Evidence Update- Neutering and Cancer Risk in Danish Dogs

One of the “hot topics” in veterinary medicine right now is the balance of risk and benefits to neutering. Even though I completed an extensive review of this subject in 2010, and updated it just last year, the new evidence is rolling in at brisk pace. The latest tidbit I have come across specifically touches on the specific issue of cancer risk.

M.M.E. Larsen, B. Børresen, A.T. Kristensen.  Neuter status and risk of cancer in a Danish dog population.

…From August 2005 to March 2014, 3801 canine neoplasms were reported to the Danish Veterinary Cancer Registry…The overall distribution of malignant neoplasia was 481 (38%) intact male dogs, 157 (12.5%) neutered male dogs, 404 (32%) intact female dogs and 220 (17.5%) neutered female dogs. The distribution was even between male and female dogs (50.5% and 49.5%). Compared to a known standard population of dogs, there was an overall statistically significant association of malignant neoplasia with neuter status in both sexes. For both genders this was significant for lymphoma, mast cell tumors and osteosarcomas. For neutered females, but not males, there was increased risk of hemangiosarcoma, squamous cell carcinoma and malignant melanoma. These findings indicate that there might be an association between neuter status and development of malignant neoplasia but larger prospective studies are needed to evaluate the risk of non-sex hormone dependent cancers in neutered dogs.

This was published as an abstract of a presentation at the European Society of Veterinary Oncology, so the full details of the study are not available. In particular, the breed and age of the dogs involved are factors which have proven critical to evaluating any link between neutering and cancer risk in previous studies. Hopefully, more data will become available in a full-length publication.

This study is in general agreement with some of the previous research in suggesting neutering may increase the risk of some specific cancers, and that this increase will differ between males and females. The tables below summarize previous studies on neutering and lymphoma, mast cell tumors, osteosarcoma, and hemangiosarcoma, so these data can be put in context.

As always, it is critical to evaluate the importance of any change in cancer risk with other health effects, including potential benefits. There is, for example, evidence that mammary cancer rates are decreased by neutering. And there is also some evidence that neutered animals live longer than intact animals, and if this is true it would certainly influence any decision about what action to take based on the new data about neutering and cancer risk. The subject is complex, and simple rules of thumb are unlikely to be very useful in making decisions about what to do for individual pets. Fortunately, as more and more data become available, we should be able to do a better job of making informed decisions about neutering in particular patients.

 

 

Table 1: Cited reports examining the relationship between neuter status and risk of osteosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Ru, G. 1998 OverallOR=2.2 Purebred dogs only, case-control study
Cooley, D. 2002 Males neutered <1yrRR=3.8

(95% CI=1.5-9.2)

 

Females neutered <1yr

RR=3.1

(95% CI=1.1-8.3)

Males neutered 1-3.5yrsRR=1.7

(95% CI=0.7–4.3)

 

Males neutered >3.5yrs

RR=1.4

(95% CI=0.6–3.5)

 

Females neutered 1-5yrs

RR=1.4

(95% CI=0.5–3.8)

 

Females neutered >5yrs

RR=1.2

(95% CI=0.4–3.2)

Rottweilers only, retrospective cohort
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.
Table 2: Cited reports examining the relationship between neuter status and risk of hemangiosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Prymak, C. 1988 FemalesOR=2.2

(95% CI=1.2-4.1)

 

Males Splenic HSA only, retrospective cohort
Ware, W. 1999 FemalesRR=5.33

(95% CI=3.96-7.19)

 

Males

RR=1.55

(95% CI=1.21-1.98)

Differences not found for all breeds, retrospective cohort, cardiac HSA only
Torres de la Riva, G. 2013 Females neutered >12mosRR=6.1

(95% CI=1.18-31.37)

MalesFemales neutered <12mos Golden retrievers only, retrospective cohort
Hart, B.L. 2014 All groups Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 Males neutered >12mosOR=5.3

(95% CI=1.5-18.2)

 

Females overall

OR=9.0

(95% CI=2.8-29.4)

 

Females neutered >12mos

OR=11.5

(95% CI=3.5-38.5)

 

Females neutered <6mos

OR=6.0

(95% CI=1.7-21.3)

Males overallOR=0.6

(95% CI=0.3-1.4)

 

Males neutered <6mos

OR=2.0

(95% CI=0.6-7.3)

Viszlas only, online owner survey

 

This study found an increased risk with neutering for females and not for males, but no information on age at neutering or breed was provided.

