FERTILITY AND STERILITYt

VOL. 70, NO. 2, AUGUST 1998

Copyright ©1998 American Society for Reproductive Medicine
Published by Elsevier Science Inc.
Printed on acid-free paper in U.S.A.

Vasectomy and prostate cancer: the

evidence to date
Herbert B. Peterson, M.D., and Stuart S. Howards, M.D.
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion,
Centers for Disease Control and Prevention, Atlanta, Georgia and Department of Urology, University of
Virginia, Health Sciences Center, Charlottesville, Virginia

In 1993, we wrote an editorial (1) to accompany the publication of two cohort studies by
Giovannucci et al. (2, 3) that found a positive association between vasectomy and prostate
cancer. We questioned at that point whether the observed association could have resulted from
chance, bias, or a causal relationship. On the basis of our analysis of the two studies, earlier
reports, and evidence on the issue of biologic plausibility, we concluded that a causal
relationship between vasectomy and the risk of prostate cancer was unlikely. Between the
publication of those reports and the present, further studies and the systematic review by
Bernal-Delgado et al. (4) were reported. What is the current evidence for a causal relationship
between vasectomy and prostate cancer?
The possibility that chance explained the positive associations between vasectomy and
prostate cancer in the earliest reports on this relationship (1990 and before) was increased by
the fact that those reports were based on multiple comparisons in studies of many exposures
and diseases, not specifically designed to test the association between vasectomy and prostate
cancer (5) Rosenberg et al. (6), authors of one of the earliest reports to find an increased risk,
found in a subsequent study that there was little, if any, increased risk of prostate cancer among
men undergoing vasectomy (7).
The study of the relationship between vasectomy and prostate cancer is complicated by a
strong potential for bias in the selection of study participants, in obtaining information about
study participants, and in confounding of the vasectomy-prostate cancer relationship. For
example, men who undergo vasectomy in association with surgery for benign prostatic
hypertrophy may be more likely than men who do not undergo vasectomy to be under greater
Received April 2, 1998. surveillance for prostate cancer. Similarly, particularly in the United States where most
Correspondence: Herbert
B. Peterson, M.D., Division
vasectomies are performed by urologists, men undergoing vasectomy subsequently may see a
of Reproductive Health, urologist more often than other men. Because prostate cancer is common and often asymp-
National Center for Chronic tomatic, more frequent evaluation by a urologist is likely to increase the possibility that
Disease Prevention and
Health Promotion, Centers
existing prostate cancers are identified.
for Disease Control and The potential for bias in selection of controls is evident from the distinction in risk estimates
Prevention, Atlanta,
Georgia (FAX: 770-488- from case-control studies with hospital patients as controls and those that used controls from
5965). the general population. Specifically, Bernal-Delgado et al. (4) found a significant increase in
The opinions and risk in hospital-based studies (relative risk 5 1.98; 95% confidence interval [CI] 1.37–2.86),
commentary expressed in but not in population-based studies (relative risk 5 1.12; 95% CI 0.96 –1.32). Studies of
Editor’s Corner articles are
solely those of the author. mortality after vasectomy suggest that men who undergo vasectomy in the United States may,
Its publication does not in general, be healthier than their counterparts who do not undergo vasectomy (8). Thus, the
imply endorsement by the prevalence of vasectomy among hospitalized men may well be lower than that in the general
Editor or American Society
for Reproductive Medicine. population. If so, the association between vasectomy and prostate cancer is likely to be
overestimated in hospital-based studies.
0015-0282/98/$19.00
PII S0015-0282(98)00139-3 The potential for bias in the collection of information about study participants is evidenced

