- Email: [email protected]
Effect of prolonged use of altrenogest on behaviour in mares
The Veterinary Journal The Veterinary Journal 169 (2005) 322–325 www.elsevier.com/locate/tvjl
Fast track
Effect of prolonged use of altrenogest on behaviour in maresq David Hodgson
a,*
, Stephanie Howe a, Leo Jeffcott b,d, Stuart Reid c, Dominic Mellor c, Andrew Higgins d
a
Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia b Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK c Comparative Epidemiology and Informatics, Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Bearsden Rd, Bearsden, Glasgow G61 1QH, UK d Fe´de´ration Equestre Internationale, Avenue Man Repos 24, 1000 Lausanne, Switzerland
Abstract Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. It was concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares had no effect on dominance hierarchies, body-mass or condition score. 2005 Elsevier Ltd. All rights reserved. Keywords: Altrenogest; Regumate; Anabolic; Behaviour; Competition
Altrenogest, a progestagen, is the 17a-allyl derivative of the potent anabolic agent trenbolone which is structurally similar to the male sex hormone, testosterone. Altrenogest is reputedly used widely, and for long periods, in female competition horses. This occurs in an attempt to ameliorate reproductive cyclicity, thus making them more tractable and suitable for training and competition. However, prolonged administration is not in accordance with manufacturersÕ recommendations. In most countries, the drug is registered only for oral administration to mares for 10 days for the purpose of induction of ovulatory oestrus in the late transitional stage of the oestrus cycle. Altrenogest suppresses behavq
PII of original article: S1090–0233(04)00126-1. Corresponding author. Tel.: +61 2 4655 0743/0777; fax: +61 2 4655 6942/1212. E-mail address: [email protected] (D. Hodgson). *
1090-0233/$ - see front matter 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2005.03.003
ioural oestrus in mares within 2–3 days of commencement of administration. The effects of long-term administration to mares of altrenogest are largely unknown, particularly with reference to those used in competition. Additionally, it is not clear whether the drug has any anabolic or significant behavioural effects in horses. A study was therefore designed to provide a preliminary assessment of prolonged administration of altrenogest to sedentary mares in terms of social hierarchy, body-mass and body condition score (BCS). Twelve mares of mixed breed (Thoroughbred and Standardbred) were acquired from a local horse dealer. The animals were kept at pasture as a single group for a total of 20 weeks. Following acquisition, all mares underwent routine health care procedures, including de-worming, dental prophylaxis, hoof care and vaccination. Mares were allowed to acclimate to the new environment for
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325
four weeks during which time they stabilised as a social group, and became accustomed to routine management procedures, e.g., being caught, weighed, placed in a crush, administration of oral medication by syringe. Throughout the entire period of study supplementary lucerne hay was fed. Mares were weighed and condition score was recorded twice weekly. A summary of the study protocol is given in Table 1. Following acclimation, at the beginning of week 5, mares commenced the pre-treatment assessment period, which ran for four weeks. The hierarchy of the group, was established using a modification of standard techniques (Houpt and Wolski, 1980; Keiper and Sambraus, 1986). This assessment was made at regular intervals throughout each of the periods in the study. Briefly, dominance was determined using a paired feeding test. During the 15 min test two horses were in a 3 m · 3 m yard and had access to one bucket of grain. The dominant horse ate from the bucket for the greater part of the 15 min. The horses received no food for 16–18 h before the test. The yard in which the tests were carried out was familiar to all horses. No horse was tested more than once a day. Each horse in the herd was paired with every other horse in the herd with each pair being tested once. Within the herd, the horse dominant to all other Table 1 Flow chart of activities Week 0 Weeks 1–4 Weeks 5–8 Weeks 9–16 Weeks 17–20
Mares acquired Acclimation (routine health care, acclimation to scales, weigh and BCS) Pre-treatment assessment period (weigh, BCS, determine hierarchy) Treatment period (weigh, BCS, determine hierarchy) Post-treatment assessment period (weigh, BCS, determine hierarchy)
323
