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Our recent study on the effects of neutering (including spaying) in Golden Retrievers in markedly increasing the incidence of two joint disorders and three cancers prompted this study and a comparison of Golden and Labrador Retrievers. Veterinary hospital records were examined over a 13-year period for the effects of neutering during specified age ranges: before 6 mo., and during 6-11 mo., year 1 or years 2 through 8. The joint disorders examined were hip dysplasia, cranial cruciate ligament tear and elbow dysplasia. The cancers examined were lymphosarcoma, hemangiosarcoma, mast cell tumor, and mammary cancer. The results for the Golden Retriever were similar to the previous study, but there were notable differences between breeds. In Labrador Retrievers, where about 5 percent of gonadally intact males and females had one or more joint disorders, neutering at <6 mo. doubled the incidence of one or more joint disorders in both sexes. In male and female Golden Retrievers, with the same 5 percent rate of joint disorders in intact dogs, neutering at <6 mo. increased the incidence of a joint disorder to 4-5 times that of intact dogs. The incidence of one or more cancers in female Labrador Retrievers increased slightly above the 3 percent level of intact females with neutering. In contrast, in female Golden Retrievers, with the same 3 percent rate of one or more cancers in intact females, neutering at all periods through 8 years of age increased the rate of at least one of the cancers by 3-4 times. In male Golden and Labrador Retrievers neutering had relatively minor effects in increasing the occurrence of cancers. Comparisons of cancers in the two breeds suggest that the occurrence of cancers in female Golden Retrievers is a reflection of particular vulnerability to gonadal hormone removal.
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Long-Term Health Effects of Neutering Dogs:
Comparison of Labrador Retrievers with Golden
Retrievers
Benjamin L. Hart
1
*, Lynette A. Hart
2
, Abigail P. Thigpen
2
, Neil H. Willits
3
1Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America,
2Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America,
3Department of Statistics, University of California Davis, Davis, California, United States of America
Abstract
Our recent study on the effects of neutering (including spaying) in Golden Retrievers in markedly increasing the incidence of
two joint disorders and three cancers prompted this study and a comparison of Golden and Labrador Retrievers. Veterinary
hospital records were examined over a 13-year period for the effects of neutering during specified age ranges: before 6 mo.,
and during 6–11 mo., year 1 or years 2 through 8. The joint disorders examined were hip dysplasia, cranial cruciate ligament
tear and elbow dysplasia. The cancers examined were lymphosarcoma, hemangiosarcoma, mast cell tumor, and mammary
cancer. The results for the Golden Retriever were similar to the previous study, but there were notable differences between
breeds. In Labrador Retrievers, where about 5 percent of gonadally intact males and females had one or more joint
disorders, neutering at ,6 mo. doubled the incidence of one or more joint disorders in both sexes. In male and female
Golden Retrievers, with the same 5 percent rate of joint disorders in intact dogs, neutering at ,6 mo. increased the
incidence of a joint disorder to 4–5 times that of intact dogs. The incidence of one or more cancers in female Labrador
Retrievers increased slightly above the 3 percent level of intact females with neutering. In contrast, in female Golden
Retrievers, with the same 3 percent rate of one or more cancers in intact females, neutering at all periods through 8 years of
age increased the rate of at least one of the cancers by 3–4 times. In male Golden and Labrador Retrievers neutering had
relatively minor effects in increasing the occurrence of cancers. Comparisons of cancers in the two breeds suggest that the
occurrence of cancers in female Golden Retrievers is a reflection of particular vulnerability to gonadal hormone removal.
Citation: Hart BL, Hart LA, Thigpen AP, Willits NH (2014) Long-Term Health Effects of Neutering Dogs: Comparison of Labrador Retrievers with Golden
Retrievers. PLoS ONE 9(7): e102241. doi:10.1371/journal.pone.0102241
Editor: Roger A. Coulombe, Utah State University, United States of America
Received March 5, 2014; Accepted June 17, 2014; Published July 14, 2014
Copyright: ß2014 Hart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Canine Health Foundation (#01488-A) and the Center for Companion Animal Health University of California, Davis (#
2009-54-F/M). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* Email: blhart@ucdavis.edu
Introduction
In the last three decades, the practice of spaying female dogs
and castrating males (both referred to herein as neutering) has
greatly increased. The current estimate is that in the U.S., 83
percent of all dogs are neutered [1] and, increasingly, neutering is
being performed prior to 6 mo., as advocated by many
veterinarians and animal activists. The impetus for this widespread
practice is presumably pet population control, and the belief that
mammary gland and prostate cancers are prevented and
aggressive male behavior is markedly less likely than in those
neutered later. This societal practice in the U.S. continues to
contrast with the general attitudes in many European countries,
where neutering is commonly avoided and not promoted by
animal health authorities [2–4].
In the last decade or so, studies have pointed to some of the
adverse effects of neutering in dogs on several long-term health
parameters by looking at one disease syndrome in one breed or in
pooling data from several breeds. With regard to cancers, a study
on osteosarcoma (OSA) in several breeds found a 2-fold increase in
neutered dogs relative to intact dogs [5], and in Rottweilers
neutering prior to 1 year of age was associated with an increased
occurrence of OSA to 3–4 times that of intact dogs [6].
A study of cardiac hemangiosarcoma (HSA) in spayed females
found that the incidence of this cancer was 4 times greater than
that of intact females [7] and another on splenic HSA in spayed
females found rates 2 times greater than of intact females [8]. A
study on lymphosarcoma (lymphoma, LSA) found that neutered
females had a higher incidence of the disease than intact females
[9]. Cutaneous mast cell tumors (MCT) were studied in several
dog breeds revealing an increase in incidence in neutered females
to 4 times that of intact females [10]. Another cancer of concern is
prostate cancer that, in contrast to humans, is potentiated by the
removal of testosterone. One extensive study found that this
cancer occurred in neutered males 4 times as frequently as in
intact males [11].
