Imagine this clinical scenario: you are a veterinary surgeon in first-opinion practice, conducting a routine health check and vaccination of a female puppy. You take this opportunity to discuss various routine and preventative healthcare options with your client, including neutering.
Your client has read an article online suggesting that neutering can cause cranial cruciate ligament disease (CCLD) and would like your professional opinion on the matter. You decide to consult the evidence first.
The evidence
You identify eight studies that are directly relevant to the PICO question: Ekenstedt et al., 2017; Hart et al., 2014, 2016 and 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. All of the studies looked at male and female dogs. Unless otherwise stated, the sample sizes provided do not include male dogs as they are not relevant to the case at hand.
The studies were cohort or case-control studies conducted retrospectively or prospectively
The three studies by Hart et al. (2014, 2016, 2020) and those by Simpson et al. (2019), Waters et al. (2023) and Torres de la Riva et al. (2013) collected data on gonadectomy status, age at gonadectomy and diagnosis of CCLD. The sample sizes of each were as follows:
- Hart et al. (2014) studied 472 Golden Retrievers (306 neutered, 166 intact) and 692 Labrador Retrievers (347 neutered, 345 intact)
- Hart et al. (2016) studied 465 German Shepherd Dogs (293 neutered, 172 intact)
- Hart et al. (2020) studied 4,580 neutered female dogs and 3,001 intact female dogs from 35 different breeds (7,581 total)
- Simpson et al. (2019) studied 2,764 Golden Retrievers, of which 1,378 were female (273 gonadectomised before six months of age, 577 gonadectomised between 6 and 12 months of age, 658 gonadectomised after 12 months of age; gender distribution within each group was not reported so these figures include both male and female dogs)
- Waters et al. (2023) studied 76 female Rottweilers (23 gonadectomised at less than 24 months of age)
- Torres de la Riva et al. (2013) studied 364 female Golden Retrievers (172 gonadectomised before one year of age, 70 gonadectomised after one year of age, 122 intact)
Ekenstedt et al. (2017) studied the medical history of 168 Labrador Retrievers (83 neutered before one year of age, 25 neutered after one year of age, 60 intact). The outcomes studied were the presence of a mutation in the dynamic 1 gene, gonadectomy status and age at gonadectomy.
Whitehair et al. (1993) studied the medical records of 10,769 dogs with CCLD and 591,548 without as a control group. Sex was not reported, so the sample size noted above includes both male and female dogs. The outcomes studied were signalment data, gonadectomy status and age at gonadectomy.
Limitations of the evidence
Methodological and study-design limitations were present in all eight studies, weakening the overall quality of evidence
The overall strength of evidence was moderate. Methodological and study-design limitations were present in all eight studies, weakening the overall quality of evidence.
Six of the eight papers reviewed were retrospective studies that drew their cohorts from historical medical records (Ekenstedt et al., 2017; Hart et al., 2014, 2016, 2020; Torres de la Riva et al., 2013; Whitehair et al., 1993). The other two were prospective studies that examined dogs of only one breed each: Golden Retrievers (Simpson et al., 2019) and Rottweilers (Waters et al., 2023).
Of the studies, only Hart et al. (2020) evaluated more than two breeds of dog, limiting the applicability of the findings to the canine population at large. This study was also limited by the small numbers of dogs within certain breed groups.
Additionally, all but two of the studies (Simpson et al., 2019; Waters et al., 2023) drew their study participants from a population of dogs attending veterinary referral hospitals, which is not necessarily representative of the overall canine population.
All studies had relatively large sample sizes, but the number of patients with CCLD within each was low. Therefore, the statistical analyses performed by each study contained small numbers of cases, limiting the reliability of the results.
Moreover, all of the papers featured dogs of both sexes; this limits their applicability to the research question, which specifically focuses on female dogs.
Summary of findings
Analysing the findings by breed does provide some insights, albeit insights that are not necessarily applicable to the general canine population
Breed differences between the studies limits the validity of comparisons between them. However, analysing the findings by breed does provide some insights, albeit insights that are not necessarily applicable to the general canine population.
Golden Retriever bitches were studied by Simpson et al. (2019), Hart et al. (2014, 2020) and Torres de la Riva et al. (2013), and their findings all point towards an increased risk of CCLD in this breed and sex. Simpson et al. (2019) and Hart et al. (2014) both reported that gonadectomy in female Golden Retrievers is associated with an increased risk of CCLD when carried out at less than six months of age (Simpson et al., 2019), and less than one year of age or more than two years of age (Hart et al., 2014). Torres de la Riva et al. (2013) found that bitches gonadectomised before one year of age are more likely to develop CCLD. Finally, Hart et al. (2020) found that Golden Retriever bitches are at an increased risk of at least one joint disorder when gonadectomised at less than 12 months of age.
Labrador Retrievers were studied by Hart et al. (2016) and Ekenstedt et al. (2017). Hart et al. (2014) did not notice a statistically significant difference in the risk of CCLD. Meanwhile, Ekenstedt et al. (2017) found an increased risk of CCLD associated with gonadectomy when under 12 months of age in their sample of Labrador Retrievers.
Waters et al. (2023) studied Rottweilers and found an increased risk of CCLD in all groups when gonadectomised under 24 months of age, with increasing risk the earlier the gonadectomy was performed.
Conclusion
A blinded control study on the link between gonadectomy and cranial cruciate ligament disease in a wide variety of dog breeds is required to ascertain a fuller picture
There is moderate evidence that gonadectomy in Labrador Retrievers, Golden Retrievers and Rottweilers can lead to an increased risk of cranial cruciate ligament disease, particularly when performed at an early age. However, there is a need for further research with more robust study design to improve the strength of evidence.
A blinded control study on the link between gonadectomy and cranial cruciate ligament disease in a wide variety of dog breeds is required to ascertain a fuller picture of the wider canine population.
| The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence. |
Disclaimer
The application of evidence into practice should take into account multiple factors, not limited to individual clinical expertise; patient’s circumstances and owner’s values; the country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.