horses was given the rank of 1 (see Table 2). The horse which failed to dominate any other horse was given the highest numeric rank (11 in a herd of 11). It was possible for two or more horses to be dominant over the same number of animals. In that case, the lower rank (dominance) was ascribed to the horse that was the dominant member of that particular pair. During the test of hierarchy the aggressive actions of each horse were recorded. The aggressive actions were scored as follows: (1) threat to bite (the aggressor laying its ears back and moving its head towards the opponent); (2) threat to kick (the aggressor turning the hindquarters towards the opponent with ears laid back and one hind leg lifted); (3) bite; (4) kick; (5) chase (the aggressor moving at least three steps away from the bucket and towards the opponent). The aggressive scoring system is an arbitrary one in which a threat is considered the mildest form of aggression and given a score of 1 each time it occurs and a chase, the most severe type of aggression, is given a score of 5 each time it occurs. Attempts to assess the activity budget (time spent eating, non-eating activity and resting) for each mare as described by Boyd et al. (1988) was attempted in week 5 However, this proved too difficult and was thus not continued throughout the study. At the beginning of week 9 (treatment period) mares were randomly divided into two groups with six mares treated daily with altrenogest (Regumate, Hoechst Roussel) at the recommended dose rate of 0.044 mg/kg body weight per os by syringe. One of the mares in the
Table 2 Hierarchies for mares throughout the period of study Order in hierarchy
Horse no: wk 5 (pre)
Horse no: wk 8 (pre)
Horse no: wk 12 (treat)
Horse no: wk 16 (treat)
Horse no: wk 18 (post)
Horse no: wk 20 (post)
1 2 3 4 5 6 7 8 9 10 11
10 3 4 2 11 5 6 7 12 1 8
10 3 4 2 11 5 6 7 12 1 8
10 3 4 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
Key: Bold, treatment group; italic, control group. Horse 1 in the hierarchy is the dominant mare, whereas 11 is the least dominant. Horse 9 died as a result of an intestinal crisis in week 7. Results for this mare were discarded from the analyses.
324
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325
Table 3 Weights of horses (kg) Horse no.
Wk 1: (accl)
Wk 5: (pre)
Wk 8: (treat)
Wk 12: (treat)
Wk 8: (post)
Wk 20: (post)
1 2 3 4 5 6 7 8 9 10 11 12
568 572 530 466 548 558 544 522 534 546 520 495
584 574 536 475 554 560 542 522 534 552 528 499
576 548 528 464 536 552 534 516 DECEASED 554 529 500
556 542 530 463 536 554 539 516 DECEASED 550 528 499
550 542 534 456 544 556 540 520 DECEASED 554 526 498
556 530 530 458 556 556 546 526 DECEASED 556 528 496
Key as for Table 2.
treatment group died as a result of an intestinal crisis in week 10 and results for this animal were excluded from analyses. The remaining six mares acted as controls and were administered a placebo (yogurt) per os q 24 h. The treatment protocol was continued for eight weeks. Again observations to determine the dominance hierarchy of the group were made weekly. Routine determination of body-mass and BCS were continued as described. A similar protocol of observation and measurement was followed for the four weeks following cessation of therapy (post-treatment assessment period). A comparison between each of the recording periods used Spearman rank correlations. This compared results for week 5 vs. week 8 (pre-treatment) to assess variation before treatment. Then, values for week 5 were dropped and possible variations due to the treatment were assessed, i.e., week 8 vs. week 12 vs. week 16 vs. week 18 vs. week 20. A post hoc two-way comparison was then performed. Significance was ascribed at P < 0.05. Statistical analyses revealed no differences in hierarchy in response to treatment with altrenogest (Table 2). All rankings were significantly correlated, even when correcting for multiple comparisons. Thus, given the primary hypothesis being tested that there is no difference in the rankings in response to prolonged treatment with altrenogest, the experimental data do not provide evidence to reject the null hypothesis (P < 0.0001). As shown in Table 3, statistical analyses also revealed no differences in body weight in response to prolonged treatment with altrenogest (P < 0.001). Similarly there was no effect of altrenogest on BCS (P < 0.001) (data not shown). A search of the literature has revealed two papers reporting the effect of altrenogest on growth (and other variables) and these are in pigs by the same group (Kluber et al., 1985, 1988). The data concluded that whereas feeding altrenogest inhibited testicular growth and steroidogenesis in boars it had no effect on body growth, carcass traits or back fat thickness. This is probably to
be expected as altrenogestÕs 17a-C3 side chain (–CH2CH@CH2), which provides the prostagenic activity, may well restrict binding to anabolic receptors. When Johnson et al. (1997) looked at the effect of high dose, prolonged oral administration of altrenogest on sexual and aggressive behaviour and semen quality in young stallions, they found no differences in body weight, BCS or metacarpal measurements between treated and control groups, although there was reduced libido and decreased flehmen frequency and duration, a fall in sperm production and a decrease in scrotal circumference, all probably as a result of the effect of the drug on the testes rather than any centrally acting effect. Recently, Goolsby et al. (2004) reported the results of a survey on the use of altrenogest in stallions. These authors found that the agent was used in an attempt to Ôcreate a more focused animalÕ during training and competition. In the present study, prolonged administration (eight weeks) of altrenogest at recommended dose rates to sedentary mares caused no effect on dominance hierarchies, body-mass or body condition score. We conclude that the evidence to date suggests that altrenogest when administered in accordance with the manufacturerÕs data sheet, has no obvious anabolic or behavioural effects that may affect the performance of a competition mare.
