KNOWLEDGE SUMMARY
Keywords: CANINE; CRUCIATE LIGAMENT; DOGS; EARLY GONADECTOMY; EARLY NEUTERING; RISK
Does early gonadectomy increase the risk of cranial cruciate ligament disease in female dogs?
Daniel Low, BVetMed MRCVS1*
1 Frank. Pet Surgeons, Leeds, LS10 1AG, United Kingdom
* Corresponding author email: daniel.kuan.chong.low@gmail.com
Vol 9, Issue 2 (2024)
Submitted 27 Feb 2023; published: 25 Apr 2024; next review: 12 Nov 2025
DOI: https://doi.org/10.18849/ve.v9i2.678
PICO question
In bitches, does gonadectomy before 1 year of age compared to gonadectomy at 1 year of age or older, increase the risk of cranial cruciate ligament disease during their life?
Clinical bottom line
Category of research
Risk.
Number and type of study designs reviewed
Eight studies were reviewed, four of which were retrospective cohort studies, two of which were prospective longitudinal cohort studies, one of which was a retrospective case-control study and one of which was a prospective case-control study.
Strength of evidence
Moderate.
Outcomes reported
The evidence was mixed, but overall was suggestive that gonadectomy before 1 year of age increased the risk of cranial cruciate ligament disease in bitches. Gonadectomy before 1 year of age was found to increase the risk of cranial cruciate ligament disease in seven of eight studies. Most studies assessed a narrow range of breeds and the generalisability of these results to all dogs is thus limited. The one study which assessed a range of 35 breeds noted an increase in risk of cranial cruciate ligament disease in 6 of 35 breeds associated with gonadectomy before 1 year of age. Direct comparison of studies is limited by the varying age stratifications, breed analyses, and study methodologies.
Conclusion
Gonadectomy before 1 year of age in Golden Retriever, German Shepherd, and Rottweiler bitches may increase the risk of cranial cruciate ligament disease. In other breeds, limited evidence is available to draw conclusions.
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Clinical scenario
You are a veterinary surgeon in first opinion practice conducting a health check and vaccination of a female puppy. You take the opportunity to discuss various aspects of routine and preventative healthcare with the clients, including gonadectomy. The client has read online that gonadectomy causes cranial cruciate ligament disease (CCLD) and is seeking your professional opinion on the matter.
The evidence
Eight studies relevant to the PICO question were reviewed (Ekenstedt et al., 2017; Hart et al., 2014; Hart et al., 2016; Hart et al., 2020; Simpson et al., 2019; Torres de la Riva et al., 2013; Whitehair et al., 1993; and Waters et al., 2023). Overall, the strength of evidence is of moderate quality, due to limitations in study design and methodologies.
Summary of the evidence
Ekenstedt et al. (2017)
Population: |
Labrador Retrievers presenting to one of four specialty referral hospitals in North America between 2010 and 2011. |
---|---|
Sample size: |
313 Labrador Retrievers, of which 168 were female Labrador Retrievers (83 neutered at or before 1 year of age, 25 neutered after 1 year of age, 60 intact). |
Intervention details: |
174 Labrador Retrievers were recruited as cranial cruciate ligament disease (CCLD) cases and 139 Labrador Retrievers were recruited as controls (no CCLD). Data collected included:
Fisher’s exact test was used. |
Study design: |
Prospective case-control study. |
Outcome studied: |
Primary outcome studied: association between presence of DNM1 and CCLD. |
Main findings |
|
Limitations: |
|
Hart et al. (2014)
Population: |
Labrador Retrievers and Golden Retrievers who presented to the University of California-Davis, Veterinary Medical Teaching Hospital, between 1 January, 2000 and 31 December, 2012. |
---|---|
Sample size: |
1015 Golden Retrievers, of which 472 female Golden Retrievers (306 neutered, 166 intact). 1500 Labrador Retrievers, of which 692 female Labrador Retrievers (347 neutered, 345 intact). |
Intervention details: |
Data collected included:
A Cox proportional hazards model was applied, with CCLD tear as the outcome. Timing of gonadectomy within the gonadectomised group was not reported. A case may be included in the intact group if disease occurred before gonadectomy and may then be included in the gonadectomised group if disease occurred after gonadectomy. |
