondrug Therapies

One of the oldest efforts to manipulate estrus involves keeping the barn light on at night to stimulate estrus earlier in the breeding season. Specialized retinal cells in the eyes signal the brain to send messages about time and season to the rest of the body, affecting hormone production. Longer artificial days “trick” the mare’s brain into coming into estrus. Irish researchers have found that blue light is more effective than typical fluorescent or incandescent lights because it’s abundant in natural daylight. They designed blue-light masks that manipulate estrus more effectively while letting mares get out of the barn and roam on pasture, says Barbara Murphy, PhD, assistant professor in University College Dublin’s School of Agriculture and Food Science.

Then there are intrauterine devices (IUDs). For decades vets have used a technique whereby they insert a glass marble into the uterus to mimic pregnancy. It works, to an extent, but the marbles can break and damage the reproductive organs, says Donnelly.

A new, safer IUD might soon become available. Carlos Gradil, DVM, PhD, Dipl. ACT, professor in Tufts University’s Department of Veterinary and Animal Sciences, in Amherst, Massachusetts, and adjunct associate professor at the school’s Cummings School of Veterinary Medicine, in North Grafton, has designed a magnetic IUD. Its three shatterproof beads self-assemble into a ring after insertion into the uterus. Early research showed it extended diestrus by an average of 74 days and stayed in place without complications for the 18-month study period. Gradil’s team easily removed the IUD with a magnetic retriever, after which all 29 study mares conceived successfully.

Plant Oils: The New Marbles?

Infusing plant oils into the uterus has shown some promise in delaying estrus, says Ellerbrock. “There’s a research publication (from 2011) indicating that intrauterine plant oil infusions (fractionated coconut or peanut oil) can work in up to 90% of mares short-term,” she says. “But we don’t know the mechanisms of action, short-term side effects, or long-term effects on fertility at this time.”

The principle is probably similar to that with marbles, in that the oil mimics gestation, says Donnelly. He’s used them “sparingly,” cautious of yet-unknown side effects but fairly confident in their efficacy.

More recently, though, in a 2016 study Canadian and Brazilian researchers indicated that these approaches “are not effective at all,” says Aurich. Evidence is lacking to show that either marbles or oil suppresses estrus or estrous behavior, she says. If owners notice a difference in their mares, it might be purely a placebo effect.

Risks: Lumps, Doping, and Twins

It’s relatively safe to manipulate estrus, our sources say. But it’s not risk-free. Hormone injection sites can swell, causing discomfort and lumps. “Steroid hormones have to be suspended in oil, and some mares really react to that,” says Donnelly.

As mentioned, for competing mares, it’s important that the drugs don’t lead to positive doping tests—for them or the horses around them. “This is a big issue in sport horses in the U.S. because of drug residues (in feed buckets, for instance), so we’re often asked for estrous management strategies that don’t involve detectable prohibited substances like altrenogest,” Donnelly explains. Due to its nature as a steroid and also as a neuroactive agent, “there’s always a question of whether it’s performance-enhancing or if it can make horses quieter,” he says.

Altrenogest is approved for mares in United States Equestrian Federation and Fédération Equestre Internationale competitions, provided handlers file a medication form. However, it’s a controlled medication in geldings and stallions.

There’s also the risk that any therapeutic approach could make a mare’s estrous behavior worse, Donnelly explains. “Each mare is different and can have different reactions,” he says. ­Ovariectomies—removal of the ovaries—are a good example. Estrogen production stops, but so does progesterone release. “We sometimes remove ovaries in teaser mares, because then they show estrous behavior all the time,” says Donnelly.

Some estrous suppression therapies might have long-term or permanent effects on future fertility, Donnelly says.

Still, there’s “no concrete evidence” of long-term effects, says Ellerbrock.

As for breeding mares, speeding up estrus or inducing ovulation can risk the chance of double ovulation, creating twins in a single gestation—which is detrimental to the health of the mare and usually deadly for the foals, Aurich says, if you’re not transferring these embryos.

Take-Home Message

Changing your mare’s estrous cycle patterns can facilitate your breeding and performance plans. As research advances in this field, your mare can benefit from improved safety and efficacy, all while helping ensure her long-term fertility.