Q: I have a mare that is on Regu-Mate (altrenogest) for mareish behavior and consumes a forage-based diet that includes ingredients like soybean oil, alfalfa pellets, and ground flax. She seems to have some behavioral issues in the early spring and late fall, despite being on Regu-Mate. I have heard that phytoestrogens in these and other ingredients can counteract the active ingredient in Regu-Mate, but I haven’t been able to find anything that supports or explains this. Do phytoestrogens in feed counteract the effects of Regu-Mate, and should ingredients with phytoestrogens be avoided if you are feeding a mare that is also on Regu-Mate?

A: Mares can be amazing, yet some can be challenging at times. To get everyone on the same page let’s start with discussing phytoestrogens because they’re more complicated than they appear at first glance.

Phytoestrogens are a family of polyphenolic plant compounds that bind to estrogen receptors and have been shown to inhibit synthesis, secretion, transport, and binding of endogenous (coming from within the body) estrogens. Exposure to phytoestrogens in horse diets is inevitable due to the consumption of large amounts of plant materials. Legume plants such as soy, lupine, clover, and alfalfa are generally highest in phytoestrogen content, but certain phytoestrogens are also found in flaxseeds, rice, and wheat. The amount and specific phytoestrogen compounds present are extremely variable across various plants, stage of maturity, plant disease state, and growing conditions and locations. 

To date, more than 8,000 polyphenolic compounds have been identified. Flavonoids, isoflavonoids, and coumestans are the major types of phytoestrogens found in common equine diets. Lignans, which are structural cell wall components of plant cells, are also common in livestock diets but are a less studied group of phytoestrogens. To add more complexity, there are multiple compounds within each phytoestrogen type and they vary in bioavailability, how they are metabolized, physiological effects, and potency.

Fermentation of plant material changes the form of some phytoestrogens from nonbioactive to bioactive. This could partially explain why differences in digestive tract architecture between livestock species, specifically ruminants (sheep and cattle) versus nonruminants (horses), contribute to variation in physiological effects of phytoestrogens.  Sheep are reportedly more sensitive to phytoestrogen consumption than cattle, and horses appear to be least sensitive. 

In a 2013 Portuguese study conducted on a small population of horses, researchers reported that plasma concentrations of the phytoestrogen coumestrol were elevated and infertility was induced in mares consuming an alfalfa-based haylage. However, this was a limited study and there is currently very little research reporting whether naturally occurring phytoestrogens in typical horse rations would have a negative impact on reproductive performance in mares. 

Due to the lack of sound science clearly identifying effects of naturally occurring phytoestrogens in normal horse diets on mare reproduction or behavior, it seems prudent to focus on choosing a well-balanced diet that provides optimal nutrition to support the age and activity level of your horse. I find no studies directly looking at interactions between dietary phytoestrogens and Regu-Mate and would suggest working with your veterinarian to determine what seasonal changes might be happening with your mare that could be negatively affecting her behavior.

References/links below:

Adkin, Angie. The Characterization of Phytoestrogens in Equine Feeds and Serum. 2018. University of Florida, PhD dissertation

Kirkland, B,. Wickens, C., Vineyard, K. and Adkin, A.  Let’s talk about Horses + Soy.  2022. Horses.Extension.org