ABSTRACT

Certain components of the metabolic syndrome, such as hyperglycaemia, hypertension and

dyslipidaemia, have been reported in recent studies to correlate to benign prostatic
hyperplasia (BPH). Although obesity represents an important parameter of the metabolic
syndrome also, its association with BPH remains controversial. The aim of this study is to
summarize the existing literature concerning the coexistence of obesity and BPH, and to
elucidate whether an association between these conditions exists. We identified studies
published from 1980 onwards by searching electronic databases, such as MEDLINE. Initial
search terms included benign prostatic hyperplasia, epidemiology, risk factor, combined
with metabolic diseases, hypertension, hyperinsulinemia, dyslipidemia and obesity.
There are several observational and epidemiological studies examining the effects of obesity
on BPH, though more studies examine the association between several metabolic or lifestyle
factors and BPH. Evidence suggests that an association between BPH and obesity is possible.
However, obesity exhibits a stronger positive correlation with BPH when its effects on BPH
are examined in combination with other disorders which constitute components of the
metabolic syndrome. When the effects of obesity on BPH are examined separately a
confounding relation is demonstrated. As the common pathophysiological pathway between
metabolic syndrome, obesity and BPH continues to be poorly highlighted, the exact relation
of obesity and BPH remains unclear.
BACKGROUND/INTRODUCTION
Benign prostatic hyperplasia (BPH) represents the most common benign clinical
entity in men, and its incidence is age related. BPH constitutes a significant problem in public
health, which globally affects 50% of men aged 60 years or older. At first BPH is detectable
around the fourth decade of life and affects nearly all men by the ninth decade (Untergasser
et al., 2005).
BPH is caused by an increase in the prostate epithelial and stromal cells (Untergasser
et al., 2005). The etiology of BPH remains still largely unresolved, as both multiple, partially
overlapping, and complementary systems (i.e. nervous, endocrine, immune and vascular
system) and local factors are likely to be involved. There is evidence that supports that the
pathogenetic mechanism of BPH is mainly endocrine controlled (Nandeesha, 2008).
Other endocrine controlled metabolic disorders, such as diabetes mellitus,
hyperinsulinaemia, yslipidaemia, and obesity have been found to be more prevalent among
men with BPH than in men without BPH (Hammarsten et al., 1998). The pathophysiology of

the metabolic syndrome is also extremely complex and it has also been only partially
elucidated. The metabolic syndrome seems to be associated to obesity, insulin esistance, and
a series of independent factors, such as aging, proinflammatory state and hormonal changes
(Poulsen et al., 2001; Grundy et al., 2004). Stress can be a contributing factor, as well as
sedentary lifestyle, that is, low physical activity and excess caloric intake (Katzmaryk et al.,
2003).
Obesity is characterized by many hormonal mechanisms that participate in the
regulation of appetite and food intake, storage patterns of adipose tissue and development of
insulin resistance. For this reason, both obesity and insulin resistance predispose to the
development of metabolic syndrome (Reavan, 1988).
Recent studies demonstrated several relations among BPH, diabetes mellitus and
hyperinsulinaemia (Vikram et al., 2010b) and several investigators proposed links associating
atherosclerosis, hypertension and dyslipidaemia with BPH development (Abdollah et al.,
2011; Jiang et al., 2011).
Although obesity is considered to be an important component of the metabolic
syndrome, its association with BPH remains controversial. The purpose of the current review
was to summarize the existing literature focusing on the coexistence of BPH and obesity, and
to elucidate whether an association between these two clinical entities exists.
Although Vikram et al. (2010a, 2010b) provided the theoretical background linking
hyperinsulinaemia and obesity with BPH and BPH related LUTS by demonstrating
enlargement of the prostate and enhanced alpha-adrenoceptor mediated contraction in the
prostate of high fat diet-fed rats (Vikram et al., 2010b), the specific etabolic pathway remains
unknown (Schenk et al., 2009).
Current clinical studies present controversial results showing risk for both obese and
lean people biologically plausible. This could be explained at least in part by differences
in the design and methodology among different studies; some studies are examining the
components of the metabolic syndrome as one entity, while others the effects of its
individual components. Moreover, the correlation between obesity and BPH is proached by
associating more than one established metrics of obesity (including adiposity, BMI, waist
circumference and waist-to-hip ratio) with a variety of clinical expressions of BPH (physician
diagnosed BPH, radiologically determined prostate enlargement, histological diagnosis, low
urinary flow rate and LUTS) and the risk of clinical BPH (as assessed by the need of medical
treatment and prostate surgery).