201
by the fact that only three of the studies (Zhu et al., Moller
et al., and Nienhuis et al.) reviewed by Bernal-Delgado et al.
(4) determined vasectomy status by means other than self-
report. None of those found an association between vasec-
tomy and prostate cancer.
Regarding confounding in studies of the vasectomy-pros-
tate cancer relationship, the bottom line is that we still know
little about the etiology of prostate cancer. As noted, men
who undergo vasectomy may have different characteristics
from those who do not. Until we have a better understanding
of the determinants of risk of prostate cancer, the possibility
that such differences explain any observed association be-
tween vasectomy and prostate cancer will remain.
The findings of Giovannucci et al. (2, 3) that the relative
risk of prostate cancer increased with increasing time since
vasectomy were interesting. Equally noteworthy, however,
are two subsequent population-based case-control studies
(9, 10)— one a study from a health maintenance organization
(HMO) in western Washington state (9) and the other a
large, multicenter study in the United States and Canada—
that found no such association (10).
In the HMO study (9), the investigators found neither an
overall increase in the risk of prostate cancer (odds ratio
[OR] 0.86; 95% CI 0.57–1.32) nor an increase among men
$20 years after vasectomy (OR 0.84; 95% CI 0.51–1.38). In
the multicenter study (10), there was, likewise, no overall
relationship between vasectomy and prostate cancer (OR
1.1; 95% CI 0.83–1.3), and the investigators had sufficient
study power to exclude an increase in risk of $30% (11).
Furthermore, they found no increase in risk among men for
whom 20 –29 years (OR 0.97; 95% CI 0.66 –1.4) or $30
years (OR 1.0; 95% CI 0.71–1.4) had elapsed since vasec-
tomy.
In an editorial by Hayes of the National Cancer Institute
that accompanied that report (11) it was concluded that,
“With the new information from this large population-based
investigation, vasectomy appears either not to cause prostate
cancer or to have only a relatively weak relationship to the
disease . . .”
In their systematic reviews, Bernal-Delgado et al. (4) used
the technique of meta-analysis that was originally intended
for use in combining results from randomized controlled
trials but has since been used to combine results from ob-
servational studies as well. Metaanalysis, is controversial,
however, and its use with observational studies, in particular,
has been called into question (12). Although a properly
conducted systematic review can provide important evidence
for clinical decision making (13), its value clearly is con-
strained by the quality of the studies being reviewed.
Several strategies for addressing variations in study qual-
ity have been used, including restricting studies in the review
to those meeting established criteria and quality scoring of
studies included in the review. The value of providing sep-
202 Peterson and Howards Vasectomy and prostate cancer
arate estimates for studies meeting specified criteria is evi-
denced by the difference in estimates for those studies con-
sidered by Bernal-Delgado et al. to be less likely to be
affected by inadequate selection of controls versus those
more likely to be affected (OR 1.11; 95% CI 0.94 –1.31 and
2.24; 95% CI 1.42–3.54, respectively) and those considered
to be less likely affected by detection bias versus those more
likely to be affected (OR 1.11; 95% CI 0.96 –1.29 and 1.91;
95% CI 1.4 –2.6, respectively).
Conversely, the danger of synthesizing all available stud-
ies into a single estimate is evidenced by the necessity to
combine studies such as the first report by Rosenberg et al.
(6), based on multiple comparisons (OR 5.3 with noncancer
controls and 3.5 with cancer controls), and the second report
by Rosenberg et al. (7) (OR 1.2).
Important criteria for establishing causal inference in
epidemiologic studies include consistency of study findings,
strength of the observed association, and biologic plausibil-
ity. The results of studies of the vasectomy-prostate cancer
relationship are inconsistent, and the observed associations
