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Abstract

Altrenogest is a progestogen substance used in equine medicine for the synchronization of ovulation during the spring breeding season and the control of estrus in mares. It accomplishes its actions by down-regulation of endometrial progesterone receptors and repression of estrogen receptor transcriptional activation. However, various groups have also measured androgen receptor binding activity for altrenogest in vitro; these findings combined with androgenic and anabolic properties roughly 1/20 in potency of testosterone and its structural similarity to the anabolic steroid trenbolone have created concerns among racing authorities of altrenogest’s potential abilities to alter the outcome of equine athletic performance, even though attempts at finding androgenic or anabolic effects of altrenogest in stallions, mares or offspring of altrenogest-treated mares have been unsuccessful. A complication is the finding that certain oral and injectable forms of altrenogest may also contain trace amounts of the anabolic steroid trenbolone and its metabolite trendione. Examination of patents for altrenogest synthesis dependent on allylating Grignard reagents reveal plausible routes to inclusion of traces of these compounds. Restrictions of altrenogest use have been introduced in many equine organizations, including the Irish Horseracing Regulatory Board, British Horseracing Association, Australian Racing Board, and Fédération Équestre Internationale. Australian authorities issued warnings against use of altrenogest owing to the identified traces of trendione and trenbolone. The Horseracing Integrity and Safety Authority in the United States has proposed moving altrenogest from its banned category to its controlled substances list, a move which may result in reduced penalties. Altrenogest is one of the most widely used veterinary steroids in the United States and United Kingdom and its widespread use by equine caregivers may be one factor responsible for its presence in the environment. Various case studies reveal significant penalties imposed on individuals whose horses gave evidence of trace level exposure to altrenogest. The published pharmacokinetics of altrenogest revealed average plasma maximum concentrations ranging 23 – 75 ng/mL. This information enabled calculation of an Irrelevant Plasma Concentration (IPC) by application of the conservative Toutain factor to give an IPC range of 46 – 150 pg/mL. Equine metabolism of altrenogest results in glucuronide and sulfate phase II conjugates, but environmental breakdown of altrenogest surprisingly results in an intramolecular [2+2] cycloaddition product dubbed Alt-CAP. This compound and its photohydration product are trapped in an equilibrium that alternates during light – dark cycles, a process repeatable over many such cycles. Further research is needed to better understand the pharmacological properties of these additional compounds in addition to determining any possible anabolic properties of altrenogest itself.

Document Type

Article

Publication Date

2025

Digital Object Identifier (DOI)

DOI 10.21836Compendium20250502

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