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)
Hypoadrenocorticism (ADD or Addison’s disease)
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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