Slov Vet Res 2023  |  Vol 60 No 4  |  213
Aggressive Behavior in a Bitch After Deslorelin 
Implant Insertion 
Key words
bitch;
aggression;
behavior;
deslorelin implant;
long-lasting GnRH 
Maja Zakošek Pipan1*, Darja Pavlin2 
1Clinic for Reproduction and Large Animals, 2Small Animal Clinic, Veterinary Faculty, University of Ljubljana, 
Gerbičeva 60, 1000 Ljubljana, Slovenia 
Both authors contributed equally to this work and share first and last authorship
*Corresponding author: maja.zakosekpipan@vf.uni-lj.si
Abstract: In male dogs, long-acting gonadotropin-releasing hormone (GnRH) analogs 
are widely accepted as an alternative to surgical castration but are also used to sup-
press and induce estrus in bitches (off label). Behavioral changes reported in bitches in 
association with the use of long-acting GnRH analogs have included male-like behav-
ior associated with triggered estrus, increased food intake, enlargement of mammary 
glands and milk production, pseudopregnancy, and urinary incontinence. In male dogs, 
intra-species and rarely inter-species aggression may occur during the flare-up effect. 
However, at the time of downregulation, this behavior should no longer occur if it is tes-
tosterone dependent.
An intact, three-year-old female cocker spaniel with Addison’s disease was admitted to 
our clinic for consultation on spaying options because of pseudopregnancies followed 
by mastitis, which had to be treated with antibiotics, after her heat cycles. The owners 
were hesitant about surgical sterilization and therefore, deslorelin implant was inserted. 
Approximately one month after implantation, owners observed the onset of aggressive 
behavior, including incessant barking, extreme irritability, and aggression toward other 
dogs and towards family members. The behavior problems started to escalate and the 
owners were not able to handle her anymore. After removal of the implant, the observed 
aggression ceased, and the bitch returned to normal behavior.
Although aggressive behavior toward other dogs and sometimes even toward owners 
has been observed after neutering or insertion of a deslorelin implant, this is the first 
report of extremely aggressive behavior toward owners and other dogs in a female dog 
after insertion of a 4.7 mg deslorelin implant. 
Received: 24 May 2023
Accepted: 25 August 2023
DOI 10.26873/SVR-1781-2023
UDC 636.7:612.621.5:577.175.6:591.5
Pages: 213–18
Case Report
Introduction 
Aggression is the most common and serious behavioral 
problem in dogs. It is also the most common reason pet 
owners seek professional help from veterinarians and be-
haviorists (1). Aggression in dogs can be directed toward 
familiar people, toward strangers, or toward other dogs. 
Aggressive behavior in dogs is a common problem in soci-
ety and a frequent cause of dog-human bites (2), surrender 
of adult dogs to shelters, and euthanasia of adult dogs (3). 
Gonadectomy is commonly used to treat and prevent be-
havior problems, including aggressive behavior in dogs 
and it is advocated by veterinarians as a way to make 
dogs better-behaved companions (4). However, research-
ers provide conflicting information. In a study by Hopkins 
et al. (5), it was found that in gonadectomized dogs, ag-
gressiveness toward other dogs decreased by 62%, but 
territorial and fear-induced aggressive behavior remained 
214  |  Slov Vet Res 2023  |  Vol 60 No 4
unchanged. The same observations were made in another 
study in which neutering had an effect on all behavioral 
problems related to aggression except aggressive behavior 
toward strangers (6). In contrast, other studies suggest no 
discernible pattern of changes in aggression (7, 8). Some 
studies note that gonadectomized dogs of both sexes are 
significantly more likely than intact dogs to bark, growl, 
lunge, snap, open their eyes wide, and raise or curl their lips 
when approached by an unknown human or dog (9, 10). A 
recent study of 15, 370 dogs concluded that no single fac-
tor is responsible for aggressive behavior in dogs, but that 
there are multiple environmental and genetic factors that 
contribute to aggressive behavior. Neutering does not re-
sult in a predictable decrease in aggressive behavior in all 
male and female dogs, although it may be effective in some 
(4). This supports the previous 2013 recommendation from 
the Society for Theriogenology and the American College 
of Theriogenology Board of Directors that gonadectomy 
should be decided on a case-by-case basis (11).
