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Vasectomy and Risk of Prostate Cancer: Population Based BMJ: First Published As 10.1136/Bmj.I5546 on 3 November 2016

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Vasectomy and Risk of Prostate Cancer: Population Based BMJ: First Published As 10.1136/Bmj.I5546 on 3 November 2016 RESEARCH OPEN ACCESS Vasectomy and risk of prostate cancer: population based BMJ: first published as 10.1136/bmj.i5546 on 3 November 2016. Downloaded from matched cohort study Madhur Nayan,1 Robert J Hamilton,1 Erin M Macdonald,2 Qing Li,2 Muhammad M Mamdani,2,3 Craig C Earle,2,4 Girish S Kulkarni,1,2 Keith A Jarvi,5 David N Juurlink2,6 for the Canadian Drug Safety and Effectiveness Research Network (CDSERN) 1Division of Urology, ABSTRACT (adjusted odds ratio 1.04, 0.81 to 1.34), or mortality Departments of Surgery and OBJECTIVE (adjusted hazard ratio 1.06, 0.60 to 1.85). Surgical Oncology, Princess To determine the association between vasectomy and Margaret Cancer Centre, CONCLUSION University Health Network and prostate cancer, adjusting for measures of health The findings do not support an independent the University of Toronto, 610 seeking behaviour. association between vasectomy and prostate cancer. University Ave 3-130, Toronto, ON, M5G 2M9, Canada DESIGN 2 Population based matched cohort study. Institute for Clinical Evaluative Introduction Sciences, Toronto, ON, Canada SETTING 3 Vasectomy is a minor outpatient procedure with few Li Ka Shing Knowledge Multiple validated healthcare databases in Ontario, Institute, St Michael's Hospital, short term complications.1 2 It is effective in most men Canada, 1994-2012. Toronto, ON, Canada and one of the most reliable and cost effective long term 4 Ontario Institute for Cancer PARTICIPANTS methods of contraception.3 4 An estimated 33 million Research, Toronto, ON, Canada 326 607 men aged 20 to 65 who had undergone women worldwide rely on their partner’s vasectomy for 5Division of Urology, vasectomy were identified through physician billing contraception.5 Department of Surgery, Mount codes and matched 1:1 on age (within two years), year Sinai Hospital, University of Several studies have explored the possible associa- of cohort entry, comorbidity score, and geographical Toronto, Toronto, ON, Canada; tion between vasectomy and prostate cancer, with con- Faculty of Medicine, Institute of region to men who did not undergo a vasectomy. 6-30 Medical Science, University of flicting results. Potential biological mechanisms Toronto, Toronto, ON, Canada; MAIN OUTCOMES MEASURES supporting an association between vasectomy and inci- Lunenfeld Tannenbaum The primary outcome was incident prostate cancer. dent prostate cancer include increases in androgen lev- Research Institute, Mount Sinai Secondary outcomes were prostate cancer related Hospital, Toronto, ON, Canada els, which are hypothesised to increase the risk of 6 grade, stage, and mortality. 31 Department of Internal prostate cancer, and impaired secretory function of http://www.bmj.com/ Medicine, Sunnybrook Health RESULTS the prostate, which might prolong exposure of the pros- Sciences Centre, University of 3462 incident cases of prostate cancer were identified tate to carcinogenic factors.11 Although some studies Toronto, Toronto, ON, Canada after a median follow-up of 10.9 years: 1843 (53.2%) in have shown an increase in serum dihydrotestosterone Correspondence to: M Nayan 32-34 [email protected] the vasectomy group and 1619 (46.8%) in the non- and testosterone after vasectomy, others have found Additional material is published vasectomy group. In unadjusted analysis, vasectomy no statistically significant change in androgen online only. To view please visit was associated with a slightly increased risk of incident levels.35 36 Similarly, findings on the association the journal online. prostate cancer (hazard ratio 1.13, 95% confidence between frequency of ejaculation and risk of prostate on 26 September 2021 by guest. Protected copyright. Cite this as: BMJ 2016;355:i5546 interval 1.05 to 1.20). After adjustment for measures of cancer are conflicting 37. 38 Thus the possible biological http://dx.doi.org/10.1136/bmj.i5546 health seeking behaviour, however, no association relation, if any, between vasectomy and prostate cancer Accepted: 05 October 2016 remained (adjusted hazard ratio 1.02, 95% confidence remains unclear. interval 0.95 to 1.09). Moreover, no association was Many of the studies that found an association found between vasectomy and high grade prostate between vasectomy and prostate cancer were limited by cancer (adjusted odds ratio 1.05, 95% confidence sample size and the potential for selection, recall, and interval 0.67 to 1.66), advanced stage prostate cancer detection biases. Given the frequency of vasectomy, even a small increased risk of prostate cancer would constitute a major public health problem. We examined WHat IS ALREADY KNOWN ON THIS TOPIC the association between vasectomy and prostate cancer Studies evaluating the association between vasectomy and prostate cancer have in a large population based cohort, adjusting for health provided conflicting results seeking behaviours that might have biased other stud- ies examining this association. These studies have