The most frequently mentioned advantage of early neutering of
female dogs is protection against mammary cancer (MC) [12].
However, a recent meta-analysis of published studies on neutering
females and MC found that the evidence linking neutering to a
reduced risk of MC is weak [13].
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Three very recent studies are particularly relevant in the
discussion of neutering and cancers. One was a comprehensive
study, from this center, on neutering in 759 Golden Retrievers
where males were compared with females and effects of neutering
were evaluated in early-neutered (,1 year), late-neutered (.1
year) and intact dogs [14]. Almost 10 percent of early-neutered
males were diagnosed with LSA, 3 times more than intact males.
There were no cases of MCT in intact females, but in late-
neutered females the rate was nearly 6 percent. The incidence of
HSA in late-neutered females was also higher than that of intact
females. The occurrence of MC was very low and was only seen in
a couple of late-neutered females.
A study utilizing the Veterinary Medical Database of over
40,000 dogs found that neutered males and females were more
likely to die of cancer than intact dogs, especially of OSA, LSA
and MCT [15]. This study included no information on age of
neutering. The most recent publication in this area is a study of
Vizslas utilizing owner-reported disease occurrence in an online
survey, in which the incidence of cancers was reported higher in
neutered dogs than in intact dogs [16]. The main cancers related
to neutering were LSA, HSA and MCT. The occurrence of MC
was very low in females left intact.
With regard to joint disorders, one study of effects of neutering
in larger breeds documents a 3-fold increase in excessive tibial
plateau angle – a known risk factor for development of cranial
cruciate ligament tears or rupture (CCL) [17]. Across several
breeds, a study of CCL found that neutered males and females
were 2 to 3 times more likely than intact dogs to have this disorder
[18]. Neither study examined early versus late neutering with
regard to this disorder. The study from this center of neutering in
Golden Retrievers (mentioned above with regard to cancers [14])
included examination of joint disorders. Of the early-neutered
males, 10 percent were diagnosed with hip dysplasia (HD), double
the occurrence of that in intact males. There were no cases of CCL
diagnosed in intact males or females, but in early-neutered males
and females the occurrences were 5 percent and 8 percent,
respectively.
One factor that merits attention with regard to the effects of
neutering on joint disorders relates to documented effects of
neutering in increasing body weight [19], as reflected in body
condition score (BCS). Additional weight on the joints is
considered to play a role in the onset of joint disorders [19,20].
While neutering is expected to increase BCS, the issue of concern
here is whether neutered dogs with a joint disorder have
consistently higher BCSs at the time of diagnosis than do neutered
dogs without the joint disorder in the same age range. In the
previous analyses on Goldens [14] there was no consistent and
major difference in BCS between early neutered dogs with and
without a joint disorder. For dogs diagnosed with a joint disorder,
some increase in BCS would be expected as a function of less
activity due to discomfort from painful joints. Therefore, a
modestly higher BCS was predicted for neutered dogs with a
joint disorder than in the neutered counterparts without a joint
disorder.
The above study on Golden Retrievers [14] raised a major
question about breed differences in the effects of neutering, which
are relevant for breeders and caregivers of puppies when deciding
if, and when, to neuter. A more basic issue concerns insights into
the possible pathogenic factors triggering the occurrence of the
cancers under consideration. The present study, using the same
veterinary hospital database, explored the effects of neutering on
joint disorders and cancers in the popular Labrador Retriever to
compare with the Golden Retriever, with an addition of several
years to the database. The age periods of neutering were refined as
,6 mo., 6–11 mo., 12–23 mo. (1 year), and 2 through 8 years to
provide more detailed information on the effects of gonadal
hormone removal. The Golden is known for being particularly
vulnerable to cancers [21], so we expected some major differences
from the Labrador where cancer-related deaths are less frequent
than in Goldens [21].
In addition to reporting on the incidence of the individual joint
disorders and cancers, a new slant on analyses in the present study
combined the incidence of all three joint disorders that have
shown evidence of being increased by neutering (HD, CCL, and
elbow dysplasia, ED) for one data-point representing the incidence
of dogs diagnosed with at least one of the joint disorders, after
controlling for multiple diagnoses. This analysis was based on the
perspective that for dog owners or breeders, avoidance of any of
the debilitating joint disorders would be of prime interest. This
analysis was also deemed logical for pathophysiological reasons
because a disruption of the growth plate closure by gonadal
hormone removal in the joint developmental stage would be
expected to apply to all the joint disorders. The study also
combined the incidence of dogs diagnosed with at least one of the
cancers (LSA, HSA, MCT) for one data point, after controlling for
multiple diagnoses, because for dog owners avoidance of any of the
cancers would be important. This analysis seemed logical, as there
may be a common factor involved in increasing these three
particular cancers in neutered dogs because these cancers are
repeatedly reported as being increased by neutering in several
studies.
Methods
Ethics Statement
No animal care and use committee approval was required
because, in conformity with campus policy, the only data used
were from retrospective veterinary hospital records. Upon
approval, faculty from the University of California, Davis
(UCD), School of Veterinary Medicine, are allowed use of the
record system for research purposes by the Veterinary Medical
Teaching Hospital (VMTH). The co-authors of this study were
given permission by the VMTH to use their veterinary hospital
records for this study.
Data Collection
The dataset used in this study was obtained from the
computerized hospital record system (Veterinary Medical and
Administrative Computer System) of the Veterinary Medical
Teaching Hospital (VMTH) at UCD. The subjects included were
gonadally intact and neutered female and male Labrador
Retrievers and Golden Retrievers, from 1 through 8 years of age
and admitted to the hospital between January 1, 2000 and
December 31, 2012, for 13 years of data. If a disease of interest
occurred before 12 months of age or before January 1, 2000, that
case was removed for that specific disease analysis, but included in
other disease analyses.
Data on patients at 9 years of age or older were not considered.
