Topics in Compan An Med 30 (2015) 25–27

Topical Review

Treatment of Canine Pyometra With the Gonadotropin-Releasing

Hormone Antagonist Acyline: A Case Series
Pablo R. Batista, MVa,b, Paula G. Blanco, MV, DMVa,b, Cristina Gobello, MV, DMV, DECARa,n

Keywords: To describe the effect of the third-generation gonadotropin-releasing hormone antagonist acyline in the
dog
treatment of 4 diestrous bitches with the cystic endometrial hyperplasia-pyometra complex. The 4
GnRH antagonist
bitches were treated with 330 μg/kg of subcutaneous acyline on day 0 and antibiotics, and followed up
corpus luteum
pyometra for 2 weeks. One closed-cervix case showed cervical dilatation 36 hours after treatment, and all the 4
acyline animals showed resolution of clinical signs starting on day 3 posttreatment. Ultrasonographic uterine
diameters and luminal contents decreased in the bitches having high progesterone serum concen-
a trations before treatment but not in those with low levels. Serum progesterone importantly decreased
Laboratory of Reproductive Physiology,
from high to basal concentrations in the 3 “ultrasonographically cured” animals. No local or systemic
Faculty of Veterinary Medicine, National
University of La Plata, La Plata, Argentina side effects related to the treatment were observed. The gonadotropin-releasing hormone antagonist
b acyline may have a promising place for the medical treatment of cystic endometrial hyperplasia-
Imaging Diagnosis Service, Faculty of
Veterinary Medicine, National University of La
pyometra complex in dogs.
Plata, La Plata, Argentina & 2015 Elsevier Inc. All rights reserved.
n
Address reprint requests to Cristina
Gobello, MV, DMV, DECAR, Laboratory of
Reproductive Physiology, Faculty of
Veterinary Medicine National University of
La Plata 60 & 118. La Plata. CC 296 (B 1900
AVW) Argentina.
E-mail: [email protected],
[email protected] (C. Gobello)

Introduction progesterone concentrations decreased to basal levels (o1 ng/mL).

Rate of progesterone decrease varied among animals and was
Cystic endometrial hyperplasia-pyometra complex (CEH-P) is temporally related to abortion when serum progesterone reached
the most common uterine disorder of intact bitches. Pathophysi- basal.9 GnRH antagonists have not been reported for use in the
ology of CEH-P includes bacterial infection of an endometrium treatment of progesterone-dependent CEH-P; the objective of this
that is under the influence of progesterone. Unlike most other report is to describe the effect of acyline in the treatment of 4 cases
female mammals, the bitch secretes ovarian progesterone for of CEH-P in the female dog.
approximately 60-70 days after ovulation (diestrus) irrespective
of whether she is pregnant. Progesterone secretion is maintained
by secretion of the hypothalamic peptide gonadotropin-releasing Clinical Cases
hormone (GnRH).1 Bitches with CEH-P may be classified as having
a closed cervix (accumulation of purulent material in the uterus Patients
without a purulent vulvar discharge) or open cervix (presence of a
purulent vulvar discharge). CEH-P can be a life-threatening con- Four purebred diestrous bitches (Table 1) diagnosed with CEH-
dition that must be managed expeditiously. Treatment of CEH-P in P were referred to our service. Uterine enlargement was con-
most bitches includes ovariohysterectomy; however, medical firmed by ultrasonography in all of the cases (Day 0).10 The bitches
treatment is desirable for bitches intended for breeding.2 were slightly febrile and dehydrated and had decreased appetite.
Peptide analogues of GnRH are used in a variety of clinical Mean serum urea and creatinine concentrations for all of the
applications for suppression of the reproductive endocrine axis in bitches were o 60 mg/dL and 1.5 mg/dL, respectively, after rehy-
both humans3,4 and dogs.5 GnRH antagonists bind to and block dration. This medical trial to decrease serum progesterone with
gonadotropin GnRH receptors from binding to endogenous GnRH, acyline was approved by the Institutional Animal Care and Use
thereby suppressing the pituitary-gonadal axis.6 Acyline is a Committee of the University of La Plata, and consent forms were
potent and safe third-generation GnRH antagonist which, in dogs, signed by all of the owners.
has been shown to rapidly decrease gonadotropins and (male)
testosterone for 9 days after a single subcutaneous administra- Treatment Protocol
tion.7 No hematologic, serum biochemical, local, or systemic side
effects have been attributed to acyline treatment in the dog.8 After the diagnoses were confirmed and uterine measures
When acyline was administered to bitches in midpregnancy, taken (described later), the bitches were treated with 330 μg/kg
gestations were terminated after a mean of 6 days and serum of subcutaneous acyline (Day 0). Acyline was provided in a

http://dx.doi.org/10.1053/j.tcam.2015.01.005
1527-3369/& 2015 Topics in Companion Animal Medicine. Published by Elsevier Inc.
26 P.R. Batista et al. / Topics in Companion An Med 30 (2015) 25–27

Table 1 Table 2
Signalment of Bitches With Cystic Endometrial Hyperplasia-Pyometra Complex Ultrasonographic and Hormonal Data in Four Bitches With CEH-P After Acyline
Treated With Acyline Treatment

