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. 2017 Sep 5;177(9):1273–1286. doi: 10.1001/jamainternmed.2017.2791

The Association Between Vasectomy and Prostate Cancer

A Systematic Review and Meta-analysis

Bimal Bhindi 1, Christopher J D Wallis 2, Madhur Nayan 3, Ann M Farrell 4, Landon W Trost 1, Robert J Hamilton 3, Girish S Kulkarni 3, Antonio Finelli 3, Neil E Fleshner 3, Stephen A Boorjian 1, R Jeffrey Karnes 1,✉
PMCID: PMC5710573  PMID: 28715534

Abstract

Importance

Despite 3 decades of study, there remains ongoing debate regarding whether vasectomy is associated with prostate cancer.

Objective

To determine if vasectomy is associated with prostate cancer.

Data Sources

The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched for studies indexed from database inception to March 21, 2017, without language restriction.

Study Selection

Cohort, case-control, and cross-sectional studies reporting relative effect estimates for the association between vasectomy and prostate cancer were included.

Data Extraction and Synthesis

Two investigators performed study selection independently. Data were pooled separately by study design type using random-effects models. The Newcastle-Ottawa Scale was used to assess risk of bias.

Main Outcomes and Measures

The primary outcome was any diagnosis of prostate cancer. Secondary outcomes were high-grade, advanced, and fatal prostate cancer.

Results

Fifty-three studies (16 cohort studies including 2 563 519 participants, 33 case-control studies including 44 536 participants, and 4 cross-sectional studies including 12 098 221 participants) were included. Of these, 7 cohort studies (44%), 26 case-control studies (79%), and all 4 cross-sectional studies were deemed to have a moderate to high risk of bias. Among studies deemed to have a low risk of bias, a weak association was found among cohort studies (7 studies; adjusted rate ratio, 1.05; 95% CI, 1.02-1.09; P < .001; I2 = 9%) and a similar but nonsignificant association was found among case-control studies (6 studies; adjusted odds ratio, 1.06; 95% CI, 0.88-1.29; P = .54; I2 = 37%). Effect estimates were further from the null when studies with a moderate to high risk of bias were included. Associations between vasectomy and high-grade prostate cancer (6 studies; adjusted rate ratio, 1.03; 95% CI, 0.89-1.21; P = .67; I2 = 55%), advanced prostate cancer (6 studies; adjusted rate ratio, 1.08; 95% CI, 0.98-1.20; P = .11; I2 = 18%), and fatal prostate cancer (5 studies; adjusted rate ratio, 1.02; 95% CI, 0.92-1.14; P = .68; I2 = 26%) were not significant (all cohort studies). Based on these data, a 0.6% (95% CI, 0.3%-1.2%) absolute increase in lifetime risk of prostate cancer associated with vasectomy and a population-attributable fraction of 0.5% (95% CI, 0.2%-0.9%) were calculated.

Conclusions and Relevance

This review found no association between vasectomy and high-grade, advanced-stage, or fatal prostate cancer. There was a weak association between vasectomy and any prostate cancer that was closer to the null with increasingly robust study design. This association is unlikely to be causal and should not preclude the use of vasectomy as a long-term contraceptive option.

This systematic review and meta-analysis investigates whether vasectomy is associated with prostate cancer.

Key Points

Question

Is there an association between vasectomy and prostate cancer, high-grade prostate cancer, advanced prostate cancer, and/or fatal prostate cancer?

Findings

In this systematic review and meta-analysis including 53 studies, there was a weak, clinically insignificant association between vasectomy and prostate cancer. No association was found between vasectomy and risk of high-grade, advanced, or fatal prostate cancer.

Meaning

At most, there is a trivial association between vasectomy and prostate cancer that is unlikely to be causal; therefore, concerns about prostate cancer should not preclude the use of vasectomy as an option for long-term contraception.

Introduction

Vasectomy is a highly efficacious long-term contraceptive method that involves a simple outpatient procedure under local anesthetic. It is less expensive and has a lower risk of complications compared with tubal ligation, the analogous female surgical sterilization procedure. Although 43 million women worldwide rely on their partner’s vasectomy for contraception, vasectomy is still considered to be underused in the United States, with only 8% to 12% of couples using vasectomy for birth control.

In the late 1980s and early 1990s, several reports began to emerge of an epidemiologic association between vasectomy and the risk of prostate cancer. This finding ignited a controversy captured in numerous editorials, reviews, and original research articles supporting or refuting the association. Several meta-analyses of this association have been performed, but they did not bring closure to the debate. One older meta-analysis pooling 5 cohort studies and 17 case-control studies found a significant association between vasectomy and prostate cancer. Meanwhile, 2 more recent meta-analyses of cohort studies found no statistically significant association, although the CIs of pooled effect estimates precluded definitive conclusions. Moreover, none of these meta-analyses included a sufficient number of studies with a low risk of bias to analyze them as a separate subset, nor were the meta-analyses able to evaluate the association between vasectomy and risk of high-grade, advanced-stage, and fatal prostate cancer.

Recently, several large, high-quality analyses demonstrating either an association or no association between vasectomy and prostate cancer have reignited the controversy. With the aim of shedding some light onto a debate that is 3 decades old, we conducted a systematic review of the literature and performed a meta-analysis, with particular attention to study quality, to determine if there is an association between vasectomy and any prostate cancer, high-risk prostate cancer, advanced prostate cancer, and lethal prostate cancer.

Methods

Research Question

Is there an association between vasectomy and a subsequent diagnosis of prostate cancer? More specifically, is vasectomy associated with a diagnosis of any prostate cancer, high-risk prostate cancer, advanced prostate cancer, and/or fatal prostate cancer? The Mayo Clinic Institutional Review Board waived the need for review of this study.

