The gonad chronicles, part 2: Veterinary research explores neutering's elusive impact

This is the second article of a two-part dvm360 series focusing on neutering and the effect of hormones on the development of both physical and behavioral concerns ((see the Related Links section below for a link to part 1). We will explore the relevant data demystifying the connection between hormones, behavior and health.

Much attention has been given to the role of sex hormones and behavioral concerns in cats and dogs, but there is surprisingly little data on the subject. The most common stereotypes involve testosterone in intact males. It may be appropriate to view testosterone as a behavioral modulator that could help bring about or escalate the aggressive state.1 An intact dog may react more easily, escalate any response more quickly, plateau at a higher level of reactivity, return to baseline at a slower rate and possibly alter his baseline to a higher level than would a neutered dog.

THINKSTOCK/ERIC ISSELÉE

That said, both neutered and intact dogs may exhibit behavioral concerns, and only some of these concerns are affected by sexual dimorphism. Dimorphic behaviors associated with the presence of testosterone include urine marking with lifted leg, roaming and some types of mounting. Mounting is an unclear issue because it occurs in a number of contexts, most of which are not sexual, and both sexes do it. Castration results in an androgen drop within six hours, and most hormones that decrease do so within 72 hours.2

In the 1976 Hopkins study, which looked at male behavioral patterns and the effect of castration, roaming decreased by approximapattely 90 percent, male-to-male aggression by approximately 75 percent, urine marking by approximately 60 percent and mounting by 80 percent in male dogs that were neutered. However, marking, mounting and fighting are complex behaviors not wholly controlled by hormones. There is a significant learning component involved in practicing these behaviors that won't be redressed by castration. Context also matters, so space and social interactions need to be considered. Finally, no distinction is made between normal and pathological behaviors, and one might expect castration to affect them differently.

Researchers have paid less attention to the role of female sex hormones and aggressive behavior, but one study has made a connection within a fairly restricted population.3 Only female puppies that were already showing signs of "dominance aggression" became worse after spaying. Spaying had no effect on any other age and behavior group combinations.4 It is possible that for these young, aggressive bitches, sex hormones play a helpful role in modulating their reactivity. If these dogs are in responsible households where breeding is prohibited, allowing them to have a heat cycle may be beneficial in terms of ameliorating their aggression, but there is little data on this.

Reasons for neutering

Neutering (castration or ovariohysterectomy) is usually recommended for aggressive dogs and cats, not because it is therapeutic but because it prevents a heritable behavior component from being passed on. If heritability is complex or has a large environmental component to expression, neutering dogs known to be aggressive may not substantially decrease genetic risk within the population of breeding dogs as much as we would like.

Owners may choose to neuter their dog for many different reasons, which can vary by sex. Common reasons for neutering male dogs include: the dog marks with urine, the dog has an enlarged prostate, the dog has prostatic or testicular neoplasia, or the working dog is more focused on other dogs' odors than on his job. Common reasons for neutering females include a desire to decrease the risks of mammary neoplasia to the fullest extent possible. In some cases, the client cannot or will not monitor for pyometra or doesn't want to deal with the behavioral and physical consequences of heat cycles.

The most common reason for ovariohysterectomy (OHE) is to spare dogs the risk of mammary neoplasia, which is extremely common in dogs, but only malignant about half the time.5 In countries where dogs are not routinely spayed, the risk for mammary neoplasia may be as high as 53 percent.6 Neutering female dogs before their first heat appears to decrease the risk of mammary neoplasia to 0.5 percent. If clients wait until the second heat, the risk is 8 percent, and after the second heat, the risk increases to 26 percent.7

While spaying after the second heat does not reduce risk, spaying at the time the mammary tumors are removed appears to have a beneficial effect on survival.8,9 Some authors don't feel that the data is strong enough to say there is any mammary sparing effect because of problems with bias in the data.10 The patterns for OHE and mammary neoplasia are similar in cats, but 85 to 90 percent of feline mammary tumors are malignant.5,11

Repeated heat cycles increase the risk of pyometra.12 In one study, by 10 years of age, 25 percent of the females studied developed pyometra. There are strong breed attributes that may increase or decrease this risk, but OHE eliminates this risk altogether.13

The risk of prostatic disease in male dogs increases with age. Benign hypertrophy may affect at least 60 percent of dogs older than 7 years.14 Castration both prevents and treats benign prostatic hyperplasia. Testicular tumors are fairly rare and most are prevented or treated by castration. However, most prostate cancer, when diagnosed, is advanced and does not respond to androgen deprivation, so monitoring is important for a favorable outcome.15

Other health issues

Additional studies have raised concerns about neutering's adverse effects on other health issues. Castration may increase the risk of bladder transitional cell carcinoma16 and prostate carcinoma,16,17 an effect augmented by breed. At least one study suggests that neutering may facilitate tumor growth while having no effect on initiating cancer development.18 Neutered dogs have been reported to have a high risk for osteosarcoma compared with intact dogs,19,20 but the studies are complicated by other factors and the neutered dogs actually lived longer than the intact dogs.

