e s t r u m a t e ® f a c t s , p u b l i s h e d s t u d i e s a n d f i e l d t r i a l d a t a

Estrumate Prostaglandin Consistently Outperforms Lutalyse®

Summary of Eight Studies

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Estrumate Prostaglandin Consistently Outperforms Lutalyse® Summary Of Eight Studies

Half-life for EstrumatE prostaglandin is three hours compared to a few minutes for Lutalyse. EstrumatE prostaglandin lasts much longer1 than Lutalyse. the sensitivity of the corpus luteum to prostaglandin injection increases progressively during the estrous cycle.2

EstrumatE prostaglandin is a more potent luteolytic agent than Lutalyse.3

EstrumatE prostaglandin quickly reduces progesterone levels4 and provides a rapid estrus response.5

EstrumatE prostaglandin features a convenient 2-mL dose for heifers and cows. a 2-mL dose is easier to use and gives you confidence in EstrumatE prostaglandin’s performance.

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e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Seguin’s Work5

Cows were treated on Day 8 of the estrous cycle.

Compared estrus response and conception rate by product.

Evaluated estrus response until Day 6 after injection.

Cows were artificially inseminated 12 hours after estrus was detected.

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Dairy

result s, es t rous response by produc t

Time to Estrus Estrumate® Lutalyse®

48 hours* 37 27

60 hours 17 21

72 hours 3 5

84 hours 0 0

96 hours 0 1

108 hours 1 0

120 hours 1 0

132 hours 0 0

144 hours 1 1

156 hours 0 0

total responses 60/62 55/62

Response rate 96.8% 88.7%

r e sult s, p e r c e n t a nim a l s in he at

Estrumate® Lutalyse®

(n=62) (n=62)

48 hours post injection* 59.7% 43.5%

60 hours post injection 87.0% 77.0%

84 hours post injection 92.0% 85.0%

156 hours post injection 96.8% 88.7%

r e sult s, c onc ep t ion r at e by p roduc t

Estrumate® Lutalyse®

(n=62) (n=62)

Conception rate 62.5% 56.3%

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Seguin’s Work5 (continued)

*p=0.07

Dairy

s t udy c onduc t e d in c a n a di a n da ir y op e r at ions f rom m ay 1, 19 9 3 t o june 1, 19 9 4

Lactating dairy cows and heifers having a corpus luteum determined by rectal palpation were randomly assigned to treatment groups.

Estrumate® Lutalyse®

Number cases 101 102

Conception rate 41.8% 33.7%

Pregnancy rate 34.9% 29.3%

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e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Martineau’s Work3

Dairy

* Differences between treatment groups not statistically significant.

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

New York Dairy Field Trial6

Compared reproductive performance of animals receiving Estrumate® vs. Lutalyse.®

Ovsynch protocol utilized.

trial began November 2003 and was completed september 2004.

br e e ding p rogr a m

the first tuesday after 45 days in milk, an injection of prostaglandin, based on the animals’ treatment group, was administered.

the following week on tuesday, the cows all received a Gnrh injection.

the following tuesday the cows received an injection of prostaglandin, based on the animals’ treatment group.

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all cows were bred the following thursday between noon and 2:00 p.m.

Cows were pregnancy checked by the dairy’s consulting veterinarian at day 32-46 after breeding.

r e sult s *

Estrumate® Lutalyse®

Number cows/treatment 232 222

First service conception rate 39% 34%

second service conception rate 43% 32%

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* Differences between treatment groups not statistically significant.

Dairy

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

California Dairy Field Trial6

Compared reproductive performance of animals receiving Estrumate® vs. Lutalyse.®

trial began January 2004 and was completed November 2005.

Cows received prostaglandin at 50-100 days in milk.

Cows were pregnancy checked by the dairy’s consulting veterinarian at day 35-49 after breeding.

r e sult s *

Estrumate® Lutalyse®

Number cows/treatment 1,555 1,491

First service conception rate 30.4% 29.9%

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ec onomic s

For every 1% increase in pregnancy rate, per cow profitability increases up to $17.00.

Calculate the economic advantage of Estrumate in your operation.

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* Differences between treatment groups not statistically significant.

Dairy

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Idaho Dairy Field Trial6

Compared reproductive performance of animals receiving EstrumatE vs. Lutalyse.®

Injected products and bred following an observed heat.

study conducted in the fall/winter 2004.

r e sult s *

2 Injections Conception rate

3 Injections Conception rate

Estrumate35.0% (39/111)

30.0% (39/131)

Lutalyse32.0%

(38/119)28.0%

(39/139)

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summ a r y

Continued trends of superior EstrumatE performance in conception rates

two injections: 35.0% vs. 32.0%

three injections: 30.0% vs. 28.0%

* Differences between treatment groups not statistically significant.

Dairy

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Canadian Work7

One injection to beef heifers, where CL was palpated before injection*

Estrumate® (n=56)

Lutalyse® (n=63)

First service Conception rate 61.0% 57.0%

Pregnancy rate 96.0% 87.0%

two injections given 11 days apart to cycling beef heifers*

Estrumate® (n=129)

Lutalyse® (n=126)

Estrus 92.0% 86.0%

Pregnancy rate 91.0% 83.0%

Beef heifers were palpated for cyclicity and randomly assigned to one of two prostaglandin treatments.

two injections were given 11 days apart and heifers bred on estrus detection, following each prostaglandin injection.

