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Effects of Gonadectomy on Orthopedic Disease and Cancer in Dogs

The connection between spay/neuter and osteoarthritis

Although CARE provides resources and education specifically about osteoarthritis in dogs, the topic of gonadectomy (i.e., spay/neuter/castration) has become complicated in recent years due to emerging evidence that these procedures may influence the development of arthritis and certain cancers in certain breeds of dogs. It is certainly unclear if there is any link between orthopedic disease and neoplasia, but for this article, it seemed prudent to include research results not only on the topic of OA but also cancer.

So, unconventionally, I am beginning this article with the conclusion statements: While a clear cause and effect relationship has not been determined for the effects of gonadectomy on the development of orthopedic disease and neoplasia in dogs, there is compelling evidence that an association does exist, and further research is warranted.

Spay/neuter early or later?

Furthermore, the optimal age, should gonadectomy be performed, has not been determined and is likely dependent on the individual dog and client.

This article will review the current evidence that is challenging the long-held American standard of spaying and neutering all dogs at a very early age.

One key point to be made is that any suggestions implied or conclusions drawn are meant to be for the individual animal and not applied to shelters and population control.  There is no argument against the need for decreasing (ideally eliminating) unwanted pets and the high volume of euthanasia performed in shelters across the country.

However, veterinarians must be prepared to have an educated conversation regarding the potential benefits and detriments of gonadectomy when pet owners present with an intact puppy.

This discussion will be limited to dogs. Furthermore, the behavioral, endocrine and immunological effects of gonadectomy will not be covered in this article.

Benefits of Gonadectomy:  Females

A primary reason that veterinarians recommend gonadectomy is to remove the reproductive capability of the dog and avoid the opportunity for unintended breeding (contributing to pet overpopulation).  Additional reasons to spay (for the sake of this article, “spay”= ovariohysterectomy or ovariectomy) a female dog include reducing the incidence of mammary, uterine, cervical and ovarian neoplasia and preventing pyometra.

Spayed (and neutered) dogs have also been shown to have increased life expectancy compared to intact dogs, yet there are a number of confounding factors that likely influence these results and a true causation effect cannot be concluded.

Furthermore, Waters et al. found that intact female Rottweilers lived significantly longer than spayed females of the same breed. The cause of death appears to differ between gonadectomized and intact dogs, with spayed/neutered dogs more likely to die of cancer or immune-mediated conditions.

Historical data for early spay

Mammary cancer is the most common tumor in intact female dogs, and 50% of these tumors are malignant.  In 1969, Schneider et al. reported the associated incidence of mammary neoplasia and timing of spay relative to the number of estrus cycles.

  • These statistics have been the foundation of our recommendations for spaying dogs for nearly 50 years:
    • When spayed before the first estrus: 0.5% increased risk of developing neoplasia (relative risk [RR]=0.005 in other words, 200x less likely to develop mammary cancer)
    • Between first and second estrus: 8% risk (RR=0.08), and after 2nd estrus: 26% (RR=0.06).

However, a recent systematic review of the literature regarding the timing of spay and mammary tumor development found that there were significant statistical flaws in the published studies and the current available evidence that age of spay influences mammary tumor development is weak.

Nonetheless, there is an increased incidence of mammary tumors in female dogs in certain European countries where spaying is uncommonly performed compared to the USA.

Furthermore, certain breeds of dogs may have an increased risk of mammary neoplasia; these include:

  • Boxer
  • Brittany spaniel
  • English Springer and Cocker spaniels
  • Dachshund
  • English Setter
  • German Shepard
  • Maltese
  • Miniature and Toy Poodles
  • Pointer
  • Yorkshire Terrier

For discussion with clients on if/when to spay

Until additional research is available that clearly describes the relationship between spaying and mammary tumor development, veterinarians should make recommendations based on the individual dog (breed) and considering additional factors listed below.

Should a dog owner elect to not spay or post-pone spaying until after maturity, they should be taught how to perform regular mammary chain examinations of their dogs to detect early tumor development.

