Benign Prostatic Hyperplasia and Metabolic Syndrome 5. Metabolic syndrome Several criteria have been used to define MetS. Hammars- ten et al defined MetS as having one or more of the following conditions: non-insulin-dependent diabetes mellitus, hy- pertension, obesity, high insulin level, and low HDL choles- terol [14]. They reported that men with MetS had a larger prostate volume (mean: 49.0 vs 28.5 ml; p=0.003) and a higher annual BPH growth rate (1.01 vs 0.69 ml/y; p=0.002) than did men without MetS. Rohrmann et al defined MetS as having at least three of the following five components [29]: (1) waist circumference ＞102 cm; (2) triglyceride con- centration ≥1.69 mmol/l; (3) HDL cholesterol level ＜1.03 mmol/l; (4) systolic blood pressure ≥130 mmHg, diastolic blood pressure ≥85 mmHg, or current use of blood pressure medication; and (5) fasting glucose concentration ≥6.1 mmol/l or current use of oral diabetes medication or insulin. Additionally, they used a second, more specific definition that included components 1-3 but only in men who reported the use of blood pressure medication and men who used oral diabetes medication or insulin. 　Rohrmann et al defined LUTS as having at least three of the following four urinary symptoms: nocturia, incom- plete bladder emptying, weak stream, and hesitancy [29]. They reported that MetS was not statistically significantly associated with LUTS (OR: 1.2; 95% CI: 0.8-1.7). However, the OR was elevated in men with at least four components of MetS (OR: 1.6; 95% CI: 1.0-2.6) compared with men who had fewer components. Similarly, when the more specific definition of MetS was used, a significant association was evident between MetS and LUTS (OR: 1.8; 95% CI: 1.1-2.9). However, the cohort of this report [29] was restricted to men aged ≥60 years and included only four of the seven urologic symptoms that make up the AUASI. 　To address the aforementioned limitations, Kupelian et al reexamined the relationship between MetS and LUTS in 1,899 men who participated in the Boston Area Community Health Survey [32]. They defined MetS ac- cording to the Adult Treatment Panel III guidelines as the presence of three or more of the following five character- istics: (1) waist circumference ＞102 cm; (2) systolic blood pressure ≥130 mmHg, diastolic blood pressure ≥85 mmHg, or antihypertensive medication use; (3) HDL cho- lesterol ＜40 mg/dl or lipid medication use; (4) self-reported type 2 diabetes or increased blood sugar or diabetes medi- cation use; and (5) triglycerides ＞150 mg/dl. In multi- variable analyses that adjusted for age, race, socio- economic status, physical activity, alcohol consumption, smoking, and LUTS medication, MetS emerged as an in- dependent predictor of moderate-to-severe LUTS, which was defined as an AUASI ≥2 (OR: 1.7; 95% CI: 1.2-2.4). 　Although several investigators have observed a sig- nificant relationship between BPH/LUTS and MetS or one of its components, others have argued against these observations. Seitter and Barrett-Connor [33] reported no relationship between BMI and the rate of surgery for BPH. Meigs et al examined the data of 1,019 men who partici- pated in the Massachusetts Male Aging Study and ob- 511 served that obesity and blood pressure were not sig- nificantly related to subsequent clinical BPH development within a mean follow-up of 8.8 years [34]. Similarly, Hong et al observed no significant difference in the IPSS between men with and those without MetS (mean: 5.03 vs 5.40; p=0.3) [35]. 　In summary, it appears that MetS and its individual components may predispose patients to a higher risk of BPH/LUTS. However, this observation should be consid- ered with caution for several reasons. The aforementioned reports defined the examined predictors in several differ- ent ways, and this variation may have affected the strength and significance level of their relationships with the exam- ined endpoint. Moreover, the lack of consensus on the exact definition of MetS makes it more difficult to document the impact of this condition on the examined endpoint, namely, BPH/LUTS. The latter was also defined in several ways that ranged from a simple enlargement of the prostate gland to severe LUTS requiring surgery. Finally, different populations may have different genetic profiles, nutri- tional habits, and environmental risk factors. All of these variables may affect the potential relationship between MetS and BPH/LUTS. HYPOTHESIZED MECHANISMS 1. Hyperinsulinemia and autonomic hyperactivity Hyperinsulinemia is one of the components of MetS. Hyperinsulinemia is associated with increased sym- pathetic activity via enhanced glucose metabolism in ven- tromedial hypothalamic neurons [36]. This may contribute to an increase in the activation of the α-adrenergic path- way, which may in turn increase smooth muscle con- traction throughout male genitourinary tract structures, including the prostate, the bladder neck, and the urethra, thereby contributing to LUTS [37,38]. 　This concept has been studied in both animal models and human subjects. In the rat model, McVary et al observed an association between autonomic neural input to the pros- tate and the prostatic growth rate such that the absence of this input resulted in regression of the gland volume [39]. In a subsequent report, the same authors investigated the relationship between autonomic tone and LUTS secondary to BPH in 38 human subjects of the Medical Therapy of Prostatic Symptoms trial [40]. They reported that markers of autonomic hyperactivity (blood pressure elevation, heart rate elevation, and elevated serum or urine catechol- amines) were positively associated with subjective mark- ers of LUTS (AUASI, quality of life score, and BPH Impact Index). Moreover, in multivariable analyses, plasma nor- epinephrine emerged as an independent predictor of the prostatic transition zone volume [40]. 　Using data from the same trial, Roehrborn et al showed that α-blockade alone may be sufficient in treating the symptoms of men with small prostate volume (＜20 ml) [41], whereas men with larger prostates benefited more from a combination of α-blockade and 5α-reductase in- Korean J Urol 2011;52:507-516