Types of Studies

We included cohort, case-control, and cross-sectional studies. Case series lacking comparator groups were excluded. Other publications, including editorials, commentaries, review articles, and those not subject to peer review (ie, reports of data from Vital Statistics and dissertations or theses), were excluded. When there was more than 1 publication resulting from the same patient cohort, we selected a single representative study, with a preference for more contemporary publications and publications with a larger number of patients and more reliable methods of exposure and outcome ascertainment.

Types of Participants and Exposure

We reviewed studies reporting on men of any age who underwent vasectomy compared with those who did not undergo vasectomy. Vasectomy exposure was determined by administrative and clinical health records, survey results, and/or patient recall.

Outcome Measures

The primary outcome was any subsequent diagnosis of prostate cancer. Secondary outcomes included the diagnoses of high-grade prostate cancer (based on individual study definition, typically Gleason score ≥8), advanced prostate cancer (based on individual study definition, typically T3/4, N+, or M+), and fatal prostate cancer.

Methods of Systematic Review

We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for reporting of this systematic review and meta-analysis.

Search Strategy

The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched by a professional librarian using the OvidSP platform for studies indexed from database inception to March 21, 2017. We used both subject headings and text word terms for vasectomy, ductus deferens, prostatic neoplasms, and related and exploded terms including MeSH terms in combination with key word searching. A full search strategy is presented in eAppendix 1 in the Supplement. No limitations were placed with respect to publication language or publication year. Following the literature search, all duplicates were excluded. References from review articles, commentaries, editorials, included studies, and conference publications of relevant medical societies were hand searched and cross-referenced to ensure completeness. Conference abstracts were included when sufficient information could be obtained from the corresponding authors.

Study Review Methods

Two of us performed study selection independently (B.B. and C.J.D.W.). Disagreements were resolved by consensus. Titles and abstracts were used to screen for initial study inclusion. Full-text review was used when abstracts were insufficient to determine if the study met inclusion or exclusion criteria. Studies were considered relevant if they reported an effect estimate for an association between vasectomy and any prostate cancer outcome, or provided sufficient data for this estimate to be calculated. One of us (B.B.) performed all data abstraction, including evaluation of study characteristics, risk of bias, and outcome measures, with independent verification performed by another one of us (C.J.D.W.).

Assessment of Risk of Bias

We used the Newcastle-Ottawa Scale for assessment of risk of bias. This scale assesses risk of bias in the following 3 domains: selection of the study groups, comparability of groups, and ascertainment of exposure and outcome. Studies with scores of less than 4 were considered to have a high risk of bias, those with scores of 4 to 6 an intermediate risk of bias, and those with scores of 7 or more a low risk of bias.

Measures of Treatment Effect

Measures of treatment effect varied among study designs. Among cross-sectional and case-control studies, we pooled odds ratios (ORs). In each case, we examined unadjusted and adjusted measures of effect separately. Among cohort studies, we first pooled ratio measures of effect (including hazard ratios [HRs], rate ratios [RRs], and ORs). Subsequently, we performed subgroup analysis using only studies that reported time-to-event data (HRs).

Assessment of Heterogeneity

We identified heterogeneity using the Q test, estimated it using the DerSimonian-Laird method, and quantified it using I2 values. Furthermore, we used random-effects models for each of our analyses, given the identified clinical heterogeneity.

Assessment of Reporting Bias

We assessed publication bias for outcomes with more than 10 included studies using funnel plots.

Data Synthesis

Meta-analysis was performed using Review Manager, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration). We used the inverse variance technique for pooling of measures of effect. Owing to the clinical heterogeneity inherent in our data, random-effects models were used for all meta-analyses. A sensitivity analysis was performed to determine if excluding any individual study altered our results.

Subgroup and Exploratory Analyses

We performed a priori subgroup analyses. First, as already mentioned, we examined cohort studies that used a time-to-event analysis separately. Second, we examined studies identified as having a low risk of bias. Third, we evaluated the studies that provided effect estimates stratified by time since vasectomy and age at which vasectomy was performed.

We also performed post hoc subgroup analyses. First, we examined cohort studies in which all patients were following a prostate-specific antigen (PSA) screening protocol or in which PSA screening was accounted for in multivariable models. Second, we examined cohort studies in which PSA screening was not performed or was very uncommon.

Finally, to facilitate interpretation of relative effect estimates for clinicians and policymakers, the pooled effect estimate from the meta-analysis was used to estimate the absolute risk increase, the number needed to harm, and the population attributable fraction. For these calculations, the lifetime risk of prostate cancer was considered to be 12.9% and the probability of undergoing vasectomy was 10%.

Results and Evidence Synthesis

Our literature search identified 433 unique references (Figure 1). After a full-text review of 115 manuscripts, 53 were selected for inclusion. The reasons for exclusion are summarized in Figure 1 and eAppendix 2 in the Supplement.

Figure 1. PRISMA Flow Diagram Outlining Search Strategy and Final Included and Excluded Studies.

Figure 1.

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Description of Studies

Among the 53 included studies, 16 were cohort studies (2 563 519 participants), 33 were case-control studies (44 536 participants), and 4 were cross-sectional studies (12 098 221 participants). Although most studies were population- or registry-based analyses, several articles presented single- or multiple-institution analyses (Table). Duration of follow-up varied widely among cohort studies, with a minimum of 1.8 years and a maximum of 24 years. In general, the patients with and the patients without a history of vasectomy were similar in age among cohort studies. Among the case-control studies, the patients with and the patients without a diagnosis of cancer were generally similar in age, although, in some analyses, patients who received a diagnosis of prostate cancer were older. The risk-adjustment approach varied across studies (eTable 1 in the Supplement).

Table. Characteristics of 53 Included Studies.