Uterine, cervical and ovarian tumors are not common (0.3-0.5% of all tumors in dogs) and rarely malignant in dogs. Ovariohysterectomy is typically curative. Because the incidence is so low, spaying a dog to prevent the development of these tumors is not warranted.

Along these lines, surgical procedures that remove only a portion of the reproductive tract, ovariectomy (rather than ovariohysterectomy) and ovarian-sparing spay (hysterectomy), are reasonable surgical procedures for population management and preventing pyometra.

Of note – ovarian sparing spay is not considered gonadectomy. The purpose of this procedure is to remove the potential for pregnancy and pyometra but save the potential benefits afforded by the hormones produced by the ovaries.

Pyometra is an infection of the uterine lining that develops under the influence of hormones secreted from the ovaries; thus, both the ovaries and uterus must be present for the condition to develop. It is a severe, life-threatening condition that typically develops in bitches between 4-10 years of age. In countries where spaying is uncommon, the incidence of pyometra is between 15-24%.

Breeds that are over-represented included Bernese Mountain Dog, Cavalier King Charles Spaniel, Chow Chow, Collie, English Cocker Spaniel, Golden Retriever, Rottweiler, and St. Bernard.  Ovariohysterectomy is curative for pyometra so long as it is performed prior to the animal developing septicemia, as the mortality rate is reported up to 17%.

In summary, benefits of gonadectomy (removal of the ovaries) in female dogs include:

  • Likely associated with decreased incidence of mammary tumors (this may be more important in certain breeds)
  • Prevents ovarian tumors (incidence of 0.5%)
  • Prevents pyometra (incidence up to 24%, certain breeds may be more at risk)
  • Potentially associated with increased life expectancy (decreased risk of death from trauma, infectious, vascular and degenerative disease)

Potential Negative Consequences of Gonadectomy in Female Dogs

Orthopedic Disorders

Estrogen and testosterone influence the time of physeal closure, such that gonadectomy prior to maturity results in delayed physeal closure. Consequently, conformation and joint biomechanics are altered, which may lead to developmental orthopedic diseases (DOD) such as hip dysplasia (HD), elbow dysplasia (ED) and cranial cruciate ligament disease (CCLD; not traditionally considered a DOD but perhaps it should be?).

Duerr et al. found that gonadectomy (male and female) prior to 6 months of age is a significant risk factor for increased tibial plateau angle, which predisposes dogs to CCLD.

A number of retrospective studies have found that spayed and neutered dogs have a higher incidence of CCLD and HD compared to intact dogs. This relationship also appears to be influenced by breed.

The overall incidence of joint disorders in intact male and female Golden Retrievers and Labradors is reported to be 5%.  A retrospective study of 759 (n=364 females) Golden Retrievers by De la Riva et al. found that no intact females had documented CCLD compared to 7.7% of females spayed at <12 months.  In this study, there was no significant difference in the development of ED or HD between intact and spayed females.

The same group of authors also retrospectively evaluated Labrador Retrievers and found that while CCLD was increased in females spayed <12 months, the difference was not significant compared to intact females. However, spayed females had a 4-5% incidence of HD compared to 1.5% in intact females (p<0.05).  There was no significant difference in ED between spayed and intact female Labradors.

Obesity

Spayed (and neutered) dogs are significantly more likely to be overweight or obese; though the age of the dog at the time of the gonadectomy does not seem to influence this risk. It is expected that the dog’s metabolism will slow by about 30% after gonadectomy.

Additionally, it is possible that estrogen acts as a satiety factor in intact female dogs, and increased appetite following spay is partially responsible for weight gain in spayed dogs.

Increased body weight/ condition/ obesity have been associated with increased incidence and clinical symptoms of HD, CCLD, and ED as well as hypothyroidism, diabetes mellitus, pancreatitis, and neoplasia.

Neoplasia

The development of cancer is multifactorial, including genetic and environmental influences. Recently, there has been evidence suggesting that gonadectomy is associated with an increased risk of certain tumors in dogs.

The cause and effect relationship is not yet known, as all published studies at this time are retrospective and correlative. However, further research is indicated so that veterinarians truly are doing no harm by recommending gonadectomy for our patients.