among most positive studies are weak in epidemiologic
terms. Furthermore, there is little biologic plausibility for an
effect of vasectomy on risk of prostate cancer, with the
arguments for a beneficial effect as strong as those for a
harmful effect (14). We consider none of the possible bio-
logic mechanisms proposed as explanations for a causal
relationship to be either compelling or supported by current
basic or clinical research. In conclusion, we believe that the
argument for a causal relationship between vasectomy and
prostate cancer remains weak.
Increasingly, U.S. couples rely on sterilization for con-
traception (15). Although tubal sterilization is safe and
highly effective, vasectomy is even safer and more effective
(16, 17). In the 1970s and 1980s, there was concern about
vasectomy and atherosclerosis after a report of an increased
risk of atherosclerosis in monkeys who had undergone the
procedure. After more than a decade, at least nine epidemi-
ologic studies found no increased risk of atherosclerosis in
men, and the investigators who reported the findings in
monkeys subsequently presented data refuting that finding
(16). Questions about the relationship between vasectomy
and prostate cancer will likely persist into the next century.
In the meantime, we believe that men considering vasectomy
should be aware that vasectomy is unlikely to be a major risk
factor for prostate cancer.
References
1. Howards SS, Peterson HB. Vasectomy and prostate cancer: chance,
bias, or a causal relationship? J Am Med Assoc 1993;269:913– 4.
2. Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ,
Willett WC. A prospective cohort study of vasectomy and prostate
cancer in U.S. men. J Am Med Assoc 1993;269:873–7.
3. Giovannucci E, Tosteson TD, Speizer FE, Ascherio A, Vessey MP,
Colditz GA. A retrospective cohort study of vasectomy and prostate
cancer in U.S. men. J Am Med Assoc 1993;269:878 – 82.
4. Bernal-Delgado E, Latour-Pérez J, Pradas-Arnal F, Gomez-López LI.
The association between vasectomy and prostate cancer: a systematic
review of the literature. Fertil Steril 70:191–200.
Vol. 70, No. 2, August 1998
 5. Anonymous. Vasectomy and prostate cancer. Lancet 1991;337:1445–6.
6. Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD,
Shapiro S. Vasectomy and the risk of prostate cancer. Am J Epidemiol
1990;132:1051–5.
7. Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Strom BL,
Harlap S, et al. The relation of vasectomy to the risk of cancer. Am J
Epidemiol 1994;140:431– 8.
8. Giovannucci E, Tosteston TD, Speizer FE, Vessey MP, Colditz GA. A
long-term study of mortality in men who have undergone vasectomy.
N Engl J Med 1992;326:1392– 8.
9. Zhu K, Stanford JL, Daling JR, McKnight B, Stergachis A, Brawer
MK, et al. Vasectomy and prostate cancer: a case-control study in a
health maintenance organization. Am J Epidemiol 1996;144:717–22.
10. John EM, Whittemore AS, Wu AH, Kolonel LN, Hislop G, Howe GR,
et al. Vasectomy and prostate cancer: results from a multiethnic case-
control study. J Natl Cancer Inst 1995;87:662–9.
11. Hayes RB. Are dietary fat and vasectomy risk factors for prostate
cancer? J Natl Cancer Inst 1995;87:629 –31.
FERTILITY & STERILITYt
12. Shapiro S. Meta-analysis/shmeta-analysis. Am J Epidemiol 1994;140:
771– 8.
13. Cook DJ, Mylrow CD, Haynes RB. Systematic reviews: synthesis of
best evidence for clinical decisions. Ann Intern Med 1997;126:376 –
80.
14. Howards SS. Possible biological mechanisms for a relationship
between vasectomy and prostate cancer. Eur J Cancer 1993;29A:
1060 –2.
15. Piccinino LJ, Mosher WD. Trends in contraceptive use in the United
States. Fam Plann Perspect 1998;30:4 –10, 46.
16. Peterson HB, Huber DH, Belker AM. Vasectomy: an appraisal for the
obstetrician-gynecologist. Obstet Gynecol 1990;76:568 –72.
17. Peterson HB, Xia Z, Hughes JM, Wilcox LS, Tylor LR, Trussell J
for the U.S. Collaborative Review of Sterilization Working Group.
The risk of pregnancy after tubal sterilization: findings from the U.S.
Collaborative Review of Sterilization. Am J Obstet Gynecol 1996;
174:1161–70.
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