Source Data Source Study Interval Follow-up Duration, y Sample Size, No. Patients With Vasectomy, No. (%) Age Outcomes Patients Diagnosed With PCa, No.
Vasectomy No Vasectomy
Cohort studies
Coulson et al, 1993 Minnesota and California, US NA Vasectomy, 8.3; no vasectomy, 8.8 21 180 10 590 (50.0) Mean, y: 36 NA PCa 13
Davenport et al, 2016 NIH-AARP Diet and Health Study, US NA 18 100 134 30 803 (30.8) NA NA PCa 14 127
Eisenberg et al, 2015 Truven Health Marketscan claims database, US 2001-2009 Summary value, NA 873 485 112 655 (12.9) No. (%): 18-19 y, 14 (0.01); 20-29 y, 10324 (9.2); 30-39 y, 64372 (57.1); 40-50 y, 37945 (33.7) No. (%): 18-19 y, 1110 (0.2); 20-29 y, 133310 (17.52); 30-39 y, 452740 (59.5); 40-50 y, 173670 (22.83) PCa 4905
Giovannucci et al, 1993 Nurses’ Health Study, US 1976-1989 11 25 340 13 034 (51.4) Mean (SD), y: 42.0 (7.0) Mean (SD), y: 42.2 (7.1) PCa 96
Goldacre et al, 2005 National Health System, Oxford, England 1963-1999 Vasectomy, 12.7; no vasectomy, NA 184 253 24 773 (13.4) No. (%): 20-24 y, 190 (0.8); 25-29 y, 2916 (11.8); 30-34 y, 8088 (32.6); 35-39 y, 7628 (30.8); 40-44 y, 3894 (15.7); 45-49 y, 1463 (5.9); 50-54 y, 435 (1.8); 55-59 y, 159 (0.6) No.: 20-24 y, 33 308; 25-29 y, 25 865; 30-34 y, 20 195; 35-39 y, 16 621; 40-44 y, 15 576; 45-49 y, 15 496; 50-54 y, 16 032; 55-59 y, 16 387 PCa 656
Hiatt et al, 1994 California, US 1979-1985 4.6 43 432 NR Mean (SD), y: 47.4 (13.0) PCa 238
Jacobs et al, 2016 CPS-II + CPS-II Nutrition, US 1982-2012 CPS-II, 21.4; CPS-II Nutrition, 12.9 CPS-II, 363 726; CPS-II Nutrition, 66 542 CPS-II, 42 015 (11.6); CPS-II Nutrition, 10 589 (15.9) %: 40-49 y, 16.6; 50-59 y, 39.2; 60-69 y, 32.1; 70-79 y, 10.9; ≥80 y, 1.2 %: 40-49 y, 37.1; 50-59 y, 48.5; 60-69 y, 12.8; 70-79 y, 1.4; ≥80 y, 0.1 PCa, HG-PCa, advanced PCa, and fatal PCa PCa, 9133; HG-PCa, 1250; advanced PCa, 939; and fatal PCa, 7451
Lynge, 2002 Danish population-based registry 1977-1995 12.7 57 931 (cohort of men who had vasectomy compared with Danish population using standardized incidence ratio) 57 931 (100) No. (%): ≤24 y, 76 (<1); 25-29 y, 5629 (10); 30-34 y, 16628 (29); 35-39 y, 18843 (33); 40-44 y, 11198 (19); 45-49 y, 4050 (7); 50-54 y, 1081 (2); 55-59 y, 292 (<1); ≥60 y, 134 (<1) NA PCa 46
Nayan et al, 2016 Ontario, Canada, population-based registry 1994-2012 10.9 653 214 326 607 (50.0) Mean (SD), y: 37.3 (6.2) Mean (SD), y: 37.3 (6.2) PCa, HG-PCa, advanced PCa, and fatal PCa PCa, 3462; and fatal PCa, 50
Rohrmann et al, 2005 CLUE II Cohort, Maryland, US 1989-2004 8.3 3373 918 (27.2) Mean (SD), y: 49.2 (9.0) Mean (SD), y: 54.8 (11.3) PCa, HG-PCa, and advanced PCa PCa, 78; HG-PCa, 24; and advanced PCa, 15
Romero et al, 2012 Curitiba, Brazil 2006-2011 1.8 2121 259 (12.2) No. (%): 40-49 y, 805 (38.0); 50-59 y, 859 (40.5); 60-69 y, 350 (16.5); ≥70, 107 (5.0) NA PCa 58
Shoag et al, 2016 PLCO trial, US 1993-2009 13 73 180 19 965 (27.3) NA NA PCa NA
Smith et al, 2017 European Prospective Investigation into Cancer and Nutrition 1992-2012 15.4 84 743 12 712 (15.0) Median (IQR), y: 52.0 (47.0-57.0) Median (IQR), y: 54.0 (48.0-60.0) PCa, HG-PCa, advanced PCa, and fatal PCa PCa, 4377; HG-PCa, 544; advanced PCa, 633; and fatal PCa, 632
Siddiqui et al, 2014 Health Professionals Follow-up Study, US 1986-2010 24 49 405 12 321 (24.9) Mean, y: 51.8 Mean, y: 55.5 PCa, HG-PCa, advanced PCa, and fatal PCa PCa, 6023; HG-PCa, 732; advanced PCa, 1052; and fatal PCa, 811
Tangen et al, 2016 PCPT trial, US 1994-2003 7 8052 2644 (32.8) No. (%): ≤59 y, 2497 (31.0); 60-64 y, 2429 (30.2); 65-69 y, 1901 (23.6); and ≥70, 1225 (15.2) PCa 574
