Everybody knows a moody mare, the one who comes into heat at every show and can’t focus on her job because she’s whinnying and flirting with the boys, or perhaps she’s kicking out at anyone who ventures too close in the warm-up ring.

For many competitors altrenogest, aka Regu-Mate, is a lifesaver when it comes to showing this type of mare. This FDA-approved steroidal progestin is widely used to suppress estrus.

Medroxyprogesterone acetate, more commonly known as Depo-Provera, is a human birth control drug, but it’s also found its way into the show world, as some mares seem to respond better to it than altrenogest, and it’s safer for female humans to administer (no gloves required).

However, geldings and stallions are routinely testing positive for both these substances. Competitors report that it reduces studish behavior and keeps their male horses’ minds on the task at hand.

“My horse is DEAD LAZY as is, but I use depo on him to reduce his chances at lunging at the mares in the barn (yes he does this sometimes, with me on him when they get too close), to enhance his focus on me and not his buddies in the barn, and to generally allow him to be happier to do his job,” wrote a Chronicle Forums user and amateur competitor. “It does not alter his performance in any other way. At shows, he’s the same as ever … but maybe he’ll be less likely to bite at another horse, or happier to walk away from his buddies into the ring. It won’t affect his gait, jump, or anything else. My friend uses it for her mare to do the same.”

In fact, owners of mares, stallions and geldings alike report that their horses just seem more at ease and focused while showing on these medications.

Medroxyprogesterone acetate, (left) more commonly known as Depo-Provera, is licensed as a human birth control drug, but people are using it to control undesirable behaviors in their horses, and the U.S. Equestrian Federation is considering banning it. ALISON THAYER PHOTO
Altrenogest, which is the active ingredient in Regu-Mate, (right) is the only FDA-approved product to suppress estrus in mares. However, when given to stallions and geldings it can reduce aggression and affect their behavior as well. JAIME HICKS LVT PHOTO

And at least in the case of medroxyprogesterone, there’s a scientific reason for that. In a January meeting of the U.S. Equestrian Federation Equine Drugs and Medication Committee, Stephen Schumacher, DVM and chief administrator of the USEF Drugs and Medications Program, revealed that new evidence about the drug’s mechanism of action shows that MPA does in fact work on the GABA receptors in the brain, much like benzodiazepines such as Valium or Xanax.

Since 2011, the Fédération Equestre Internationale rules have categorized MPA for all horses and altrenogest for males as controlled medications, and they are prohibited in competition.

“Altrenogest and MPA have the possibility to be misused as a calmative, especially if used on stallions and geldings, affecting performance and therefore contrary to FEI rules on clean sport,” was the reason behind this categorization according to an FEI spokesperson.

Now the USEF is considering following their lead.

This article appears in the Feb. 27 print issue of The Chronicle of the Horse, which is the Legends & Traditions Issue. See what other great articles are in the issue—what are you missing if you don’t subscribe?

It’s Not Intended For Horses

Schumacher explained some of the issues with MPA.

“It’s intended for birth control in women,” he said. “It’s to be injected every 12 weeks. That’s the FDA approval for it. In horses, what we have reported from the field is that horses are getting a variety of doses, but they’re getting it every seven to 10 days in some cases. We don’t know the long-term effects of this drug. There are some concerns about this drug in women because it also has an impact on bone demineralization. There are some concerns with women on it for a prolonged period of time. We don’t know what it does to horses over time.”

Since MPA isn’t U.S. Food and Drug Administration-approved for horses, it’s usually purchased in a compounded form, and dosing practices are all over the map.

Mark Baus, DVM, of Grand Prix Equine, which is based in Connecticut, said he’d had a horse die from a systemic reaction after receiving MPA. “As far as we can tell it was an anaphylaxis, which is the most severe form of hypersensitivity or allergic response,” he said.

Baus pointed out that there is some risk associated with injecting any medication into muscle and that he did think MPA, compared to other intramuscular injections, was a relatively safe drug.