Gonadotropin-releasing hormone (GnRH) is a key regulator 
of reproductive function. It is released in a pulsatile fashion 
from hypothalamic neurons. The peptide binds to specific 
GnRH receptors on pituitary gonadotrophs. Its activation 
leads to synthesis and secretion of LH and FSH. In females, 
gonadotropin secretion from the pituitary gland is modulat-
ed by estradiol and progesterone. These feedback effects 
of ovarian steroids initiate the LH surge and lead to sup-
pression of GnRH release in the luteal phase. The pulsatile 
release of GnRH from the hypothalamus is essential for the 
maintenance of ovarian function (12). Slow-release GnRH 
agonist implants are widely accepted as an alternative to 
surgical castration in male dogs and cats. Although deslo-
relin implants are approved in the EU for male dogs and, as 
of June 2022, for male cats and prepubertal bitches (13), 
numerous studies have been conducted in the adult bitch 
to investigate its use as a contraceptive and/or method of 
estrus induction (14, 15, 16). The first step in the mecha-
nism of action is a flare-up effect with an increase in go-
nadotropin synthesis. Such increased gonadotropin syn-
thesis leads to estrus induction in females, when treated in 
anestrus (14, 15). This was indeed observed when females 
in anestrus were treated with GnRH analog (14). However, 
when females in diestrus with P4 > 5 ng/ml were treated, 
the first report concluded that there is no flare-up effect 
(17). Later studies showed that the initial flare up effect 
is associated with estrus induction when deslorelin is ad-
ministered to bitches both in anestrus as well as (although 
more rarely) in diestrus (18). Most authors have confirmed 
that all adult bitches respond in the same manner regard-
less of size and age; however, depending on the stage of 
the cycle, the bitch’s response may vary (19, 20, 21). After 
the flare-up effect desensitization of the GnRH receptors 
occurs, resulting in a transient, long-term, and fully revers-
ible down-regulation of reproductive endocrine functions in 
dogs (21, 22, 23). These promising results led to the use of 
the implants for estrus induction and suppression in bitch-
es predisposed to the side effects of sterilization (off-label 
use). Although many adult bitches do well when treated 
with deslorelin, some signs such as persistent oestrus, 
pyometra, urinary incontinence, ovarian tumors, and minor 
behavioral and physical changes may occur (24).
Case
An intact, three-year-old female cocker spaniel was admit-
ted to our hospital for consultation on spaying options. The 
dog was diagnosed with Addison’s disease at one year of 
age and was well controlled with a combination of oral hy-
drocortisone (Hydrocortisone Roussel, Sanofi Winthorp 
Industrie, France) at a dosage of 0.4 mg/kg/12h and subcu-
taneous desoxycorticosterone pivalate (Zycortal, Dechra, 
UK) at a dosage of 1.3 mg/kg/30 days. Based on clinical 
response to therapy and biannual laboratory checks, her 
disease was stable. Her first heat occurred at 9 months 
of age, and since then she has had regular cycles every 6 
months. After the fourth cycle, she developed pseudopreg-
nancy followed by mastitis, which had to be treated with 
antibiotics. The owners wanted to stop the cycles and pre-
vent the pseudopregnancy but were hesitant about surgical 
sterilization because of the risk of anesthesia, due to her 
condition. Moreover, they feared irreversible consequences 
of gonadectomy, especially weight gain. They decided to 
use a deslorelin implant because its effect is reversible and 
can be implanted without surgical intervention. 
Deslorelin (Suprelorin 4.7 mg implant for dogs, Virbac, 
France) was implanted subcutaneously in the umbilical 
region on day 23 after the onset of visible signs of proes-
trus. Diestrus was confirmed by vaginal cytology, but pro-
gesterone was not measured. Approximately one month 
after implantation, owners observed the onset of aggres-
sive behavior, including incessant barking, extreme irritabil-
ity, and aggression toward other dogs. Such behavior was 
not normal for this previously very well-mannered dog. The 
aggression escalated rapidly with her becoming aggres-
sive also toward people, firstly toward strangers but later 
toward family members as well, culminating in a bite attack 
requiring medical intervention on one of the owners. The 
change in behavior was so extreme that the owners were 
unable to physically interact with her any more as she at-
tacked anyone who approached her. About 70 days after 
implantation signs of pseudopregnancy became visible 
with enlarged mammary glands but no milk production and 
lethargy. Another side effect of the implant was polyphagia 
and about 10% weight gain. 
Approximately two and a half months after administration, 
the implant was removed. All signs of aggressive behavior 
ceased within the next few months, and according to the 
owners, she returned to the gentle dog she was prior to im-
plantation. Within two weeks, she also lost 600 g in weight 
despite being fed the same diet. In the two years after the 
implant removal, once resolved, the aggressive behav-
ior never reoccurred although her heat cycles returned to 
Slov Vet Res 2023  |  Vol 60 No 4  |  215
normal as before deslorelin implantation. The exact course 
of events are shown in Figure 1. 
