Does Body Mass Index Have an Impact on Prostate Volume and Serum Prostate Specific Antigen ? A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms

negative impact on quality of life [2-5]. Serum Prostate Specific Antigen (PSA) is a globally used screening tool for carcinoma prostate, based on which prostate biopsy largely recommended when PSA value exceeds 4 ng/ mL [6]. PSA blood level variation had been studied with respect to numerous factors including age, race, prostate volume (PV), androgen level, body mass index (BMI), creatinine, liver enzymes [7], and genetic polymorphisms [8].


Introduction
Carcinoma prostate is on rising trend since last two decades causing significant morbidity and mortality in Asian countries.Indian registries had revealed rising incidence of prostatic carcinoma with mean percentage change of 0.14-8.6 annually [1].On the other hand, the incidence and the prevalence of benign prostatic hyperplasia (BPH) also increases with increasing age and leading significant morbidity of urinary tract infection, and/ or vesical calculus, acute urinary retention, acute renal failure and Prostate Symptom Score (IPSS), physical examination including digital rectal examination (DRE), anthropometry including height, weight and BMI calculation.Patients with a history of trans urethral resection of prostate, carcinoma prostate, urethral stricture or with a history of any trans urethral procedure were excluded from the study.The blood sample was obtained at the first visit for serum PSA determination (chemiluminescent enzyme immunoassay method).Those patients having suspicious finding on DRE or trans rectal ultrasound (TRUS) or PSA > 4 ng/dl underwent TRUS guided prostate biopsy and excluded if positive for prostatic malignancy.BMI was calculated by dividing the weight in kilograms by the square of the height in meters (kg/m2).Prostate volume (cm3) was measured by a single experienced radiologist by TRUS (LOGIQ CS Premium).Participants were categorized as being normal weight (BMI 17.50 to 22.99 kg/m2), overweight (BMI 23.00 to 27.99 kg/m2), or obese (BMI > 28.00 kg/m2) according to the Asian population [14].

Statistical Analysis
BMI stands as the variable of interest in this study and PSA, PV as variables for the outcome measure.Continuous data are given as mean ± SD while discrete (categorical) are presented in percentages.The categorical variables were compared by chisquare (χ2) test.Spearman's correlation was used.A two-sided (α=2) p < 0.05 is considered statistically significant.All statistical analyses were performed using statistical package for Social Sciences, version 16.0 (SPSS, Chicago).

Results
We conducted a prospective cross-sectional study enrolling 1100 patients during 2012-2014.All the patients were Indian with a mean age of 58.18 years (range; 41-76 years).The majority of patients were in the range of 55 -65 years.According to BMI, the majority of patients (58%) were in the overweight group (BMI 23.00-27.99),and 10.82% were in the obese group with a BMI > 28.00.Mean PSA of the study population was 1.93+ 1.79 ng/ml.PSA value was < 4 ng/ml in 1048 patients (90.73%) and rest with PSA > 4 ng/ml underwent TRUS guided prostate biopsy which revealed benign pathology.The mean serum PSA level had no significant difference across three BMI categories (p > 0.05) No significant differences were observed in IPSS among BMI categories.Use of alpha blocker, and combination with 5 alpha reductase inhibitor (5-ARI) did not reveal any significant differences among BMI categories.