A summary of currently available evidence regarding cancer development in spayed versus intact female dogs:

  • Dogs neutered <12 months have 2x increased risk of osteosarcoma; Rottweilers have 3-4 x increased risk. There does not appear to be a sex predilection.
  • 2-11.5 x increased risk of splenic hemangiosarcoma in spayed female dogs
  • Golden Retrievers that were spayed after 12 months of age had a 4x increased risk of developing hemangiosarcoma compared to early (<12 months) spayed or intact.
  • Spayed Vizslas were 9 times more likely to have hemangiosarcoma compared to intact Vizslas.  Vizslas spayed >12 months had 11.5 times increased risk whereas those spayed <12 months had a 6 times increased risk.
  • Increased risk of cardiac tumors in spayed females.
  • 5x increased in cardiac hemangiosarcoma in spayed females.  The overall incidence of cardiac tumors is low, 0.19%. Spayed females have a 338% greater risk of developing cardiac tumors vs. intact females.
    • Certain breeds may have an increased risk, including
      • Saluki, French Bulldog, Irish Water Spaniel, Flat Coated Retriever, Golden Retriever, German Shepard, English Setter, and Boxer.
      • Overall, intact female dogs are half as likely to develop lymphoma compared to spayed females and all males. Female Golden Retrievers spayed >12 months had 4 x increased risk of lymphoma compared to early spay or intact. Spayed Vizslas had 4.3 times as high risk of lymphoma versus intact.
  • Spayed females have 4x increased risk of mast cell tumor (MCT)
    • Predisposed breeds include Boxer, Vizsla, Boston terrier, Weimaraner, Bullmastiff, Pug, Labrador, Pitbull, Golden Retriever.
  • In Golden Retrievers, late (>12 months) spay may increase the risk compared to early spay or intact females. Spayed Vizslas had a 2-4.5 increased risk of MCT compared to intact females.

These results are complicated and it is challenging to draw clinically relevant conclusions.

Benefits of Gonadectomy: Males

The primary reasons to castrate male dogs include: population control, preventing roaming behavior, eliminating the chance of testicular cancer, decreasing the risk of non-neoplastic prostatic enlargement, decreasing perianal fistuals, decreasing unwanted sexual behaviors and urine marking, and possibly decreasing other behavioral problems.

A common misconception is that castration will decrease prostatic neoplasia and aggression. Rather, prostatic neoplasia is increased four-fold in neutered dogs compared to intact males.

With regard to aggression and other behaviors such as fear and anxiety, the evidence is contradictory.  Some authors have found decreased aggression toward humans and other dogs following castration, while others have found increased aggressive behavior in dogs neutered before 6 months of age.

One thing that most behaviorists will agree upon is that intact dogs displaying behavioral disorders, particularly aggression, should not be bred and should ideally be neutered.

In summary, the potential benefits of castration include:

  • Decrease roaming, unwanted breeding, urine marking and sexual behaviors
  • Possibly decrease other unwanted behaviors including aggression
  • Eliminate the risk of testicular tumors (incidence of 7-8%; mortality risk <1%)
  • Reduce the risk of non-neoplastic prostatic enlargement (BPH, prostatitis)
  • Reduce the risk of perianal fistulas (most important for German Shepherds and Irish Setters)

Potential Negative Consequences of Gonadectomy in Male Dogs

Orthopedic Disorders

Witsberger et al. published a cross-sectional study of 1.2 million dogs evaluating the prevalence of and risk factors for HD and CCLD in dogs. This study reported that castrated male dogs were significantly more likely than other cohorts to have HD (OR= 1.21) and CCLR (OR=1.68). Breed was also highly correlated to the risk of developing both conditions, with 17-18 breeds having an increased risk of developing CCLD or HD, respectively.

Golden Retrievers and Labradors were among the breeds with increased risks of both conditions. In the De la Riva et al. Golden Retriever retrospective study (n=395 male dogs), males castrated at less than 12 months of age were twice as likely to develop HD as intact males.

