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Thursday, February 28, 2013

Finishing up the lit search stuff


More pics from last Wednesday's ride just because - do you notice the difference between the mane shown here and the pics in the last post which are post-shaving? Long manes are beautiful, but they can make the horse look so bedraggled if they are muddy and tangled. I must admit I sort of miss her beautiful mane, but this is so much more functional.

Continung on our literature discussion:

3. Look at the figure next. This was a tip I picked up during an onco journal club last block. Look at the figures, decipher what they are saying and what they mean and decide what your conclusions would be based on the figures. You may need to refer to the method and results section to find out what the different definitions are that are represented in the graph.

4. Methods and Results section. And then the conclusions. Are their conclusions supported by their results? You may (like me) have your eyes glaze over in these sections, but if you've got in your head straight what they are trying to prove (from the abstract), what kind of study they are running and what their figures say, then you should be able to muddle through the jargon enough to figure out whether the research really is promising, or if someone's grant money was running out and they really needed another publication.

5. At some point browse the intro and conclusions. It's also useful to use these sections as references if you aren't sure what they are talking about or are using vocab that isn't familiar - however, remember that no matter how interesting and enteratining these sections are, they aren't the meat of the paper. They are telling you what other people found, and then telling you what they are going to prove.

Shall we apply this? Absolutely! Here's an annoucement that showed up in my inbox a couple of days ago "Golden retriever study suggests neutering affects dog health".

I haven't reviewed this yet, so we will go through this together. Here's the link:

1. This is a news release based on a study. Let's see what I can get from the news article first.

  • Study examined health records of 759 golden retrievers.
  • A single hospital database was used.
  • Point of the study was to examine effects of neutering on the risks of several diseases (2 joint disorders and 3 cancers) in the same breed, distinguish between males and females and between early/late/non-neutering.
  • Early/late neutering break point was 12 months.
  • Dog ages in study ranged from 1-8 years
  • Results: doubling of hip dysplasia among male dogs neutered before one year of age, increases in all five diseases significantly higher in both males and females that were neutered early or late when compared to not altered animals.
Besides confirming all the results/study design from the actual study, here are my inital thoughts/questions based on the news release: Could there be a bias because of a single database: a tertiary referral hospital who may see disproportionately higher numbers difficult cases, or unaltered "quality non-pet quality" animals because they are considered valuable and thus owners bring them to the university hospital? How have the authors controlled for this?

Some biases that I am aware of that I have going into this study are:

1. I believe that in most cases, assuming responsible ownership, dogs shouldn't be altered before they hit puberty and their growth plates close.

2. I believe in most cases, unless planning on breeding, adult dogs should be altered.

3. I believe that hormones are important and the lack of them, or presence of them, can be a signicant factor in disease formation. Nothing is done without consequence in biology, including removing hormones from the system. Growth is a critical time for hormones, thus I like to see altering wait until after the growth period, but I am open to the fact that removing hormones may influence other disease processes, while keeping in mind that hormone presence can exacerabe/increae the risk of other diseases........

Going on to the actual research!!!!!!

1. Read the abstract: Objective was to examine the variables of gender and age at time of neutering (versus leaving dogs in intact) on all disease occuring with sufficient frequency that they could be statistically evaluated. The abstract confirmed the information in the news release such as the sample size, breed and age range chosen etc. Hip (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA) and mast cell tumor (HCT) were the diseases that were chosen.

Results according to abstract:

Hip dysplasia and lymphosarcoma is more common in early neutered males as compared to intact males. (My bias from previous research, knowledge, and personal experience tells me to believe the hip dysplasia component of this. I know that hormones affect bone growth and those males neutered before 12 months would have had the hormones removed during their growth period. However, I also wonder whether those early neutered males were pet quality with perhaps contracts from the breeding requiring neutering and thus a higher number of poorer quality dogs are represented in the neutered group. Knowing the dog isn't breeding quality may have motivated advice by the breeder and the vet to neuter the dog early, which would skew the results. This argument could also be applied to the lymphosarcoma cases - If more lower quality animals are part of the early neutered category, and if lymphosarcoma has a genetic component associated with these types of backyard breeding programs - as compared to the guide dog organization for example - than it's possible that the trend has more to do with genetics than the neutering status).