“I don’t think it is irritating to the muscle tissues significantly,” he said. “However, these occasional sensitivities and reactions do occur, and I don’t know what the mechanism of that is.

“It’s simply that there are a lot of these injections given, so they are bound to occur periodically,” he continued. “I’ve had trainers and other colleagues come out of the woodwork when this happened. They said, ‘Oh yeah, I’ve heard of this one; I heard of that one.’ It doesn’t appear to be highly publicized, but they’re out there.”

He also ran into a situation where two horses went into a Cushing’s state temporarily after receiving high doses of MPA.

“They did come out of it when it was stopped,” Baus said. “It wasn’t a serious situation, but there is a potential mechanism for why that would happen.”

Baus also expressed concern over the compounding issue. “The fact that this is a compounded medication makes it inherently risky,” he said. “There are no real standardized formulations. Every pharmacy that is producing this is going to have their own formulation, and this is what makes it fundamentally unsafe.”

He added one last concern, which was dosage. “A lot of my clients are taking the advice of fellow trainers,” Baus said. “My preference would be to administer this every four weeks. Many of my trainers have chosen to administer it weekly. This is another reason I’m not in favor of this medication: There is no standardized dosing, so it is prone to being over-administered.”

Competitors in the United States have been using medroxyprogesterone to manage naughty behavior and keep their horses more focused on the job at a horse show, but new research shows this drug works on the GABA receptors in the brain, much like Valium or Xanax. FRANK SORGE FOR ARND.NL

A. Kent Allen, DVM, and chair of the USEF Drugs & Medications Committee and the Veterinary Committee, reminded committee members that MPA has not been shown to reliably prevent ovulation in horses. So when it seems to be working better than altrenogest for mares, it’s likely because it’s working on the GABA receptors in their brains rather than preventing them from suffering the discomfort of ovulating at a show.

“Medroxy is probably our single most abused drug currently,” said Allen. “If we had nothing to control estrus behavior in the mare, then it would be a different question, but we do [have altrenogest], and it’s approved, and it’s FDA approved. I don’t see how we can let it go.”

The USEF Drugs and Medications rules already explicitly say, “Any product is forbidden if it contains an ingredient that is a forbidden substance, or is a drug which might affect the performance of a horse and/or pony as a stimulant, depressant, tranquilizer, analgesic, local anesthetic, psychotropic (mood and/or behavior altering) substance, or might interfere with drug testing procedures.”

Since stallions and geldings don’t ovulate, it’s pretty clear these medications are being given to affect mood or behavior.

The FEI even details this use explicitly in their description of altrenogest: “Altrenogest is licensed for veterinary surgeon use in the synchronisation of oestrus in mares and gilts, for oestrus suppression, and calming effects when showing or racing mares; off licence use in stallion aggression reduces fertility, and has behavioural and hormonal effects.”

An information page about MPA written by Barbara Forney, VMD, and listed on the website of Wedgewood Pharmacy, a company that compounds the medication for veterinary use, stated this about the drug:

“MPA is used for estrus suppression in performance horse mares and to diminish inappropriate sexual behavior in ‘studish’ geldings. There also is some thought that progestins such as MPA may calm the behavior of ‘hot’ horses. This is an extrapolation based on work done with progestins in other species.

“Although the published studies on its use do not show any effect on estrus suppression, there are many practitioners who feel that they have seen a positive response,” she continued. “Anecdotally, there are some mares that respond well to MPA and others that do not seem to respond at all.”

“Administration of medroxyprogesterone goes against the spirit of the rule about medicating horses,” said Baus. “We’re not giving it for therapeutic reasons. We’re not giving it necessarily to keep mares out of heat. We are specifically giving it to affect their behavior.”

But that doesn’t mean this is an open and shut case. There are reasons, both practical and philosophical, to consider all the repercussions of changing the rules regarding these medications.

Altrenogest doesn’t work for every mare. Some still ovulate or at least show stereotypical “heat” behaviors while on it. Allen countered this argument by saying he’d worked on a safety trial of altrenogest and found, “You could double the dose and catch the outliers, and there were no safety effects.”