van Leeuwen et al, 2011 ERSPC-Rotterdam screening arm, the Netherlands 1993-2008 11.1 19 950 5141 (25.8) Median, y: 63 Advanced PCa;
PCa mets; and
fatal PCa		 Advanced PCa: 2420; and
fatal PCa: 104
Case-control studies Cases Controls
Andersson et al, 1996 Orebro County, Sweden 1989-1991 NA 508 9 (1.8) Mean (SD), y: 70.0 (6.1) Mean (SD), y: 69.8 (6.2) PCa 256
Cossack et al, 2014 Creighton University, Northeast, US NA NA 74 17 (23.0) NA NA PCa 24
Cox et al, 2002 New Zealand Cancer Registry 1996-1998 NA 2147 549 (25.6) Mean, y: 66.3 Mean, y: 65.1 PCa and advanced PCa 923
Emard et al, 2001 Quebec, Canada, population-based registry 1984-1993 NA 6349 110 (1.7) Mean (SD), y: 68.2 (2.8) Mean (SD), y: 67.9 (2.9) PCa 2962
Ewings et al, 1996 Taunton, Yeovil, Exeter Hospitals, England 1989-1991 NA 484 8 (1.7) No. (%): <70 y, 33 (21); 70-79 y, 90 (57); ≥80 y, 36 (23) No. (%): <70 y, 86 (26); 70-79 y, 172 (53); ≥80 y, 67 (21) PCa 159
Ganesh et al, 2011 Tata Memorial Hospital, India 1999-2001 NA 275 39 (14.2) Mean, y: 64 Mean, y: 45 PCa 123
Hayes et al, 1993 Population-based cancer registries in Michigan, Georgia, and New Jersey, US 1986-1989 NA 2257 139 (6.2) No. (%): 40-59 y, 279 (29); 50-69 y, 338 (35); ≥70 y, 348 (36) No. (%): 40-59 y, 537 (42); 50-69 y, 395 (31); ≥70 y, 360 (28) PCa 965
Hennis et al, 2013 Barbados nationwide cohort 2002-2011 NA 1904 1.5% of Cases; 0.7% of controls (exact number not given) Mean (SD), y: 67.2 (9.0) Mean (SD), y: 67.0 (9.2) PCa 963
Holt et al, 2008 Seattle-Puget Sound Tumor Registry, Washington, US 2002-2005 NA 1943 36% (exact number not given) %: 40-49 y, 7.9; 50-54 y, 9.4; 55-59 y, 19.1; 60-64 y, 21.2; 65-69 y, 23.8; 70-74 y, 18.5 %: 40-49 y, 11.5; 50-54 y, 13.5; 55-59 y, 18.1; 60-64 y, 19.1; 65-69 y, 20.1; 70-74 y, 17.8 PCa 1001
Honda et al, 1988 Los Angeles, California, US, population-based registry 1979-1982 NA 392 103 (26.3) No. (%): <53 y, 32 (15); 53-57 y, 67 (31); 58-60 y, 117 (54) NA PCa 1988
Hsing et al, 1994 Multi-institutional Chinese cohort 1989-1992 NA 776 33 (4.3) No. (%): 40-59 y, 13 (9.6); 60-69 y, 54 (39.7); ≥70 y, 69 (50.7) No. (%): 40-59 y, 69 (10.8); 60-69 y, 252 (39.5); ≥70 y, 317 (49.7) PCa 138
John et al, 1995 Population-based registries in US and Canada 1987-1991 NA 3278 336 (10.3) Mean, y: 70.5 Mean, y: 70.0 PCa 1642
Kobayashi et al, 2012 Kingston General Hospital, Ontario, Canada 1997-1999 NA 414 116 (28.0) Mean (SD), y: 65.1 (6.0) Mean (SD), y: 63.6 (6.9) PCa 80
Lesko et al, 1999 Massachusetts, US, Cancer Registry 1992-1996 NA 2616 414 (15.8) Vasectomy (%): <60 y, 46; 60-64 y, 28; ≥65 y, 26. No vasectomy (%): <60 y, 20; 60-64 y, 29; ≥65 y, 50 Vasectomy (%): <60 y, 40; 60-64 y, 33; ≥65 y, 27. No vasectomy (%): <60 y, 22; 60-64 y, 29; ≥65 y, 49 PCa and advanced PCa 1216
Liang et al, 2007 Multi-institutional Chinese cohort 2005-2006 NA 186 16 (8.6) Median, y: 69.5 Median, y: 69.0 PCa 62
Lightfoot et al, 2004 Northeastern Ontario, Canada 1995-1999 NA 2354 449 (19.1) No. (%): 45-49 y, 8 (1.1); 50-54 y, 25 (3.3); 55-59 y, 50 (6.6); 60-64 y, 134 (17.6); 65-69 y, 222 (29.2); 70-74 y, 181 (23.8); 75-79 y, 109 (14.3); 80-84 y, 31 (4.1) No. (%): 45-49 y, 19 (1.2); 50-54 y, 69 (4.2); 55-59 y, 138 (8.5); 60-64 y, 271 (16.6); 65-69 y, 445 (27.3); 70-74 y, 389 (23.8); 75-79 y, 205 (12.6); 80-84 y, 96 (5.9) PCa 744
Mazdak et al, 2012 Isfahan, Iran 2005-2009 NA 190 22 (11.6) Mean (SD), y: 73.1 (7.5) Mean (SD), y: 67.9 (8.3) PCa 95
Mettlin et al, 1990 Roswell Park Memorial Institute, New York, US 1982-1988 NA 3202 154 (4.8) Mean (SD), y: 68.4 (7.5) Mean (SD), y: 64.9 (8.5) PCa 614
Nair-Shalliker et al, 2017 New South Wales, Australia 2006-2014 NA 2056 NR Median, y: 65.6 Median, y: 59.0 PCa 1181
