Effect of body mass index and waist circumference on prostate specific antigen and prostate volume in a generally healthy Korean population.

Abstract

We examined the influences of age, body mass index and waist circumference on prostate specific antigen before and after adjusting for prostate volume. We also examined associations among age, body mass index, waist circumference and prostate volume.
We analyzed 38,380 Korean men 30 to 79 years old who received regular checkups at our health examination center. We had prostate volume data for 3,593 of them. We divided the subjects into 5 groups by age, 4 groups by body mass index and waist circumference (using Asia-Pacific obesity reference values), and quartiles for prostate volume. We compared prostate specific antigen and prostate volume by multivariate regression analysis across body mass index and waist circumference after adjusting for age and/or prostate volume.
Increasing body mass index or waist circumference was associated with decreasing prostate specific antigen (with or without prostate volume adjustment) and increasing prostate volume (p for trend <0.01). When we stratified prostate volume by quartile, age was not associated with prostate specific antigen except in quartile 4 (p for trend by quartile 0.402, 0.639, 0.056 and <0.01). Mean prostate specific antigen of the group with a body mass index less than 23 in prostate volume quartile 4 was approximately 3 times that of the group with a body mass index greater than 30 in prostate volume quartile 1 (1.42 vs 0.55).
Obesity had a negative association with prostate specific antigen regardless of prostate volume, and a positive association with prostate volume. Age was not associated with prostate specific antigen after prostate volume adjustment. Obese men, especially those with a small prostate volume, may have lower baseline prostate specific antigen and, thus, be at higher risk for having prostate cancer undetected in a prostate specific antigen screening test.

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Effect of Body Mass Index and Waist Circumference on Prostate
Specific Antigen and Prostate Volume in a Generally Healthy
Korean Population
Jin-Ho Park, Be-Long Cho,* Hyuk-Tae Kwon, Cheol-Min Lee and Hyun-Jin Han
From the Department of Family Medicine, Healthcare System Gangnam Center of Seoul National University Hospital (JHP, HTK, CML),
Department of Family Medicine, Seoul National University Hospital (BLC) and School of Public Health, Seoul National University (HJH),
Seoul, South Korea
Abbreviations
and Acronyms
BMI ? body mass index
PSA ? prostate specific antigen
PV ? prostate volume
WC ? waist circumference
Submitted for publication November 21, 2008.
Study received institutional review board ap-
proval.
* Correspondence: Department of Family
Medicine, Seoul National University Hospital,
Yeongeon-dong 28, Jongno-gu, Seoul, South
Korea 110-744 (telephone: 82-2-2072-2195,
82-16-9865-2195; FAX: 82-2-766-3276; e-mail:
belong@snu.ac.kr).
See Editorial on page 14.
Purpose: We examined the influences of age, body mass index and waist circum-
ference on prostate specific antigen before and after adjusting for prostate vol-
ume. We also examined associations among age, body mass index, waist circum-
ference and prostate volume.
Materials and Methods: We analyzed 38,380 Korean men 30 to 79 years old who
receivedregularcheckupsatourhealthexaminationcenter.Wehadprostatevolume
datafor3,593ofthem.Wedividedthesubjectsinto5groupsbyage,4groupsbybody
mass index and waist circumference (using Asia-Pacific obesity reference values),
and quartiles for prostate volume. We compared prostate specific antigen and pros-
tate volume by multivariate regression analysis across body mass index and waist
circumference after adjusting for age and/or prostate volume.
Results: Increasing body mass index or waist circumference was associated with
decreasing prostate specific antigen (with or without prostate volume adjust-
ment) and increasing prostate volume (p for trend ?0.01). When we stratified
prostate volume by quartile, age was not associated with prostate specific antigen
except in quartile 4 (p for trend by quartile 0.402, 0.639, 0.056 and ?0.01). Mean
prostate specific antigen of the group with a body mass index less than 23 in
prostate volume quartile 4 was approximately 3 times that of the group with a
body mass index greater than 30 in prostate volume quartile 1 (1.42 vs 0.55).