There were cases of CCL in early neutered males and females, but none in the unaltered animals. (see my comments for hip dysplasia.)

Late neutered females: Had 4 times more HSA cases than the intact or early-neutered females. No MCT cases in intact females, but an occurance of nearly 6% in the late-neutered females. (This is interesting and I have no prior knowledge or experience that tells me whether there might be a confounding factor like in the early neutered male dog/lymphosarcoma link. Late spayed females covers a wide range of dogs - from those dogs like Tess that were neutered after their first heat at 14 months, to those retired breeding bitches who were neutered at 5 years of age after many heat cycles and/or pregnancies, because of the risk of pyometria etc. in an unbred intact bitch. Thus, I don't think that there is an inherent bias in dog quality in the late neutered females, like the early neutered dogs. I'm not sure what the mechanism would be for the increase in neoplasia, but I'm willing to consider this link as I know that hormones are powerful stuff and according to my experence so far, I don't see any obvious confounding factors with this link).

So what did I get out of the abstract? I'm still concerned about an inherent bias in the early neutered groups. The hip dysplasia/CCL link has been fairly well documented even though there's the confounding factor of dog quality, I think that previous research does a good job of linking hormones with bone development. I'm curious about the increased neoplasia in the late-neutered females and what the authors have to say about a potential mechanism, or if there's been other research that talks about this potential link.


2. Type of study and other general info......

The type of study is a retrospective review of records from a referral hospital at a vet school. As far as I can tell how the dogs were screened and chosen, it is in line with what is said in the news release and the abstract. I do wish that this study had taken related puppies/littermates and done a cohort study with them --> randomly neutering some early and late and leaving some intact. I feel that it would have been more valid. There is the argument that all golden retrievers are incredibly related thus genetics aren't a big deal and has actually been controlled for in this study by picking a single breed.....however being this is a referral hospital, I know they see quite a few very well bred Golden retrievers (out of the guide dog programs) that may or may not be altered, and I think it's unfair to compare them against golden retrievers that are almost a completely different breed - that of the backyard golden retriever (I have one, I know the difference!). Cohort studies are costly and take time, thus a retrospective is a viable alternative. I think another thing that would have made me more comfortable with the results in the expand the databases used - screen hospitals not considered referrals for the same breed/age range/diseases and add them to the results.

3. The figures!

Very nice graphs!!!!! that are actually self explanatory. Would have liked to see the confidence intervals/error bars so that it was more apparent what was statistically significant.

No CCL cases among intact males (and CCL cases occur in both early and late neutered males). Mean age of CCL onset in early neutered males is 3.6 years (the single late-neutered dog was diagnosed at 7.4 years). There is aboslutely no cases of lymphosarcoma in late neutered males (yet cases among both early neutered and intact males) - which is weird because if it's hormonally dependent I would have expected the late neutered dog to have some cases. According to the text in the actual paper, the age of onset for LSA in intact males and early neutered males is nearly identical (5.3 versus 5.8 years).

Bottom line: while the CCL condition seems to have some correlaton with neutering status for males, I'm not seeing it for LSA

In the female graph, there doesn't appear to be any difference between the 3 categories of dogs and hip dysplasia - why would presence/absence of gonadal hormones matter in the male but not the female? Weight is one factor thorugh to contribute to joint disease, and according to the text the BCS in the male dogs (ie how fat they were) was compared to the results and no difference was found between early-neutered dogs with and without HD when compared to their BCS scores (even though the early-neutered dogs were slighly fatter). Since female dogs tend to be smaller than their male counterparts, weight was one theory I had why HD would be significant in the male category and not here, but for there not to be a correlation between weight and HD among the males, makes me doubt that female dogs being smaller is the entire explanation.......something else is going on.

Another point in the female graph: Like in the intact male group NO cases of CCL in the unaltered group. However, there is also no CCL cases in the female neutered late group. Thus in terms of CCL, the late neutered female behaves like a unaltered female. Similarly in LSA the late neutered female is similar to the unaltered.