Patel et al, 2005 Wayne County, Michigan, US 1996-1998 NA 1304 164 (12.6) No. (%): 50-54 y, 59 (8.4); 55-59 y, 93 (13.3); 60-64 y, 135 (19.3); 65-69 y, 205 (29.3); 70-74 y, 208 (29.7) No. (%): 50-54 y, 73 (12.1); 55-59 y, 97 (16.1); 60-64 y, 93 (15.4); 65-69 y, 179 (29.6); 70-74 y, 162 (26.8) PCa 700
Platz et al, 1997 Bombay Cancer Registry, India 1993-1994 NA 1153 100 (8.7) Mean, y: 67.3 Mean, y: 59.1 PCa 175
Pourmand et al, 2007 Multi-institutional Iranian cohort 2005-2007 NA 205 19 (9.3) Mean (SD), y: 70.5 (8.3) Mean (SD), y: 65.7 (9.9) PCa 130
Rosenberg et al, 1994 Multi-institutional US cohort: Boston, New York, Philadelphia, and Baltimore 1977-1992 NA 7580 468 (6.2) No. (%): 30-49 y, 19 (34.3); 50-59 y, 119 (21.5); 60-69 y, 415 (75.0) No. (%): 30-49 y, 3769 (53.6); 50-59 y, 1817 (25.9); 60-69 y, 1441 (20.5) PCa and
advanced PCa		 553
Ross et al, 1983 Los Angeles, California, US, population-based registry 1972-1980 NA 220 15 (6.8) NA NA PCa 110
Schwingl et al, 2009 Multi-institutional cohort from China, Nepal, and Korea 1994-1997 NA 1173 120 (10.2) Mean (SD), y: 66.6 (6.1) Mean (SD), y: 66.4 (6.1) PCa and advanced PCa 294
Spitz et al, 1991 MD Anderson Cancer Center, Texas, US NA NA 703 NR NA NA PCa 343
Sridhar et al, 2010 Virginia, US, private urology practice 2000-2005 NA 3710 348 (9.4) No. (%): ≤60 y, 70 (13.2); 61-70 y, 183 (34.4); >70 y, 279 (52.4) No. (%): ≤60 y, 375 (59.7); 61-70 y, 175 (27.9); >70 y, 78 (12.4) PCa 1237
Stanford et al, 1999 Seattle-Puget Sound Cancer Registry, Washington, US 1993-1996 NA 1456 562 (38.6) NA Vasectomy (%): 40-49 y, 7.9; 50-54 y, 21.9; 55-59 y, 40.8; 60-64 y, 29.4. No vasectomy (%): 40-49 y, 8.4; 50-54 y, 18.3; 55-59 y, 35.6; 60-64 y, 37.7 PCa, HG-PCa, and advanced PCa 753
Sunny, 2005 Bombay Cancer Registry, India 1998-2000 NA 1170 136 (11.6) Mean, y: 71.2 Mean, 64.4 PCa 390
Tyagi et al, 2010 Delhi Cancer Registry, India 1998-2000 NA 909 119 (13.1) Mean, y: 69.7 Mean, y: 65.6 PCa 303
Wei et al, 1994 First Affiliated Hospital of West China University of Medical Sciences NA NA 81 4 (4.9) NA NA PCa 27
Weinmann et al, 2010 Kaiser Permanente California and Northwest Region and Henry Ford Health System, US 1974-2000 NA 1697 101 (6.0) No. (%): <60 y, 91 (11.8); 60-69 y, 326 (42.4); 70-79 y, 326 (42.4); 80-84 y, 25 (3.3) NA Fatal PCa 768
Zhu et al, 1996 Group Health Cooperative of Puget Sound, Washington, US 1989-1991 NA 433 154 (35.6) NA NA PCa 175
Cross-sectional studies Participants With or Without Vasectomy
Alqahtani et al, 2015 Nationwide Inpatient Sample, US 2007-2011 NA 12 000 718 0.03% of Cohort (exact number not reported) Mean (SD), y: 64.2 (14.7) PCa 642 383
Chacko et al, 2002 Stanford Medical Center, California, US 1998-2001 NA 303 101 (33.3) Mean (range), y: 65 (39-86) PCa and HG-PCa 144
DeAntoni et al, 1997 Multi-institutional PCa screening cohort, US 1993-1995 NA 95 961 26 632 (27.8) Mean (SD), y: 61.7 (8.0) PCa 766
Garzotto et al, 2003 Portland Veterans Affairs Hospital, Oregon, US 1993-2000 NA 1239 NR Median, y: 66 PCa 300
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Abbreviations: CLUE II, Cohort Study–CLUE II [see Cancer Epidemiology Descriptive Cohort Study Database website, Johns Hopkins Bloomberg School of Public Health]; CPS-II, Cancer Prevention Study II; ERSPC, European Randomized Study of Screening for Prostate Cancer; HG-PCa, high-grade prostate cancer; IQR, interquartile range; NA, not available; NIH-AARP, National Institutes of Health–American Association of Retired Persons; NR, not reported; PCa, prostate cancer; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer screening trial; PCPT, Prostate Cancer Prevention Trial; US United States.