Conclusions: Obesity had a negative association with prostate specific antigen
regardless of prostate volume, and a positive association with prostate volume.
Age was not associated with prostate specific antigen after prostate volume
adjustment. Obese men, especially those with a small prostate volume, may have
lower baseline prostate specific antigen and, thus, be at higher risk for having
prostate cancer undetected in a prostate specific antigen screening test.
Key Words: body mass index, waist circumference, organ size,
prostate-specific antigen, mass screening
THE serum prostate specific antigen
test is the most important prostate
cancer screening tool we have and
most prostate cancers are detected on
biopsy after abnormal PSA test re-
sults. The widespread use of PSA
screening has resulted in a signifi-
cant increase in diagnosed cancer
cases, particularly early stage cases,
and a decrease in prostate cancer
mortality in some countries.1–3De-
spite its widespread use the PSA test
is limited by low specificity and re-
duced sensitivity beyond a specific
cutoff value. Another problem is that
PSA is affected by many noncancer
106
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0022-5347/09/1821-0106/0
THE JOURNAL OF UROLOGY®
Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 182, 106-111, July 2009
Printed in U.S.A.
DOI:10.1016/j.juro.2009.02.130

Page 2

related factors. Understanding those factors and
how they interrelate would increase test usefulness.
PSA is known to increase with age and prostate
volume, and investigators have suggested that age
specific PSA and density might provide more accu-
rate clinical assessments than a single reference
range applied to men of all ages.4Recently, many
studies have examined the association between PSA
and obesity.5–15Some have shown an inverse rela-
tionship between BMI and PSA5–11while others
have not.12–15Most studies were conducted in the
United States and results from the 2 studies that
targeted Asian men differed from each other.5,15
Several studies did not target a general screening
population but focused on men with suspected or
proven prostate cancers.6,7,12,14Waist circumfer-
ence, which represents central obesity, is an impor-
tant clinical parameter that has a greater impact
than BMI on metabolic disease incidence and its
related mortality. However, only 1 study investi-
gated the association between WC and PSA, and the
association was negative.8To clarify the influence of
obesity, defined by BMI or WC, on serum PSA, we
examined a community based screening population
that encompassed all possible age groups and had no
known prostate related diseases, and we corrected
for possible confounding factors such as PV, which
has a significant association with obesity and PSA.
We examined the magnitude of the association
among BMI, WC, PV and PSA, and we examined
how adjusting for PV affected the associations
among age, BMI, WC and PSA.
MATERIALS AND METHODS
Study Population
Eligible subjects were men 30 to 79 years old who received
routine comprehensive health evaluations from March
2004 to June 2008 at the Healthcare System Gangnam
Center of Seoul National University Hospital in Korea. All
subjects provided written informed consent and the insti-
tutional review board approved the protocol. A self-admin-
istered medical questionnaire collected previous and cur-
rent heath status information including prostate related
problems, and a family physician conducted a medical
interview and basic physical examination. Anthropomet-
ric measurements including height, weight and WC were
performed, and BMI was calculated as weight in kilo-
grams divided by the square of the height in meters (kg/
m2). Blood tests including PSA concentration were per-
formed after subjects fasted overnight. A radiologist
performed transrectal prostate ultrasound for the subjects
who chose a more intensive evaluation. PSA measurement
preceded prostate ultrasound and we did not perform rou-
tine digital rectal examinations.
We excluded from study men who had a history of
prostate cancer, prostate surgery or prostatitis, were tak-
ing an antiandrogenic medication such as finasteride, or
did not give proper information about prostate related
medical problems (2,600). We then excluded men whose
serum PSA concentration was greater than 10 ng/ml (87)
because of the increased probability of prostate related
disease or data error. Of the men who had undergone
transrectal ultrasound we excluded those with a PV less
than 10 cc (4) because such outliers had a high chance of
data registration error. Finally 38,380 men were included
in this study and we had PV data for 3,593.