This was deemed an appropriate cut-off point in order to exclude
disease information on advanced-aged dogs where the effects of
aging would confound interpreting the disease effects related to
neutering. Additional inclusion criteria were requirements for
information on date of birth, age at neutering (if neutered) and age
of diagnosis (or onset of clinical signs) of the joint disorder or
cancer. The age at neutering was classified as ,6 mo., 6–11 mo.,
1 year (12 - ,24 mo.), and 2–8 years (2 - ,9 years). For all
neutered dogs, the neuter status at the time of each visit was
reviewed to ensure that neutering occurred prior to onset of the
Effects of Neutering in Labrador Retrievers and Golden Retrievers
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first clinical signs or diagnosis of any disease of interest. If a disease
of interest occurred before neutering, the diseased dog was
recorded as intact for that specific disease analysis. For the same
dog where a different disease occurred after neutering, the dog was
recorded as neutered for that disease analysis. Detailed reviews of
patient records were performed for evidence of disease occurrence
meeting specific diagnostic criteria (see below). Using this
screening, only diseases with at least 15 cases in the database
were included in the study.
For both breeds, many cases with neutering did not include
detailed data on age at neutering. With a very large database for
the Labrador, there was a sufficient number of dogs with these
data to restrict the analyses to cases for which the age at time of
neutering was available from the record system. For the Golden
with fewer cases, where additional neutering date information was
necessary, telephone calls to the referring veterinarians were made
to obtain the neutering dates for case patients born after 2000.
Because of the number of neutered dogs where age at neutering
was not available from either the record or by phone call, there
were proportionately more intact cases in the final data set than
would be expected in the population at large.
Golden Retriever cases with complete data for analyses totaled
1,015, with 543 males (315 neutered and 228 intact) and 472
females (306 neutered and 166 intact). Labrador Retriever cases
with complete data for analyses totaled 1,500 cases with 808 males
(272 neutered and 536 intact) and 692 females (347 neutered and
345 intact). The number of cases analyzed for each disease varied
somewhat among diseases because a case could be excluded for
one disease analysis, if the diagnosis was made prior to 1 year of
age, was unconfirmed, or was outside of study range, but would be
included for other diseases if no diagnosis was made or where the
diagnoses were confirmed after 1 year of age and within the study
range.
Table 1 defines the categories of diagnoses based on informa-
tion in the record of each case. A patient was considered as having
a disease of interest if the diagnosis was made at the VMTH or by
a referring veterinarian and later confirmed at the VMTH.
Patients diagnosed with HD, ED and/or CCL presented with
clinical signs such as difficulty moving, standing up, lameness,
and/or joint pain; diagnoses were confirmed with radiographic
evidence, orthopedic physical examination and/or surgical con-
firmation. Diagnoses of the various cancers (LSA, HSA, MCT,
MC) were accompanied by clinical signs such as enlarged lymph
nodes, lumps on the skin or presence of masses, and confirmed by
imaging, appropriate blood cell analyses, chemical panels,
histopathology and/or cytology. Pyometra was confirmed by
ultrasonic evidence and/or post-surgically after removal of the
uterus. When a diagnosis was listed in the record as ‘‘suspected’’
based on clinical signs, but the diagnostic tests were inconclusive,
the case was excluded from the analysis for that specific disease,
but included for other diseases.
The analyses used in Figures 1 and 2 portray single data-points
representing the incidence of dogs diagnosed with at least one joint
disorder or at least one cancer, after controlling for multiple
diagnoses. The data for incidence of individual joint disorders and
cancers are presented in Tables 2 through 5.
Given that body weights are difficult to compare among dogs
because of the confounding factor of variations in body height,
BCSs were used. The BCS system used by the VMTH is the
standard 1–9 range where a score of 5 is the goal [22]. Typically,
the clinician assigns the BCS at the time of a patient’s visit to the
hospital. For this study the BCSs at the time of diagnosis (or
clinical signs) of neutered dogs with joint disorders were compared
with BCSs of neutered dogs without the disorder at an age that fell
within the range representing 80 percent of the ages of dogs with
the disorder at the time of diagnosis. The BCSs were compared
between neutered dogs with and without joint disorders for the
disorders that were significantly increased in incidence over that of
intact dogs and for just the neuter periods where there were such
differences. For the few joint disorders associated with neutering at
one year or beyond, the BCSs were not included for comparison to
maintain uniformity across comparisons. The data are represented
as medians to reduce the impact of outliers.
Statistical Analyses
While the study set out to estimate incidence rates of each
disease related to age at neutering, patients were diagnosed at
different ages and with differing durations of the disease as well as
varying years at risk from the effects of gonadal hormone removal.
Cox proportional hazard models (CPH) [23,24] were used to test
for group differences with respect to the hazard of a disease while
adjusting for the time of neutering and the animal’s age at
diagnosis. All analyses were run using the SAS software package,
version 9.3. Post hoc comparisons among the subgroups were
based on least squares means of the hazard within each subgroup.
In the Results section the p-values were based on these
proportional hazard models. For all statistical tests the two-tailed
statistical level of significance was set at p,0.05.
Data Availability
In compliance with journal policy the final dataset used for
statistical analyses, with the client information removed for
confidentiality, is publically available at figshare.com: http://dx.
doi.org/10.6084/m9.figshare.1038819.
Results
With regard to joint disorders and cancers, the incidence rates
at various neuter ages were much more pronounced in the Golden
Retrievers than in the Labrador Retrievers. Therefore, results will
be presented first for the Golden, and then the Labrador, with the
two breeds contrasted. For joint disorders, BCSs are reported for
those that differed significantly from the intact dogs, only for the
neuter periods where the differences occurred. The mean age of
diagnosis of joint disorders and cancers for each sex and breed is
given to the nearest 0.5 years.