Assessment of Risk of Bias

Assessment of risk of bias was performed according to study methods (eTable 2 in the Supplement). Nine of the cohort studies (56%) were assessed as having a low risk of bias. Exposure was ascertained by self-report or questionnaire results in several of these studies. Eight of 16 cohort studies (50%) accounted for PSA testing and/or health-seeking behavior. Most case-control studies (26 [79%]) were considered to have a moderate to high risk of bias. Although cases were typically well defined, the use of hospital-based instead of community-based controls was considered a potential source of bias among many case-control studies. Ascertainment of exposure was also a common source of bias among case-control studies. All 4 cross-sectional studies were thought to have a moderate to high risk of bias.

All Prostate Cancer

To assess the association between vasectomy and any diagnosis of prostate cancer, we first pooled results from cohort studies (Figure 2). Among the 13 of 16 cohort studies reporting on 2 563 519 patients that used adjusted measures of effect, we found a small but statistically significant increased risk of any diagnosis of prostate cancer among patients with a history of vasectomy (adjusted RR, 1.08; 95% CI, 1.02-1.14; P = .006; I2 = 63%) (Figure 2A). A similar outcome was observed among cohort studies using a time-to-event analysis (9 studies; adjusted HR, 1.09; 95% CI, 1.03-1.15; P = .004; I2 = 70%) (eFigure 1 in the Supplement). The effect estimate among studies deemed at low risk of bias remained statistically significant but was closer to the null (7 studies; adjusted RR, 1.05; 95% CI, 1.02-1.09; P < .001; I2 = 9%) (Figure 2B). Results were not meaningfully different when abstracts were excluded (eTable 3 in the Supplement).

Figure 2. Forest Plots for Meta-analyses of the Adjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer by Study Design and Risk of Bias (Cohort Studies).

Figure 2.

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Data were pooled separately by study design type using random-effects models; the inverse variance technique was used for pooling of measures of effect. NR indicates not reported.

Among cohort studies in which all patients explicitly underwent PSA screening (as in the screening arm of the PLCO [Prostate, Lung, Colorectal and Ovarian] Cancer Screening trial) or in which PSA screening was accounted for in multivariable models, the association between vasectomy and prostate cancer was consistent with our overall findings (6 studies; adjusted RR, 1.06; 95% CI, 1.02-1.09; P < .001; I2 = 16%) (eFigure 2 in the Supplement). Furthermore, among studies that reported on populations in which PSA screening was not performed or very uncommonly performed, we observed no association between vasectomy and prostate cancer, although this finding was limited by few studies and significant heterogeneity (2 studies; adjusted RR, 1.26; 95% CI, 0.51-3.07; P = .62; I2 = 84%).

We then separately assessed the association between vasectomy and any diagnosis of prostate cancer among case-control studies (Figure 3). Meta-analysis of studies reporting adjusted ORs demonstrated a statistically significant association between vasectomy and prostate cancer (17 studies; adjusted OR, 1.31; 95% CI, 1.12-1.53; P < .001; I2 = 66%) (Figure 3A). When we restricted analysis to 6 studies deemed to have low risk of bias, there was no significant association (adjusted OR, 1.06; 95% CI, 0.88-1.29; P = .54; I2 = 37%) (Figure 3B).

Figure 3. Forest Plots for Meta-analyses of the Adjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer by Study Design and Risk of Bias (Case-Control Studies).

Figure 3.

Open in a new tab

Data were pooled separately by study design type using random-effects models; the inverse variance technique was used for pooling of measures of effect. NA indicates not available.

There were no cross-sectional studies reporting adjusted measures of effect. Analyses of cohort, case-control, and cross-sectional studies reporting unadjusted measures of effect were performed for completeness and are summarized in eAppendix 3 and eFigure 3 in the Supplement. These results did not meaningfully alter conclusions. In the sensitivity analysis, excluding any individual study did not alter the results in each of the respective meta-analyses.

Secondary Outcomes

Among cohort studies, there was no statistically significant association noted between vasectomy and the diagnosis of high-grade prostate cancer (6 studies; adjusted HR, 1.03; 95% CI, 0.89-1.21; P = .67; I2 = 55%), advanced prostate cancer (6 studies; adjusted HR, 1.08; 95% CI, 0.98-1.20; P = .11; I2 = 18%), or fatal prostate cancer (5 studies; adjusted HR, 1.02; 95% CI, 0.92-1.14; P = .68; I2 = 26%) (Figure 4).

Figure 4. Forest Plots for Meta-analyses of the Associations Between Vasectomy and High-Grade, Advanced, and Fatal Prostate Cancers.

Figure 4.

Open in a new tab

Data were pooled separately by study design type using random-effects models; the inverse variance technique was used for pooling of measures of effect.

Five case-control studies assessed the association between vasectomy and prostate cancer, stratified by stage. The varied definitions of advanced prostate cancer in these studies precluded meta-analysis of these results. Qualitatively, there was a greater association between vasectomy and low-risk prostate cancer than between vasectomy and advanced disease among these studies. Meanwhile, a single case-control study assessed the association between vasectomy and fatal prostate cancer and found no association (unadjusted OR, 1.3; 95% CI, 0.85-1.9). Similarly, a single cross-sectional study examined the association between vasectomy and high-grade prostate cancer and found no association (unadjusted OR, 0.69; 95% CI, 0.37-1.27).

Duration of Exposure and Age at Vasectomy

Six cohort studies, 15 case-control studies, and 1 cross-sectional study reported on the association of time since vasectomy with the development of prostate cancer (eTable 4 in the Supplement). Of these, 1 cohort study and 6 case-control studies suggested a stronger association between vasectomy and prostate cancer with increasing time since vasectomy, although in several instances the CIs of the individual strata included unity and formal tests for trend were only performed in 3 studies. The remainder of these studies did not find any such biological gradient associated with time since vasectomy.

Four cohort studies and 11 case-control studies reported effect estimates stratified by age at vasectomy (eTable 5 in the Supplement). Of these, 1 cohort study and 4 case-control studies found that the association between vasectomy and prostate cancer was stronger among men who had their vasectomy performed at a younger age. Conversely, 1 cohort study and 1 case-control study found that men who were older when they had their vasectomy were at greater risk for incident prostate cancer. The remainder of these studies did not find any association of age at vasectomy with development of prostate cancer. Effect estimates for time since vasectomy and age at vasectomy could not be pooled owing to the varying types of effect estimates and time intervals used by the individual studies.