Statistical Analysis
We used the Pearson correlation test to evaluate associa-
tions among age, BMI, WC, PV and PSA, and we used a
partial correlation test to evaluate associations among
BMI, WC, PSA and PV after adjusting for age and/or PV.
We divided the continuous variables into several sub-
groups. Age was divided into 5 groups of 30 to 39, 40 to 49,
50 to 59, 60 to 69 and 70 to 79 years. BMI was grouped
according to the Asia-Pacific criteria of obesity into under-
weight or normal—less than 23, overweight—23 to 24.9,
obese—25 to 29.9 and extremely obese—30 or greater.16
WC was divided into 4 groups of less than 80, 80 to 89.9,
90 to 99.9 and 100 cm or greater. The threshold value
for abdominal obesity in Korea is 90 cm. We used multi-
variate linear regression analysis to examine the associa-
tion among BMI, WC, and the outcome variables PSA and
PV, adjusting by age and/or PV. We tested for trends by
regressing PSA on BMI or WC on a continuous scale and
simultaneously adjusting for age and/or PV. We log trans-
formed PSA and PV data to obtain a more normal distri-
bution, and then back-transformed for interpretation. Af-
ter linear regression we predicted age adjusted means and
95% CI of PSA by BMI or WC, with age set to means of
each category of BMI or WC. We used the chi-square test
to check for trends in the proportion of subjects with an
abnormal PSA for each cutoff value (greater than 3.0
ng/ml, greater than 4.0 ng/ml) according to obesity cate-
gories. We performed all statistical analyses using Stata®
10.0 and considered 2-sided p values less than 0.05 signif-
icant.
RESULTS
The analysis included 38,380 men with PSA test
results and 3,593 with prostate ultrasound test re-
sults. Table 1 shows the general characteristics of
the study population. In the Pearson correlation
analysis of the PSA groups PSA correlated most
strongly with age (r ? 0.171, p ?0.01), and inversely
and significantly with BMI (r ? ?0.057, p ?0.01)
and WC (r ? ?0.022, p ?0.01). For subjects with
PV data (3,593) PV correlated positively and sig-
nificantly with PSA (r ? 0.321, p ?0.01), age (r ?
0.321, p ?0.01), BMI (r ? 0.114, p ?0.01) and WC
(r ? 0.207, p ?0.01). The age adjusted partial
correlation coefficient was 0.305 between PSA and
PV, ?0.056 between PSA and BMI, and ?0.045
between PSA and WC (p ?0.01 for all). When
adjusted for age and PV, the partial correlation
coefficient increased to ?0.089 between PSA and
BMI, and to ?0.081 between PSA and WC.
EFFECT OF OBESITY ON PROSTATE SPECIFIC ANTIGEN AND PROSTATE VOLUME
107

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Table 2 shows mean PSA by age group and PV,
and age adjusted mean PSA by BMI and WC. Mean
PSA increased significantly with age group and in-
creases in BMI or WC were associated with lower
age adjusted mean PSAs (p ?0.01) (table 2). In-
creases in BMI or WC were associated with a higher
age adjusted PV in all age groups (table 3).
When we stratified the subjects with PV data into
PV quartiles (to exclude the possible confounding
effects of PV) we found that increases in PV quartile
were significantly associated with higher age ad-
justed mean PSAs (table 2). We also found that the
association between age and PSA disappeared in all
but PV quartile 4. Age was no longer significantly
associated with PSA (table 4). A decreasing trend in
age adjusted PSA across BMI or WC groups was
significant for all PV quartiles, although only mar-
ginally so in the first (table 4). The proportion of
subjects with abnormal PSA (defined as greater
than 3.0 ng/ml or greater than 4.0 ng/ml) increased
significantly with BMI (p for trend ?0.01) (table 5).