It’s also a drug that can disrupt the hormonal cycles of human females, which means women who administer it have to be extra careful to wear gloves and avoid any accidental contact with the medication. Altrenogest does have an injectable form, although some veterinarians have said it’s not as effective.

Weighing Fairness Against Horse Health

But Paul McClellan, DVM and president and founder of SanDieguito Equine Group in San Marcos, Calif., raised some philosophical arguments as well. He pointed to two goals of the USEF: to maintain a fair and level playing field and to safeguard the health of the horse.

“In practice sometimes those two goals can be conflicting,” McClellan said. “That’s not always apparent to everyone. Trying to achieve both of those is not always easy.”

He gave the examples of Adequan, Legend, Gastrogard and phenylbutazone.

“All of these legal medications that are allowed under certain guidelines clearly improve the performance of the individual over not having them,” said McClellan.

And unlike race horses, show horse trainers don’t have to disclose legal medications.

“You can’t tell which horses are benefiting from it and which ones are not,” McClellan said. “However, the committee, in its judgment, has stated that in the instance of these particular medications, the goal of safeguarding the health of the horse is enhanced through the appropriate use of those medications. They’re available to anyone. We’re not going to track who is on them and who is not and disclose that. But if you choose to use them the performance of the horse will be better than if he was on hay, oats and water.”

While the U.S. Equestrian Federation does have a list of common prohibited substances, any product is forbidden if it “might affect the performance of a horse and/or pony as a stimulant, depressant, tranquilizer, analgesic, local anesthetic, psychotropic (mood and/or behavior altering) substance, or might interfere with drug testing procedures.” AMY DRAGOO PHOTO

Allowing horses to compete on certain medications has the benefit of keeping horses in the show ring who otherwise might be out of a job due to a minor issue.

“What I appreciate about the USEF drugs and medications rules is that they recognize that horses do benefit from medication that allows them to remain competitive,” Baus said. “As an ideal, obviously it would be perfect if horses were not on any medication and competing, but realistically there are many conditions that should not render a horse to be non-competitive if indeed all it takes is a safe and effective medication that does not affect their performance.”

He pointed to the much-loved and oft-abused medication dexamethasone.

“The vast majority of those doses are given to modify behavior,” Baus said. “But on the other hand there are horses with respiratory issues, allergic issues, that if they were not allowed to have dex, they wouldn’t be able to compete, yet their condition is fully compatible with the competition scenario.”

McClellan said that’s where the value judgments of the committee and experience of the people on those committees who help establish the rules come into play.

“The reasonableness of the exceptions is based on the weighting of those two goals and which goals should have greater priority when the purity of those goals is compromised,” he said. “You can take every single medication and weigh the value of its contribution for improving the one goal of the USEF and not impeding on the alternative goal of the USEF. At some point someone has to simply make a judgment about that.”

So back to altrenogest and MPA. McClellan boiled down the decision to allow or not allow these medications to: “People have to decide whether the use of progesterones create an unfair advantage, and if they do, what exceptions might apply for their use.”

He pointed out that most competitors don’t actually care if their mare is ovulating at a show, as she’s not likely to get bred by accident.

“What is important to people is the behavior,” said McClellan. “So the drug, when given, is affecting the behavior. The question is: Is this secondary effect of affecting the behavior due to its action in the GABA pathway?

“As you know from Carolina Gold and other such products, that’s their mechanism of action, and that’s been determined that that is not only unsafe, but it also doesn’t meet the other objective of USEF,” he continued. “It doesn’t meet the fair playing issue, and it doesn’t meet the safety issue.”

McClellan went on to ask this question about altrenogest: “Should mares be given the benefit of having improved behavior, and stallions and geldings do not get the benefit of having improved behavior by the use of this drug?

“It’s entirely the prerogative of the rule-making body to say: This is the exception we’re making, and we believe it’s reasonable, and we’re going to make that exception,” he added. “That mare behavior is on the order of much more difficult to deal with, and it cannot be easily managed through better training and better management of the horse.”

