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Obesity and Benign Prostatic Hyperplasia: Clinical Connections,

Emerging Etiological Paradigms and Future Directions


J. Kellogg Parsons,*, Aruna V. Sarma, Kevin McVary and John T. Wei
From the Division of Urologic Oncology, Moores Cancer Center, University of California, San Diego and Section of Surgery, San Diego
Veterans Affairs Medical Center (JKP), La Jolla, California, Departments of Epidemiology (AVS) and Urology (AVS, JTW), Ann Arbor,
Michigan, and Department of Urology, Northwestern University (KM), Chicago, Illinois

Abbreviations
and Acronyms
BLSA Baltimore Longitudinal
Study of Aging
BMI body mass index
BPH benign prostatic
hyperplasia
HPS Health Professionals
Follow-up Study
I-PSS International Prostate
Symptom Score
LUTS lower urinary tract
symptoms
NHANES National Health and
Nutrition Examination Survey
PCPT Prostate Cancer
Prevention Trial
* Correspondence: Division of Urology, University of California-San Diego, 200 West Arbor Dr.,
No. 8897, San Diego, California 92103-8897 (telephone: 619-543-2630; FAX: 619-543-6573; e-mail:
leparker@ucsd.edu).
Financial interest and/or other relationship
with American Medical Systems.
Financial interest and/or other relationship
with GlaxoSmithKline, Pfizer, Lilly/ICOS, SanofiAventis, Allergan and National Institute of Diabetes and Digestive and Kidney Diseases.
Financial interest and/or other relationship
with Sanofi, American Medical Systems, Envisioneering, Gen-Probe and Beckman.

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www.jurology.com

Purpose: Benign prostatic hyperplasia is a highly prevalent disease in older men


with substantial adverse effects on public health. Classic etiological paradigms
for benign prostatic hyperplasia focus on nonmodifiable risk factors. However,
obesity also potentially promotes benign prostatic hyperplasia.
Materials and Methods: We performed a structured, comprehensive literature
review to identify studies of obesity, benign prostatic hyperplasia, lower urinary
tract symptoms and physical activity.
Results: A preponderance of published evidence suggests strong positive associations of obesity with benign prostatic hyperplasia and lower urinary tract
symptoms. This evidence encompasses most established metrics of adiposity,
including body mass index, waist circumference and waist-to-hip ratio, and falls
under 3 general categories, including prostate volume, clinical benign prostatic
hyperplasia and lower urinary tract symptoms. 1) Prior studies consistently
showed that increased adiposity is positively associated with radiographically
determined prostate volume and enlargement, suggesting that obesity promotes
prostate growth. 2) Most studies revealed that obesity increases the risk of
clinical benign prostatic hyperplasia by several measures, including the initiation
of benign prostatic hyperplasia medical treatment, noncancer prostate surgery,
physician diagnosed benign prostatic hyperplasia, histological diagnosis and
urinary flow rate. 3) Prior studies demonstrated that obesity increases the risk of
lower urinary tract symptoms, as measured by a validated questionnaire. Also,
most studies showed that physical activity significantly decreases the risk of
benign prostatic hyperplasia.
Conclusions: Obesity markedly increases the risk of benign prostatic hyperplasia. Since physical activity decreases the risk of benign prostatic hyperplasia,
these observations support the development of novel prevention strategies and
treatment targeted toward adiposity, weight loss and lifestyle.
Key Words: prostate, prostatic hyperplasia, urination disorders, obesity,
metabolic syndrome X
BENIGN prostatic hyperplasia is a highly
prevalent disease in older men with
substantial adverse effects on public
health since 3 of 4 men 60 to 69 years
old in the United States are affected, 21
to 38 million hours of productivity are
lost annually and more than $1 billion

per year in direct health care expenditures are consumed exclusive of outpatient medication.1 The primary clinical
manifestation of BPH is the LUTS complex. As a result, BPH and LUTS remain inextricably interconnected in
the contemporary study of and treat-

0022-5347/13/1891-0102/0
THE JOURNAL OF UROLOGY
2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION

http://dx.doi.org/10.1016/j.juro.2012.11.029
Vol. 189, S102-S106, January 2013
RESEARCH, INC.
Printed in U.S.A.