Discussion
The present case is the first report of the occurrence of 
severe aggression in a bitch after the insertion of a des-
lorelin implant. Surgical sterilization is often suggested to 
the owners to alleviate unwanted and aggressive behavior 
in some dogs (25). Because of their ability to suppress sex 
steroid hormones, GnRH agonist-releasing implants may 
also be useful in modifying or minimizing testosterone-re-
lated behaviors. In castrated male dogs and dogs with des-
lorelin implants, improvements have been noted in sexually 
dimorphic male behaviors described as libido, hypersexu-
ality, intermale conflict, and excessive urine marking (26). 
Therefore, it has been suggested that implants releasing 
GnRH agonists are an alternative for clients seeking to alter 
testosterone-mediated behavior in their male dogs without 
having to perform castration or as a trial to what could be 
achieved by permanent sterilization (27). On the other hand, 
recent studies have shown that the likelihood of undesir-
able behavior increases significantly in neutered animals. 
Neutered dogs were more aggressive, more fearful, more 
restless, more difficult to train, and less responsive to sig-
nals (2, 4, 23). In addition, and of bigger importance, there is 
a risk of an increase in dominance aggression toward fam-
ily members (28), with owners (2) and children (29) being 
bitten more likely by neutered animals. Another study found 
that these effects were more pronounced when animals 
were neutered before puberty (27). 
The behavioral aspect of GnRH agonist implants in bitch-
es has not yet been described, but it is generally expected 
that the effects should be similar to those of sterilization. 
However, there is a major difference between surgical and 
medical castration, namely that gonadotropin levels are 
very high after surgical castration (30) whereas they are 
likely to be low to basal during deslorelin treatment be-
cause of the inhibitory effect of deslorelin on gonadotropin 
release. In general, it is not known whether such a change 
may have an impact on disease and possibly on behavior. 
In the present case, severe aggressive behavior toward oth-
er dogs and strangers was initially observed. Subsequently, 
the aggression toward family members escalated and the 
dog became so aggressive that the owners could no longer 
safely handle her. Most studies have found that the risk of 
unwanted aggressive behavior after sterilization is higher in 
dogs that already showed behavioral problems before go-
nad removal (31). However, in our case, no aggression was 
observed in this bitch before implant placement, and the 
aggression resolved after implant removal.
We must mention that the dog suffered from Addison’s 
disease and was treated with a physiological dose of corti-
costeroids and mineralocorticoids. Exogenous corticoste-
roids are synthetic analogues of natural steroid hormones 
and are used in both human and veterinary medicine mainly 
for their anti-inflammatory and immunosuppressive ef-
fects. The synthetic analogues of cortisol have increased 
glucocorticoid activity (32). Exogenous corticosteroid 
treatments have been reported to cause negative emotion-
al states in human patients and laboratory animals, with 
similar changes noted in domestic dogs (33). Behavioral 
changes associated with exogenous corticosteroid treat-
ments in dogs have been reported in only a few studies (33, 
34), showing increased anxious behavior and avoidance of 
contact with humans. This may include a greater tendency 
to retreat when approached or attempts to snap or bite un-
der these circumstances. It has been reported by owners 
that dogs treated with corticosteroids tended to react ag-
gressively when petted or even approached, and that their 
dogs also appeared to be significantly more prone to avoid 
people or situations (34, 35, 36). It was also found that dogs 
receiving corticosteroids after being referred for behavioral 
Figure 1: The exact course of events that took place from the insertion of the implant to its removal
216  |  Slov Vet Res 2023  |  Vol 60 No 4
problems were significantly more likely to exhibit negative 
behavior compared to dogs not treated with these medi-
cations (33). Thus, aggressive behavior in this bitch could 
potentially be caused by treatment with corticosteroids. 
However, it should be mentioned that the bitch had been 
taking these medication for more than two years before im-
plantation of deslorelin and returned to her normal behavior 
after the implant was removed despite continued treatment 
with the same dose and type of corticosteroids.
In humans, it has recently been found that Addison’s dis-
ease can cause psychiatric symptoms that often accom-
pany the cardinal symptoms of adrenal insufficiency and 
are related to the severity of the disease (37). Therefore, un-
treated and uncontrolled Addison’s disease in dogs could 
cause similar problems and lead to aggressive behavior. 
However, as mentioned earlier, the bitch had been treated 
with medication for more than two years and was very well 
controlled. Because both corticosteroids and gonadecto-
my produce behavioral changes in some animals, it is pos-
sible that the corticosteroid treatment with the implant in-
creased the behavioral changes. Despite physiologic doses 
of corticosteroids used in this case such scenario can not 
be fully excluded. 