Spayed females have been reported to have an increased risk of hemangiosarcoma, when compared with intact females,21,22 a finding that may be heavily influenced by breed, but not supported by the PLoS One study that stimulated this debate.23 Transitional cell carcinoma may affect more neutered than intact females, but it is rare, although more common in females.24

Early neutering, as practiced on shelter dogs to reduce the number of unwanted animals, may have different effects on health than neutering later in life. Early neutering increases long bone growth, which may pose risks for later skeletal conformations, potentially affecting hip dysplasia,25-28 but these findings are not supported by all studies,29 and even when present, the effect may be relatively weak.28

If OHE for female shelter puppies can be delayed until 3 months of age, risks for temporal, related cystitis and later urinary incontinence may be decreased,28 but this may matter less than anticipated.29 If the risk is that the pup would not otherwise be neutered, neutering of shelter dogs is always preferred. One retrospective case series evaluating the true prevalence of urinary incontinence in spayed female dogs that were neutered across ages produced two findings: acquired urinary incontinence had a low prevalence (N=29 or 5.12 percent in 566 dogs), and there was no effect of age at OHE between the continent and incontinent dogs.30

Chemical castration with implantable deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, is occasionally used because it renders animals functionally sterile, a condition that is reversible with removal of the implant.31 Deslorelin decreases testosterone and luteinizing hormones to undetectable levels in dogs and so may also affect testosterone-modulated behaviors. When alpha-agonists fail, deslorelin may successfully treat estrogen-dependent urinary incontinence in female dogs.32

In ferrets, those treated with deslorelin showed decreased fighting associated with sexual behavior and increased play behavior when compared with ferrets who had been surgically castrated.33 One study that examined play, fear and aggressive behaviors in dogs treated with deslorelin compared with those surgically castrated found no differences between groups.34

When given to cats, deslorelin rendered them infertile, caused decreases in testicular volume and disappearance of penile spines.35 Cats that were implanted experienced decreased libido, decreases in mounting and mating behaviors, and decreased spraying, but food intake increased, a potential concern given the obesity epidemic in cats.

Recommendations

Any causal attribution for neutering and problematic behavior is premature, although I have not touched on hormones and brain aging—an even more complex issue. Frankly, behavioral studies are much harder to do than studies focusing purely on somatic conditions. When one considers the difficulty of identifying physical pathologies that may be affected by neutering, one should take special care with behavioral evaluations, which are much more difficult to evaluate in an unbiased, valid and repeatable manner.

So what do I recommend to owners seeking guidance? If the dog has any pathology that might be heritable—behavioral or otherwise—the dog should not be bred unless the breeding is part of a funded, approved, controlled study in collaboration with researchers to study the putative defect. Neutering is not the only way of preventing breeding but it is the easiest.

If the dog has no behavioral concerns and the owners are responsible, discuss all of the health information outlined above. While the Hopkins study has never been replicated or expanded, I still note to clients that dogs that are searching for mates are a lot like college students in bars: They are not typically thinking about the consequences of their behavioral choices. Too often these dogs roam and are killed by cars. Clients keeping intact males must be mindful of keeping them safe.

In summary, we need to learn more about patterns of all pathologies in all breeds so we can help produce physically and behaviorally healthier animals that are excellent at their jobs—whether they're bred to be excellent pets or to be service, working, trial or hunting dogs—and that will always have caring, humane homes.

Neutering naysayers

One study has suggested that neutered dogs are more fearful, excitable, aggressive and less trainable than are intact dogs.36 Unfortunately, this study is flawed in that it does not follow dogs through time and instead relies on unmatched cohorts. We do not know whether these dogs were all evaluated at the same age (a control for ontogeny) or at a predetermined time after neutering (a control for postoperative effects). Without these controls, most correlations—especially using scored and ranked data, as is the case here—are likely to be spurious. There are other major methodological issues that preclude accepting these conclusions as valid and they are common enough mistakes in studies to warrant an outline here.

> The data are scored clients' assessments of their dog's behaviors using a scale that was not validated to ensure it represented reliable, repeatable behaviors (e.g., whether the dog was actually "aggressive" if she barked).

> No inter-rater reliability data are provided. In other words, we have no idea how variable clients' interpretations of the dogs' behaviors were or how variable their interpretation of the terms and scales were.

> Scaled data are difficult to interpret because they are so subjective and without inter- and intra-rater reliabilities, it is impossible to know, for example, if person A's 4.5 is equivalent to person B's 4.5. This is one reason why such scales should be avoided in population studies unless they are defined, validated and tested for inter-rater agreement (e.g., Kappa scores)..

> The data are presented graphically and the axes are not the same. As a result, differences appear larger than they truly are. When plotted on the same scale, differences are modest, especially given that very small changes in scores obtained from scaled responses are calculated for a very large number of responses.

> The sample size is huge, because this is a survey study, and with a sample size so large it would be odd if some findings were not significant, by chance alone. This effect is magnified when scores are calculated from scales. Even for those relationships that are statistically different, we have no idea if the differences noted are biologically meaningful.

> Analysis of ratios is complex (in this case, bone length), and requires certain assumptions which we cannot know were met here.

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33. Vinke CM, van Deijk R, Houx BB, et al. The effects of surgical and chemical castration on intermale aggression, sexual behaviour and play behaviour in the male ferret (Mustela putorius furo). Appl Anim Behav Sci 2008;115(1-2):104-121.

34. Steur ER. Chemical and surgical castration of male dogs: behavioral effects. Doctoral thesis, University of Utrecht, Utrecht, Holland, 2011.

35. Goericke-Pesch S, Georgiev P, Antonov A, et al. Clinical efficacy of a GnRH-agonist implant containing 4.7 mg deslorelin, Suprelorin, regarding suppression of reproductive function in tomcats. Theriogenology 2011;75(5):803-810.

36. Farhoody P, Zink MC. Behavioral and physical effects of spaying and neutering domestic dogs (Canis familiaris). Unpublished summary of a Masters thesis, Hunter College, New York, NY, 2010.

Dr. Karen L. Overall is a researcher, editor of The Journal of Veterinary Behavior: Clinical Applications and Research, and author of more than 100 publications, dozens of chapters and a new book, The Manual of Clinical Behavioral Medicine for Dogs and Cats.