Study design: |
Retrospective cohort study. |
Outcome studied: |
Age at gonadectomy and risk of CCLD, hip dysplasia, elbow dysplasia, lymphoma, haemangiosarcoma, mast cell tumour, and mammary cancer compared to control population of intact dogs of a specific breed. |
Main findings |
Golden Retrievers
Labrador Retrievers
|
Limitations: |
|
Hart et al. (2016)
Population: |
German Shepherd dogs who presented to the University of California-Davis, Veterinary Medical Teaching Hospital between 1 January, 2000 and 30 June, 2014. |
---|---|
Sample size: |
1170 dogs, of which 705 male and 465 female. Of the 465 females, 293 were neutered and 172 were intact. |
Intervention details: |
Data was collected from the computerised medical records at the University of California-Davis, Veterinary Medical Teaching Hospital. Data collected included:
A Cox proportional hazards model, or Kaplan-Meier life table analysis if the former was not applicable, was applied, with CCLD tear as the outcome. Timing of gonadectomy within the gonadectomised group was not reported. A case may be included in the intact group if disease occurred before gonadectomy and may then be included in the gonadectomised group if disease occurred after gonadectomy. |
Study design: |
Retrospective cohort study. |
Outcome studied: |
To determine the effect of a single IV injection of paracetamol on the MAC of sevoflurane in response to noxious mechanical stimuli in dogs. |
Main findings |
|
Limitations: |
|
Hart et al. (2020)
Population: |
Hospital records of dogs of 35 breeds presented to the University of California-Davis, Veterinary Medical Teaching Hospital over a 15 year undefined time period. |
---|---|
Sample size: |
4580 gonadectomised females, 3001 entire females, 3925 gonadectomised males, 4458 entire males. |
Intervention details: |
Data collected included:
A Kaplan-Meier survival analysis model was used, followed by a log-rank and generalised Wilcoxon test. |
Study design: |
Retrospective cohort study. |
Outcome studied: |
Age at gonadectomy and risk of CCLD tear compared to control population of intact dogs of the same breed. |
Main findings |
With respect to bitches, the following findings are reported:
|
Limitations: |
|
Simpson et al. (2019)
Population: |
Female Golden Retrievers in the United States enrolled in the Golden Retriever Lifetime Study (Guy et al., 2015). |
---|---|
Sample size: |
2764 Golden Retrievers, of which 1378 were female. Of the 2764 dogs of both genders, 1246 were intact, 273 were gonadectomised younger than 6 months of age, 577 were gonadectomised between 6–12 months of age, 658 were gonadectomised after 12 months of age. Gender distribution within each group was not reported. |
Intervention details: |
Data collected included:
A Cox proportional hazards model was applied, with either osteoarthritis or CCLD as the outcome. |
Study design: |
Prospective longitudinal cohort study. |
Outcome studied: |
Age at gonadectomy and risk of osteoarthritis or CCLD compared to control population of intact Golden Retrievers. |
Main findings |
|
Limitations: |
|
Torres de la Riva et al. (2013)
Population: |
Golden Retrievers who presented to the University of California-Davis, Veterinary Medical Teaching Hospital between 1 January, 2000 and 31 December, 2009. |
---|---|
Sample size: |
759 Golden Retrievers, of which 364 were female Golden Retrievers (172 gonadectomised before 1 year of age, 70 gonadectomised after 1 year of age, 122 intact). A case may be included in the intact group if disease occurred before gonadectomy and may then be included in the gonadectomised group if disease occurred after gonadectomy. |
Intervention details: |
Data collected included:
A Kaplan-Meier survival analysis model was used, followed by a log-rank and generalised Wilcoxon test. |
Study design: |
Retrospective cohort study. |
Outcome studied: |
Age at gonadectomy and risk of CCLD compared to control population of intact dogs of the same breed. |
Main findings |
|
Limitations: |
|
Waters et al. (2023)
Population: |
Rottweilers enrolled on the Exceptional Ageing in Rottweilers Study (EARS). |
