Cancer Causes and Control (2005) 16:1189–1194
Springer 2005

DOI 10.1007/s10552-005-0304-8

Association of vasectomy and prostate cancer among men in a Maryland cohortw

Sabine Rohrmann1, Dina N. Paltoo2, Elizabeth A. Platz1,3,4,*, Sandra C. Hoffman1, George W. Comstock1 &
Kathy J. Helzlsouer1,3
1
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 21205, Baltimore, MD, USA;
2
Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, MD, USA; 3Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; 4James
Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Received 21 December 2004; accepted in revised form 22 June 2005

Key words: epidemiology, prostate cancer, risk, vasectomy.

Abstract

Objectives: To evaluate the association of vasectomy with prostate cancer.

Methods: Participants were male members of the CLUE II cohort followed since 1989. On a questionnaire mailed
in 1996, the men were asked if they had had a vasectomy and their age at vasectomy. Between 1996 and April 2004,
78 prostate cancer cases were confirmed among the 3373 men who were at least 35 years old at baseline and who
completed the questions about vasectomy. Cox proportional hazards regression was used to estimate age-adjusted
hazard ratios (HR) of prostate cancer.
Results: The HR for prostate cancer for men who had had a vasectomy was 2.03 (95% CI: 1.24 3.32). Risk of low-
grade disease (HR=2.87; 95% CI 1.49 5.54), but not high-grade disease (HR=0.99; 95% CI 0.36 2.76), was
higher in men who had had a vasectomy. No statistically significant associations were observed for low- or high-
stage disease. The association for vasectomy was more pronounced in men who were 740 years at the time of
vasectomy (HR=2.63; 95% CI 1.40 4.94) than in men who were younger at vasectomy.
Conclusions: The results from this prospective study suggest a positive association between vasectomy and prostate
cancer, especially low-grade disease.