Bottom line for me: Assuming there is a link between the muscularskeletal system and neutering, it's a male problem and mostly related to early neutering, not late. LSA is much higher in early neutered dogs, but considering that there are ZERO cases in late neutered dogs (there are cases in intact dogs) I think it is valid to question whether this is a neutering related problem, or a genetic problem. There seems to be a stronger link between late female neutering and specific types of neoplasia (with the exception of LSA which seems to be relateded to early neutering, similar to the males). Neutering females late seems to eliminate any CCL risk related to neutering.

If I have a male dog.........wait to neuter until after 12 months to reduce hip dysplasia, while also reducing risk for CCL and LSA. Neutering late as opposed to not neutering at all seems to reduce the chances of LSA.

If I have a female dog......wait until after 12 months to reduce CCL risk (and LSA). Realize that by neutering late, there may be an creased risk of HSA and MCT as opposed to doing it early or keeping the bitch intact.

4. Methods section:

1. Besides the structure of the study already mentioned, another important point is that the neutering of animals occured PRIOR to the diagnosis of the condition. For example, there's a difference between a dog neutered at 8 months of age, then diagnosed with hip dysplasia at 18 months, and a dog that was diagnosed with hip dsyplasia at 18 months and then neutered at 20 months because he wasn't breeding quality due to the development of hip dysplasia. In the first case, an argument could be made that the neutering could affect the development of hip dysplasia, but in the second case, hip dysplasia was the cause of the neutering!

2. Only diseases with at least 15 cases found in the record database when screening based on the breed and age range were considered.

Bottom line: Overall seems sound. I think the inherent problem of there being a bias of lower quality animals in the early neutering group exists.

5. browsing other sections

In the second paragraph of the discussion section I run across this sentence: "for all five diseases analyzed in the present study, the disease rates in males and/or females were significantly increased when neutering was performed early and/or late. " Whoa whoa whoa!!!! Say what?

-- In male, the late neutered hip dysplasia rate was the same/less than the intact males. No difference in the females.

-- LSA risk is highest in early male neutered dogs, but there were NO cases in the late-neutered group, while there were a significant number of cases in the unaltered group.

--CCL numbers in female late neutered and unaltered females is the SAME. Same for LSA.

Thus I vementantly DISAGREE with that statement and do NOT believe that the authors have results that support that statement. If someone reads this and sees something I don't, please enlighten me

Reasons/mechanisms given for the musculoskeletal diseases described didn't introduce anything new. The authors give several suggestions for why the neoplasia numbers look like they do - mostly having to do with hormones sensitizing various cells, etc., all of which seem like valid working theories for future research.

How do I use this research?

I think that there is clear evidence for waiting to neuter males and females in regards to musculoskeletal conditions, keeping in mind that genetics may play a large factor is whether the animal actually develops the disease. However, I do NOT think that this study gave me a good reason to not neuter after 12 months and keep an animal intact as a way of avoiding disease, including neoplasia. A cohort study, or a retrospective that controlled for genetic pools of animals, and/or records pulled from a larger sampling of hospitals is needed for me to change my mind regarding not neutering for the health of an animal beyond 12 months of age.

Bottom line: Interesting, but I need to see further research before I start making animal health decisions based on this paper, especially in regards to the development of neoplasia. Definitely not a paper I would wave around as justification for not neutering my dog at any point.

As you can see, going through this process is a lot of work. It obviously is a lot more work and time to put it down on paper, and you aren't going to have to go through every point listed here for every paper. I do like this approach because it forces me to focus on the meat of the study and what they did or didn't do - not how well their introduction is written etc. By focusing on the claims, the method, and the figures/results, you can decide how far to take the reserach.



  1. I would also be interested to know the relative weights of the dogs. I know in speaking with a local ortho surgeon he was saying that he beleives the early neutering corrolation you see may also have to do with the weight of the dogs.

    1. Although they didn't look at the absolute weight of the dogs, they did compare bcs scores of all the early neutered dogs with and without.hip dysplasia and found no significant difference between the bcs who developed hip dysplasia and those that did not.


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