---|---|
Sample size: |
123 Rottweilers, 76 female (23 gonadectomised ≤ 24 months of age). Gender and gonadectomy timing distribution was not reported. |
Intervention details: |
Data collected included:
A Kaplan-Meier survival analysis model was used, followed by a log-rank and Cox proportional hazards model. |
Study design: |
Prospective longitudinal cohort study. |
Outcome studied: |
Cranial cruciate ligament survival and relation to age at gonadectomy or gonadectomy status. |
Main findings |
|
Limitations: |
|
Whitehair et al. (1993)
Population: |
Dogs examined at one of 23 veterinary medical teaching hospitals in the United States, with medical records on the Veterinary Medical Data Base (VMDB) between 1 July, 1967 and 31 March, 1987. |
---|---|
Sample size: |
10,769 dogs with cranial cruciate ligament disease (CCLD), and 591,548 dogs without CCLD as the control population. |
Intervention details: |
Medical records from the VMDB were extracted for dogs between 1 and 15 years of age and categorised as cases (CCLD) or controls (no CCLD) and then further sub-categorised by age, bodyweight, sex, and gonadectomy status. Data collected included:
Chi-squared test was used. |
Study design: |
Retrospective case-control study. |
Outcome studied: |
Prevalence of CCLD for each group and epidemiological risk factors predisposing to CCLD. |
Main findings |
From 244 dogs, there was no difference in prevalence of CCLD in dogs who had been spayed at a young age and dogs whose age group at the time of gonadectomy was the same as their age group at the time of diagnosis (i.e. gonadectomised close to the time of diagnosis). |
Limitations: |
|
Appraisal, application and reflection
Eight studies were identified which were directly relevant to the PICO question (Ekenstedt et al., 2017; Hart et al., 2014; Hart et al., 2016; Hart et al., 2020; Simpson et al., 2019; Torres de la Riva et al., 2013; Whitehair et al., 1993; and Waters et al., 2023). The studies were cohort or case-control studies, conducted retrospectively or prospectively, and are only able to provide moderate-quality evidence, at best.
Breed differences and differences in methodologies limits the validity of comparison between studies. Breed-specific studies were evaluated head-to-head, where appropriate, and methodological differences were evaluated. Different measures of outcome were employed between studies. For example, Simpson et al. (2019) evaluated cranial cruciate ligament disease (CCLD) together with osteoarthritis, and Hart et al. (2020) evaluated joint disorders as a composite outcome, in addition to evaluating the primary outcomes of CCLD, hip dysplasia, or elbow dysplasia.
Golden Retriever bitches were evaluated in Simpson et al. (2019), Hart et al. (2014), Torres de la Riva et al. (2013), and Hart et al. (2020). Simpson et al. (2019) reported that in Golden Retrievers, gonadectomy at less than 6 months of age was significantly associated with an increased risk of CCLD or osteoarthritis. Hart et al. (2014) reported that in Golden Retriever bitches, gonadectomy was significantly associated with CCLD, if gonadectomised at less than 1 year of age, or at more than 2 years of age. From Hart et al. (2014), gonadectomy at 1 year of age (12–24 months) was not associated with CCLD. In Hart et al. (2014), it is also notable that 11/101 (10.89%) of Golden Retrievers gonadectomised before 6 months of age developed CCLD, compared to those gonadectomised between 6–11 months (4/81 [4.94%]) and 2–8 years (3/89 [3.37%]). Torres de la Riva et al. (2013) reported an increased risk of CCLD when dogs were gonadectomised before 1 year of age. Finally, Hart et al. (2020) reported that the Golden Retriever was at increased risk of at least one joint disorder when gonadectomised at less than 12 months of age.
For Labrador Retrievers bitches, Hart et al. (2014) did not find a statistically significant difference in risk of CCLD in gonadectomised Labradors compared to intact Labradors, although a trend was noted with gonadectomy under 12 months of age. Ekenstedt et al. (2017) did however find an increased risk of CCLD in their sample of Labrador Retrievers associated with gonadectomy before 12 months of age.