AND

Please cite this article as J Urol 2013;189: S102-S106. DOI: http://dx.doi.org/10.1016/j.juro.2012.11.029

OBESITY AND BENIGN PROSTATIC HYPERPLASIA

ment for urinary symptoms in older men. LUTS


affects 15% to 60% of males older than 40 years and
is associated with an increased risk of falls, significantly decreased quality of life, sadness, depression,
impaired instrumental activity of daily life and decreased SF-12 scores.25
Classic causal paradigms for BPH concentrated
on relatively nonmodifiable etiological stimuli, including sex steroid hormones, genetic predisposition
and age related detrusor changes. However recent
observations indicate that systemic metabolic disturbances may also contribute substantially to BPH
pathogenesis.6 These data intimate that many of the
metabolic disturbances associated with cardiovascular disease and the lifestyle factors that modulate
these disturbances are associated with BPH onset
and progression. In this context accumulating evidence suggests that obesity promotes BPH. We reviewed published data on obesity, BPH, LUTS and
physical activity.

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passes most established metrics of adiposity, including BMI, waist circumference and waist-to-hip ratio,
and involves 3 general categories of outcome, that is
prostate volume, BPH and LUTS (see table).

RESULTS

Obesity and Increased Prostate Volume


Prior studies consistently showed that increased adiposity, as determined by most anthropometric measures, is positively associated with ultrasound and
magnetic resonance imaging measured prostate volume. The greater the adiposity, the greater the prostate volume. Increased prostate volume is clinically relevant, in that it strongly predicts adverse
clinical outcomes associated with BPH, including
acute urinary retention and renal failure.8,9 Body
weight,10,11 BMI1115 and waist circumference11,13
were positively associated with prostate volume in
multiple study populations. In the BLSA cohort
each 1 kg/m2 increase in BMI corresponded to a
0.41 cc (95% CI 0.15 0.84) increase in prostate
volume (p-trend 0.06).11
Moreover, obesity is associated with prostate enlargement. In BLSA obese (BMI 35 kg/m2 or greater)
participants were at 3.5-fold increased risk for prostate enlargement, defined as magnetic resonance imaging determined prostate volume 40 cc or greater,
compared to nonobese (BMI less than 25 kg/m2) participants.11 A recent analysis of more than 16,000
radical prostatectomy specimens validated these
findings (Parsons et al, unpublished data). Multivariate adjusted analysis revealed that each 1 kg/m2
increase in preoperative BMI was associated with a
0.45 gm (95% CI 0.35 0.55) increase in total prostate weight (p-trend 0.001). Moreover, there was a
41% increased risk of prostate enlargement, defined
as total prostate weight 40 gm or greater, in obese
(BMI 35 kg/m2 or greater) compared to nonobese
(BMI less than 25 kg/m2) men (OR 1.41, 95% CI
1.011.95). These observations suggest that adiposity is linked to prostate growth.

This review revealed a number of subjective and


objective clinical definitions of BPH. Some entailed
validated questionnaires for LUTS combined with
prostate examination and urinary flow rate, and
others entailed medical or surgical treatment, patient reported history, physician diagnosis and histological diagnosis.
Also, obesity is a component of metabolic syndrome, a clinical constellation of metabolic abnormalities that increases the risk of cardiovascular
disease. In the several published definitions of metabolic syndrome there is no consensus about which
anthropometric measures should be used to define
obesity, that is BMI, waist circumference or waistto-hip ratio.7
Overall published evidence supports strong associations of obesity with BPH. This evidence encom-

Obesity and BPH


Most studies showed that obesity increases the risk
of BPH, as defined by several measures. Of almost
26,000 male participants in HPS those with an obese
waist circumference (greater than 109 cm) were 38%
(OR 1.38, 95% CI 1.011.95) more likely to undergo
BPH surgery than those with a nonobese waist circumference (less than 89 cm).16 In a case-control
study of 500 Chinese men those with the highest
waist-to-hip ratio were 41% more likely (OR 1.41,
95% CI 1.011.95) to undergo BPH surgery than
those with the lowest waist-to-hip ratio.17 Finally, in
5,700 American men participating in the PCPT the
incidence of BPH, defined as consistently severe urinary symptoms on the I-PSS, initiation of medical
therapy or surgery, increased 10% for each 0.05
increase in the waist-to-hip ratio.18 Also, a BMI of 30

MATERIALS AND METHODS


We performed a structured, comprehensive literature
review to identify studies of obesity, BPH, LUTS and
physical activity. We completed separate searches of the
MEDLINE database (January 1966 to April 2009), The
Cochrane Library Central Search and the EMBASE
database (1980 to 2009). Initial search terms were benign
prostatic hyperplasia, lower urinary tract symptoms and
obesity. Subsequent search terms were physical activity
and exercise. To maximize inclusion of the most recent
pertinent data we also examined reference sections in
published articles, abstracts presented at the annual
meeting of the American Urological Association (2002 to
2007) accessed on the American Urological Association
website (www.auanet.org) and unpublished data to which
we had access.