 

 

Table 3: Cited reports examining the relationship between neuter status and risk of lymphosarcoma in dogs

Study More Common Neutered More Common Intact No Difference Comments
Villamil, JA. 2009 Intact Female OR=0.69(95% CI=0.63-0.74) Intact MaleOR=1.32

(95% CI=1.24-1.41)

 

Neutered Male

OR=0.91

(95% CI=0.85-0.97)

Neutered FemaleOR=1.02 (95% CI=0.96-1.08) Multiple breeds, matched case-control study, OR is for development of lymphoma in each sex category
Torres de la Riva, G. 2013 Males neutered <12mos FemalesMales neutered >12mos Golden retrievers only, retrospective cohort
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort
Hart, B.L. 2014 Male & Female Goldens neutered 6-11mos  Males and Female Goldens neutered <6mos and >1year 

All Labradors

Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 OverallOR= 4.3

(95% CI=1.9-9.7)

 

Neutered <6mos

OR=3.5

(95% CI=1.3-9.6)

 

Neutered 7-12mos

OR=3.1

(95% CI=1.0-9.4)

 

Neutered >12mos

OR=5.2

(95% CI=2.2-12.0)

Viszlas only, online owner survey, OR reference category is intact animals

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.

 

Table 4: Cited reports examining the relationship between neuter status and risk of mast cell neoplasia in dogs

Study More Common Neutered More Common Intact No Difference Comments
White, CR. 2011 FemalesOR=4.11

(95% CI=2.19–7.69)

MalesOR=1.37

(95% CI=0.90–2.09)

Case/control study, multiple breeds
Hoffman, J.M. 2013 Overall Multiple breeds/mixed-breeds, retrospective cohort
Torres de la Riva, G. 2013 Females2.3% of neutered <12mos

5.7% of neutered >12mos

No cases in intact

Males1.7% of neutered <12mos

4.2% of neutered >12mos

2.8% of intact

Golden retrievers only, retrospective cohort
Hart, B.L. 2014 Female Goldensneutered <6mos & >1yr All Golden MalesAll Labradors Golden retrievers & Labrador retrievers, retrospective cohort
Zink, M.C. 2014 OverallOR=3.5

(95% CI=2.3-5.4)
Neutered <6mos

OR=2.8

(95% CI=1.6-5.0)

 

Neutered 7-12mos

OR=2.0

(95% CI=1.1-3.9)

 

Neutered >12mos

OR=4.5

(95% CI=2.9-7.0)

Viszlas only, online owner survey, OR reference category is intact animals

 

This study found an increased risk with neutering for both males and females, but no information on age at neutering or breed was provided.

 

 

 

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10 Responses to Evidence Update- Neutering and Cancer Risk in Danish Dogs

  1. Kelly says:

    ok – You summarized the Danish study stating: “This study is in general agreement with some of the previous research in suggesting neutering may increase the risk of some specific cancers . . .” But that doesn’t jibe with the abstract – which states that “distribution of malignant neoplasia” was [greater] in “intact” males (38%) and females (32%) vs neutered (12.5% and 17.5% respectively); so either the data from the Danish study was flipped, or the Danish study seems to contradict all (most) of the other studies. Yes, I see in the abstract where neutered females are more likely to get some forms of specific cancers, but that also seems to contradict the overall study.

    What did I miss here? I’ve read it 20 times now and come to the same conclusion .

  2. skeptvet says:

    The the vast majority of dogs in Denmark are intact, and the numbers that indicate more neoplasia in intact dogs are not corrected for the proportion of the population intact and neutered. The overall number of cancers are greater in intact dogs because there are a lot more intact dogs, but the relative rate of occurrence of some cancers (corrected for the proportion of the population intact and neutered) is greater in neutered dogs.

  3. I was about to say the exact same thing as Kelly, because it sure seemed that the study was saying 180 opposite of what you were saying. Whew.

  4. Jen Robinson says:

    Sorry to be dense, but what do OR and RR stand for?