Discussion
In our cross-sectional study of Indian population, BMI was found to have a significant positive association with prostate volume (rs=0.132).Obesity is the excessive fat accumulation in adipose tissue, not mere a passive energy depot, but acts like an endocrine organ secreting a number of mediators, including, adipokines, acute phase reactants, growth factors and numerous other cytokines [15].In 1999, Colao et al conducted a study of acromegaly patients and age matched controls and found significantly higher prostate volume in the acromegalic patients than the control group [16].The association between Insulin like growth factor-1 (IGF-1) and prostate volume was not found significant by Harman et al [17].Sarma et al in 2001 in a population-based study of black men residing in Michigan, found a positive association between BMI and Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) with prostate volume but no association between IGF-1 and prostate volume found [18].Positive association between BMI and prostate volume in our study support cytokines mechanism which needs further molecular study.Clinical application of this association may illustrate the growth mechanism in benign prostatic hyperplasia or in the natural history of carcinoma prostate and may provide target for growth suppression and tumour control.In literature, studies describe positive or no significant association between BMI and prostate volume in different geographic and ethnic groups as shown in .
In our study, we observed no significant correlation between serum PSA value and BMI in male patients presenting with LUTS (rs=0.039).In literature PSA and BMI relationship had been studied in asymptomatic patients of different ethnic group and found inverse or no significant correlation [Table -4] [ [23][24][25][26].The underlying mechanism for the BMI and serum PSA relationship is still unidentified.The hypothesis supporting inverse relationship include hemodilution and low androgen level.In obese patients due to high volume of distribution inverse correlation measured [27].Obesity affects hormonal milieu by increasing free and total estradiol, lowering free and total testosterone and sex hormone binding globulin level [28].This inverse result could be due to confounding; because high BMI patients usually had a high cholesterol level requiring statin therapy which leads to decrease in serum PSA level.
We observed no association between BMI and LUTS measured by IPSS, even on stratification by alpha blocker alone or combination with 5-ARI (rs=0.013).Kristal et al [29] and Lee et al. [30] observed positive correlation between BMI and LUTS while many other studies found no significant association between BMI and LUTS.
The strengthening features of our study include: (1) Prospective cross-sectional study where anthropometric measurements and blood sampling done on the first visit.

Does Body Mass Index Have an Impact on Prostate Volume and Serum Prostate Specific Antigen? A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms
Copyright: © 2016 Sokhal, et al.We identified certain limitations of our study.Being cross section observational nature of study, this study cannot institute cause and effect relationship.We used BMI as the only measure of obesity, which has its own limitation of classifying man with large muscle mass but less fat as obese or overweight.

Conclusions
In conclusion, we establish a positive correlation of BMI with prostate volume among Indian ethnic patients presenting with LUTS.We found no significant association of BMI with serum PSA and IPSS.To establish an underlying mechanism a further research at a molecular and genetic level as warranted.

Does Body Mass Index Have an Impact on Prostate Volume and Serum Prostate Specific Antigen? A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms
(2) We studied the association of BMI with PV and serum PSA in patients having LUTS not in asymptomatic population, so including clinically coherent cohort.(3) To the author's knowledge this is the first prospective study from Indian ethnicity even from the South Asia region studying the association between BMI and PV Volume and Serum Prostate Specific Antigen?A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms.J Urol Nephrol Open Access 2(3): 1-5.
Volume and Serum Prostate Specific Antigen?A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms.J Urol Nephrol Open Access 2(3): 1-5.

Figure 1 :
Figure 1: Relationship of PSA; IPSS and prostate volume among different BMI groups

Table - 1
: Characteristics of the 1100 Indian Men and the relationship between BMI, PSA and PV

Table - 2
: Stratified analysis of BMI groups demonstrating effect over prostate volume; Prostate Specific Antigen level and International Prostate Symptom Score BMI: Body Mass Index; PV: Prostate Volume; PSA: Prostate Specific Antigen; IPSS: International Prostate Symptom Score; 5-ARI: 5-Alpha Reductase Inhibitor

Table 3 :
Spearman's correlations between body mass index; prostate volume; Prostate Specific Antigen and International Prostate Symptom

Table 4 :
Summary of published studies on relationship with BMI; PV and PSA among different ethnic groups Published

Published studies on relationship between BMI and PV Reference Ethnicity Sample size Mean PSA BMI/PSA relationship Kim et al. 2007 [32]
NS: Not significant; Positive-Significant positive association; Inverse-Significant inverse association; BMI: Body mass index; PV: Prostate volume; PSA: Prostate Specific Antigen; IPSS; International Prostate Symptom Score Volume and Serum Prostate Specific Antigen?A Prospective Observational Study in Patients with Lower Urinary Tract Symptoms.J Urol Nephrol Open Access 2(3): 1-5.Does Body