effect of prolonged use of altrenogest on behaviour in mares

4
Fast track Effect of prolonged use of altrenogest on behaviour in mares q 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. Ó 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 struc- turally similar to the male sex hormone, testosterone. Altrenogest is reputedly used widely, and for long peri- ods, in female competition horses. This occurs in an at- tempt to ameliorate reproductive cyclicity, thus making them more tractable and suitable for training and com- petition. 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 behav- ioural oestrus in mares within 2–3 days of commence- ment of administration. The effects of long-term administration to mares of altrenogest are largely un- known, particularly with reference to those used in com- petition. 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 prelimin- ary assessment of prolonged administration of altreno- gest to sedentary mares in terms of social hierarchy, body-mass and body condition score (BCS). Twelve mares of mixed breed (Thoroughbred and Standard- bred) were acquired from a local horse dealer. The ani- mals 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 1090-0233/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2005.03.003 q 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). www.elsevier.com/locate/tvjl The Veterinary Journal 169 (2005) 322–325 The Veterinary Journal

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www.elsevier.com/locate/tvjl

The Veterinary Journal 169 (2005) 322–325

TheVeterinary Journal

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, Australiab 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, UKd Federation 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 derivativeof the potent anabolic agent trenbolone which is struc-

turally similar to the male sex hormone, testosterone.

Altrenogest is reputedly used widely, and for long peri-

ods, in female competition horses. This occurs in an at-

tempt to ameliorate reproductive cyclicity, thus making

them more tractable and suitable for training and com-

petition. However, prolonged administration is not in

accordance with manufacturers� recommendations. Inmost 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 behav-

1090-0233/$ - see front matter � 2005 Elsevier Ltd. All rights reserved.

doi:10.1016/j.tvjl.2005.03.003

q 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).

ioural oestrus in mares within 2–3 days of commence-ment of administration. The effects of long-term

administration to mares of altrenogest are largely un-

known, particularly with reference to those used in com-

petition. 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 prelimin-

ary assessment of prolonged administration of altreno-gest to sedentary mares in terms of social hierarchy,

body-mass and body condition score (BCS). Twelve

mares of mixed breed (Thoroughbred and Standard-

bred) were acquired from a local horse dealer. The ani-

mals 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. Mareswere allowed to acclimate to the new environment for

D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325 323

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 conditionscore 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 tech-

niques (Houpt and Wolski, 1980; Keiper and Sambraus,

1986). This assessment was made at regular intervalsthroughout 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 domi-

nant horse ate from the bucket for the greater part of

the 15 min. The horses received no food for 16–18 h be-

fore the test. The yard in which the tests were carried out

was familiar to all horses. No horse was tested morethan 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 Mares acquired

Weeks 1–4 Acclimation (routine health care, acclimation to

scales, weigh and BCS)

Weeks 5–8 Pre-treatment assessment period (weigh, BCS,

determine hierarchy)

Weeks 9–16 Treatment period (weigh, BCS, determine

hierarchy)

Weeks 17–20 Post-treatment assessment period (weigh, BCS,

determine hierarchy)

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)

1 10 10 10

2 3 3 3

3 4 4 4

4 2 2 2

5 11 11 11

6 5 5 7

7 6 6 5

8 7 7 6

9 12 12 1

10 1 1 12

11 8 8 8

Key:

� Bold, treatment group; italic, control group.

� Horse 1 in the hierarchy is the dominant mare, whereas 11 is the least d

� Horse 9 died as a result of an intestinal crisis in week 7. Results for this

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 (domi-

nance) was ascribed to the horse that was the dominantmember 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 hindquar-ters 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 inwhich a threat is considered the mildest form of aggres-

sion 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 eat-

ing, non-eating activity and resting) for each mare as de-

scribed by Boyd et al. (1988) was attempted in week 5

However, this proved too difficult and was thus not con-tinued 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

Horse no:

wk 16 (treat)

Horse no:

wk 18 (post)

Horse no:

wk 20 (post)

10 10 10

4 4 4

3 3 3

2 2 2

11 11 11

7 7 7

5 5 5

6 6 6

1 1 1

12 12 12

8 8 8

ominant.

mare were discarded from the analyses.

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)

1 568 584 576 556 550 556

2 572 574 548 542 542 530

3 530 536 528 530 534 530

4 466 475 464 463 456 458

5 548 554 536 536 544 556

6 558 560 552 554 556 556

7 544 542 534 539 540 546

8 522 522 516 516 520 526

9 534 534 DECEASED DECEASED DECEASED DECEASED

10 546 552 554 550 554 556

11 520 528 529 528 526 528

12 495 499 500 499 498 496

Key as for Table 2.

324 D. Hodgson et al. / The Veterinary Journal 169 (2005) 322–325

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 hierar-chy of the group were made weekly. Routine determina-

tion of body-mass and BCS were continued as

described. A similar protocol of observation and mea-

surement was followed for the four weeks following ces-

sation 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 variationbefore treatment. Then, values for week 5 were dropped

and possible variations due to the treatment were as-

sessed, 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. Statis-

tical analyses revealed no differences in hierarchy in re-

sponse to treatment with altrenogest (Table 2). All

rankings were significantly correlated, even when cor-recting for multiple comparisons. Thus, given the pri-

mary hypothesis being tested that there is no difference

in the rankings in response to prolonged treatment with

altrenogest, the experimental data do not provide evi-

dence 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 therewas 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 (Klu-

ber et al., 1985, 1988). The data concluded that whereas

feeding altrenogest inhibited testicular growth and ste-

roidogenesis in boars it had no effect on body growth,carcass traits or back fat thickness. This is probably to

be expected as altrenogest�s 17a-C3 side chain

(–CH2CH@CH2), which provides the prostagenic activ-

ity, 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 inyoung stallions, they found no differences in body

weight, BCS or metacarpal measurements between trea-

ted and control groups, although there was reduced libi-

do and decreased flehmen frequency and duration, a fall

in sperm production and a decrease in scrotal circumfer-

ence, all probably as a result of the effect of the drug on

the testes rather than any centrally acting effect. Re-

cently, Goolsby et al. (2004) reported the results of asurvey on the use of altrenogest in stallions. These

authors found that the agent was used in an attempt

to �create a more focused animal� during training and

competition.

In the present study, prolonged administration (eight

weeks) of altrenogest at recommended dose rates to sed-

entary mares caused no effect on dominance hierarchies,

body-mass or body condition score. We conclude thatthe evidence to date suggests that altrenogest when

administered in accordance with the manufacturer�sdata 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) 322–325 325

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 Veteri-

nary Science 18, 249–253.

Keiper, R.R., Sambraus, H.H., 1986. The stability of equine domi-

nance hierarchies and the effects of kinship, proximity and foaling

status on hierarchy rank. Applied Animal Behaviour Science 16,

121–130.

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.