DISCUSSION
In this large study of 30 to 79-year-old Korean men
from a generally healthy screening population with
no known prostate disease we examined the associ-
ations and interactions of BMI, WC, PSA, PV and
age. Previous studies have shown that obesity is
positively associated with the risk of prostate can-
cer, delayed cancer diagnosis and an increased pros-
tate cancer specific mortality rate.17,18Most prostate
cancers are signaled by an abnormal PSA test, but if
obesity lowers baseline PSAs, obese men with early
disease are at increased risk for having PSAs lower
than the screening cutoff values. Thus, it is impor-
tant to examine the influences of obesity and its
related factors, including PV, on PSAs in the general
screening population. To our knowledge no studies
have considered PV effects in that setting.
A recent United States study of men who had
undergone radical prostatectomy reported that BMI
was not associated with PSA and was positively
associated with PV only in those younger than 63
years.12However, in the present study BMI (and
Table 1. Study population characteristics
Mean age (SD)
Mean ng/ml PSA (SD)
Mean kg/m2BMI (SD)
Mean cm WC (SD)
Mean ml PV (SD)*
No. age (%):
30–39
40–49
50–59
60–69
70 or Older
No. kg/m2BMI (%):
Less than 22.9
23–24.9
25–30
Greater than 30
No. cm WC (%):
Less than 80
80–89.9
90–99.9
Greater than 99.9
No. ml PV (%):*
Less than 22.1
22.1–27.3
27.4–33.7
Greater than 33.7
50.05 (9.5)
1.07 (0.88)
24.5
87.5
29.2 (10.4)
(2.6)
(7.2)
5,732
13,660
13,348
5,592
1,048
(14.9)
(35.6)
(32.2)
(14.6)
(2.7)
10,111
12,114
15,160
995
(26.3)
(31.6)
(39.5)
(2.6)
5,110
19,418
12,222
1,630
(13.3)
(50.6)
(31.8)
(4.3)
899
900
896
898
(25.0)
(25.1)
(24.9)
(25.0)
* Data available for 3,593 men.
Table 2. PSA according to age, BMI, WC and PV
Geometric Mean ng/ml PSA
(95% CI) p for Linear Trend
Age:
?0.001
30–39
40–49
50–59
60–69
70 or Older
BMI (kg/m2):
Less than 23
23–24.9
25–30
Greater than 30
WC (cm):
Less than 80
80–89.9
90–99.9
Greater than 100
PV (ml):†
Less than 22.1
22.1–27.3
27.4–33.7
Greater than 33.7
0.93 (0.91–0.95)
0.98 (0.96–0.99)
1.06 (1.05–1.08)
1.32 (1.29–1.35)
1.69 (1.59–1.78)
?0.001*
0.89 (0.87–0.90)
0.86 (0.85–0.87)
0.83 (0.82–0.84)
0.73 (0.70–0.76)
?0.001*
0.88 (0.87–0.90)
0.86 (0.85–0.86)
0.84 (0.83–0.85)
0.75 (0.73–0.78)
?0.001*
0.76 (0.72–0.79)
0.88 (0.84–0.92)
0.95 (0.91–1.00)
1.29 (1.24–1.35)
* Age adjusted data.
† Data available for 3,593 men.
Table 3. Prostate volume according to BMI and WC
by age group
Geometric Mean (ml) Prostate Vol (95% CI)
49 Yrs or Younger
(1,234 men)
50–59 Yrs
(1,404 men)
60 Yrs or Older
(955 men)
BMI (kg/m2):
Less than 23
23–24.9
25–30
Greater than 30
p for Trend*
WC (cm):
Less than 80
80–89.9
90–99.9
Greater than 100
p for Trend*
23.0 (22.4–23.8)
23.4 (22.8–24.0)
25.0 (24.4–25.7)
27.8 (25.3–30.6)
?0.001
26.3 (25.5–27.1)
28.2 (27.5–28.9)
28.8 (28.1–29.5)
28.7 (25.2–32.6)
?0.010
29.5 (28.3–30.8)
31.7 (30.5–33.0)
33.2 (32.1–34.5)
34.5 (28.7–41.5)
?0.001
21.6 (20.8–22.5)
23.9 (23.4–24.4)
25.6 (24.8–26.4)
27.7 (25.3–30.3)
?0.001
24.5 (23.5–25.4)
27.8 (27.3–28.4)
29.5 (28.8–30.3)
32.3 (29.5–35.3)
?0.001
28.3 (26.7–30.1)
30.9 (29.9–31.9)
33.9 (32.6–35.2)
34.6 (31.5–37.9)
?0.001
* Age adjusted data.
