QUESTION: If some progesterone is good, is more better? Should you be supplementing with progesterone during pregnancy?
DR. CHARLIE SCOGGIN: Speed or stamina? Pedigree or performance? Regu-MateTM or redundant? These are all questions to ponder as the breeding stock sales season approaches. And, for each one of these questions, opinions will abound by the boatload.
Now, some of you may be scratching your head at the significance of the last question, but when you drill down deeper, you find there are actually many layers to the question of the need for Regu-MateTM in pregnant mares. These would include, but are not limited to: the body of scientific work supporting the use of Regu-Mate (or a related substance); case selection and indications for use; cost of purchasing and administering the product; occupational hazards and exposures; and usage in animals destined for sale, whether being sold privately or publicly.
To begin, Regu-MateTM is an FDA-approved oral medication that hit the market in the 1980s. It contains the active ingredient, altrenogest, which is a synthetic progestin. Progestins' primary mode of action is to support a developing pregnancy and/or suppress behavioral signs of heat or estrus. Regu-Mate is only labeled for estrus suppression, but studies quickly followed revealing its ability to support or rescue pregnancies under experimental conditions. Also, its widespread use over the past three decades has allowed for accumulation of a lot of “real-world” data or experience demonstrating its benefit in pregnant mares subject to stress, such as an acute case of colic or a chronic case of laminitis.
Progesterone is a member of the progestin family. In horses, it is commonly administered as a compounded intramuscular injection and given on a daily or weekly basis. When administered appropriately, progesterone appears to be equally effective as Regu-MateTM in preventing heat and maintaining pregnancies. Interestingly, only progesterone and altrenogest (Regu-MateTM) have measurable behavioral and physiological effects in mares. Studies evaluating other progestins commonly used in cattle (e.g., MGATM or HeifermaxTM) and humans (e.g., Depo-ProveraTM) have failed to show measureable effects when given to mares at various doses and frequencies.
The proven efficacy of progesterone and Regu-MateTM make them relative mainstays for the reproductive management of pregnant mares, especially on commercial breeding farms. However, their use on farms is highly variable, and issues such as dose, frequency and length can generate a heated debate amongst broodmare managers and veterinarians akin to the great Miller Lite debate: is it less filling or does it taste great?
As far as I'm concerned, progestin supplementation is neither light nor delicious. Instead—and much like alcohol in general—it is best used in moderation. Firstly, natural progesterone deficiencies in pregnant mares are very rare. Studies have shown the incidence to be around 1 percent, so not every mare in a herd should require supplemental progestins.
Second, there is some evidence too much supplemental progesterone or altrenogest during pregnancy could actually be a bad thing. A few studies suggest a link between altrenogest administration and a decrease in natural concentrations of progesterone. An extreme case could lead to dependence on the drug to maintain the pregnancy. Accordingly, if treatments are missed or discontinued, an abortion could ensue. Also, progestins can suppress immune function, whether locally within the uterus or systemically to affect the entire body. If suppression is significant enough, fetuses or mares may be incapable of warding off infections, leading to compromise of the pregnancy. Finally, progestin supplementation is not a silver bullet in preventing reproductive loss in mares. Mares can and will lose their pregnancies while being treated with progestins, and will do so regardless of the dose or frequency given.
Not to be lost in this discussion are cost of the product and potential hazards with administration. Even when sourced at wholesale value, treatment with Regu-MateTM isn't necessarily cheap, costing up to $200 or more for 100 days of treatment. Conversely, this amount may pale in comparison to the overall investment in the mare and stud fee. As stated succinctly yet truthfully by Benjamin Franklin, “An ounce of prevention is worth a pound in cure,” and this same axiom can hold true when using Regu-MateTM, especially in instances where mares have a history of pregnancy loss or are carrying highly valuable pregnancies. Concerning potential administration hazards, Regu-MateTM is manufactured using an oil-based carrier, which has the capability of penetrating human skin. Occupational exposure thus exists; for women, repeated contact can interfere with menstruation; for men, long-term exposure can lead to singing an octave or two higher. Progesterone injections are also worthy of mention. Repeated administration can cause sore necks, and all the grain in the world won't help you catch some mares when they see you coming with a needle in your hand.
Hopefully, I've conveyed the point that there are pros and cons to progestin supplementation. Like other prescribed and labeled medications, their use should be preceded by considering the risks and rewards of administration. In my opinion, doing so constitutes responsible use. I am also of the opinion that another tenet of responsible use is disclosing long term administration in an animal being sold publicly or privately. Disclosure is an act of good faith and an easy means of establishing a seller's credibility. To wit, I'd imagine most consignors would rather be answering questions why they sold a future classic winner in utero than why they didn't tell a buyer a mare was on Regu-MateTM until after she lost her pregnancy. In a nutshell, it all boils down to communication; a concept never deficient in importance but sometimes lacking in execution.
Don't get me wrong…I'm not naïve. Long term Regu-MateTM treatment may cause some prospective buyers to back off a mare—but so too will a crooked knee, special shoes or previous colic surgery. Subjectively, these conditions carry more concern than whether or not a mare was on a supplemental progestin. Plus, I would argue Regu-MateTM administration is usually a minor management issue at most farms, thereby making it relatively easy to follow through on once the mare changes hands. As mentioned above, where supplemental progestins can become a big deal is when their use is not disclosed but something untimely happens to the pregnancy.
Therefore, I will conclude by stating my answer to the title question: No; more is not always better. Mother Nature and biology are too powerful of foes in some instances, rendering supplemental progestins frail in comparison. Rather, they should be used responsibly, which entails, among other things, disclosing their long term use to prospective buyers. If you agree with me, then I'll meet you in the bar, and we'll toast to moderation. If you disagree with me, I'll still meet you in the bar, but you're going to need something more than Miller Lite to change my mind.
Dr. Scoggin grew up in Boulder, CO, but traveled east to Colgate University in Hamilton, NY for his undergraduate degree, majoring in chemistry and minoring in religion. He traveled back home to attend both graduate and veterinary school at Colorado State University where he obtained an MS in equine reproductive physiology in 2001 and his DVM in 2005. Following vet school, he served a one year internship at Hagyard Equine Medical Institute and then was an associate veterinarian at a referral practice in California. Dr. Scoggin then accepted a position as a resident veterinarian at a Thoroughbred breeding farm outside Paris, KY, where he practiced from 2008-2015. He became a Diplomate of the American College of Theriogenologists (animal reproduction) in 2012, and he joined the team at Rood and Riddle Equine Hospital in July 2015.
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