Bitch Breed Age (y) Body Weight (kg) Time After Estrus (d) Cervix* Bitch Day Uterine Uterine Serum
Diameter Luminal Progesterone
Miniature Poodle 7 7.3 26 Closed (mm) Diameter (mm) (ng/mL)
Shar-pei 6 18 15 Open
Canary Dog 2 37 33 Open Miniature Poodle 0 46.2 35 22.1
Giant Schnauzer 8 39 66 Open 3 20.6 10
7 15.8 3 1.5
n
Open: purulent vulvar discharge. Closed: no vulvar discharge. 14 13.6 3

Shar-pei 0 46.3 36.5 18.5

3 21.1 12.1
lyophilized powder that was suspended in sterile distilled water at 7 16.3 2.9 3.5
a concentration of 2 mg/mL. The dosage was selected based on a 14 15.6 1.3
previous report.9 Amoxicillin-clavulanate administered twice a Canary Dog 0 28 22 25.2
day at 12.5 mg/kg orally (Clavamox, Pfizer, Argentina) was admin- 3 21.5 3
istered for 7 days, and rehydration was accomplished in the first 7 16.5 2 1.7
14 14.9 2
24 hours.
Giant Schnauzer 0 67 49 3
3 54.6 43
Follow-Up
7 63 51 2
14 65.1 55
On day 0 (before treatment) and day 7, blood samples were
collected for serum progesterone determination by electrochemi-
luminescence immunoassays (Elecsys Progesterone II, Roche Diag-
nostics, Mannheim, Germany). appeared to vary with progesterone concentrations when treat-
On days 3, 7, and 14 following treatment, the bitches were ment was administered. Canine luteal function is known to be
clinically and ultrasonographically evaluated. Clinical examination independent of gonadotropins during the early luteal phase,
included body temperature, hydration, presence of vulvar dis- whereas corpora lutea depends on luteotrophic hormones
charge if any, and appearance of clinical local or systemic side as diestrus progresses. Serum progesterone concentrations
effects. Total external and luminal maximal uterine diameters decrease to basal levels by approximately day 75 when anestrus
were measured by transabdominal ultrasonography (Toshiba Core commences.1
Vision Pro, Shimoishigami, Otawara-Shi, Tochigi-Ken, Japan) using In the late diestrous Giant Schnauzer, serum progesterone
an 8-MHz linear-array transducer.10 For imaging, the bitches were concentration was already low at treatment onset and treat-
positioned in lateral recumbency and the ventral abdomen shaved. ment did not appear to reverse the already established patho-
Acoustic gel was applied to the transducer and coupled directly to logic condition. Conversely, the other 3 bitches treated during
the skin. Additionally, 2-dimensional ultrasound was used to high progesteronemia, showed decrease in uterine diameters
identify the uterine body in a transverse axis. by approximately 50% a week after a single acyline adminis-
tration. In the Miniature Poodle, the cervix opened in 36 hours,
Outcome of the Clinical Cases causing a dramatic improvement in the patient's condition. No
adverse effects were observed in association with the acyline
The Miniature Poodle (closed cervix, Table 1) showed cervical treatment.
dilatation 36 hours after treatment, as evidenced by a heavy These results contribute to the understanding of the role of the
purulent vulvar discharge. By day 3, all 4 animals were afebrile gonadotropin, luteinizing hormone, in maintaining the middies-
and hydrated and had normal appetite. Vulvar discharges were trus canine corpus luteum. Similar findings previously were
copious in the Miniature Poodle, Shar-pei, and Canary Dog and reported in pregnant (days 25-351; day 30 onward11); and non-
mild in the Giant Schnauzer. Uterine diameters and luminal pregnant12 diestrous bitches using second- and third-generation
contents importantly decreased throughout the trial in the in GnRH antagonists.
the first 3 bitches but not in the Giant Schnauzer (Table 2). Serum GnRH antagonists may have promise in the medical treatment
progesterone levels importantly decreased from high to basal of the CEH-P complex in high progesterone bitches. This report
concentrations in the 3 “ultrasonographically cured” bitches provides preliminary data for further studies that may define the
(Table 2). On days 7 and 14, all 4 bitches appeared clinically window of efficacy, effect on CEH, and future fertility and
healthy and had no vulvar discharge. The Giant Schnauzer bitch recurrence rate, if any, before GnRH antagonists can be recom-
was ovariohysterectomized immediately after ultrasound on day mended for this hormone-dependent uterine condition of female
14. No local or systemic side effects related to the treatment were dogs.
observed in any of the bitches at any time during the follow-up
period.
Acknowledgments

Discussion The authors thank the Contraception and Reproductive Health

Branch, Center for Population Research, National Institute of Child
In women, third-generation GnRH antagonists have been Health and Human Development, National Institutes of Health,
shown to be useful in the medical management of nonmalignant USA for provision of acyline. This study was partially funded by
uterine conditions such as endometriosis and uterine fibroids.3,4 If the University Incentive Program for Teaching and Research at the
treatment success is defined as uterine diameter within normal National University of La Plata, La Plata, Argentina. The authors are
limits and absence of luminal fluids in the ultrasound examination Career Scientists (C.G. and P.G.B.) and Fellow (P.B.) of the National
of clinically healthy bitches, the response to this treatment Research Council, Argentina.
 P.R. Batista et al. / Topics in Companion An Med 30 (2015) 25–27 27

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