The off-label use of altrenogest in stallions

The off-label use of altrenogest in stallions

Scientific Papers The Off-label Use of Altrenogest in Stallions: A Survey H. A. Goolsby, PhD,a H. A. Brady, PhD,a and S. D. Prien, PhDa,b REFEREED SU...

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Scientific Papers The Off-label Use of Altrenogest in Stallions: A Survey H. A. Goolsby, PhD,a H. A. Brady, PhD,a and S. D. Prien, PhDa,b REFEREED

SUMMARY Within the equine industry, overly aggressive stallion behavior related to various factors including genetics, dominance, or mating can create a dangerous environment and present several training challenges. In attempt to reduce this behavior, some performance trainers are administering altrenogest, an oral synthetic progestogen (Regu-Mate®, Intervet Inc, Millsboro, Del) in an off-label use. Regu-Mate® is commonly used in the equine industry to suppress estrus in performance mares and to synchronize estrous cycles for breeding. Although several articles have been published concerning the possible negative effects of this off-label use of altrenogest in stallions on spermatogenesis and steroid production with varying behavioral effects, the use within the industry continues. However, there are currently no known estimates of the extent to which this exogenous hormone is being utilized in stallions. Our objective was to survey the rate of Regu-Mate use in Quarter horse stallions during 2002. Two hundred questionnaires were sent to Quarter horse stallion owners, trainers, and exhibitors in the United States. The answers presented give a type reference of the equine facilities that responded, as well as details concerning those that administered Regu-Mate®. Sixty-three of the surveys were competed and returned (32%), with ReguMate® use occurring in stallions identified by 18 of 63 facilities (29%). Most of the stallions receiving ReguMate® were not used for breeding at the time of dosing; however most were intended for breeding at a later point. The primary use of altrenogest given to stallions 2

From Department of Animal and Food Science, Texas Tech Universitya; and the Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center.b J Equine Vet Sci 2004;24:$$$. 0737-0806/$ - see front matter © 2004 Elsevier Inc. All rights reserved doi:10.1016/j.jevs.2004.01.013

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years and older in a performance setting was to create a more focused animal. (J Equine Vet Sci 2004;24:72-75)

Keywords: Altrenogest, Stallion, Survey, Use INTRODUCTION

Stallion sexual/aggressive behavior can create several management problems including training challenges and unsafe working environments. This type of behavior, which develops with the onset of puberty, is consistent with the actions and communications intended for fighting and/or mating.1 In the equine industry, castration is primarily used on males lacking genetic or conformational superiority to diminish this male-related aggressive behavior by reduction of testosterone production.2 However at or near puberty, a stallion’s true athletic and genetic potential may not be fully realized. It has been reported that stallion trainers and handlers are administering oral altrenogest to temporarily create a more manageable animal.3-7 The oral altrenogest, ReguMate® (Intervet Inc), is a synthetic progestogen that can suppress estrus in 95% of mares administered a daily recommended dose of 0.044 mg/kg body weight within 3 days.8 Several studies in males of various species, including mice,9 boars,10 rams,11 and humans,12 have demonstrated that exogenous progesterone can cause a reduction of serum testosterone concentrations. Within the last 10 years, several articles concerning use of oral altrenogest on stallions have been published. Study observations have varied widely, appearing to be dependent on dose, duration of administration, and the ages of stallions treated. On younger stallions ranging in age from 2 to 4 years, treatments caused hormonal, testicular, and behavioral alterations when administering 0.088 mg/kg body weight daily for 56 days. However, some of the seminal and behavioral traits did not return to normal 60 days post-treatment.3 In 2-year-old stallions, Heninger et al demonstrated reductions in estrogen