Introduction

A possible positive association between vasectomy and

w
Supported by National Cancer Institute Grant CA 08030,
National Institute of Aging Grant AG18033, and Department of
Defense Grant DAMD17-94-J-4265. Dr. Rohrmann is supported by
the Fund for Research and Progress in Urology, Johns Hopkins
Medical Institutions. Dr. Paltoo was supported by the Cancer Pre-
vention Fellowship Program, Office of Preventive Oncology, Division
of Cancer Prevention, National Cancer Institute, Bethesda, MD
20892, during the time she was working on this project. Dr. Comstock
was partially supported by Research Career Award HL 21670 from the
National Heart, Lung, and Blood Institute. These data were supplied
in part by the Maryland Cancer Registry, the Department of Mental
Hygiene, Baltimore, Maryland. The Department of Health and Mental
Hygiene specifically disclaims responsibility for any analyses, inter-
pretations or conclusions.
* Address correspondence to: Dr. Elizabeth A. Platz, Department of
Epidemiology, Johns Hopkins University Bloomberg School of Public
Health, 615 N. Wolfe St., Room E6138, Baltimore, MD 21205; E-mail:
eplatz@jhsph.edu
prostate cancer has raised concern since the early 1990s,
although the use of vasectomy for male contraception has
remained relatively stable [1]. Approximately 500,000
vasectomies are performed annually in the United States
[2]. About 12% of married men have had a vasectomy
and are generally under the age of 40 years when the
procedure is performed [3, 4]. The procedure is more
common among white men, men with at least a high
school education, and residents of the Midwest or West
[3, 4].
Vasectomy has been hypothesized to increase the risk
of prostate cancer by diminishing the secretion of
prostatic fluid or by altering immune response to sperm
antigens [5]. In some, but not all epidemiologic studies,
vasectomy has been associated with an overall increased
1190
risk of prostate cancer (reviewed by Dennis et al. [6]).
For those studies supporting a positive association be-
tween vasectomy and prostate cancer, the strength of the
association has depended on age and time since vasec-
tomy and family history of prostate cancer [5, 7 10]. In
one case-control study, men who had had a vasectomy
were more likely to have earlier-stage, lower-grade
prostate cancers at diagnosis [11]. In contrast to these
findings, a large prospective cohort study [12] and a
recent large population-based case-control study [13] did
not observe any associations between vasectomy and
prostate cancer risk.
In the present study, we evaluated the association of
vasectomy with subsequent diagnosis of prostate cancer,
including by stage and grade of disease, in men from
Washington County, MD. In addition, we assessed
whether time since vasectomy and age at vasectomy
modified the association of prostate cancer.
Materials and methods
Study population
The men included in this analysis were residents of
Washington County, Maryland, who participated in
the prospective CLUE II cohort study, which was
conducted from May through October 1989. CLUE II
receives its name from the slogan of the Campaign
against Cancer and Heart Disease: ‘Give us a clue to
cancer and heart disease’. Trained interviewers took a
brief history, including weight, height, and cigarette
smoking status. Additionally, participants were asked
to complete an abbreviated version of the Block food
frequency questionnaire, which comprised 60 food
items [14]. 25,080 Washington County residents,
approximately 30% of this county’s population par-
ticipated in the study. 10,457 participants were men
and, reflecting the demographic composition of
Washington County, 97% of the participants were
white. An exposure and outcome questionnaire was
subsequently mailed to the participants in 1996, which
included questions about vasectomy and prostate can-
cer screening.
For the present analysis, we excluded men who were
younger than 35 years of age at baseline in 1989
(n=3150), men with cancer (other than non-melanoma
skin cancer) at baseline in 1989 (n=279), and men with
a cancer diagnosis prior to 1996 (n=507). Of the
remaining 6521 men, 3763 had answered the follow-up
questionnaire in 1996, which included questions on
vasectomy. Of these men, we excluded those 390 who
had not answered the questions on vasectomy, leaving
S. Rohrmann et al.
3373 men. Follow-up, that is, knowledge of a partici-
pant’s vital status, was 93% complete for participants 35
to 44 years of age at baseline and more than 95%
complete for participants 45 years of age and older at
baseline. Approval for this analysis was obtained from
the Johns Hopkins Bloomberg School of Public Health
Committee on Human Research.
Case ascertainment
Prostate cancer cases were ascertained between 1996 and
April 2004 from the Washington County Cancer Reg-
istry. Linkage to the Maryland Cancer Registry was also
done for the period 1992 1996. We have found good
agreement in the ascertainment of cases between the two
registries. Since 1996, 138 men were diagnosed with
prostate cancer. Of these, 78 (56.6%) answered the 1996
questionnaire and reported on vasectomy status and
were included in the analysis. High-stage cases were
defined as SEER stages 3 (tumors extend through the
prostatic capsule and/or to the seminal vesicles and no
metastases to the lymph nodes or distant sites) or 4
(tumors have invaded tissues next to the prostate other
than the seminal vesicles or have metastasized to the
lymph nodes or distant sites) (n=15) and low-stage
cases were defined as SEER stages 1 (clinically inap-
parent cancers found on surgery for BPH or detected on
biopsy following an elevated PSA test and no metastases
to the lymph nodes or distant sites) or 2 (organ-confined
tumors that were detected following an abnormal digi-
tal-rectal examination and no metastases to the lymph
nodes or distant sites) (n=23) [15]. High-grade cases
were men with Gleason sum 77 (n=24) and low-grade
cases were men with Gleason sum <7 (n=40). Half of
the 78 cases did not have a stage available. The majority
of men (87%) had a Gleason sum available. Missing
stage and grade was due to the information not being
available in the cancer registries.
Assessment of vasectomy and other factors
On the 1996 follow-up questionnaire, male participants
were asked whether they had ever had a vasectomy and
the age at which they had the procedure. Self-reported
marital status, education, current weight and height,
weight at age 21, and cigarette smoking history were
obtained from the baseline questionnaire. Dietary fac-
tors were obtained from the food frequency question-
naire, which was completed by 70% of the cohort
participants at baseline. Family history of prostate
cancer and ever having been screened for prostate can-
cer by digital rectal examination (DRE) or prostate
Vasectomy and prostate cancer 1191
specific antigen (PSA) test were reported on the 1996 with prostate cancer varied by age at vasectomy (<40
questionnaire. and ‡40 years old) or time since vasectomy (<20 and
‡20 years) overall. All analyses were conducted using
Statistical analysis SAS version 8.01 (SAS Institute, Cary, North Carolina).