EFFECT OF OBESITY ON PROSTATE SPECIFIC ANTIGEN AND PROSTATE VOLUME
108

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WC) was negatively associated with age adjusted
PSA across all age groups regardless of PV, and
positively associated with age adjusted PV in all age
groups, including the group older than 65 years (ta-
ble 3). In another Korean study BMI and WC were
positively associated with PV after age adjustment
even when the effects of overt obesity related meta-
bolic disease were excluded from analysis.19In a
United States study of men shown by biopsy to be
without prostate cancer, BMI was directly associ-
ated with PV, not PSA.14
There are conflicting data regarding the associa-
tion between age and PSA after adjustment for PV.
When we examined the relationship according to PV
quartile, age was associated with PSA after adjust-
ment for PV only in quartile 4. Therefore, we con-
cluded that PSA is negatively associated with obe-
sity (measured by BMI or WC), positively associated
with PV in all age groups, and not associated with
age except in the high PV group. In fact, the mean
PSA of the group with a BMI less than 23 in PV
quartile 4 was approximately 3 times that of the
group with a BMI greater than 30 in PV quartile 1
(1.42 vs 0.55), and the mean PSA of men with a WC
less than 80 cm in PV quartile 4 was approximately
2.5 times that of men with a WC greater than 100
cm in PV quartile 1 (1.52 vs 0.61).
Some studies report that obese young men with
an enlarged prostate would have the highest rate of
undetected cancer because of low PSA and the tech-
nical difficulty of adequately sampling an enlarged
prostate by needle biopsy.12Biopsies are generally
done for subjects with increased PSA values. How-
ever, the men most at risk for having undetected
prostate cancer are those in whom the level is below
the cutoff value and, therefore, are regarded as nor-
mal. Those would be obese men with a small pros-
tate.
Our study demonstrated that although obese men
generally have a higher PV than nonobese men, they
have a lower PSA, but the reason for that is not
known. Obesity leads to greater aromatization of
testosterone to estradiol, which results in lower se-
rum testosterone and may be associated with lower
PSA production.20A more recent suggestion is that
lower PSAs are largely due to hemodilution by the
large plasma volume in obese men.6,8However, this
Table 4. PSA according to age, BMI and WC by PV quartile
Geometric Mean ng/ml PSA (95% CI)
PV Less Than 22.1 ml (899 men)PV 22.1–27.3 ml (900 men) PV 27.4–33.7 ml (896 men)PV Greater Than 33.7 ml (898 men)
Age:
30–39
40–49
50–59
60–69
70 or Older
p for Trend
BMI (kg/m2):
Less than 23
23–24.9
25–30
Greater than 30
p for trend*
WC (cm):
Less than 80
80–89.9
90–99.9
100 or Greater
p for Trend*
0.88 (0.78–0.98)
0.93 (0.84–1.02)
0.97 (0.86–1.07)
1.02 (0.86–1.18)
0.63 (0.48–0.78)
0.402
1.09 (0.92–1.26)
1.01 (0.92–1.09)
1.11 (1.02–1.21)
1.22 (1.03–1.40)
1.10 (0.80–1.39)
0.639
1.02 (0.78–1.25)
1.09 (1.00–1.18)
1.18 (1.09–1.27)
1.40 (1.20–1.61)
1.43 (0.80–2.06)
0.056
1.04 (0.44–1.63)
1.40 (1.18–1.62)
1.67 (1.52–1.82)
1.88 (1.70–2.05)
2.28 (1.87–2.68)