Golden Retriever Males: Joint Disorders
Figure 1-A presents the incidence of dogs having at least one of
the joint disorders. The incidence of at least one joint disorder
occurring in intact males was 5 percent. At neuter age ,6 mo., at
least one of the joint disorders occurred in 27 percent of the males,
or five times the incidence of intact males (p,0.0001). At neuter
age 6–11 mo., this incidence was 14 percent or almost three times
that of intact males (p,0.005). In the 2–8 year neutering period
there was a moderate rise in this measure to double that of intact
males (p= 0.02).
As shown in Figure 1-A and in Table 2, the main joint disorder
related to neutering in males was HD, which was significantly
higher than that of intact males for the ,6 mo. and 6–11 mo.
neuter periods (p,0.001; p,0.05, respectively). The mean age of
diagnosis of HD in males was 4 years. The other important joint
disorder was CCL, which was never diagnosed in intact males, and
was significantly higher than intact males in the ,6 mo. and 6–
11 mo. neuter periods (p,0.001; p= 0.004, respectively). The
mean age of diagnosis of this joint disorder in males was 5 years. In
this breed the occurrence of ED was relatively minor compared
with the other joint disorders and not significantly above that of
Effects of Neutering in Labrador Retrievers and Golden Retrievers
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intact males for any neuter period. When it did occur, mean age of
diagnosis of ED was 2.5 years.
The median BCS of neutered males with HD was 6.0, and the
median BCS of neutered males without HD was 5.5. In intact
males with and without HD the median BCS was 5. For neutered
males with CCL, the median BCS was 5.5 and for neutered males
without CCL, 6.0. In intact males without CCL the median BCS
was 5.0.
Golden Retriever Males: Cancers
Figure 2-A presents the incidence in dogs having at least one of
the cancers followed. The level in the intact males was 11 percent.
At neuter ages ,6 mo. and 6–11 mo. the occurrence of one or
more cancers was 15–17 percent, but not significantly different
than intact males. However, as Table 3 reveals, the main cancer
elevated by neutering in males, LSA, reached 11.5 percent at the
6–11 mo. period, significantly higher than the 4 percent level of
intact males (p= 0.007). The mean age of diagnosis of LSA in
males was 5.5 years.
Golden Retriever Females: Joint Disorders
Figure 1-A portrays the incidence of dogs having at least one of
the joint disorders at different neuter periods. The incidence of at
least one joint disorder occurring in intact females was 5 percent,
virtually the same as males. At neuter age ,6 mo. at least one of
the joint disorders occurred in 20 percent of dogs, four times that
of the intact females (p,0.001). At the 6–11 mo. neuter age, 13
percent had at least one joint disorder, which was over twice that
of intact females, but did not reach significance.
As shown in Table 2, the main joint disorders related to
neutering females at the ,6 mo. period were HD and CCL,
occurring at 10–11 percent. The occurrence of HD did not reach
significance compared with intact females (4 percent), but CCL,
which was not seen in any of the intact females, was significantly
higher at the ,6 mo., 6–11 mo. and 2–8 year neuter periods (p,
0.001 to p= 0.03). The mean age of diagnosis of CCL in females
was 5.5 years. As with males, the occurrence of ED in neutered
females was not significant over that of intact females. The mean
age of diagnosis of ED in females, when it did occur, was 1.5 years.
The median BCS of neutered females with CCL was 6.0 and
the median BCS of the neutered females without CCL was 5.5. In
intact females without CCL the median BCS was 5.0.
Golden Retriever Females: Cancers
Figure 2-A presents the incidence of females having at least one
of the cancers where the incidence of cancers in intact females was
just 3 percent. The increase in cancers over all the neuter periods
ranged from 8 to 14 percent. Combining all of the neuter periods
beyond 6 mo. (to have a larger data set for analyses), the elevated
incidence level across all these neuter periods was significantly
higher than that of intact females (p= 0.049). The results reveal
that neutering through 8 years of age increases the risk of
acquiring at least one of the cancers to a level 3–4 times that of
leaving the female dog intact.
Examination of Table 3 shows that the main cancer resulting
from neutering females at ,6 mo. and 6–11 mo. was LSA where
at 6–11 mo. the increased risk over that of intact females reached
significance (p= 0.014). The mean age of diagnosis of LSA in
females was 5.5 years. The main cancer that was increased at the
2–8 year period of neutering was MCT (p= 0.013). The
occurrence of HSA, although increased by neutering beyond 1
year, did not reach significance over intact females. The mean age
of diagnosis of both MCT and HSA in females was 6.5 years.
The occurrence of MC was not seen in any of the intact females.
This cancer was seen only in dogs neutered in the 2–8 year period
where the incidence was 3.5 percent. The occurrence of pyometra
in intact females was 1.8 percent, which was diagnosed at the
mean age of 6 years.
Labrador Retriever Males: Joint Disorders
Figure 1-B illustrates the incidence of males having at least one
of the joint disorders. The only neuter period where this measure
was significantly increased above the 5 percent level of intact
males, was at ,6 mo., where this measure was 12.5 percent
(p= 0.014). Examining the joint disorders individually (Table 4),
HD was not increased by neutering at any time. However, at the
,6 mo. neuter period, both CCL and ED were significantly
increased over that of intact males (p= 0.02; 0.02). For ED, there
was a moderate increased risk with the 2–8 year neuter period to
about 2 percent compared with the low 0.57 percent incidence in
intact males (p= 0.006). The mean age of diagnosis of ED in males
was 3 years, considerably less than that for CCL, which was 4.5
years.
The median BCS of neutered males with CCL was 6.0 and the
median BCS of the neutered males without CCL was 5.0. In intact
males with CCL the median BCS was 6.0 and for intact males
without CCL the median BCS was 5. The median BCS of
neutered males with ED was 6.5 and the median BCS of the
neutered males without ED was 5.0. In intact males with and
without ED the BCS was 5.0.
