Benign Prostatic Hyperplasia and Metabolic Syndrome 509 TABLE 1. Continued Author Gupta et al [25] Ozden et al [38] Kristal et al [12] Laven et al [16] Temml et al [86] Tomita et al [87] Hammarsten et al [13] 2009 Kupelian et al [32] Hong et al [35] 2009 2010 Year 2006 2007 2007 2008 2009 2009 Number of patients 1,206 78 5,667 27,858 2,371 1,511 159 1,899 538 Risk Factor/s DM Metabolic syndrome Metabolic syndrome Body mass index (≥35 vs. ＜25 kg/m2) Waist-hip ratio (≥1.05 vs ＜0.95%) DM Waist-hip ratio (＞0.98 vs. ＜0.90%) Metabolic syndrome Medication for DM type II Medication for hyperten- sion Medication for hyperlipi- demia Fasting insulin Lean body mass Metabolic syndrome Metabolic syndrome OR (95% Confidence Interval) 1.5 (1.2-1.8) 1.2 (0.9-1.6) Direct relationship 1.2 (0.9-1.6) 1.3 (1.0-1.8) 0.9 (0.6-1.2) 1.2 (1.1-1.4) No relationship 1.9 (1.1-3.2) 1.5 (1.0-2.1) 1.6 (1.0-2.5) Direct relationship Direct relationship 1.7 (1.2-2.4) No relationship p-value 0.004 0.1 0.01 0.01 0.02 0.3 ＜0.05 0.8 - - - 0.02 0.03 - 0.3 Endpoint/s BPH Annual BPH growth rate LUTS Moderate-sever LUTS LUTS LUTS LUTS LUTS Prostate gland volume BPH: benign prostatic hyperplasia, DM: diabetes mellitus, LUTS: lower urinary tract symptoms TABLE 2. Definition of metabolic syndrome according to the National Cholesterol Education Program adult treatment panel III (2005 revision) Criteriaa 1. Abdominal obesity (for men, waist circumference ＞102 cm) 2. Hypertriglyceridemia (＞1.69 mmol/l; ＞150 mg/dl) or treat- ment 3. Low high-density lipoprotein cholesterol (for men, ＜1.04 mmol/l; ＜40 mg/dl) or treatment 4. High blood pressure (＞130/85 mmHg) or treatment 5. High fasting glucose (＞6.1 mmol/l; ＞110 mg/dl) or treatment a: the presence of three or more pathologies is necessary to make a diagnosis of metabolic syndrome BASIC SCIENCE AND EPIDEMIOLOGIC EVIDENCE 1. Obesity Several anthropometric measures have been used to define obesity, including waist circumference, waist-to-hip ratio, and body mass index (BMI). Giovannucci et al examined the data of 25,892 men who participated in the Health Professionals Follow-up Study (HPFS) and observed that patients with an obese waist circumference (＞109 cm) had a 2.4-fold higher risk (p＜0.001) of being surgically treated for BPH than did those with a nonobese waist circum- ference (＜89 cm) [8]. 　Dahle et al examined the relationship between waist-to-hip ratio (examined as quartiles) and LUTS in 502 Chinese men. In their analyses [9], individuals with a waist-to-hip ratio of ≥92% (highest quartile) had a 2.0-fold (p=0.01) higher risk of BPH (defined as symptomatic en- larged prostate requiring surgery) compared with their counterparts with a waist-to-hip ratio of ≤85% (lowest quartile). In the same report, no significant relationship was observed between BMI and BPH (p=0.1). The authors attributed this observation to the limited variation in BMI among study subjects (mean: 22.3 kg/m2 for BPH cases vs 21.9 kg/m2 for controls; p=0.1). In fact, only 4% of the study subjects were overweight. Nevertheless, even in such a lean population, the waist-to-hip ratio was an important independent predictor of BPH. 　Parsons et al observed that men with BMI ≥35 kg/m2 had a 3.5-fold higher risk of harboring a large prostate (＞40 ml) than did their counterparts with a BMI ＜25 kg/m2 [10]. Seim et al examined the data of 21,694 male residents of Norway and found that both BMI (odds ratio [OR]: 1.4) and waist-to-hip ratio (OR: 1.3) were significant predictors of moderate to severe LUTS [11], defined as an International Prostate Symptom Score (IPSS) of ≥8. Kristal et al further corroborated these observations in 5,677 participants of the Prostate Cancer Prevention Trial. In this cohort [12], men with BMI ≥35 kg/m2 had a 1.2-fold higher risk of de- veloping LUTS (defined as IPSS ≥15 or a LUTS-specific treatment) compared with their counterparts with BMI ＜25 kg/m2. Several other investigators corroborated the significant direct relationship between obesity and BPH/ LUTS [4,13-16]. 　Taken together, it appears that obesity predisposes pa- tients to a higher risk of BPH/LUTS. This may be due to the development of insulin resistance and secondary hy- Korean J Urol 2011;52:507-516