For Rottweilers, Waters et al. (2023) reported an increased risk of CCLD in all gonadectomy groups when gonadectomised before 24 months of age, with increasing risk the earlier gonadectomy was performed.
The only study to evaluate a large number of various breeds was Hart et al, 2020. However, this study was limited by small numbers of dogs in certain breed groups, especially those of the less common breeds.
Studies differed in cohort definitions, with Hart et al. (2016) and Hart et al. (2014) evaluating early gonadectomy with < 6 month and 6–12 month groups, whereas Torres de la Riva et al. (2013) and Ekenstedt et al. (2017) collectively evaluated these groups together as a < 1 year group. Simpson et al. (2019) did not stratify between sex therefore further comparison was not possible. Hart et al. (2020) defined gonadectomy groups of < 6 months, 6–12 months, 1–2 years, and 2–8 years. However, composite groups were created for statistical analysis, where convenient. Overall, different definitions between studies limits direct comparison.
In general, the majority of studies (Ekenstedt et al., 2017; Hart et al., 2014; Hart et al., 2016; Torres de la Riva et al., 2013; Hart et al., 2020; and Waters et al, 2023) found that spaying < 1 year of age was associated with an increased risk of CCLD, however Hart et al. (2014) also reported that spaying between 2–8 years of age was associated with an increased risk. Whitehair et al. (1993) did not find that early spaying increased the risk of cranial cruciate ligament disease however several methodological limitations were present in this study. Where multiple breeds were analysed in Hart et al. (2020), most breeds were not found to have an increased risk of CCLD with gonadectomy.
Methodological limitations limited the strength of evidence provided by all studies. Simpson et al. (2019) utilised inclusion criteria which would likely have simultaneously under- and over-estimated the true incidence of disease, which was a significant confounding factor. One of two of the longitudinal studies (Simpson et al., 2019) was limited in its length of follow-up and none of the study participants were followed for life, for logistical or study design reasons. Of the one study with lifetime follow-up (Waters et al., 2023), the exceptional longevity of the study population cannot be said to be representative of the general population of Rottweilers. Statistical analysis was also confounded by the use of composite outcomes and composite groups, which limits the direct applicability of the studies to the PICO question. Most of the studies, with the exception of Hart et al. (2020) evaluated one or two breeds of dog, which limits the ability to generalise their findings to the canine population at large. In the studies where gonadectomy status was collected retrospectively (Hart et al., 2014; Simpson et al., 2019; Torres de la Riva et al., 2013; Hart et al., 2020; and Waters et al., 2023), these data may have been subject to incorrect reporting or inaccuracies in recall. Next, despite the relatively large sample sizes, the incidence of cranial cruciate ligament disease was low. Therefore, statistical analysis was performed on small numbers of cases, some of which were in the single digits, and limits the reliability of results. Finally, most of the study participants were drawn from a narrow population of dogs attending veterinary referral hospitals in all but Simpson et al. (2019) and Waters et al. (2023).
Overall, the evidence is mixed and of moderate quality. There is evidence to support the assertion that gonadectomy in bitches before 1 year of age is associated with an increased risk of CCLD in three breeds – the Golden Retriever, German Shepherd, and Rottweiler. There was also contradictory evidence to suggest that gonadectomy in bitches at 6–12 months of age was not associated with CCLD and that gonadectomy in bitches, regardless of timing, was associated with CCLD. There was a trend towards an increased risk of CCLD associated with gonadectomy in bitches, in the narrow range of breeds represented throughout most studies, but particularly in the Golden Retriever. Overall, no firm conclusions can be drawn. Further studies are required, particularly in the subgroup of dogs gonadectomised < 1 year of age.
