Evidence Update: Potential Associations Between Neutering and Immune System Disorders

The risks and benefits associated with neutering are a complex and active area of research and debate in veterinary medicine. I have written several extensive summaries of the literature and numerous articles here evaluating the burgeoning research evidence. One subject that has seldom come up is the potential influence of neutering on the occurrence of diseases of the immune system. Although it is well established that sex hormones have variable and significant effects on the immune system, and that there are frequently sex differences in the risk of autoimmune and immune-mediated diseases, which suggests that sex hormones influence this risk, there has not been much direct research evaluating the relationship, if any, between neutering and the occurrence of diseases involving the immune system. A retrospective study published last year attempts to add to the very limited evidence previously published on this subject.

Sundberg CR. Belanger JM. Bannasch DL. et al. Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study. BMC Veterinary research. 2016;12:278.

The authors looked back at a university veterinary college database of patients seen over a 15-year period. They first identified diagnoses of a number of conditions involving the immune system an then looked for differences in the occurrence of these conditions between males and females and between intact and neutered animals. The conditions evaluated included:

Atopic dermatitis (atopy or environmental allergies)
Autoimmune Hemolytic Anemia (AIHA)
Myasthenia gravis (CMG)
Colitis
Hypoadrenocorticism (ADD or Addison’s disease)
Hypothyroidism
Immune-mediated polyarthropathy (IMPA)
Immune-mediated thrombocytopenia (ITP)
Inflammatory bowel disease (IBD)
Lupus erythematosus (systemic SLE and discoid DLE)
Pempigus complex (PEMC)

These conditions were chosen because they all occurred in at least 0.1% of the dogs in the database. These are the most common of a group of conditions which are still, as a whole, usually very uncommon. The authors also looked at the occurrence of pyometra or uterine infections, a condition known to be common in intact females and to be prevented by neutering, which served as a control condition.

The study found an association between being neutered and the occurrence of 7/11 of the autoimmune diseases evaluated: ATOP, AIHA, ADD, HYPO, ITP, IBD, and LUP. Of these and increases occurrence of LUP was only seen for females, and for females appeared to be at greater risk than males for all of the conditions except ADD.

For those animals in which the age of neutering was known, no association was found between disease occurrence and age at neutering.

As expected, pyometra was significantly more common in intact females compare to neutered females.

While these data do suggest that there may be some protective effect of sex hormones against autoimmune disease, the authors correctly identify a number of important caveats:

  1. Retrospective studies are NEVER proof of a causal relationship because there are too many variables that cannot be identified or controlled.
  2. The study population at a university hospital is often very different from the population in general, which makes it unreliable to extrapolate associations from one to the other. For example, atopic dermatitis is one of the most common conditions seen in dogs with rates up to 19% reported. This study population only had a rate of 1.8%, which is much lower than expected. In general, university patients are much sicker and have more unusual conditions than typically seen in the general pet population, so they aren’t always good examples of health and disease in more normal populations.
  3. Even if there is some causal role of neutering in the occurrence of these conditions, it is not the only or primary cause. Genetic variables and environmental triggers have been identified for many of these conditions, so any role played by neutering is just one of multiple factors to consider in the genesis of these conditions.
  4. These conditions are mostly quite uncommon, and any increase in risk that might be associated with neutering has to be balanced against the established benefits of neutering to the health of individuals and to the pet population as a whole.

Bottom Line
This paper adds some useful information to the complex and ongoing assessment of the risks and benefits of neutering. It does not establish that neutering causes autoimmune disease, and it is not justification for dramatic changes in neutering practices. However, it support continued study and consideration of the potential negative effects of neutering on the immune system.

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10 Responses to Evidence Update: Potential Associations Between Neutering and Immune System Disorders

  1. A. Jeffers says:

    I wonder if this may relate to the Pigpen Hypothesis – perhaps neutered pets lead a more antigenically “sheltered” existence. Just a thought.

  2. Katie says:

    I’m curious about your thoughts on neutering a dog that has already been diagnosed with an autoimmune disease. My 1 year old male lab was diagnosed with IMPA just before he was going to be neutered. It was a severe flare up that affected his airways in addition to his joints. Our vet has told us to wait on any elective anesthesia procedures for at least a year.

    There is a lot of research on humans that indicates testosterone protects against autoimmune disease. I am wondering if the role of testosterone is similar in dogs. We want to do what is best for him but can’t seem to find clear direction.

  3. skeptvet says:

    While there is some evidence that female dogs are more susceptible to autoimmune diseases than males, I don’t think we have any data comparing intact and neutered males. In general, I don’t see a strong medical benefit to neutering, so unless there are particular reasons for doing so (behavior, for example), I don’t think there is a compelling reason to neuter him.

  4. Katie says:

    Thank you for your quick and helpful response!

  5. Iris fields says:

    My wee dog has colitis she is s chiwawhs 6 yrs old is there any medication to help her thanks

  6. skeptvet says:

    There are many potential causes of colitis with various treatments. You really should have her seen by a local vet to discuss your options.

  7. Tastentier says:

    Unlike estrogen, testosterone acts as an immunosuppressant (which is one of the reasons why human men have a shorter life expectancy than women). I suppose this explains the sex disparity in this study.

  8. skeptvet says:

    An reasonable theory, but not one that has actually been proven to be true. Immunosuppressive effects in the lab don’t always correlate with real-life survival and disease outcomes, and the whole constellation of risk factors is complex with many interaction effects, so single-cause hypotheses often turn out to be wrong or incomplete.

  9. Kris says:

    I find this to be an interesting topic. We have a 6 year old female, just recently neutered. About 18 months ago, while still intact, she was diagnosed with idiopathic IMHA and ITP (non regenerativ anemia). After treating her with immunosupressants she stayed healthy for about 6 months. Then she was diagnosed with idiopathic IMPA, and recovered well on cyclosporine. Both conditions started a few months after being in heat, while she had imaginary pregnancies that just wouldnt end. We then decided to neuter her, hoping that might prevent future relapses. I guess only time will tell.

  10. skeptvet says:

    I think the relationship between hormones and immune system dysfunction is indeed interesting and complex. Females appear to be more susceptible to autoimmune disease across species, which is an interesting observation. I have also had a patient who had recurring episodes of sterile meningitis every time she came into heat and who never had another episode once neutered. Biology is certainly complicated! 🙂

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