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OBESITY AND BENIGN PROSTATIC HYPERPLASIA

Select studies of obesity, BPH and LUTS


Study Population (outcome measure)

Risk Factor

Referent

OR (95% CI)

BLSA11 (prostate vol 40 cc or greater)


HPS:16
BPH surgery
LUTS
Nord-Trndelag Health Study 224 (LUTS)
PCPT18 (incident BPH*)
Shanghai case-control17 (BPH surgery)
NHANES III23 (LUTS)
Flint Mens Health Study26 (LUTS)
Hong Kong cohort27 (LUTS)

BMI greater than 35 mg/kg2


Waist circumference greater than 109 cm

BMI less than 25 kg/m2


Waist circumference less than 89 cm

3.52 (1.458.56)

BMI 40 mg/kg2 or greater


BMI 3035 mg/kg2
Waist-to-hip ratio greater than 0.923
Waist circumference greater than 102 cm
BMI 30 mg/kg2 or greater
BMI 25 mg/kg2 or greater

BMI less than 25 mg/kg2


BMI less than 25 mg/kg2
Waist-to-hip ratio less than 0.856
Waist circumference less than 94 cm
BMI less than 25 mg/kg2
BMI less than 23 mg/kg2

2.38 (1.423.99)
2.00 (1.472.72)
1.79 (0.903.56)
1.30 (1.081.57)
1.41 (1.011.95)
1.48 (0.872.54)
1.13 (0.751.70)
1.08 (0.841.38)

* Defined as consistently severe urinary symptoms on I-PSS, initiation of medical therapy or BPH surgery.

to 34 kg/m2 was associated with a 30% increased


risk of BPH relative to a BMI of less than 25 kg/m2
(OR 1.30, 95% CI 1.08 1.57). Notably the PCPT
tracked incident BPH for up to 7 years and to our
knowledge is the largest incident analysis of obesity
and BPH to date.
Results in a case-control study of 3,000 Italian
men also showed a link between obesity and BPH
but were somewhat more equivocal.19 Men with a
lowest lifelong BMI of 23.7 kg/m2 or greater were
56% more likely to have histological BPH than men
with a lowest lifelong BMI of 20.7 kg/m2 or less but
BMI and waist circumference at evaluation were
inversely associated with BPH risk, as defined by
histological diagnosis. Furthermore, 2 smaller studies showed no links between obesity and BPH. An
analysis of 475 American men enrolled in the Olmsted County cohort showed no associations of obesity
with peak urinary flow rate or acute urinary retention,20 while a case-control study in 870 Western
Australian men revealed no associations of obesity
with BPH surgery.21 Although a cohort analysis of
United States Air Force veterans did not demonstrate any linear associations of BMI with physician
diagnosed BPH, this study did not present data on
BPH and obesity.22
Obesity and LUTS
Several studies showed that obesity increases the
risk of LUTS, as measured by a questionnaire.
Obese men in the HPS were 100% more likely (OR
2.00, 95% CI 1.011.95) to report LUTS, defined as
responses to a questionnaire encompassing storage
and voiding symptoms, compared to men with a
nonobese waist circumference.16 In 2,800 men in
NHANES III an increase in BMI during adulthood
and obese waist circumference were associated with
increased LUTS, defined as at least 3 of certain
symptoms, including nocturia, incomplete emptying,
weak stream and hesitancy.23 In the second NordTrndelag Health Study in 21,700 Norwegian men
obese BMI and an increased waist-to-hip ratio were
associated with increased LUTS, as measured by