References Boyd, L.E., Carbonaro, D.A., Houpt, K.A., 1988. The 24-h time budget of Przewalski horses. Applied Animal Behaviour Science 21, 5–17. Goolsby, H.A., Brady, H.A., Prien, D., 2004. The off-label use of altrenogest in stallions: a survey. Journal of Equine Veterinary Science 24, 72–75. Houpt, K.A., Wolski, T.R., 1980. Stability of equine hierarchies and the prevention of dominance related aggression. Equine Veterinary Journal 12, 15–18.
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325 Johnson, N.N., Brady, H.A., Whisnant, C.S., LaCasha, P.A., 1997. Effects of oral altrenogest on sexual and aggressive behaviors and seminal parameters in young stallions. Journal of Equine Veterinary Science 18, 249–253. Keiper, R.R., Sambraus, H.H., 1986. The stability of equine dominance hierarchies and the effects of kinship, proximity and foaling status on hierarchy rank. Applied Animal Behaviour Science 16, 121–130.
325
Kluber, E.F., Pollman, D.S., Davis, D.L., Stevenson, J.S., 1985. Body growth and testicular characteristics of boars fed a synthetic progestogen, altrenogest. Journal of Animal Science 61, 1441–1447. Kluber, E.F., Minton, J.E., Stevenson, J.S., Hunt, M.C., Davis, D.L., Hoagland, T.A., Nelssen, J.L., 1988. Growth, carcass traits, boar odor and testicular and endocrine functions of male pigs fed a progestogen, altrenogest. Journal of Animal Science 66, 470–478.
Fast track
Effect of prolonged use of altrenogest on behaviour in maresq David Hodgson
a,*
, Stephanie Howe a, Leo Jeffcott b,d, Stuart Reid c, Dominic Mellor c, Andrew Higgins d
a
Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia b Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK c Comparative Epidemiology and Informatics, Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Bearsden Rd, Bearsden, Glasgow G61 1QH, UK d Fe´de´ration Equestre Internationale, Avenue Man Repos 24, 1000 Lausanne, Switzerland
Abstract Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. It was concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares had no effect on dominance hierarchies, body-mass or condition score. 2005 Elsevier Ltd. All rights reserved. Keywords: Altrenogest; Regumate; Anabolic; Behaviour; Competition
Altrenogest, a progestagen, is the 17a-allyl derivative of the potent anabolic agent trenbolone which is structurally similar to the male sex hormone, testosterone. Altrenogest is reputedly used widely, and for long periods, in female competition horses. This occurs in an attempt to ameliorate reproductive cyclicity, thus making them more tractable and suitable for training and competition. However, prolonged administration is not in accordance with manufacturersÕ recommendations. In most countries, the drug is registered only for oral administration to mares for 10 days for the purpose of induction of ovulatory oestrus in the late transitional stage of the oestrus cycle. Altrenogest suppresses behavq
PII of original article: S1090–0233(04)00126-1. Corresponding author. Tel.: +61 2 4655 0743/0777; fax: +61 2 4655 6942/1212. E-mail address: [email protected] (D. Hodgson). *
1090-0233/$ - see front matter 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2005.03.003
ioural oestrus in mares within 2–3 days of commencement of administration. The effects of long-term administration to mares of altrenogest are largely unknown, particularly with reference to those used in competition. Additionally, it is not clear whether the drug has any anabolic or significant behavioural effects in horses. A study was therefore designed to provide a preliminary assessment of prolonged administration of altrenogest to sedentary mares in terms of social hierarchy, body-mass and body condition score (BCS). Twelve mares of mixed breed (Thoroughbred and Standardbred) were acquired from a local horse dealer. The animals were kept at pasture as a single group for a total of 20 weeks. Following acquisition, all mares underwent routine health care procedures, including de-worming, dental prophylaxis, hoof care and vaccination. Mares were allowed to acclimate to the new environment for