Table 1. Categories used in determining diagnosis for joint disorders and cancers of interest in Golden Retrievers and Labrador
Retrievers (1–8 years old) admitted to the Veterinary Medical Hospital, University of California, Davis, from 2000–2012.
Classification Definition
No disease No evidence of a joint disorder or cancer of interest in the medical records
VMTH Diagnosed at the VMTH
Referring Veterinarian/VMTH Diagnosed by referring veterinarian and confirmed at the VMTH through treatment or further testing
Referring Veterinarian Diagnosed by referring veterinarian but no confirming diagnostic tests done at the VMTH. Unconfirmed cases
were excluded from analysis for the specific joint disorder or cancer
Invalid (suspected) Diagnosis was suspected based on clinical signs, but diagnostic tests were inconclusive or not done. Unconfirmed
cases were excluded from analysis for the suspected joint disorder or cancer
Invalid (confirmed) Diagnosed prior to January 2000 or before 1 year of age. Invalid cases were excluded from analysis for the specific
joint disorder or cancer.
doi:10.1371/journal.pone.0102241.t001
Effects of Neutering in Labrador Retrievers and Golden Retrievers
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Figure 1. Incidence of the occurrence of at least one joint disorder in male and female Golden Retrievers (top) and Labrador
Retrievers (bottom), as a function of age at neutering. The occurrences in intact males and females for the same measure are shown by the
horizontal lines. The asterisks indicate significance from the intact level, and the abbreviations reveal the joint disorders contributing to the dots
when significant.
doi:10.1371/journal.pone.0102241.g001
Effects of Neutering in Labrador Retrievers and Golden Retrievers
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Figure 2. Incidence of the occurrence of at least one cancer in male and female Golden Retrievers (top) and Labrador Retrievers
(bottom), as a function of age at neutering. The occurrences in intact males and females for the same measures are shown by the horizontal
lines. The asterisks indicate significance from the intact level, and the abbreviations reveal the cancers contributing to the dots when significant.
doi:10.1371/journal.pone.0102241.g002
Effects of Neutering in Labrador Retrievers and Golden Retrievers
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Labrador Retriever Males: Cancers
The underlying rate of intact males having at least one of the
cancers was 4.6 percent. Neutering at any age period had virtually
no effect on this measure of cancer occurrence above the level of
intact males (Figure 2-B and Table 5).
Labrador Retriever Females: Joint Disorders
As portrayed in Figure 1-B, at neuter periods ,6 mo. and 6–
11 mo. the risk of dogs having at least one of the joint disorders
increased to about double the 5 percent level of intact females
(p= 0.044; 0.043). In contrast to male Labradors, the females
seemed to be vulnerable to the effects of early neutering on HD
but not on ED. The neutering effects on HD were evident through
1 year, where the incidence was 4–5 percent compared to 1.5
percent in intact females (Table 4) (p= 0.02–0.046). The mean age
of diagnosis of HD was 3.5 years, and for ED, 2.5 years. As in male
Labradors, CCL in females was increased by early neutering, but
in this sex, not significantly so. The mean age of diagnosis of CCL
in females was 5.5 years.
The median BCS of neutered females with HD was 5.5, and the
median BCS of neutered females without HD was 5.5. In intact
females with HD the median BCS was 7 and for those without HD
the median BCS was 5.0.
Labrador Retriever Females: Cancers
As seen in Figure 2-B, the underlying rate of intact females
having at least one cancer of those tracked was 3.2 percent, close
to that of males. In contrast to female Goldens, the only increase in
the incidence of dogs having at least one cancer, was with the 2–8
year neuter period where the incidence was modestly increased to
5.6 percent (p= 0.03), a reflection of the increased occurrence of
LSA and MCT (Table 5). The mean age of diagnosis of these two
cancers in females was 5.5 and 6.5 years, respectively.
With regard to MC, only 1.4 percent of the intact females were
diagnosed with MC. With the 2–8 year neuter period MC was
diagnosed in 2 percent of females. Pyometra was diagnosed in just
less than 4 percent of intact females. The mean age of diagnosis of
pyometra was 5.5 years.
Discussion
Both the Golden Retriever and Labrador Retriever are very
popular breeds that have found wide acceptance as family pets and
Table 2. Golden Retriever males and females, joint disorders.
HD CCL ED
Male ,6 months 11/75 (14.67) 8/89 (8.99) 5/84 (5.95)
Male 6–11 months 9/113 (7.96) 4/123 (3.25) 4/116 (3.45)
Male 1 year 1/38 (2.63) 0/41 (0) 0/38 (0)
Male 2–8 years 4/55 (7.27) 2/59 (3.39) 0/59 (0)
Male Intact 9/221 (4.07) 0/226 (0) 5/222 (2.25)
Female ,6 months 9/92 (9.78) 11/101 (10.89) 0/97 (0)
Female 6–11 months 4/79 (5.06) 4/81 (4.94) 3/81 (3.7)
Female 1 year 0/30 (0) 0/32 (0) 1/30 (3.33)
Female 2–8 years 4/86 (4.65) 3/89 (3.37) 0/88 (0)
Female Intact 6/163 (3.68) 0/165 (0) 2/164 (1.22)
For ages 1 through 8 years, for each neuter period, the joint disorders are: hip dysplasia (HD), cranial cruciate ligament tear or rupture (CCL), and elbow dysplasia (ED).
Shown are number of cases over number in the pool, with percentages given in parentheses. When bolded the incidence is significantly above that of intact dogs.
doi:10.1371/journal.pone.0102241.t002
Table 3. Golden Retriever males and females, cancers.