Heat detection and aI continued after synchronization for approximately one month.

at that time, red angus bulls were used for the remainder of the breeding season.

Cows were artificially inseminated 12 hours after estrus was detected.

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Beef

* Differences between treatment groups not statistically significant.

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Oregon Beef Herd Field Trial6

Compared reproductive performance of animals receiving Estrumate® vs. Lutalyse.®

two injections 11 days apart, with breeding 12 hours after estrus detected.

study conducted in summer 2004.

r e sult s

Estrumate® Lutalyse® P Value

Heifer Conception rate

39.6% (143/361)

35.0% (130/371)

0.2009

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Beef

Evaluated pregnancy rates to a timed aI program in Bos indicus x Bos taurus cows.

used Gnrh, PG F2a and mGa.

Cosynch hybrid program Day 0: Gnrh Day 1-7: mGa, 0.5 mg/head/day Day 7: EstrumatE or Lutalyse® Day 10: timed aI plus Gnrh

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results, conception rates by products*

EstrumatE: 41% (n=297)

Lutalyse: 36% (n=297)

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Florida Beef Herd Study 8,9

* Differences between treatment groups not statistically significant.

Beef

m at e ri a l s a nd me t hods

Presynchronization with a two-dose modified protocol.

– Lutalyse® 25 mg on D -14 – Lutalyse 12.5 mg on D -3 and D -2

Estrus detected with HeatWatch.

GnrH injected in four different days of the estrous cycle.

– Days 2, 5, 12, 18

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three different PGF protocols injected seven days after GnrH.

– Lutalyse 25 mg – Lutalyse 12.5 mg (day 7 and 8) – EstrumatE 0.5 mg

Blood samples collected before injection and at every 48 hours until estrous response and/or ovulation.

ultrasound imaging.

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e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Stage of Cycle Effects on Response to Different GnRH + Prostaglandin F2a Treatments6

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Stage of Cycle Effects on Response to Different GnRH + Prostaglandin F2a Treatments6

110%

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

% C

ows

Estrous response (%), CL regression (%) and Interval to Estrus of Different PGF Products Injected 7 Days after GnrH Injection

Lutalyse® 25 mg Estrumate®

Estrous response 5 days after PGF injection

Percentage of cows with CL regression

Interval (hours) from PGF injection to onset of estrus

95

90

85

80

75

70

Inte

rval

to

Est

rus

(h)

63%

81%74%

95%

90

77* Differences between treatment groups not statistically significant.

Cloprostenol sodium, the active ingredient in EstrumatE, has a longer half-life than dinoprost tromethamine, the active ingredient in Lutalyse.®

Cloprostenol is a more potent luteolytic agent than dinoprost.

Cloprostenol is not degraded by 15-hydroxydehydrogenase and 13,14-reductase.

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Estrumate®* Lutalyse®**

Half-life 3 hoursExtremely short (few minutes)

ClearanceNot degraded by 15-hydroxy-dehydrogenase and 13,14-reductase

almost completely cleared after one or two passages through the liver and/or lungs

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

Why Estrumate Is Superior to Lutalyse

* EmEa, the European agency for the Evaluation of medicinal Products. Committee for Veterinary medicinal Products. Cloprostenol and r-Cloprostenol summary report, april 1997.

** EmEa, the European agency for the Evaluation of medicinal Products. Committee for Veterinary medicinal Products. Dinoprost, summary report, June 1997.

e s t r um at e ® fa c t s , p ub l i s he d s t udi e s a n d f i e l d t r i a l data

References

1 EmEa, the European agency for the Evaluation of medicinal Products. “Cloprostenol and r-Cloprostenol.” summary report, april 1997.

1 EmEa, the European agency for the Evaluation of medicinal Products. “Dinoprost.” summary report, June 1997.

2 Berardinelli, J.G., et al. "Effect of prostaglandin dosage and stage of estrous cycle on the estrous response and corpus luteum function in beef heifers.” Theriogenology, 32: 301-314, 1989.

3 martineau, r. “Dinoprost Versus Cloprostenol: Does route of Injection modulate their Efficacy in Dairy Cattle?” The Bovine Practitioner, pp. 10-19, February 2003.

4 Hayashi, K., et al. "Changes in Prostaglandin secretion by the regressing Bovine Corp Luteum.” Elsevier – Prostaglandins & Other Lipid mediators. 70:339-349, 2003.

5 seguin, B., et al. “Cloprostenol and Dinoprost tromenthamine in Experimental and Field trials treating unobserved Estrus in Dairy Cows.” The Bovine Practitioner, pp. 85-90, November 1985.

6 Data on file at schering-Plough animal Health Corporation.7 Comparison of Estrumate and Lutalyse in Beef Heifers. Joint Federal Provincial Demonstration Project at Douglas, manitoba, Canada 1981-1983.

8 Hiers, Ea. 2003 Florida Beef report, pp 77-79.9 Hiers, Ea et al. Journal of Animal Science 81:830-835, 2003.

Copyright © 2006, schering-Plough animal Health Corporation. all rights reserved. EstrumatE is a trademark of schering-Plough animal Health Corporation. LutaLysE is a registered trademark of Pfizer animal Health. sPaH-Est-48a