    Is anyone presuming a mechanism, like estrogen or testosterone affecting cancer risk?

  5. skeptvet says:

    OR is Odds Ratio and RR= Risk Ratio. These are standard measures of the difference in the risk or the odds of an outcome in an epidemiologic study.

    In the case of some cancers, there are known or presumed mechanisms of association between sex hormones and cancer. For example, the effect of estrogen exposure on mammary cancer development is well-established. For most other cancers, the question is still IF there is an association, rather than what the mechanisms of any association might be. It is possible to look for mechanisms without definitive evidence that an association actually exists, but that is a less common way to go about such research.

  6. Jen Robinson says:

    Thanks for the answer. Not what I hoped for. Ratio based indices are so hard to interpret. Am I right in thinking an RR of 2 means treatment doubles risk over control? But what is the risk of the control? If the risk goes from 1:10,000 to 2:10,000, it doesn’t worry me much. If it goes from 1:10 to 2:10 it becomes serious. I gather the mammary tumor problem is on the order of 2:10 over an intact bitch’s lifetime . . . but I’d guess the risks are lower for male cancers.

    Also, the high CI’s in your tables tend to the high side . . . some are extremely high. They suggest small sample sizes and high variances. Virtually all statistical analyses assume an unbiased sample . . . and it’s absurdly difficult to find sample that represents all dogs.

    Once again . . . .lots of room for skepticism.

  7. skeptvet says:

    Absolutely. Relative risk can be misleading when the absolute risk is low, which is something I tried to address in my own review of the literature concerning neutering and health. When relative risk is very different and absolute risk is high, as in the case of the risk of pyometra in neutered and intact dogs, then it is fair to conclude a clear effect (a benefit, in this case). When relative risk is fairly high but absolute risk is low, as in many of the cancers studied, it becomes harder to determine whether the specific risk factor should have a meaningful influence on the overall risk assessment and the decision to neuter or not and when. This is further influenced by breed, since risk varies with breed. In breeds predisposed to certain cancers, it may make more sense to delay neutering or not neuter if neutering significantly affects the relative risk of those cancers since the absolute risk is higher, whereas the situation may be different in breeds at lower absolute risk even if the relative risk difference is the same.

    As you say, no simple answers. But given the unthinking, automatic recommendations most vets have made for decades, the very fact that we are more widely acknowledging that there is real uncertainty is an indication that we may be taking a more evidence-based approach, even if that means less clarity in our recommendations.

  8. Axolotl says:

    I would like to see greater awareness in vets of alternatives to spaying and neutering that remove fertility but preserve the gonads and the normal function of the animals’ endocrine system, such as a vasectomy for a dog or a hysterectomy with retention of ovaries for a bitch (which, if done correctly, eliminates the risk of pyometra).

  9. skeptvet says:

    Certainly, research into the pros and cons of such procedures is needed. You seem to be assuming that overall these would be better than gonadectomy in terms of health, and if so I would point out that this is not proven yet, merely a hypothesis, but certainly studying the long-term effects of such procedures would be useful information.

  10. WeatherBoy says:

    Evolution is also “merely” a theory, but that doesn’t make it incorrect. I fail to understand how the majority of vets and pet owners, within the span of a few decades, have arrived at the default conclusion–based on minimal evidence–that removing a major part of an animal’s endocrine system is in the best interests of it’s health, at least until an overwhelming amount of new evidence to the contrary comes along. Intuitively, this seems suspicious, so it’s great to see some researchers willing to investigate this issue recently.

    I’m fairly certain that amputating a dog’s legs will be 100% effective against all forms of leg cancer as well as roaming, leg lifting, humping, aggression, jumping up, digging, foot chewing, running away, scratching, and other unwanted behaviors, so it therefore seems logical to recommend every responsible pet owner have their dog’s legs amputated as soon as possible.

    Aside from the myriad biological variables at play, the political, public policy, and profit-driven factors in the neutering debate are powerful and contentious, so it is a very tricky question to investigate objectively. I’d be curious to know why the neutered dogs in the study cited above were neutered, since in Scandinavia and most of Europe that isn’t normally done unless for specific medical reasons, and how the study controlled for that.

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