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325
four weeks during which time they stabilised as a social group, and became accustomed to routine management procedures, e.g., being caught, weighed, placed in a crush, administration of oral medication by syringe. Throughout the entire period of study supplementary lucerne hay was fed. Mares were weighed and condition score was recorded twice weekly. A summary of the study protocol is given in Table 1. Following acclimation, at the beginning of week 5, mares commenced the pre-treatment assessment period, which ran for four weeks. The hierarchy of the group, was established using a modification of standard techniques (Houpt and Wolski, 1980; Keiper and Sambraus, 1986). This assessment was made at regular intervals throughout each of the periods in the study. Briefly, dominance was determined using a paired feeding test. During the 15 min test two horses were in a 3 m · 3 m yard and had access to one bucket of grain. The dominant horse ate from the bucket for the greater part of the 15 min. The horses received no food for 16–18 h before the test. The yard in which the tests were carried out was familiar to all horses. No horse was tested more than once a day. Each horse in the herd was paired with every other horse in the herd with each pair being tested once. Within the herd, the horse dominant to all other Table 1 Flow chart of activities Week 0 Weeks 1–4 Weeks 5–8 Weeks 9–16 Weeks 17–20
Mares acquired Acclimation (routine health care, acclimation to scales, weigh and BCS) Pre-treatment assessment period (weigh, BCS, determine hierarchy) Treatment period (weigh, BCS, determine hierarchy) Post-treatment assessment period (weigh, BCS, determine hierarchy)
323
horses was given the rank of 1 (see Table 2). The horse which failed to dominate any other horse was given the highest numeric rank (11 in a herd of 11). It was possible for two or more horses to be dominant over the same number of animals. In that case, the lower rank (dominance) was ascribed to the horse that was the dominant member of that particular pair. During the test of hierarchy the aggressive actions of each horse were recorded. The aggressive actions were scored as follows: (1) threat to bite (the aggressor laying its ears back and moving its head towards the opponent); (2) threat to kick (the aggressor turning the hindquarters towards the opponent with ears laid back and one hind leg lifted); (3) bite; (4) kick; (5) chase (the aggressor moving at least three steps away from the bucket and towards the opponent). The aggressive scoring system is an arbitrary one in which a threat is considered the mildest form of aggression and given a score of 1 each time it occurs and a chase, the most severe type of aggression, is given a score of 5 each time it occurs. Attempts to assess the activity budget (time spent eating, non-eating activity and resting) for each mare as described by Boyd et al. (1988) was attempted in week 5 However, this proved too difficult and was thus not continued throughout the study. At the beginning of week 9 (treatment period) mares were randomly divided into two groups with six mares treated daily with altrenogest (Regumate, Hoechst Roussel) at the recommended dose rate of 0.044 mg/kg body weight per os by syringe. One of the mares in the
Table 2 Hierarchies for mares throughout the period of study Order in hierarchy
Horse no: wk 5 (pre)
Horse no: wk 8 (pre)
Horse no: wk 12 (treat)
Horse no: wk 16 (treat)
Horse no: wk 18 (post)
Horse no: wk 20 (post)
1 2 3 4 5 6 7 8 9 10 11
10 3 4 2 11 5 6 7 12 1 8
10 3 4 2 11 5 6 7 12 1 8
10 3 4 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
10 4 3 2 11 7 5 6 1 12 8
Key: Bold, treatment group; italic, control group. Horse 1 in the hierarchy is the dominant mare, whereas 11 is the least dominant. Horse 9 died as a result of an intestinal crisis in week 7. Results for this mare were discarded from the analyses.
324
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325
Table 3 Weights of horses (kg) Horse no.