Anthropometric and lifestyle characteristics of the men

who had had a vasectomy and men who had not had a
vasectomy were examined by directly standardizing to
the age distribution of the analytical cohort. To evaluate
the association of vasectomy with prostate cancer and
by stage and grade, we estimated hazard ratios (HR)
and corresponding 95% confidence intervals (CI) using
Cox proportional hazards regression models. Because
age was a strong negative confounder in these data, we
controlled finely for age by entering it into the model as
a continuous term. Covariates were included in the
model one at a time to determine if they confounded
the association between vasectomy and prostate cancer.
The factors we considered were: body mass index (BMI)
at age 21 years old, cigarette smoking history, father or
brother with prostate cancer, and in the subset of men
who completed the food frequency questionnaire, total
alcohol consumption, intake of processed meat, intake
of tomatoes and tomato juice, and use of a vitamin E
supplement. Because none of these factors appeared to
confound the association, we present age-adjusted esti-
mates only.
The Cox proportional hazards regression models were
stratified to assess whether the association of vasectomy
Table 1. Age-standardizeda baseline characteristics by vasectomy status among 3373 men in the CLUE II study, 1996 2004
Results
Men who had had a vasectomy were younger at baseline
than men who had not had a vasectomy (Table 1). The
mean age at vasectomy was 35.2±6.9 years. After age
standardization, men who had had a vasectomy and had
not had a vasectomy did not differ by race, BMI at age
21, cigarette smoking status, or use of a vitamin E
supplement. Men who had had a vasectomy were more
likely to be married, to have completed high school, to
consume at least one alcoholic beverage per week, and
to have been screened for prostate cancer (Table 1). The
mean age at prostate cancer diagnosis was 64.7±8.1 for
men who had had a vasectomy and 71.2±9.4 years for
men who had not had a vasectomy. After standardizing
by age, among men who had had a vasectomy 3.8%
were diagnosed with prostate cancer and among men
who had not had a vasectomy 2.0% were diagnosed
with prostate cancer.
After adjusting for age, the HR of prostate cancer
comparing men who had had a vasectomy to men
who had not was 2.03 (95% CI 1.24 3.32). Vasectomy
was not statistically significantly associated with an