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concentrations, total scrotal widths, and spermatid counts when administering 0.044 mg/kg body weight over 67 days.4 In 3-year-old stallions, similar reductions of estrogen concentrations and spermatid counts were found when altrenogest was administered at 0.088 mg/kg body weight intermittently over 60 days.5 Evaluations of specific age categories did not show significant behavioral changes, yet high individual variations were noted. In mature stallions ranging in age from 3 years to 18 years, Squires et al administered a 0.088 mg/kg body weight dose over 150 days, 240 days, and 240 days with the addition of gonadotropinreleasing hormone (GnRH) supplement. With GnRH, the altrenogest effects on behavior were not observed, although altrenogest alone caused lowered libido, testicular measurements, and hormonal parameters with partially reversible effects.6 In stallions more than 5 years old that were given altrenogest at a daily dose of 0.044 mg/kg body weight over 30 days, minor differences in behavior and seminal quality were reported.7 From the review of these studies, an effective amount and dosing schedule of altrenogest to suppress the sexual/aggressive behavior without limiting fertility potential has not been found. Our objective was to estimate the rate of ReguMate® use in Quarter horse stallions during 2002. MATERIALS AND METHODS

Two hundred surveys were mailed to Quarter horse stallion owners, trainers, and exhibitors in more than 30 states within the United States. Recipients were blocked into four groups: halter, performance, racing, or cowwork, as determined by the ability of the associated stallion or stallion’s progeny. The questionnaire contained 15 questions pertaining to stallion possession, purpose, and use of the oral altrenogest, Regu-Mate®, during 2002. RESULTS

Sixty-three of the 200 surveys distributed were completed and returned. Question 1: During the year of 2002, how many stallions were housed on the premises or in your care for at least 30 days? (respondents n=63) Of the 63 responding facilities, average number of stallions per facility: 9 stallions (range, 1-65) Of the 18/63 facilities using Regu-Mate®, average number of stallions per facility: 9 stallions (range, 1-25) Question 2: Of these Quarter horse stallions, please mark the number of stallions that fit into each of these age groups that were housed on the premises or in your care for at least 30 days? (respondents n=63) Of the 63 responding facilities, average number of stallions per facility based on age:

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Weanling colts: 2 colts (range, 0-20); Yearling colts: 2 colts (range, 0-20); 2-year-old stallions: 2 stallions (range, 0-15); 3-year-old stallions: 1 stallion (range, 015); 4-year-old stallions: 1 stallion (range, 0-6); 5-yearold or older stallions: 2 stallions (range, 0-6) Of the 18/63 facilities using Regu-Mate®, average number of stallions per facility based on age: Weanling colts: 2 colts (range, 0-12); Yearling colts: 2 colts (range, 0-6); 2-year-old stallions: 1 stallion (range, 0-11); 3-yr-old stallions: 1 stallion (range, 0-4); 4-yearold stallions: 1 stallion (range, 0-3); 5-year-old or older stallions: 2 stallions (range, 0-4) Question 3: Of these Quarter horse stallions, please mark the numbers used in each age category involved with breeding? (respondents n=63) Of the 63 responding facilities, the number of facilities using the following ages of stallions for breeding: 2year-old stallions: 2 facilities; 3-year-old stallions: 6 facilities; 4-year-old stallions: 18 facilities; 5-year-old or older stallions: 47 facilities. Of the 18/63 facilities using Regu-Mate®, the number of facilities using the following ages of stallions for breeding: 3-year-old stallions: 1 facility; 4-year-old stallions: 6 facilities; 5-year-old or older stallions: 13 facilities Question 4: In 2002, please mark the primary use of the Quarter horse stallion(s) housed at this facility? (respondents n=63) Of the 63 responding facilities: 0 sales (0%); 12 breeding (19%); 3 training (5%); 13 showing/or racing (21%); 35 combination of uses (55%) Of the 18/63 facilities using Regu-Mate®: 0 sales (0%); 0 breeding (0%); 1 training (5%); 3 showing/or racing (17%); 14 combination of uses (78%) Question 4a: If you marked “showing/racing” or “training” in the question #4, please mark the type of exhibition the Quarter horse stallion was (or majority of the stallions) involved in? (respondents n=51). Of the 51 responding facilities: 4 racing (8%); 14 halter (29%); 15 cow-work (26%); 14 performance (29%); 4 combination of exhibit types (8%). Of the 18/51 facilities using Regu-Mate®: 0 racing (0%); 1 halter (6%); 7 cow-work (38%); 9 performance (50%); 1 combination of exhibit types (6%) Question 5: Did anyone administer Regu-Mate® to any Quarter horse stallion(s) at this facility? (respondents n=63) 18 yes (29%); 45 no (71%) Question 6: Please mark the age(s) of the Quarter horse stallion(s) that received Regu-Mate: (respondents n=18)