A possible mechanism to investigate may be that deslore-
lin treatment somehow stimulated minor adrenal function 
by stimulating ACTH-secreting neurons of the pituitary 
gland, thereby increasing adrenal cortisol production and 
causing a hyperadrenocortical state (due to concomitant 
exogenous corticosteroid administration). A recent article 
(13) reported the development of pituitary carcinoma caus-
ing a Cushing-like syndrome in a bitch chronically treated
with deslorelin for urinary incontinence. A relationship be-
tween the pituitary tumor and the clinical signs could not
be confirmed, but the possibility that deslorelin causes a
minor stimulation of the pituitary corticotrophs should not
be discounted. From this point of view, it would have been
interesting to know the status of Na-K balance in this bitch
during the period of increased aggressiveness, but we do
not have these data.
This case also raises the question of the risk of taking mul-
tiple endocrine drugs at the same time and their possible 
interactions on general health and behavior. Since inappro-
priate behavior is the most common cause of animals end-
ing up in shelters or abandoned by their owners, it is very 
important to inform owners before sterilization about pos-
sible behavioral side effects which, although rare, are irre-
versible following surgical gonadectomy. The use of GnRH 
agonist implants to determine the effects of gonad removal 
is therefore beneficial and strongly recommended for male 
dogs and cats, perhaps even prepubertal females, but we 
cannot say with certainty at this time that such treatment 
is also recommended for adult females, given all the report-
ed side effects. The veterinary profession should increase 
awareness about treatments that alter animal behavior and 
the importance of monitoring and reporting behavioral side 
effects as adverse events. Drug-drug interactions should 
be discussed more frequently, as they can affect the ef-
fectiveness of the medication and treatment, cause unex-
pected side effects, or enhance the effects of a particular 
medication.
Acknowledgements
Authors would like to thank owners for their cooperation.
Conflict of Interest: The authors declare that the research 
was conducted in the absence of any commercial or finan-
cial relationships that could be construed as a potential 
conflict of interest.
Author Contributions: Both authors contributed equally to 
this paper.
Funding: The authors acknowledge the financial support 
from the Slovenian Research Agency (research core fund-
ing No. P4-0053).
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218  |  Slov Vet Res 2023  |  Vol 60 No 4
Agresivno vedenje psice po vstavitvi implantata deslorelina
M. Zakošek Pipan, D. Pavlin
Izvleček: V veterinarski praksi so dolgo delujoči analogi gonadotropin-sproščujočega hormona (GnRH) široko sprejeta 
alternativa kirurški kastraciji psov. Uporabljajo se tudi pri psicah bodisi za supresijo ali indukcijo estrusa, pri čemer gre za 
neoznačeno uporabo zdravila. Pri uporabi dolgo delujočih analogov GnRH so pri psicah opazili vedenjske spremembe, 
kot so moško obnašanje, povečan apetit, rast mlečnih žlez, laktacija, navidezna brejost in urinska inkontinenca. Pri pasjih 
samcih pa se lahko v začetnem obdobju, ko implantat spodbudi izločanje testosterona, pojavlja agresivnost do drugih 
psov ali redko drugih živali.
Na naši kliniki smo obravnavali nesterilizirano, tri leta staro psico pasme koker španjel z diagnosticirano Addisonovo 
boleznijo. Lastniki so želeli nasvet glede možnosti kontracepcije, saj je pri psici v preteklih ciklusih prihajalo do navidezne 
brejosti in posledičnega mastitisa, ki je zahteval antibiotično zdravljenje. Lastniki so bili zadržani do kirurške sterilizaci-
je, zato so se odločili za vstavitev deslorelinskega implantata. Približno mesec dni kasneje so pri psici opazili začetek 
agresivnega vedenja, ki je vključevalo stalno lajanje, izjemno razdražljivost in agresijo do drugih psov ter do družinskih 
članov. Neželeno vedenje se je stopnjevalo do te mere, da lastniki niso mogli več obvladovati svoje psice. Po odstranitvi 
implantata je opažena agresija umirila, in psica se je vrnila v normalno stanje. 
Čeprav je agresivno vedenje do drugih psov in včasih tudi do lastnikov opisano po kirurški kastraciji ali vstavitvi deslo-
relinskega implantata pri psih, je ta prispevek prvi, ki opisuje izjemno agresivno vedenje do psov in lastnikov pri psici po 
vstavitvi 4,7 mg deslorelinskega implantata.
Ključne besede: psica; agresija; vedenje; deslorelinski implantat; dolgo delujoči GnRH