No vasectomy Vasectomy p-value

Number of men 2455 918

Age at baseline in 1989 (mean, ±SD) 54.8±11.3 49.2±9.0 <0.0001
Age at vasectomyb (mean, ±SD) 35.2±6.9
Caucasian (%) 99.1 99.6 0.07
Married (%) 87.7 92.1 <0.0001
Completed high school (%) 82.0 85.2 0.03
Body mass index (BMI)
BMI at age 21 (% ‡25 kg/m2) 24.9 27.3 0.85
Current BMI (% ‡25 kg/m2) 69.3 69.6 0.60
Family history of prostate cancer (father or brother, %) 6.3 6.7 0.78
Prostate cancer screening (% had PSA or DRE)b 93.4 96.4 <0.0001
Cigarette smoking history (%) 0.12
Current 14.4 15.1
Former 44.8 45.0
Never 40.8 39.9
Total alcohol use (% that drink ‡2 g/day)c 36.9 43.8 0.0003
Processed meat (% that eat ‡once/week) 71.5 68.2 0.59
Tomato and tomato juice (% that consume ‡1/week) 49.1 47.9 0.57
Regular use of vitamin E supplementsd (%) 8.0 7.0 0.58
a
All factors were directly age-standardized to the entire study population except age at baseline and age at vasectomy.
b
Information obtained from 1996 questionnaire.
c
2 g/day is approximately one alcoholic beverage per week.
d
At least once per week during the year prior to baseline in 1989.
1192 S. Rohrmann et al.
increased risk of high-stage, low-stage, or high-grade cancer of 1.37 (95% CI 1.15 1.62) for vasectomy [6],
disease (Table 2). However, men who had had a vasec- which is lower than that observed in our analysis. Two
tomy had a higher risk of low-grade prostate cancer. prospective cohort studies were included in that meta-
Ninety-four percent of the men in the analysis cohort analysis. Giovannucci et al. observed an increased RR
had ever been screened for prostate cancer. Including of prostate cancer of 1.66 (95% CI: 1.25 2.21) for
only these men in the analysis for opportunity to have vasectomy in the Health Professionals Follow-up Study
an occult prostate cancer detected, the results were [7], whereas Sidney et al. [12] did not observe an asso-
similar to what we observed overall (HR=2.01, 95% CI ciation for vasectomy (RR=1.0, 95% CI 0.7 1.6)
1.20 3.36). among members of the Northern California Kaiser
The hazard of prostate cancer was 2.6 times higher in Permanente Medical Care Program. Among three ret-
men who had had a vasectomy at age 40 years or older rospective cohort studies [5, 16, 17], only one, which was
compared to men who had never had a vasectomy conducted among husbands of participants in the Nur-
(Table 3). The elevated hazard of prostate cancer for ses’ Health Study, reported an increased risk of prostate
vasectomy compared to no vasectomy was less pro- cancer in men who had had a vasectomy (RR=1.56,
nounced and not statistically significant in men who 95% CI 1.03 2.37) [5]. Among the larger case-control
were younger than 40 years of age when they had a studies, only a case-control study in Quebec, Canada
vasectomy. The association between vasectomy and found a strong association between vasectomy and
prostate cancer did not vary by time since vasectomy. prostate cancer (OR=2.6, 95% CI: 1.7 4.3) [18]; the
The risk was increased in both, men whose vasectomy others did not observe statistically significant associa-
was less than 20 years ago as well as in those, whose tions between vasectomy and prostate cancer, with ORs
vasectomy was 20 or more years ago. However, the ranging from 0.9 to 1.2 [11, 13, 19 22].
association was statistically significant only in men Explanations for the inconsistent findings among
whose vasectomy was 20 or more years ago. these studies are not known, but might include varying
extents of detection bias. Men who seek medical con-
Discussion sultation for a vasectomy also may be more likely to
return to their physicians for prostate cancer screening
Our findings suggest that men who have had a vasec- than men who do not choose to have a vasectomy.
tomy are more likely to be diagnosed with prostate Although the majority of men in the analysis cohort had
cancer than men who have not had a vasectomy. The been screened for prostate cancer and the results were
increased risk was only seen for low-grade disease, but similar after excluding the small percentage of men who
not for high-grade disease. had not been screened, we cannot exclude residual
A meta-analysis of five cohort and 17 case-control detection bias due to differential intensity of screening
studies reported a pooled relative risk (RR) of prostate between men who had had and had not had a vasec-
tomy. However, in the Health Professionals Follow-up
Table 2. Hazard ratiosa (HR) and 95% confidence intervals (CI) for Study, including only men who had been screened by
prostate cancer by vasectomy status among 3373 men in the CLUE DRE (cases were detected mainly in the pre-PSA era)
II study, 1996 2004
did not attenuate the vasectomy association [5]. Future
No vasectomy Vasectomy studies on vasectomy should assess screening intensity
by PSA and DRE to be able to more closely address a
All cases/ person-years 51/20,211 27/7785
HR (95% CI) 1.0 2.03 (1.24 3.32)
potential detection bias by men who undergo screening
Low-stage casesb/ person-years 17/20,211 6/7785 more often than others.
HR (95% CI) 1.0 1.47 (0.55 3.90) We observed a stronger positive association between
High-stage casesb/ person-years 11/20,211 4/7785 vasectomy and prostate cancer for men who had a
HR (95% CI) 1.0 1.52 (0.46 5.06) vasectomy at age 40 years or older than for men who
Low-grade casesc/ person-years 22/20,211 18/7785
HR (95% CI) 1.0 2.87 (1.49 5.54)
had a vasectomy at a younger age, which has previously