More precisely, BMI does not always reflect the impact of obesity and often, clinical
markers of obesity are rather associated with BPH individually than all together. A large, long
term, questionnaire based follow up study by Giovannucci et al. (1994), failed to demonstrate
an association between BPH and three clinical markers of obesity; however, the study has
linearly related increased waist circumference to both symptoms severity and need for
surgery (Giovannucci et al., 1994). Anthropometric factors other than obesity may also
influence the interpretation of the results. Gupta et al. (2006) demonstrated that height was an
independent predictor of BPH, while weight, waist and hip circumference were not.
Similarly, Zhuang et al. (2005) found a positive correlation between height and total, central,
and peripheral prostate volume. However, two other cross-sectional studies did not find any
association between height and BPH (Morrison, 1992; Zucchetto et al., 2005). Obviously
taller men have proportionally larger prostates independently of the presence of BPH and
therefore it is plausible that patients with a greater baseline prostate volume will have a
greater absolute increase in their prostate volume on follow-up (Mohr et al., 2001). In
addition, it seems that because of an age related decrease in stature and change in bone
density, BMI turns to an increasingly invalid measure of obesity in the elderly (Lisko et al.,
2011). As self-reported information regarding symptoms severity and anthropometrical data
are likely to be less accurate, several studies present limitations despite the relatively large
number of participants included. In the study of Gupta et al. (2006), participants were
classified as having BPH rather because of the presence of LUTS than by histologic
confirmation of BPH, while in the study of Zucchetto et al. (2005), data on patients height
and weight was obtained by self-reported information. Actually, data based on symptoms
could lead to misclassification because not all men with BPH develop LUTS and vice versa.
Moreover, the discomfort due to BPH as assessed by questionnaires does not correlate to
symptom severity (Yalla et al., 1995). It should also be noticed that disorders other than BPH
may contribute to the development and progression of LUTS (Stamatiou, 2009). The
distinction between BPH related LUTS and LUTS associated to these other disorders is often
difficult, especially in the elderly patient (Parsons, 2007). In the studies of Giovannucci et al.
(1994) and Morrison (1992) participants were classified as having BPH accordingly to the
digital rectal examination and the need of a prostate operation (Morrison, 1992; Giovannucci
et al., 1994). However, digital rectal examination provides poor estimates of the prostate
gland volume and, as also shown by Kim et al. (2011), despite the larger adenomas, no
increase in obstructive uropathy among obese men was proved (Mohr et al., 2001).

While in some studies it has been shown that increased adiposity is positively
associated with radiographically determined prostate volume and enlargement, in others no
association is found. Controversy may be because of limitations of imaging based studies. In
fact, despite the remarkable improvements in the prostate imaging, some of the pitfalls of
abdominal ultrasonography for the evaluation of the prostate volume still remain as a result of
external factors, such as the obesity of the patient and the insufficient bladder distension,
while the adequacy of the test depends on the experience and skill of the person performing
the examination (Hunter et al., 1982). Given that studies based on more accurate imaging
techniques (such as pelvic Magnetic Resonance Imaging- MRI) also fail to associate obesity
with BPH (Parsons et al., 2008), it is possible that total prostate volume is not as accurate
metric of BPH as transitional zone volume is (Glynn et al., 1985; Xie et al., 2007).
Studies based on BPH surgery material obesity are generally considered more reliable
in determining the possible association between BPH and obesity. However, when examined
in association with histologically confirmed BPH, obesity showed little or no correlation.
This could be explained by the fact that the need of a prostate operation is poorly correlated
with the extent of BPH (Arrighi et al., 1990). Moreover, the resection weight examination
provides poor estimates of the prostate gland volume (Yalla et al., 1995). Interestingly,
Sidney et al. (1991) found that surgery is performed less frequently among overweight men, a
fact that may also influence the incidence of obesity in pathology based studies (Hammarsten
and H ogstedt, 1999). Interestingly, in the study of Lee et al. (2006) prostate volume was
greater in the obesity groups than in the normal groups after patients with overt obesityrelated metabolic diseases were excluded.
This observation may suggest that rather genetic than metabolic factors play an
important role in the evolution of BPH and also may explain the positive relation between
obesity and risk of BPH development through steroid hormones alterations Up to now, few
data demonstrating a genetic basis for BPH exists, as relevant studies face several difficulties
(Mongiu and McVary, 2009). Currently, a genetic cytosine-adenine repeat polymorphism in
the insulin-like growth factor- gene has been associated with increased risk of BPH (Tsuchiya
et al., 2005), while the CAG repeat polymorphism in the androgen receptor gene is not
associated with increased risk of BPH (Kristal et al., 2010).
CONCLUSIONS
Obesity and BPH represent common disorders and their incidence is age related.
Evidence suggests that obesity may increase the risk of BPH; however, associations reported

in published studies are conflicting. This can be attributed to the technical difficulties in
performing epidemiologic studies about BPH incidence due to the absence of consensus in
the definition for BPH. As the specific etiology of BPH initiation and progression is not yet
known, more prospective epidemiologic studies are needed to confirm the above hypothesis
and to explain underlying genetic mechanisms.