Publication Bias

We assessed publication bias using funnel plots comparing effect size and measure of precision of the effect size among case-control studies reporting unadjusted and adjusted measures of effect and cohort studies reporting adjusted measures of effect (eFigure 4 in the Supplement). There was potential publication bias among cohort studies, with a relative paucity of small studies demonstrating a large increased risk, and among case-control studies reporting adjusted measures of effect, with a relative paucity of small studies demonstrating no increased risk.

Exploratory Estimations

Using the pooled effect estimate from the meta-analysis of cohort studies with a low risk of bias, we found that the absolute increase in lifetime risk of prostate cancer is estimated to be 0.6% (95% CI, 0.3%-1.2%), that the number needed to harm (assuming a causal association, the number of men who would need to undergo vasectomy to result in 1 incident case of prostate cancer) is estimated to be 156, and that the population attributable fraction (assuming a causal association, the proportion the lifetime risk of prostate cancer would be reduced if no vasectomies were performed) is estimated to be 0.5% (95% CI, 0.2%-0.9%) (eAppendix 4 in the Supplement).

Discussion

To date, the potential for bias in the studies on the association between vasectomy and prostate cancer has been a major focus of criticism of this body of literature. Accordingly, we found that the effect estimates of the association between vasectomy and prostate cancer were increasingly closer to the null when examining studies with increasingly robust study design and study quality. In our meta-analysis of cohort studies with a low risk of bias, we found a 5% increase in the risk of incident prostate cancer with vasectomy. This result was not driven by any single study alone. Meanwhile, the associations between vasectomy and high-grade, advanced, and fatal prostate cancer were not statistically significant, although the point estimates were similar to those for total diagnoses of prostate cancer. If assuming causality, for the individual patient, the effect estimate for overall prostate cancer corresponds to a 0.6% absolute increase in lifetime risk of incident prostate cancer, or a number needed to harm of 156. At the population level, only 0.5% of prostate cancers are estimated to be associated with vasectomy. It is questionable whether such a small increased risk is important to the public.

Although meta-analyses have been previously performed, an analysis of cohort studies with a low risk of bias has only recently been possible, with 6 of 7 such studies reported within the last 3 years. One meta-analysis published in 2002 pooled data from 5 cohort and 17 case-control studies and found a significant association between vasectomy and prostate cancer. Meanwhile, 2 more recent meta-analyses combined data from 9 cohort studies and found no significant association but had wide CIs. Another meta-analysis combined data from 10 cohort studies and found no association, but the lower limit of its CI barely crossed 1 (RR, 1.11; 95% CI, 0.98-1.27). Our meta-analysis, which included 53 studies, was able to separately analyze case-control, cross-sectional, and cohort studies and was well powered and achieved effect estimates with narrow CIs.

In our assessment, most of the 33 case-control studies, all 4 of the cross-sectional studies, and almost half of the 16 cohort studies had a moderate to high risk of bias. Accordingly, the point estimates for association between vasectomy and prostate cancer were furthest from the null among pooled analyses of case-control and cross-sectional studies. Publication bias might also have contributed, in part, based on funnel plots. In contrast, the observed association was smaller in magnitude in the pooled analysis of cohort studies, and even smaller when restricted to studies (cohort and case-control designs) deemed as having a low risk of bias. In addition, despite methodological rigor, failure to account for differential use of PSA screening may bias results because patients who have undergone vasectomy are more likely to undergo PSA screening and thus receive a diagnosis of prostate cancer. In our study, the association between vasectomy and prostate cancer held in a subset analysis restricted to studies that accounted for PSA screening. Our analysis illustrates the susceptibility of observational studies to bias and highlights the importance of meticulous study design.

More important, simply because a statistically significant association was detected, one cannot confirm with certainty that a causal association exists. Owing to the observational nature of pooled studies, residual unmeasured bias is still possible. Residual detection bias remains an ongoing concern, even though several studies accounted for serum PSA screening and/or contact with the health care system. A recent article by Tangen et al illustrated that detection bias influences the evaluation of several risk factors that have been described as associated with decreased or increased prostate cancer risk. The only way to address this source of bias would be a trial randomizing men to undergo vasectomy vs no vasectomy. However, a sufficiently powered trial with long enough follow-up would be neither practical nor ethical. Therefore, the present meta-analysis likely approaches the highest level of clinical evidence reasonably attainable in evaluating the association of vasectomy with risk of prostate cancer.

If applying the criteria of Hill, which have been widely accepted as aiding in making causal inferences, one cannot make a strong argument for a causal association between vasectomy and prostate cancer (eAppendix 5 in the Supplement). Moreover, the case for biological plausibility is tenuous. Although hormonal imbalances, immunologic effects, and cell proliferative changes have been suggested to play a role, the exact mechanisms remain to be described in animal models. Although 1 study found that serum testosterone levels are elevated in men who underwent a vasectomy more than 20 years ago relative to men who did not undergo a vasectomy, most studies have shown no changes in testosterone levels following vasectomy. Moreover, there is no established association between elevated serum testosterone level and risk of prostate cancer. Although vasectomy may lead to the development of antisperm antibodies, there is no evidence that these antibodies or the subsequent formation of immune complexes leads to prostate cancer. One study found increased cell proliferation 7 days after vasectomy in the ductal system of the rat ventral prostate, although the mechanism remains unclear.

