A.T. Kristensen; M.M.E. Larsen
Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
Androgens, oestrogen and progesterone are all steroid hormones produced mainly in the gonads of both male and female dogs in varying amounts. Small amounts are produced in other tissues, such as the adrenals, in amounts overall negligible in the intact individual. These extra gonadal production sites may increase their production in the gonadectomised individual.
Steroid hormones have hydrophobic properties, and diffuse passively across cell membranes. The hormonal receptors are nuclear transcription factors, bound to the nuclear DNA, and when activated by different processes, result in gene transcription. The tissue and cellular distribution of the different receptors determines the physiological effect of the hormone-hormone receptor binding.
Gonadal hormones are needed to obtain the sexual characteristics for the individual as whole and for development of specific tissues in the dog, as well as other mammals. Oestrogen and progesterone are hormones essential to the normal development of mammary tissue in the female, and early gonadectomy will hinder the natural proliferation of tissue and thereby decrease the risk of mammary neoplasia. Contrary to previous beliefs, gonadectomy in the mature female has been shown to exert a preventive effect on neoplastic development of the mammary glands.1,2 In the male dog, androgens promote perianal adenomas, but seems to have a protective effect against prostate tumours.3
In 1999, Ware showed a significant correlation between gonadectomised females and cardiac haemangiosarcoma,4 and since then several studies have shown correlations between gonadectomy and several cancers outside the reproductive system, previously believed to be independent of gonadal hormones.5-10
Significant correlations have been shown for mast cell tumour, lymphoma, haemangiosarcoma and osteosarcoma. Several studies are breed specific and in a retrospective case-control study of Hart and others,9 a difference was found between incidence of cancer in gonadectomised Golden Retrievers and Labrador Retrievers, suggesting that there is a true breed difference to the influence of gonadectomy on occurrence of specific cancers.
The incidence of cancer is normally low within a population, with a long induction time, therefore prospective studies are not economically and time-wise considered feasible. When the incidence of disease is low, large populations are needed when analyzing for risk factors. Accordingly studies are mostly case-control studies, or retrospective cohort studies within a breed with a high breed prevalence, as for Cooley et al.7 in the study of correlation of osteosarcoma within a cohort of Rottweiler.
In human cancer medicine, public registration is mandatory in many countries resulting in large, multi institutional data collection. In companion animals, national cancer registries exist in smaller numbers and many inactive. One of the larger, active databases is The Veterinary Medical Database (VMDB), initiated in 1964 and still receiving registrations.
In Denmark, the Danish Veterinary Cancer Registry was established in 2005, based on the University of Copenhagen and supported by The Danish Kennel Club. The registry is web-based and voluntary, collecting data of registered neoplasm of dogs and cats across the country.
In 2014, a preliminary study showed significant correlation between gonadectomy and several cancers outside the reproductive system, while no correlation was shown for other investigated cancers. The results were presented as an abstract at ECVIM 2014, and further studies are ongoing.
In Denmark, dogs are not routinely gonadectomised before puberty contrary to many other countries, which gives a unique possibility to investigate the correlation between timing of gonadectomy and cancer incidence. Therefore, a study was carried out correlating the age at gonadectomy to occurrence of any of the four cancers; mast cell tumour, lymphoma, hemangiosarcoma and osteosarcoma, showing significant correlation for age of gonadectomy and occurrence of some cancers. These findings are supported by previous studies, though the results are not directly comparable as the stratification of age at gonadectomy were different between studies.5,7,8 Selected data from the preliminary study and the current study will be presented at the WSAVA 2017 conference.
1. Sorenmo KU, Shofer FS, Goldschmidt MH. Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma. J Vet Intern Med. 2000;14(3):266–270. Available from http://doi.wiley.com/10.1111/j.1939-1676.2000.tb01165.x.
2. Kristiansen VM, Ndtvedt A, Breen AM, Langeland M, Teige J, Goldschmidt M, et al. Effect of Ovariohysterectomy at the time of tumor removal in dogs with benign mammary tumors and hyperplastic lesions: a randomized controlled clinical trial. J Vet Intern Med. 2013;27(4):935–942.
3. Teske E, Naan EC, Garderen ME, Van E, Schalken JA. Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs. Mol Cell Endocrinol. 2002;197(1–2):251–255. https://www.ncbi.nlm.nih.gov/pubmed/12431819
4. Ware WA, Hopper DL. Cardiac tumors in dogs: 1982–1995. J Vet Intern Med. 1999;13:95–103.
5. Zink MC, Farhoody P, Elser SE, Ruffini LO, Gibbons TA, Rieger RH. Evaluation of the risk and age of onset of cancer and behavioral disorders in gonadectomized vizslas. J Am Vet Med Assoc. 2014;244(3):309–319. http://avmajoumals.avma.org/doi/abs/10.2460/javma.244.3.309 (VIN editor: URL was not accessible as of 5-17-2018).
6. Griintzig K, Graf R, Boo G, Guscetti F, Hassig M, Axhausen KW, et al. Swiss Canine Cancer Registry 1955–2008: Occurrence of the most common tumour diagnoses ano influence of age, breed, body size, sex and neutering status on tumour development. J Comp Pathol. 2016;1–15.
7. Cooley OM, Beranek BC, Schlittler DL, Glickman NW, Glickman LT, Waters DJ. Endogenous gonadal hormone exposure and bone sarcoma risk. Cancer Epidemiol Biomarkers Prev. 2002;11(11):1434–1440.
8. Torres de la Riva G, Hart BL, Farver TB, Oberbauer AM, Messam LLM V, Willits N, et al. Neutering dogs: effects on joint disorders and cancers in Golden Retrievers. PLoS One. 2013;8(2).
9. Hart BL, Hart LA, Thigpen AP; Willits NH. Long-term health effects of neutering dogs: comparison of Labrador retrievers with golden retrievers. PLoS One. 2014;9(7).
10. White CR, Hohenhaus AE, Kelsey J, Procter-Gray E. Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster. J Am Anim Hosp Assoc. 2011;47(3):210–216. http://jaaha.org/doi/abs/10.5326/JAAHA-MS-5621.