generally been limited by sample size and are prone to selection, recall, and detection biases Methods Given the frequency of vasectomy, even a small increased risk of prostate cancer Setting and data sources would constitute a major public health problem We conducted a population based matched cohort study WHat THIS stUDY ADDS of residents in Ontario, Canada. With a population of about 14 million in 2016,39 Ontario is Canada’s most In this large population based study using validated healthcare databases, vasectomy populous province, and residents have universal access does not seem to be independently associated with risk of prostate cancer to physician services and hospital care. We used the These findings have important implications for patients, clinicians, guidelines, Ontario health insurance plan database to identify phy- policy makers, and family planning support groups, and support the use of sician claims for vasectomy. The Ontario Cancer Regis- vasectomy as a safe method of contraception in men try40 was used to identify patients with incident prostate the bmj | BMJ 2016;355:i5546 | doi: 10.1136/bmj.i5546 1 RESEARCH cancer (international classification of diseases, ninth ity. We categorised prostate cancer grade as low (Gleason BMJ: first published as 10.1136/bmj.i5546 on 3 November 2016. Downloaded from and 10th revisions (ICD-9: 185 and ICD-10: C61, respec- score 2-6), intermediate (Gleason score 7), or high (Glea- tively), characteristics of their tumour, and date and son score 8-10), and prostate cancer stage as either local- cause of death, where applicable. It is a validated, pop- ised (stage T1-2) or advanced (stage T3+, N+, or M+). ulation based tumour registry maintained by Cancer We followed participants until their date of last con- Care Ontario and is estimated to be more than 95% com- tact with health services, death, or the end of the study plete.40 41 We obtained data on admissions to hospitals period, whichever occurred first. For the analysis of from the Canadian Institute for health information dis- mortality, we followed patients until 31 December 2012, charge abstract database,42 national ambulatory care the last date for which cancer specific mortality data reporting system, and same day surgery database, were available. For all other outcomes, we followed which contain detailed clinical information on admis- patients until 31 March 2014. sions to hospitals and emergency departments and out- patient surgical procedures in Ontario. We obtained Covariates basic personal data from the registered persons data- To deal with the possibility of healthy user bias, we base, a registry of all Ontario residents eligible for health obtained data on the number of admissions to hospitals insurance. These databases were linked in an anony- and the number of visits to general practitioners, spe- mous fashion using encrypted health card numbers, cialists, urologists, and emergency departments. For and are routinely used to study the long term conse- each of these, we identified the number of interactions quences of medical care.43-45 Details of the databases in the year preceding the index date and between the used and their validity have been described elsewhere.46 index date and end of follow-up. To account for survival bias, whereby those who survive longer are likely to Study participants have a higher number of interactions with healthcare We identified all men aged 20 to 65 who underwent a services, we standardised interactions with healthcare vasectomy between 1 April 1994 and 31 December 2012. services to duration of follow-up by dividing the num- We excluded those with a diagnosis of prostate cancer ber of interactions by follow-up time. before vasectomy, those who underwent a vasovasos- To adjust for potential detection bias, we obtained data tomy (vasectomy reversal) at any time before the cen- on the number of colonoscopies, faecal occult blood tests, soring date, and those who underwent other procedures and cholesterol tests. We chose these tests as they are on the same day that were inconsistent with receipt of a insured under the universal healthcare system in Ontario vasectomy for the purpose of contraception—for exam- and therefore the data were available within the data- http://www.bmj.com/ ple, vasectomy performed on the same day as prostatec- bases used for this study, whereas testing for prostate spe- tomy or vesiculectomy (removal of seminal vesicles). cific antigen is not. We assumed that patients undergoing The date of vasectomy served as the index date. these prevention tests would also be likely to undergo For each man who underwent vasectomy, we selected testing for prostate specific antigen. Indeed, the associa- one man who did not, matching on age (within two tion between prostate and colorectal cancer screening years), comorbidity score (defined using the Johns Hop- has been shown among men in Alberta, another province kins adjusted clinical groups case mix system),47 geo- in Canada with universal healthcare.50 We similarly on 26 September 2021 by guest. Protected copyright. graphical area (defined by the first three digits of the divided these tests into subcategories according to postal code), and index date.
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