Wk 1: (accl)
Wk 5: (pre)
Wk 8: (treat)
Wk 12: (treat)
Wk 8: (post)
Wk 20: (post)
1 2 3 4 5 6 7 8 9 10 11 12
568 572 530 466 548 558 544 522 534 546 520 495
584 574 536 475 554 560 542 522 534 552 528 499
576 548 528 464 536 552 534 516 DECEASED 554 529 500
556 542 530 463 536 554 539 516 DECEASED 550 528 499
550 542 534 456 544 556 540 520 DECEASED 554 526 498
556 530 530 458 556 556 546 526 DECEASED 556 528 496
Key as for Table 2.
treatment group died as a result of an intestinal crisis in week 10 and results for this animal were excluded from analyses. The remaining six mares acted as controls and were administered a placebo (yogurt) per os q 24 h. The treatment protocol was continued for eight weeks. Again observations to determine the dominance hierarchy of the group were made weekly. Routine determination of body-mass and BCS were continued as described. A similar protocol of observation and measurement was followed for the four weeks following cessation of therapy (post-treatment assessment period). A comparison between each of the recording periods used Spearman rank correlations. This compared results for week 5 vs. week 8 (pre-treatment) to assess variation before treatment. Then, values for week 5 were dropped and possible variations due to the treatment were assessed, i.e., week 8 vs. week 12 vs. week 16 vs. week 18 vs. week 20. A post hoc two-way comparison was then performed. Significance was ascribed at P < 0.05. Statistical analyses revealed no differences in hierarchy in response to treatment with altrenogest (Table 2). All rankings were significantly correlated, even when correcting for multiple comparisons. Thus, given the primary hypothesis being tested that there is no difference in the rankings in response to prolonged treatment with altrenogest, the experimental data do not provide evidence to reject the null hypothesis (P < 0.0001). As shown in Table 3, statistical analyses also revealed no differences in body weight in response to prolonged treatment with altrenogest (P < 0.001). Similarly there was no effect of altrenogest on BCS (P < 0.001) (data not shown). A search of the literature has revealed two papers reporting the effect of altrenogest on growth (and other variables) and these are in pigs by the same group (Kluber et al., 1985, 1988). The data concluded that whereas feeding altrenogest inhibited testicular growth and steroidogenesis in boars it had no effect on body growth, carcass traits or back fat thickness. This is probably to
be expected as altrenogestÕs 17a-C3 side chain (–CH2CH@CH2), which provides the prostagenic activity, may well restrict binding to anabolic receptors. When Johnson et al. (1997) looked at the effect of high dose, prolonged oral administration of altrenogest on sexual and aggressive behaviour and semen quality in young stallions, they found no differences in body weight, BCS or metacarpal measurements between treated and control groups, although there was reduced libido and decreased flehmen frequency and duration, a fall in sperm production and a decrease in scrotal circumference, all probably as a result of the effect of the drug on the testes rather than any centrally acting effect. Recently, Goolsby et al. (2004) reported the results of a survey on the use of altrenogest in stallions. These authors found that the agent was used in an attempt to Ôcreate a more focused animalÕ during training and competition. In the present study, prolonged administration (eight weeks) of altrenogest at recommended dose rates to sedentary mares caused no effect on dominance hierarchies, body-mass or body condition score. We conclude that the evidence to date suggests that altrenogest when administered in accordance with the manufacturerÕs data sheet, has no obvious anabolic or behavioural effects that may affect the performance of a competition mare.
References Boyd, L.E., Carbonaro, D.A., Houpt, K.A., 1988. The 24-h time budget of Przewalski horses. Applied Animal Behaviour Science 21, 5–17. Goolsby, H.A., Brady, H.A., Prien, D., 2004. The off-label use of altrenogest in stallions: a survey. Journal of Equine Veterinary Science 24, 72–75. Houpt, K.A., Wolski, T.R., 1980. Stability of equine hierarchies and the prevention of dominance related aggression. Equine Veterinary Journal 12, 15–18.
D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325 Johnson, N.N., Brady, H.A., Whisnant, C.S., LaCasha, P.A., 1997. Effects of oral altrenogest on sexual and aggressive behaviors and seminal parameters in young stallions. Journal of Equine Veterinary Science 18, 249–253. Keiper, R.R., Sambraus, H.H., 1986. The stability of equine dominance hierarchies and the effects of kinship, proximity and foaling status on hierarchy rank. Applied Animal Behaviour Science 16, 121–130.
325
Kluber, E.F., Pollman, D.S., Davis, D.L., Stevenson, J.S., 1985. Body growth and testicular characteristics of boars fed a synthetic progestogen, altrenogest. Journal of Animal Science 61, 1441–1447. Kluber, E.F., Minton, J.E., Stevenson, J.S., Hunt, M.C., Davis, D.L., Hoagland, T.A., Nelssen, J.L., 1988. Growth, carcass traits, boar odor and testicular and endocrine functions of male pigs fed a progestogen, altrenogest. Journal of Animal Science 66, 470–478.