LSA MCT HSA
Male ,6 months 6/89 (6.74) 3/90 (3.33) 5/90 (5.56)
Male 6–11 months 14/122 (11.48) 4/124 (3.23) 2/122 (1.64)
Male 1 year 0/41 (0) 1/40 (2.5) 1/39 (2.56)
Male 2–8 years 0/58 (0) 2/60 (3.33) 0/59 (0)
Male Intact 9/226 (3.98) 8/225 (3.56) 8/220 (3.64)
Female ,6 months 4/98 (4.08) 3/102 (2.94) 1/102 (0.98)
Female 6–11 months 9/82 (10.98) 1/81 (1.23) 1/79 (1.27)
Female 1 year 2/32 (6.25) 1/32 (3.13) 1/32 (3.13)
Female 2–8 years 1/84 (1.19) 5/88 (5.68) 2/84 (2.38)
Female Intact 3/166 (1.81) 0/165 (0) 2/165 (1.21)
For ages 1 through 8 years, for each neuter period, the cancers are: lymphosarcoma (LSA), mast cell tumor (MCT), and hemangiosarcoma (HSA). Shown are number of
cases over number in the pool, with percentages given in parentheses. When bolded the incidence is significantly above that of intact dogs.
doi:10.1371/journal.pone.0102241.t003
Effects of Neutering in Labrador Retrievers and Golden Retrievers
PLOS ONE | www.plosone.org 7 July 2014 | Volume 9 | Issue 7 | e102241
as service dogs for those with disabilities. The two breeds are
similar in body size, conformation and in behavioral character-
istics [25], and they share a similar developmental background as
upland game retrievers. Using the same database and methodol-
ogy, the two breeds were contrasted with regard to the effects of
neutering on three joint disorders (HD, CCL, ED) and three
cancers (LSA, HSA, MCT). In addition to reporting the
occurrence of the three joint disorders and the three cancers, an
analysis of cases with at least one of the joint disorders, or at least
one of the cancers, was plotted graphically (Figures 1 and 2). The
findings on the Golden Retriever closely resemble the picture
presented in the earlier study drawn from this same database with
a somewhat smaller data set [14].
The present study reveals that the breeds respond very
differently to the effects of neutering on joint disorders and certain
devastating cancers. With regard to the occurrence of one or more
joint disorders, in Golden Retrievers, neutering at ,6 mo. resulted
in an incidence of 27 percent in males and 20 percent in females,
4–5 times the 5 percent level for intact males and females. In male
and female Labrador Retrievers, with the same underlying
occurrence of joint disorders in intact dogs, neutering at ,6 mo.
resulted in an incidence of 11–12 percent for one or more joint
disorders, roughly double that of intact males and females. Thus,
for both breeds, neutering at the standard ,6 mo. period
markedly and significantly increased the occurrence of joint
disorders, although the increase was worse in the Golden than the
Labrador. A difference in the specific joints affected was that in
male Goldens HD and CCL were mostly increased, but in male
Labradors CCL and ED were increased. The effects of neutering
in the first year of a dog’s life, especially in larger breeds,
undoubtedly reflects the vulnerability of joints to delayed closure of
long-bone growth plates from gonadal hormone removal [26,27].
Differences in the two breeds studied here could be due to
differences in sensitivities of the growth plates to gonadal hormone
removal.
The BCSs in neutered dogs with the different joint disorders
were compared with neutered dogs without the joint disorders.
Although dogs with the disorders were expected to have a
modestly higher BCS as a function of reduced activity from painful
joints, the issue of concern was if those with a joint disorder had a
consistently and markedly higher BCS than comparable neutered
dogs without a joint disorder. The BCS comparisons revealed
variable differences, in the range of 0.5 to 1.0 (except for ED in
male Labradors where the difference was 1.5). The general picture
Table 4. Labrador Retriever males and females, joint disorders.
HD CCL ED
Male ,6 months 0/48 (0) 4/53 (7.55) 2/48 (4.17)
Male 6–11 months 1/68 (1.47) 2/72 (2.78) 0/67 (0)
Male 1 year 1/50 (2.00) 1/52 (1.92) 0/49 (0)
Male 2–8 years 0/92 (0) 0/93 (0) 2/93 (2.15)
Male Intact 9/528 (1.7) 12/531 (2.26) 3/525 (0.57)
Female ,6 months 3/56 (5.36) 3/59 (5.08) 1/57 (1.75)
Female 6–11 months 5/99 (5.05) 5/101 (4.95) 0/103 (0)
Female 1 year 2/47 (4.26) 0/50 (0) 0/50 (0)
Female 2–8 years 0/131 (0) 1/128 (0.78) 0/132 (0)
Female Intact 6/345 (1.74) 8/343 (2.33) 4/343 (1.17)
For ages 1 through 8 years, for each neuter period, the joint disorders are: hip dysplasia (HD), cranial cruciate ligament tear or rupture (CCL), and elbow dysplasia (ED).
Shown are number of cases over number in the pool, with percentages given in parentheses. When bolded the incidence is significantly above that of intact dogs.
doi:10.1371/journal.pone.0102241.t004
Table 5. Labrador Retriever males and females, cancers.
LSA MCT HSA
Male ,6 months 0/52 (0) 2/53 (3.77) 0/53 (0)
Male 6–11 months 0/72 (0) 0/73 (0) 1/73 (1.37)
Male 1 year 1/52 (1.92) 0/51 (0) 1/51 (1.96)
Male 2–8 years 0/93 (0) 2/89 (2.25) 1/93 (1.08)
Male Intact 4/530 (0.75) 12/533 (2.25) 7/531 (1.32)
Female ,6 months 0/59 (0) 0/60 (0) 0/60 (0)
Female 6–11 months 0/104 (0) 2/103 (1.94) 0/104 (0)
Female 1 year 0/49 (0) 1/50 (2) 0/50 (0)
Female 2–8 years 2/131 (1.53) 5/126 (3.97) 0/133 (0)
Female Intact 4/342 (1.17) 6/344 (1.74) 1/345 (0.29)
For ages 1 through 8 years, for each neuter period, the cancers are: lymphosarcoma (LSA), mast cell tumor (MCT), and hemangiosarcoma (HSA). Shown are number of
cases over number in the pool, with percentages given in parentheses. When bolded the incidence is significantly above that of intact dogs.
doi:10.1371/journal.pone.0102241.t005
Effects of Neutering in Labrador Retrievers and Golden Retrievers
PLOS ONE | www.plosone.org 8 July 2014 | Volume 9 | Issue 7 | e102241
of BCSs of neutered dogs with joint disorders being usually, but
not always, a bit higher than the BCSs of neutered dogs without
joint disorders, is consistent with the perspective that the increase
in joint disorders in neutered dogs is primarily due to the effect of
gonadal hormonal removal on bone growth plates and not to
greater weight on the joints.