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0 facilities administered Regu-Mate® to weanling and yearling colts; 6 facilities administered Regu-Mate® to 2-year-old stallions; 6 facilities administered ReguMate® to 3-year-old stallions; 4 facilities administered Regu-Mate® to 4-year-old stallions; 9 facilities administered Regu-Mate® to 5-year-old and older stallions Question 7: Was the Quarter horse stallion(s) used for breeding while on Regu-Mate®? (respondents n=18) 2 facilities administered Regu-Mate® to a stallion(s) while also using the stallion for breeding (11%); 16 facilities did not administer Regu-Mate® while breeding (89%) Question 8: In regards to the stallion(s) that received Regu-Mate®, will this stallion(s) be used for breeding purposes in the future? (respondents n=18) 16 facilities had stallions intended for breeding (89%); 2 facilities had stallions not intended for future breeding (11%) Question 9: When a stallion is receiving ReguMate®, please mark how often a dose is usually given to a stallion: (respondents n=18) Administration occurs only once a day (100%) Question 10: Please estimate the amount given to a stallion(s) by age: For 2-year-old stallions 4 facilities administered 10 mL; 2 facilities administered 20 mL; for 3-year-old stallions 4 facilities administered 10 mL; 2 facilities administered 20 mL; for 4-year-old stallions 3 facilities administered 10 mL; 1 facility administered 20 mL; for 5-year-old and older stallions 5 facilities administered 10 mL; 3 facilities administered 20 mL; 1 facility administered 40 mL Question 11: In regards to the dose given to this stallion(s), please mark the area in which the dose or amount given is based upon: (respondents n=18) 6 facilities responded behavioral changes (33%); 5 facilities responded professional advice (28%); 3 facilities responded body weight and age (17%); 3 facilities responded mare dose recommendations (17%); 1 facility responded to body weight/age and mare dose recommendations (5%) Question 12: Please mark the length of time a normal Regu-Mate® dosage duration lasts: (respondents n=16) 3 facilities responded with 1 week (19%); 4 facilities responded with 2 weeks (25%); 6 facilities responded with 1 month (38%); 2 facilities responded with 2 to 3 months (12%); 1 facility responded with 4 to 6 months (6%) Question 13: Of the stallions two years old and younger that received Regu-Mate®, which factor determines the duration of dosing? (respondents n=6)

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4 showing/or racing schedule (66%); 1 both showing/or racing and training schedules (17%); 1 training schedule (17%) Question 14: Of the stallions three years old or older that received Regu-Mate®, which factor determines the duration of dosing? (respondents n=16) 11 showing/or racing schedule (69%); 2 training schedule (12%); 2 both showing/or racing and training schedules (12%); 1 training and breeding schedule (6%) Question 15: Please mark the main reason why Regu-Mate® is administered to a stallion(s)? (respondents n=18) 11 to create a more focused animal in a performance setting (61%); 7 combination of reasons including creating an easier to handle stallion, a more focused animal in a performance setting, a safer environment, and/or to reduce aggressiveness (39%) DISCUSSION