It was pointed out during the committee discussion that gelding a stallion is the most common solution for these types of unwanted behaviors, but that spaying a mare is expensive and risky.

No veterinarian in the Equine Drug and Medication Committee meeting or the Veterinary Committee meeting held during the USEF Annual Meeting in January knew of any scientific evidence to explain why altrenogest works to affect the mood of stallions and geldings, but Schumacher did hazard a guess that it was likely this drug also worked on the GABA pathways in the brain.

“I personally don’t know how solid the evidence is that the progesterones’ secondary effects, and all of the progesterones and their analogs, which includes altrenogest, how well established it is that the secondary effect of calming horses, whether they are mares, stallions or geldings, is through the GABA system,” said McClellan. “If we can assume for a moment that it is, then we are clearly making an exception to say that mare behavior is so atrocious, or can be that we’re going to make an exception for mares, but we’re not going to make an exception for stallions. That’s a value judgment.”

McClellan also said he was unaware of studies on the long-term safety of altrenogest in sport horses. Many show mares are on it year round and at a higher dose than the recommended amount. This leads him to believe they aren’t getting it just to manage the side effects of ovulation.

“The reality is that many of these mares that are on it every day for months and months, it’s not a cyclical behavioral issue,” he said. “They’re on it for the same calming reasons in general that the stallions and geldings are on it.

“This is where you find you’re making a gender exception for anxious behaviors that are not necessary cyclical,” he concluded.

Every Mare Is Different

McClellan also pointed to the fact that not every animal reacts the same way to a drug, a concern that many competitors echo. Some mares seem to get much more relief from MPA than they do from altrenogest alone, or even from altrenogest combined with a legal non-steroidal anti-inflammatory drug. Is that because of the effect MPA is having on the GABA receptors, or is it just the natural spectrum of any animal’s response to a particular substance?

“There’s a bell curve,” said McClellan. “Some horses are refractory. Some horses are very sensitive. There’s a bell curve where most horses fall. You’re also stating that we’re only going to allow one drug. If your mare happens to be the one that’s refractory to that analog, you’re out of luck.”

In the end McClellan wasn’t interested in making a statement about whether or not the USEF should change the rules regarding these two substances. “What I really ask of the committee when I am in these committee meetings, is that they don’t obfuscate the rationale,” he said. “That they clearly come out and say: ‘We’re making an exception because we believe on a value basis that is in the best interest of the majority of stakeholders in the business.’ That’s the statement I wish they would put forth and not try to rationalize medical reasons where there are none.

“If the majority of people want a level playing field more than anything else, then no horse should be given altrenogest,” he continued. “I don’t know where they’re ultimately going to find themselves in that regard. Is it primary or secondary effects? How are we weighting the two goals of the USEF to make it fair and transparent for the greatest number of people?

“We all want to do what’s best for the horse,” McClellan concluded. “We just can’t all agree on what that is.”

While no USEF official wished to discuss this potential rule change in an interview, USEF CEO Bill Moroney offered this statement: “At USEF’s Annual Meeting in January, the USEF Veterinary Committee and Drugs and Medications Committee discussed whether the USEF rules should forbid the use of medroxyprogesterone in competition. Currently, the FEI and Canada both prohibit the use of medroxyprogesterone in competition. The committees also discussed whether the use of the substance altrenogest in competition should be limited to use in mares only. A final decision about the use of these substances in USEF competitions has not been made.”

The USEF will host a public workshop on the use of medroxyprogesterone on March 13 in Orlando, Fla., at the Orlando Airport Marriott Lakeside Hotel. An expert panel from the USEF will present, as well as members and stakeholders.

“The purpose of the workshop is to address concerns that have been voiced regarding the efficacy, safety, and use of this substance in competition horses,” read the press release.

This article appears in the Feb. 27 print issue of The Chronicle of the Horse, which is the Legends & Traditions Issue. See what other great articles are in the issue—what are you missing if you don’t subscribe?