High-grade casesc/ person-years 19/20,211 5/7785 been seen in other studies. Both cohort and case-control
HR (95% CI) 1.0 0.99 (0.36 2.76) studies reported a higher risk in men who were 40 years
a
or older at the time of vasectomy [5, 7 9, 19]. In con-
Estimated from a Cox proportional hazards regression model after trast, Hayes et al. [22] observed an increased odd of
adjusting for age as a continuous variable.
b
Low-stage cases = SEER stage 1 or 2; high-stage cases = SEER
prostate cancer when vasectomy was performed at less
stage 3 or 4. than 35 years of age (OR=2.2, 95% CI 0.9 4.4) in a
c
Low-grade cases = Gleason sum <7; high-grade cases = Gleason U.S. case-control study of black and white men. An
sum ‡7. increase in the risk of prostate cancer with time since
Vasectomy and prostate cancer
Table 3. Hazard ratiosa (HR) and 95% confidence intervals (CI) for prostate cancer according to age at vasectomy and time since vasectomy
among 3330b men in the CLUE II Study, 1996 2004
No vasectomy
Cases/person years 51/20,211
HR (95% CI) 1.00
Cases/person years 51/20,211
HR (95% CI) 1.00
a
Estimated from Cox proportional hazards regression models after adjusting for age as a continuous variable.
b
Information on age at vasectomy is missing for 43 men who had had a vasectomy.
vasectomy, with the highest risk being among men who
had a vasectomy 20 or more years ago, has been shown
previously in some [5, 7, 9], but not all studies [10 12,
20]. In our study, when stratifying by time since vasec-
tomy, we observed an increased risk of prostate cancer
irrespective of the time since vasectomy. Explanations
for why age at vasectomy and time since vasectomy
might influence the association between vasectomy and
prostate cancer are unclear.
We considered whether other sources of bias might
account for our results. Vasectomy was self-reported in
this study, which is generally accurate [11, 20], and given
that this study was prospectively conducted, differential
accuracy of report of vasectomy by future prostate
cancer status is unlikely. Potential confounders that we
could not address in this study include androgen levels or
history of sexually transmitted diseases (STDs). Men
who have higher testosterone levels might be more likely
to be sexually active and undergo vasectomy to control
fertility. Although circulating testosterone concentra-
tions have not been consistently linked to prostate cancer
risk [23], androgens are permissive for prostate cancer
development. Positive associations between STDs and
prostate cancer have been observed [24]. Men who are
sexually more active may be more likely to acquire sex-
ually transmitted diseases than men who are less sexually
active. Unaccounted for associations of vasectomy with
androgen levels and STDs might lead to a very modest
overestimation in the RR of prostate cancer.
Half of cases did not have a stage available, although
the majority of men had a Gleason sum available. Of the
men with missing stage, but a known grade (n=27), the
distribution of Gleason sums is consistent with the
Gleason sum distribution in the PSA era. Of the 39 cases
with known stage only nine are stage 1, despite a high
percentage of the men in the cohort having had a PSA
test. The relative paucity of cases being recorded as stage
1193
Age at vasectomy
<40 years of age ‡40 years of age
14/5556 12/1854
1.77 (0.93 3.37) 2.63 (1.40 4.94)
Time since vasectomy
<20 years ago ‡20 years ago
7/3107 19/4294
2.21 (0.92 5.34) 2.03 (1.19 3.47)
1 combined with the relatively low Gleason sum (67%
are Gleason 6 and below) suggests that some men with a
clinical presentation of only an elevated PSA are likely
early stage cases that were abstracted as being unstaged.
Given the hypothesis that some of the cases with missing
stage are men with early stage disease, in a sensitivity
analysis, we included the men with missing stage along
with the early stage cases and observed a statistically
significant association between vasectomy and low-stage
prostate cancer [HR=2.01 (1.20 3.36)]. This result is
similar to the association of vasectomy with low-grade
prostate cancer.
Our results were based on men who had answered the
questions on vasectomy in the 1996 questionnaire.
However, in a subanalysis, we evaluated the results of men
who had not stated on the 1996 questionnaire whether
they had or had not had a vasectomy (402 men including
19 prostate cancer cases). Concerning their baseline
characteristics they did not differ from men who had
answered the vasectomy question (data not shown).
Compared to men who had not had a vasectomy, men
who skipped the question had an HR=1.63 (95%
CI=0.96 2.76).
This prospective study adds to the evidence for a
positive association between vasectomy and prostate
cancer. However, because vasectomy is an established
and effective method of birth control and because the
causality of the vasectomy and prostate cancer associa-
tion remains unclear, at this time no recommendation
against the use of vasectomy is warranted.
Acknowledgements
We thank Judy Hoffman-Bolton and Alyce Burke at the
George W. Comstock Center for Public Health
Research and Prevention, Johns Hopkins Bloomberg
1194
School of Public Health in Hagerstown, MD, for their
continued efforts in the ongoing CLUE II study. We
also thank Ruitao Zhang and Lucy Thuita in the
Department of Epidemiology, Johns Hopkins Bloom-
berg School of Public Health for CLUE II programming
support.
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