I-PSS.24 In a cohort of 1500 Austrian men there was


a trend toward higher I-PSS with increased waist
circumference but not with increased BMI.25 There
were no associations of BMI determined obesity with
LUTS in a cohort of black American men26 or in a
cohort of Chinese men.27
Physical Activity, BPH and LUTS
Obesity is strongly associated with a lack of physical
activity. Accordingly increased physical activity has
been linked to a decreased risk of BPH surgery,28,29
clinical BPH,30,31 histological BPH32 and LUTS.29,33
A meta-analysis of 11 published studies indicated
that moderate to vigorous physical activity decreased the risk of BPH or LUTS by as much as 25%
relative to a sedentary lifestyle.34 The strength of
the protective effect appeared to be greater at higher
activity levels but there was a nonsignificant trend
toward a protective effect with even light physical
activity. Adjusting for multiple confounders underscored the independence of the protective effect of
physical activity toward BPH.
A decreased risk of BPH with increased physical
activity provides further evidence of a link between
obesity and BPH. Moreover, this observation intimates that lifestyle changes may alter the natural
history of BPH.

DISCUSSION
Thus, obesity increases the risk of BPH by multiple
outcome measures. The public health import of this
observation is considerable. The prevalence of obesity continues to increase and obesity now affects
more than a third of American men.35 BPH also
affects a broad swath of the older male population,
which (like obesity) grows larger each year. By 2030,
20% of the American population will be 65 years old
or older, including more than 20 million men.36 The
confluence of these 3 trends, that is an increased
BPH risk with obesity, the obesity epidemic and the
rapid aging of the population, suggests the gathering of a perfect storm that will markedly swell the

OBESITY AND BENIGN PROSTATIC HYPERPLASIA

ranks of men with BPH in the near future and place


ever greater burdens on finite health care resources.
These observations are also important because
they intimate the existence of modifiable pathways
for BPH that represent novel targets for prevention
and treatment by modulating adiposity. Also, the
robust, significant inverse association of physical
activity with BPH justifies the design and implementation of clinical trials using weight loss, exercise and lifestyle alterations. To our knowledge
there are no published studies to date of the effect of
such interventions on BPH or LUTS. Further studies should determine optimum physical activity levels and the relative importance of targeting adiposity vs overall body weight to achieve a therapeutic
effect.
These data are observational and, thus, should
serve primarily as a guide to inform the design of
future clinical trials. However, there is little if any
negative side to promoting healthy lifestyle interventions, specifically increased physical activity and
weight loss, in obese older men to prevent or attenuate BPH, particularly since such interventions
have proven benefits to overall and cardiovascular
health.
To our knowledge the physiological mechanisms by
which obesity promotes BPH remain to be described. A
potential explanation is systemic inflammation. Obesity is a component of metabolic syndrome,7 and obesity and metabolic syndrome are associated with systemic inflammation and oxidative stress.37 There are
multiple lines of evidence connecting BPH with inflammation. 1) BPH in surgical specimens is associated with inflammation,38 40 and the extent and severity of inflammation correspond to the amount of
prostate enlargement.41 2) In NHANES III higher serum C-reactive protein was associated with an increased risk of LUTS.42 3) In the Olmsted county cohort daily nonsteroidal anti-inflammatory use was

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associated with a 27%, 49% and 47% decreased risk of


LUTS, low urinary flow rate and enlarged prostate,
respectively.43 Thus, it is possible that BPH represents
a nonmalignant pathway of unregulated prostate
growth promoted by oxidative stress and inflammatory mediators.
The extent to which obesity may influence BPH
independent of sex steroid hormones is also unclear.
Since increased adiposity promotes increased aromatization of circulating testosterone into estrogen,
alterations in the balance between testosterone and
estrogen in prostate tissue may possibly contribute
to BPH pathogenesis. However, the BLSA controlled
for serum total and free testosterone, suggesting
that obesity may influence prostate growth through
mechanisms other than sex steroid growth pathways.11
While these data are compelling, they are primarily cross-sectional. Moreover, it is unclear as to how
obesity interacts with other components of metabolic
syndrome, including glucose insensitivity, dyslipidemia and hypertension. Additional longitudinal analyses of incident BPH and LUTS may be needed to
elucidate these pathways. These analyses should
explore correlations among variables and incorporate evaluations of prevalent and incident health
conditions that could confound associations of obesity with BPH and LUTS. Such analyses would facilitate the development and implementation of efficacious prevention strategies.

CONCLUSIONS
Obesity substantially increases the risk of BPH.
Since physical activity decreases BPH risk, these
observations support the development of novel strategies for BPH prevention and treatment targeted
toward adiposity, weight loss and lifestyle interventions.

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