?0.001
0.77 (0.72–0.83)
0.75 (0.70–0.81)
0.72 (0.67–0.78)
0.55 (0.37–0.82)
0.097
0.97 (0.89–1.05)
0.90 (0.84–0.97)
0.79 (0.74–0.85)
0.78 (0.56–1.09)
?0.001
1.07 (0.98–1.17)
0.96 (0.90–1.04)
0.91 (0.85–0.97)
0.61 (0.46–0.81)
?0.001
1.42 (1.29–1.58)
1.43 (1.32–1.55)
1.22 (1.13–1.31)
0.88 (0.64–1.20)
0.001
0.81 (0.74–0.88)
0.73 (0.69–0.78)
0.73 (0.66–0.80)
0.61 (0.44–0.84)
0.05
0.96 (0.86–1.06)
0.89 (0.84–0.94)
0.81 (0.75–0.88)
0.82 (0.63–1.06)
0.01
1.13 (0.99–1.28)
0.96 (0.91–1.02)
0.93 (0.86–1.00)
0.64 (0.51–0.80)
?0.001
1.52 (1.27–1.81)
1.43 (1.34–1.53)
1.21 (1.12–1.31)
1.00 (0.82–1.21)
?0.001
* Age adjusted data.
Table 5. Proportion of subjects with abnormal PSA by BMI
and WC
No.
Subjects
% Subjects With PSA (No.)
Greater Than 3.0
ng/ml
Greater Than 4.0
ng/ml
BMI (kg/m2):
Less than 23
23–24.9
25–30
Greater than 30
p for Trend*
WC (cm):
Less than 80
80–89.9
90–99.9
Greater than 100
p for Trend*
10,111
12,114
15,160
995
3.46 (350)
3.28 (397)
2.78 (422)
1.21 (12)
?0.001
1.9 (192)
1.75 (212)
1.5 (228)
0.5
0.002
(5)
5,110
19,418
12,222
1,630
3.72 (190)
2.87 (557)
3.24 (396)
2.33 (38)
0.003
2.0 (102)
1.59 (308)
1.7 (208)
1.17 (19)
0.08
* Chi-square test.
EFFECT OF OBESITY ON PROSTATE SPECIFIC ANTIGEN AND PROSTATE VOLUME
109

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explanation is based on simple estimates of plasma
volume using height and weight; it needs to be con-
firmed by more exact measurements.
Our study had some limitations. We targeted only
Korean men. Asian men are generally leaner, and
have smaller prostate glands and a much lower
prostate cancer incidence rate than their Western
counterparts, so our findings may not be generaliz-
able. We also relied on self-reported data for past
and current prostate related diseases, and did not
perform digital rectal examinations, so men with
undiagnosed prostate disease might have been in-
cluded in analysis.
CONCLUSIONS
In this study targeting generally healthy Korean
men BMI and WC were negatively associated with
PSA in all age groups, and the result was not af-
fected by PV. BMI and WC were also positively
associated with PV in all age groups but age was not
associated with PSA after PV adjustment. Because
obese men, especially those with a small prostate,
have a lower baseline PSA than nonobese men,
obese men with early prostate cancer are at in-
creased risk for having a PSA below the screening
cutoff value and, thus, of their cancer being unde-
tected until it is more advanced.
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EDITORIAL COMMENTS
Difficulties detecting early stage prostate cancer in
obese men may contribute to their higher prostate
cancer mortality rate. Park et al report an inverse
association between BMI and PSA in Korean men,
consistent with that of white and black men (reference
9 in article). Obese men were less likely to have an
increased PSA in the range approaching clinical sus-
picion, suggesting that obesity could delay biopsy re-
ferral and cancer detection. However, the sample of
men with an increased PSA was small, and any delay
EFFECT OF OBESITY ON PROSTATE SPECIFIC ANTIGEN AND PROSTATE VOLUME
110