Methodology
Search strategy
Databases searched and dates covered: |
CAB Abstracts on OVID Platform covering from 1973 to 2023 Week 45 |
---|---|
Search strategy: |
CAB Abstracts:
Pubmed:
|
Dates searches performed: |
12 Nov 2023 |
Exclusion / inclusion criteria
Exclusion: |
Opinion pieces, articles on neuter status and risk of cranial cruciate ligament rupture but not on timing of neutering, articles on timing of neutering but not on cranial cruciate ligament rupture, and articles that were not relevant to the PICO question. |
---|---|
Inclusion: |
Articles that were relevant to the PICO question. |
Search outcome
Database |
Number of results |
Excluded – Opinion pieces |
Excluded – Not on timing of neutering |
Excluded – Not on risk of cruciate disease |
Excluded – Not relevant to the PICO question |
Excluded – Not accessible |
Total relevant papers |
---|---|---|---|---|---|---|---|
CAB Abstracts |
65 |
9 |
9 |
3 |
38 |
0 |
6 |
PubMed |
48 |
2 |
10 |
0 |
28 |
0 |
8 |
Total relevant papers when duplicates removed |
8 |
ORCiD
Daniel Low: https://orcid.org/0000-0003-0215-4997
Conflict of interest
The author declares no conflicts of interest.
References
- Ekenstedt, K.J., Minor, K.M., Rendahl, A.K. & Conzemius, M.G. (2017). DNM1 mutation status, sex, and sterilization status of a cohort of Labrador retrievers with and without cranial cruciate ligament rupture. Canine Genetics and Epidemiology. 4(2). DOI: https://doi.org/10.1186/s40575-017-0041-9
- Guy, M. K., Page, R. L., Jensen, W. A., Olson, P. N., Haworth, J. D., Searfoss, E. E. & Brown, D. E. (2015). The Golden Retriever Lifetime Study: establishing an observational cohort study with translational relevance for human health. Philosophical Transactions of the Royal Society of London. Series B. Biological sciences. 370(1673), 20140230. DOI: https://doi.org/10.1098/rstb.2014.0230
- Hart, B.L., Hart, L.A., Thigpen, A.P. & Willits, N.H. (2014). Long-Term Health Effects of Neutering Dogs: Comparison of Labrador Retrievers with Golden Retrievers. PLoS ONE. 9(7), e102241. DOI: https://doi.org/10.1371/journal.pone.0102241
- Hart, B.L., Hart, L.A., Thigpen, A.P. & Willits, N.H. (2016). Neutering of German Shepherd Dogs: associated joint disorders, cancers and urinary incontinence. Veterinary Medicine and Science. 2(3), 191–199. DOI: https://doi.org/10.1002/vms3.34
- Hart, B.L., Hart, L.A., Thigpen, A.P. & Willits, N.H. (2020). Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence. Frontiers in Veterinary Science. 7, 2297-1769 . DOI:https://doi.org/10.3389/fvets.2020.00388
- Simpson, M., Albright, S., Wolfe, B., Searfoss, E., Street, K., Diehl, K. & Page, R. (2019). Age at gonadectomy and risk of overweight/obesity and orthopedic injury in a cohort of Golden Retrievers. PLoS ONE. 14(7), e0209131. DOI: https://doi.org/10.1371/journal.pone.0209131
- Torres de la Riva, G., Hart, B.L., Farver, T.B., Oberbauer, A.M., Messam, L.L.M., Willits, N. & Hart, L.A. (2013). Neutering dogs: Effects on Joint Disorders and Cancers in Golden Retrievers. PLoS ONE. 8(2), e55937. DOI: https://doi.org/10.1371/journal.pone.0055937
- Waters, D.J., Fu, R., Carrillo, A.E., Chiang, E.C., Maras, A.H., Kengeri, S.S. & Suckow, C.L. (2023). Correlates of estimated lifetime cruciate ligament survival inform potential rupture risk reduction strategies: findings from the Exceptional Aging in Rottweilers Study. Scientific Reports. 13, 13920. DOI: https://doi.org/10.1038/s41598-023-39288-y
- Whitehair, J. G., Vasseur, P. B., & Willits, N. H. (1993). Epidemiology of cranial cruciate ligament rupture in dogs. Journal of the American Veterinary Medical Association. 203(7), 1016–1019.
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