For stallion trainers, owners, and handlers, there is a pressure to present their horses at their fullest potential. This goal can be difficult to obtain because of the aggressive male behavior observed in some stallions caused by such factors as inherited disposition, mating or poor handling.2 Although there were 63 total respondents to our survey, only 18 (29%) facilities reported the hormonal manipulation of stallions through the administration of Regu-Mate. All 18 of these facilities reported the primary use of the stallions involved showing or training. Of the 51 of 63 facilities that reported to have a performance purpose, 35% (18/51) admitted the hormonal manipulation. This point is further emphasized by the answers to Question 13, 14, and 15. For both the younger and older age categories, the Regu-Mate® dosing duration was mostly based on show schedules. Seventeen of the 18 (94%) facilities also answered either solely or in combination with others that the primary reason for using oral altrenogest in stallions was to create a more focused animal in a performance setting. In reviewing these results, concern about future fertility arises when reflecting on the amount and dosing duration of altrenogest given to these stallions. Of all the age groups a 10-mL dose appeared the most common, even though 20 mL and 40 mL were also reported. Durations reported to the survey ranged from 1 week to 4 to 6 months. Previous studies demonstrated partially reversible negative effects on spermatogenesis and steroid production for both the 0.044 mg/kg body weight and 0.088 mg/kg body weight dosing amounts for 60 days or more.3,4,6 Although some equine farms reported only du-

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rations of 1 week, 2 weeks, or 1 month, the frequencies of these durations were not surveyed. Previous studies have also demonstrated negative fertility effects when dosing intermittently.5 Though this survey is an estimate of a subpopulation of stallions in 2002, it should be recognized that more than one survey reported using altrenogest in stallions during previous years.

REFERENCES 1. 2. 3. 4.

Wingfield JC, Marler P. Endocrine basis of communication in reproduction and aggression. In: Knobil E, Neill UJ, eds. Physiology of Reproduction. New York: Raven Press; 1988. p. 16-47. Beaver BV. Aggressive behavior problems. Vet Clin North Am Equine Pract 1986;2:635-44. Johnson NN, Brady HA, Whisnant CS, LaCasha PA. Effects of altrenogest on sexual/aggressive behavior, hormonal profiles, and testicular parameters in young stallions. Equine Vet J 1997;18:249-53. Heninger NL, Brady HA, Herring AD, Prien SD, KA Guay, LA Janecka. The effects of oral altrenogest on hormonal, seminal and behavioral profiles of two-year-old stallions. Prof Anim Sci 1999;17:75-80.

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Vartorella HA, Brady HA, Herring AD, Prien SD. Case study: the effects of an intermittent regimen of altrenogest on behavioral, hormonal, and testicular parameters of three-year-old stallions. Prof Anim Sci 2001;17:317-21. 6. Squires EL, Badzinski SL, Amann RP, McCue PM, Nett TM. Effects of altrenogest on total scrotal width, seminal characteristics, concentrations of LH and testosterone, and sexual behavior of stallions. Therio 1994;48:313-28. 7. Miller CD, Dickerson DV, Blanchard TL, Thompson JA, Johnson L. Effects of a commonly-used progestogen on behavior and reproductive function of stallions. Proc Fourth Ann Race Horse Conf, 1997, Austin, Texas, 1-2. 8. Daels PF, Hughes JP. The abnormal estrous cycle. In McKinnon A, Voss JL, eds. Equine reproduction. Philadelphia: Lea and Febiger; 1993. p. 144-60. 9. Erpino M. Temporary inhibition by progesterone of sexual behavior in intact male mice. Horm Behav 1973;4:335. 10. Kluber EF 3rd, Pollman DS, Davis DL, Stevenson JS. Body growth and testicular characteristics of boars fed a synthetic progestogen, altrenogest. J Anim Sci 1985;61:1441-7. 11. Echternkamp SE, Lunstra DD. Relationship between LH and testicular development in progesterone-implanted prepubertal ram lambs. J Anim Sci 1984;59:411-53. 12. Kravitz HM, Haywood TW, Kelly J, Liles S, Cavanaugh JL Jr. Medroxyprogesterone and paraphiles: do testosterone levels matter? Bull Am Acad Psychiatry Law 1996;24:73-83.

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