There were no reports of CCLD in intact male Goldens and 5% incidence in those neutered at <12 months. Hart et al. reported the neuter status of Labradors (n=808 male dogs) was not associated with an increased incidence of HD, but neutering <6 months of age did significantly increase the incidence of CCLD and ED (p=0.02).

In summary, it appears that neuter status likely does influence the development of HD, CCLD, and ED in certain breeds, though the cause and effect relationship has not been identified.

Gonadectomy at < 6 months has been associated with increased risk of orthopedic disease in Golden Retrievers, Labradors, and other breeds. As there is no clear medical benefit to castration of male dogs <6 months (or <12 months for that matter), it is advisable that male dogs be neutered following skeletal maturity.

Again, this recommendation will not hold true for dogs in a shelter environment where population control is prioritized.

Obesity

As discussed above with regard to female dogs, castration has been linked to increased obesity, which in turn, contributes to the development of orthopedic, endocrine, and immune disorders.

As is the theme with this topic, the true cause-and-effect relationship is yet unknown but is postulated to be due to decreased metabolic demands (i.e., need for less calorie intake) following castration. De la Riva and Hart failed to find a significant relationship between BCS and orthopedic disease in male Golden Retrievers and Labradors.

Preventing obesity is not a reason to recommend against gonadectomy (there are plenty of other potential reasons), as careful and responsible control of caloric intake and expenditure (exercise) can prevent obesity in nearly all dogs.

Neoplasia

A summary of currently available evidence regarding cancer development in neutered versus intact male dogs:

  • Dogs neutered <12 months have increased risk of osteosarcoma. Rottweilers have 3-4 x increased risk. There does not appear to be a sex predilection.
  • Neutered dogs have increased risk of hemangiosarcoma; there was not an association of neuter status in Male Golden Retrievers.  Vizslas castrated >12 months had 5-time increase risk compared to intact males.
  • Neutered males have 63% increased risk of cardiac tumors (overall incidence of these tumors is low, 0.19%)
  • Neutered male dogs have a significantly increased risk of prostate neoplasia compared to intact dogs.  However, it is important to note that the overall incidence of prostate cancer is low (<0.1%).  Breeds with increased risk include mix-breed, Sheltie, Scottish Terrier, Beagle, German shorthaired pointer, Airedale, Norwegian elkhounds.
  • Male Golden Retrievers neutered <12 months of age have 3x increased risk of lymphoma. Castrated Vizslas had 4.3 times as high risk of lymphoma versus intact males.
  • Neutered males have 1.37 x increased risk of mast cell tumors; predisposed breeds include:
    • Boxer, Vizsla, Boston terrier, Weimaraner, Bullmastiff, Pug, Labrador, Pitbull, Golden Retriever. There was not an association of neuter status in Male Golden Retrievers.  Neutered Vizslas had a 2-4.5 increased risk of MCT compared to intact males.
  • Neutered dogs have increased risk of urinary tract neoplasia; incidence overall of these tumors are low, <1%; certain breeds such as Scottish Terriers, Shelties, and West Highland white terriers have an increased incidence.
  • These results are complicated and it is challenging to draw clinically relevant conclusions.

Conclusion (again)

In conclusion, the recommendations for if or when to spay and neuter pet dogs should be made on a case by case basis, considering the breed, intended job or activity of the dog, temperament, and ability of the client to responsibly prevent unwanted pregnancy should their dog remain intact for any period of time.

Weighing the incidences and severity (treatability) of diseases prevented or increased with gonadectomy should be considered. Gonad-sparing surgery (hysterectomy, vasectomy) may also be discussed.

The gonadectomy discussion should also include recommendations for weight management and optimal nutrition, behavior training and socialization, and the importance of monitoring and early detection of conditions such as mammary and testicular cancer, mast cell tumor, and orthopedic disease.

In the future, we will hopefully have additional evidence from prospective, randomized trials from which to base our medical recommendations.

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Duerr FM, Duncan CG, Savicky RS, et al. risk factors for excessive tibial plateau angle in large-breed dogs with cranial cruciate ligament disease.  JAVMA 231:1688-1691, 2007.

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