Data on the effects of neutering on the occurrence of cancers in
the two breeds also reveal important breed differences. In both
breeds the occurrence of one more cancers in intact dogs ranged
from 3 to 5 percent, except for Golden Retriever males where the
level in intact dogs was 11 percent. In Golden Retriever females
neutering females at any neuter period beyond 6 months elevated
the risk of one or more cancers to 3 to 4 times the level of intact
females (Figure 2). In male Golden Retrievers neutering appeared
to have little effect in the occurrence of one or more of the three
cancers. An exception was LSA that was increased significantly at
the ,6 mo. period. In both male and female Labrador Retrievers,
neutering at any period appeared to have little effect in increasing
cancers.
The striking effect of neutering in female Golden Retrievers
compared to male and female Labradors, and male Golden
Retrievers, suggests that for this gender and breed the presence of
gonadal hormones has a protective effect against cancers over
most years of the dog’s life. This may reflect a particular sensitivity
of receptor sites of some potentially metastatic cancer cells to
gonadal hormone removal and/or prolonged levels of the
gonadotropin hormone, follicle stimulating hormone [28]. Go-
nadotropin receptors have been identified in some extragonadal
tissues. For example, in the dog these receptor sites have been
found in the skin [29] and urinary tract [30]. Treatment of one or
more of these cancers by a receptor-site blocking agent may be
worth exploring. The relatively high occurrence of one or more of
these cancers in intact male Goldens, coupled with the relative
absence of an effect of neutering, except with regard to LSA,
points to a relatively high underlying rate of cancer occurrence in
this gender and breed that is not affected by gonadal hormone
removal.
The findings presented here are clinically relevant in two
realms. For dog owners of the popular Golden Retrievers and
Labrador Retrievers, the study points to the importance of
acquiring information needed to decide if, and when, to neuter.
Aside from avoiding increased risks of joint disorders and cancers,
there is an indication that age-related cognitive decline could be
accelerated by neutering [31]. This is particularly relevant for
service dogs where active cognition is important for the expected
tasks.
The findings of this study also have important implications for
investigators looking for canine models for research on various
forms of cancer [32,33]. For some cancers of interest, not only may
breeds vary in predisposition but also the possibility of interactions
between gender, gonadal hormone influences, and timing of
gonadal hormone alteration should be taken into account in
selecting the model and in investigating causal factors to be
explored.
Acknowledgments
Special thanks are extended to Marty Bryant, Cristina Bustamante, Valerie
Caceres, Madeline Courville, Siobhan Aamoth and Roger Pender.
Author Contributions
Conceived and designed the experiments: BLH LAH. Performed the
experiments: APT BLH LAH. Analyzed the data: NHW APT BLH LAH.
Wrote the paper: BLH LAH APT. Edited manuscript: NHW.
References
1. Trevejo R, Yang M, Lund EM (2011) Epidemiology of surgical castration of
dogs and cats in the United States. J Am Vet Med Assoc 238: 898–904.
2. Sallander M, Hedhammer A, Rundgren M, Lindberg JE (2001) Demographic
data of population of insured Swedish dogs measured in a questionnaire study.
Acta Vet Scand 42: 71–80.
3. Kubinyi E, Turcsan B, Miklosi A (2009) Dog and owne r demographic
characteristics and dog personality trait associations. Behav Processes 81: 392–
401.
4. Diesel G, Brodbelt D, Laurence C (2010) Survey of veterinary practice policie s
and opinions on neutering dogs. Vet Rec 166: 455–458.
5. Ru G, Terracini B, Glickman LT (1998) Host related risk factors for canine
osteosarcoma. Vet J 156:31–39.
6. Cooley DM, Beranek BC, Schlittler DL, Glickman MW, Glickman LT, et al.
(2002) Endogenous gonadal hormone exposure and bone sarcoma risk. Cancer
Epidemiol Biomarkers Prevent 11: 1434–1440.
7. Ware WA, Hopper DL (1999) Cardiac tumors in dogs: 1982–1995. J Vet Intern
Med 13: 95–103.
8. Prymak C, McKee LJ, Goldschmidt MH, Glickman LT (1988) Epidemiologic,
clinical, pathologic, and prognostic characteristics of splenic hemangiosarcoma
and splenic hematoma in dogs: 217 cases (1985). J Am Vet Med Assoc 193: 706–
712.
9. Villamil JA, Henry CJ, Hahn AW, Bryan JN, Tyler JW, et al. (2009) Hormonal
and sex impact on the epidemiology of canine lymphoma. J Cancer Epidemiol
2009: 1–7. doi:10.1155/2009/591753
10. White CR, Hohenhaus AE, Kelsey J, Procter-G rey E (2011) Cutaneous MCTs:
Associations with spay/neuter status, breed, body size, and phylogenetic cluster.
J Am Anim Hosp Assoc 47: 210–216.
11. Teske E, Naan EC, van Dijk E, Van Garderen E, Schalken JA (2002) Canine
prostate carcinoma: epidemiological evidence of an increased risk in castrated
dogs. Mol Cell Endocrinol 197: 251–255.
12. Root Kustritz MV (2007) Determining the optimal age for gonadectomy of dogs
and cats. J Am Vet Med Assoc 231: 1665–1675.