On the other hand, the benefits of vasectomy as a method of contraception must be considered. More than 99% of women who have ever been sexually active have used a form of contraception at some point. However, according to the most recent data, 45% of pregnancies in 2011 in the United States were unintended; 41% of these pregnancies occurred among women who used contraception inconsistently. Two-thirds of women using contraception rely on nonpermanent methods, many of which have a higher failure rate with typical use vs perfect use. Meanwhile, 25% of women rely on surgical sterilization for contraception and 8% rely on male surgical sterilization. Given the lower costs and lower risk of complications for vasectomy compared with tubal ligation, it is clear that vasectomy is underused and should be offered more routinely to couples seeking a long-term method of contraception.

Strengths and Limitations

There are several strengths to this study, including its size, its comprehensive search strategy in all languages, its careful review for study inclusion, its thorough assessment of study quality, and its use of a priori secondary analyses. This study is the first, to our knowledge, to separately evaluate studies with a low risk of bias and to evaluate high-grade, advanced, and fatal prostate cancers as secondary outcomes. Furthermore, we used relative effect estimates to calculate absolute effect estimates, which are more useful and more readily interpretable for clinicians, policymakers, and patients.

There are also limitations to our study. First, this meta-analysis is based on observational data because randomized trials are neither presently available nor likely to be performed in the future. As such, the unmeasured biases present in the individual studies must be taken into account. Our analytic approach addressed this issue in part by separately evaluating cross-sectional, case-control, and cohort studies and, additionally, separately evaluating the cohort and case-control studies with a low risk of bias. Second, publication bias cannot be ruled out. On the other hand, publication bias would have had outcomes in opposite directions in case-control and cohort meta-analyses, yet these analyses were consistent with each other. Finally, our analysis cannot definitively prove or disprove causality. However, as already outlined, a strong argument for a causal association between vasectomy and prostate cancer does not exist based on our data and on other existing literature.

Although it is tempting to consider potential avenues of further research on the link between vasectomy and prostate cancer, there are many other research topics that warrant greater priority in a system with finite health care research resources. We have demonstrated that any risk, if present, is sufficiently small that it is unlikely to be of clinical importance. We believe that this meta-analysis, drawing on 3 decades of epidemiologic literature, provides sufficiently robust data to inform clinical care and supports the current guidelines of the American Urological Association.

Conclusions

Our meta-analysis found a weak association between vasectomy and the risk of prostate cancer among cohort studies with a low risk of bias and a similar but nonsignificant association among case-control studies with a low risk of bias. There was a similar nonsignificant association between vasectomy and high-grade, advanced-stage, or fatal prostate cancer. The association between vasectomy and prostate cancer was stronger when studies with moderate to high risk of bias were included. If assuming a causal association, which is unlikely based on our data and other existing literature, vasectomy would confer only a 5% relative increase or a 0.6% absolute increase in lifetime risk of prostate cancer, and would be responsible for only 0.5% of cases of prostate cancer in the population. Therefore, although patients should be appropriately counseled, concerns about the risk of prostate cancer should not preclude clinicians from offering vasectomy to couples seeking long-term contraception.

Supplement.

eAppendix 1. Literature Search Strategy

eAppendix 2. Exclusion Following Full Text Review

eAppendix 3. Pooled Estimates of Studies Reporting Unadjusted Effect Estimates

eAppendix 4. Calculation of Estimates for Absolute Risk Increase, Number Needed to Harm, and Population-Attributable Fraction

eAppendix 5. Discussion of Hill’s Criteria of Causation

eFigure 1. Forest Plots for Meta-Analyses of the Adjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer for Cohort Studies Reporting on Time-to-Event Analyses

eFigure 2. Meta-Analysis of Cohort Studies That Accounted for PSA Testing

eFigure 3. Forest Plots for Meta-Analyses of Unadjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer by Study Design and Risk of Bias

eFigure 4. Funnel Plots

eTable 1. Risk Adjustment for Each Included Study

eTable 2. Newcastle-Ottawa Scale for Risk of Bias Assessment of Studies Included in the Meta-Analysis

eTable 3. Pooled Adjusted Estimates for Association Between Vasectomy and Prostate Cancer, Excluding Abstracts

eTable 4. Studies Reporting on the Impact Time Since Vasectomy on the Association Between Vasectomy and Prostate Cancer

eTable 5. Studies Reporting on the Impact of Age at Vasectomy on the Association Between Vasectomy and Prostate Cancer

eReferences.

Click here for additional data file. (236.4KB, pdf)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement.

eAppendix 1. Literature Search Strategy

eAppendix 2. Exclusion Following Full Text Review

eAppendix 3. Pooled Estimates of Studies Reporting Unadjusted Effect Estimates

eAppendix 4. Calculation of Estimates for Absolute Risk Increase, Number Needed to Harm, and Population-Attributable Fraction

eAppendix 5. Discussion of Hill’s Criteria of Causation

eFigure 1. Forest Plots for Meta-Analyses of the Adjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer for Cohort Studies Reporting on Time-to-Event Analyses

eFigure 2. Meta-Analysis of Cohort Studies That Accounted for PSA Testing

eFigure 3. Forest Plots for Meta-Analyses of Unadjusted Estimates for the Association Between Vasectomy and Any Prostate Cancer by Study Design and Risk of Bias

eFigure 4. Funnel Plots

eTable 1. Risk Adjustment for Each Included Study

eTable 2. Newcastle-Ottawa Scale for Risk of Bias Assessment of Studies Included in the Meta-Analysis

eTable 3. Pooled Adjusted Estimates for Association Between Vasectomy and Prostate Cancer, Excluding Abstracts

eTable 4. Studies Reporting on the Impact Time Since Vasectomy on the Association Between Vasectomy and Prostate Cancer

eTable 5. Studies Reporting on the Impact of Age at Vasectomy on the Association Between Vasectomy and Prostate Cancer

eReferences.

Click here for additional data file. (236.4KB, pdf)

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