13. Beauvais W, Cardwell JM, Brodbelt DC (2012) The effect of neutering on the
risk of mammary tumours in dogs – a systematic review. J Small Anim Pract 53:
314–322.
14. Torres de la Riva G, Hart BL, Farver TB, Oberbauer AM, McV Messam LL, et
al. (2013) Neutering Dogs: Effects on Joint Disorders and Cancers in Golden
Retrievers. PLOS ONE 2013; 8(2): e55937. doi:10.1371/journal.pone.0055937
15. Hoffman JM, Creevy KE, Promislow DEL (2013) Reproductive capability is
associated with lifespan and cause of death in companion dogs. PLOS ONE
2013; 8(4): e6 1082. doi: 10.1371/journal.pone.0061082
16. Zink MC, Farhoody P, Elser SE, Ruffini LD, Gibbons TA, et al. (2014)
Evaluation of the risk and age of onset of cancer and behavioral disorders in
gonadectomized Vizslas. J Am Vet Med Assoc 244: 309–319.
17. Duerr FM, Duncan CG, Savicky RS, Park RD, Egger EL, et al. (2007) Risk
factors for excessive tibial plateau angle in large-breed dogs with cranial cruciate
disease. J Am Vet Med Assoc 231: 1688–1691.
18. Witsberger TH, Villamil JA, Schultz LG, Hahn AW , Cook JL (2008) Prevalence
of, and risk factors for, hip dysplasia and cranial cruciate ligament deficiency in
dogs. J Am Vet Med Assoc 232: 1818–1824.
19. Dobson JM (2013) Breed-predispositions to cancer in pedigree dogs. Vet Sci
2013: 1–23.
20. Kasstro¨m H (1975) Nutrition, weight gain and development of hip dysplasia. An
experimental investigation in growing dogs with special reference to the effect of
feeding intensity. Acta Radiologica 344: 135–179, Supplementum.
21. Duval JM, Budsberg SC, Flo GL, Sammarco Jl (1999) Breed, sex, and body
weight as risk factors for rupture of the cranial cruciate ligament in young dogs.
J Am Vet Med Assoc 215: 811–814.
22. Baldwin K, Bartges J, Buffington T, Freeman LM, Grabow M, et al. (201 0)
AAHA nutritional assessment guidelines for dogs and cats. J Am Anim Hosp
Assoc 46: 285–296.
23. Cox DR (1972) Regression models and life tables (with discussion). Journal of the
Royal Statistical Society, series B, 34: 187–220.
24. Rothman KJ, Greenland S (1998) Modern Epidemiology. Philadelphia:
Lippincott Williams & Wilkins.
25. Hart BL, Hart LA (1988) The Perfect Puppy. How to Choose Your Dog by Its
Behavior. New York: W.H. Freeman and Co.
26. Salmeri KR, Bloomberg MS, Scruggs SL, Shille V (1991) Gonadectomy in
immature dogs: Effects on skeletal, physical, and behavioral development. J Am
Vet Med Assoc 198: 1193–1203.
27. Grumbach M (2000) Estrogen, bone growth and sex: a sea of change in
conventional wisdom. J Ped Endocrinol Metab 13: 1439–1455.
28. Concannon PW (1993). Biology of gonadotrophin secretion in adult and
prepubertal female dogs. J Reprod Fert Supp 47: 3–27.
29. Reichler IM, Welle M, Eckrich C, Sattler U, Barth A, et al. (2008) Spaying-
induced coat changes: the role of gonadotropins, GnRH and GnRH treatment
on the hair cycle of female dogs. Vet Dermatol 19: 77–87.
Effects of Neutering in Labrador Retrievers and Golden Retrievers
PLOS ONE | www.plosone.org 9 July 2014 | Volume 9 | Issue 7 | e102241
30. Fields MJ, Shemesh M (2004) Extragonadal luteinizing hormone receptors in the
reproductive tract of domestic animals. Biol Reprod 71: 1412–1418.
31. Hart BL (2001) Effects of gonadectomy on subsequent development of age-
related cognitive impairment in dogs. J Am Vet Med Assoc 219: 51–56.
32. Vail DM, MacEwen EG (2002) Spontaneously occurring tumors of companion
animals as models for human cancer. Cancer Invest 18: 781–792.
33. Khanna C, Lindblad-Toh K, Vail D, London C, Bergman P, et al. (2006) The
dog as a cancer model. Nat Biotechnol 24: 1065–1066.
Effects of Neutering in Labrador Retrievers and Golden Retrievers
PLOS ONE | www.plosone.org 10 July 2014 | Volume 9 | Issue 7 | e102241
... Bitches spayed early (before 6 months of age) were found to have a 20% incidence of at least one of the orthopaedic disorders (hip dysplasia, elbow dysplasia, and cranial cruciate ligament rupture) was seen in a sample of 472 Golden Retriever females. In contrast, only a 5% prevalence was found in intact Golden Retriever females (Hart et al., 2014). Bitches spayed early (before 6 months of age) were found to have a 20% incidence of at least one of the orthopaedic disorders (hip dysplasia, elbow dysplasia, and cranial cruciate ligament rupture) which was seen in a sample of 472 Golden Retriever females. ...
... A study of 58 dogs with tibial plateau angle higher than 35 degrees plateau and 58 control dogs, found out that dogs from case group were more likely to have been spayed prior to six months of age (Duerr et al., 2007;Griffon et al., 2010). In addition, a study on Golden Retrievers found that spayed females were at substantially higher risk of cranial cruciate ligament rupture (Hart et al., 2014). ...
... Furthermore, in a study that included 339 female Golden Retrievers with hip dysplasia no association was found between female sterilisation and hip dysplasia (Torres de la Riva et al., 2013). A report by Hart et al. in 2014 showed that the association between the incidence of hip dysplasia and spaying wasn't compelling. ...
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