Benign prostatic hyperplasia (BPH) is one of the most common conditions in elderly men [1]. Although not fatal, BPH leads to troublesome lower urinary tract symptoms (LUTS) that can diminish quality of life (QoL) and results in economic and social consequences [2]. However, the etiology and pathogenesis of BPH remain unclear. Previous studies have shown that BPH is associated with sex steroid hormone levels and has a genetic predisposition [3]. Recently, attention has been focused on diet, exercise, lifestyle, and metabolic disturbances as risk factors for BPH, in addition to well-established factors, such as age and testosterone level [4,5].

Since the concept of syndrome X was introduced as comprising risk factors for atherosclerosis in 1987, metabolic syndrome (MetS) has had wide-ranging effects on modern medical care [6]. MetS is a combination of medical disorders, including obesity, impaired glucose metabolism, hypertension (HTN), hypertriglyceridemia, and low high density lipoprotein cholesterol; these affect the occurrence of cardiovascular diseases (CV) and diabetes mellitus (DM) type 2 [4,5]. Although risk factors for MetS have been identified, insulin resistance is likely to be a significant link between the components of MetS. Moreover, it seems clear that obesity results in the development of insulin resistance and has triggered the escalating incidence of MetS [7].

Obesity is a medical condition in which excess body fat has accumulated and, particularly in the Western world, is a well-known problem in society. However, the prevalence of obesity in developing countries is increasing toward that currently seen in developed countries. Thus, the increase in obesity rates is becoming a serious health problem, leading the American Medical Association to classify obesity as a disease in 2013 [8]. Accordingly, obesity is projected to be the most common modifiable factor among preventable causes of death in the world [8].

Interestingly, a few large cohort studies found that obesity was correlated with the risk of symptomatic BPH [9,10]. In addition, a recent study found that serum adipokines, which are metabolically active hormones secreted by excess adipose tissue, were associated with the risk of symptomatic BPH [11]. Therefore, we evaluated obesity-related factors and their association with BPH in a population-based cohort in Korea.

Of 571 participants, the mean age was 58.53±7.01 years (range, 40–72 years), and the mean serum PSA level was 1.41±2.48 mg/mL (range, 0.02–40.10 mg/mL). The mean PV was 27.82±11.08 mL (range, 10.00–128.30 mL), and mean IPSS was 11.28±7.50 (range, 0–35). The mean Qmax rate was 12.43 ±7.33 mL/sec (range, 0.70–42.60 mL/sec). The mean PSA level increased significantly in accordance with PV, but other prostate-specific characteristics were not significantly different (Table 1).

Growing evidence suggests that obesity, which is a component of MetS, has been associated with an increased risk of several common adult cancers [14]. From a urological standpoint, an association between obesity and an increased cancer risk has been reported in renal cell carcinoma [15]. Additionally, epidemiologic studies and a meta-analysis have shown that obesity has been consistently associated with poorer outcome and a higher-grade disease in prostate cancer [16-18]. Aside from urinary cancer, a recent review found an association between obesity and nonmalignant urological disease, such as BPH [19,20]. Moreover, in a prospective cohort, each 1-kg/m² increase in BMI was associated with a 0.41-cm³ increase in PV [21]. In the Prostate Cancer Prevention Trial, the incidence of BPH, which was defined as severe urinary symptoms as determined by the IPSS or the initiation of medical or surgical therapy, increased 10% for each 0.05 increase in waist-to-hip ratio [10]. This is consistent with the present findings, which showed that obesity, as determined by anthropometric measures, is positively associated with PV. Furthermore, WC was a significant factor in predicting the presence of high-volume BPH.

Although the molecular mechanisms and the pathophysiology by which obesity may promote BPH are not fully understood, the likely biologic mechanism seems to be insulin resistance [4]. Briefly, the chronic elevation of insulin is associated with the increased availability of insulin-like growth factor-1 (IGF-1). Insulin has been suggested to stimulate tumorigenesis by inducing IGF-1 synthesis and activating insulin and IGF-1 receptors, which are often overexpressed in cancer cells. Moreover, insulin and IGF-1 interactions with downstream signaling pathways may impact the growth of hormonally driven tumors, such as prostate cancer; they may also stimulate BPH [11,22]. In addition, insulin may influence the transcription of genes involved in sex hormone metabolism; these genes alter the androgen/estrogen ratio and circulating level of sex hormonebinding globulin. Such alterations in the testosterone to estrogen ratio in prostate tissue may contribute to BPH development [21,23]. Another potential explanation involves chronic inflammation and oxidative stress. Increased BMI is associated with adipocyte hypertrophy and death, which cause excessive cytokine production and leukocyte recruitment. These inflammatory changes in the tissue may provide a pro-neoplastic microenvironment [22,24]. However, in the present study, serum insulin level and HOMA-IR, which are indicators of insulin resistance, were not significantly different according to PV, although they were higher in patients with high-volume BPH than in those without BPH. Furthermore, the number of leukocytes and serum CRP level, which are markers of inflammation, were not statistically higher in the participants with prostatic enlargement. The reasons for this finding are unclear and should be further examined in future studies. Finally, adipokines, such as leptin and adiponectin, which maintain metabolic homeostasis and balance cell proliferation and apoptosis, may play a key role in BPH pathogenesis due to their vital role in regulating body weight [25]. Leptin promotes cell proliferation through alteration of cell cycle checkpoints and upregulation of specific genes, advancing cell cycles from G1 to S phase. Leptin also has both proinflammatory and angiogenic effects, which may result in carcinogenesis [22,26]. Adiponectin has properties in apoptosis and metabolism of glucose and fatty acids [25]. In vitro, adiponectin suppresses dihydrotestosterone-stimulated cell proliferation, which is involved in the regulation of prostatic growth [27]. In addition, adiponectin enhances insulin sensitivity by inhibiting both the expression of hepatic gluconeogenic enzymes and endogenous production of glucose [28]. This suggests that adiponectin may indirectly affect prostatic growth via insulin sensitivity. Previous studies showed that altered levels of adipokines, particularly increased leptin and decreased adiponectin, are commonly associated with obesity [29]. Schenk et al. [25] reported an association of high adiponectin concentrations with a reduced risk of BPH. However, they found that leptin and CRP were not associated with BPH risk. The current study showed that the highest leptin level quartile was significantly correlated with high-volume BPH and the highest adiponectin level quartile was inversely correlated with high-volume BPH. These findings suggest that the balance between these two adipokines may be associated with obesity-induced prostatic growth.

The present study has several limitations. Firstly, although we used the data of KoGES-ARIRANG, we retrospectively conducted a cross-sectional study. Secondly, there may be selection bias, as the study participants participated in KoGES-ARIRANG and were further recruited to participate in the Korean Prostate Health Council Screening Program. Thus, many of these participants may already be proactively concerned with their health and have a good doctor-patient relationship. Thirdly, definitions regarding the appropriate BPH cutoff points are controversial. However, we used PV as the only measure for diagnosis of BPH to focus on the relationship between obesity and PV. Finally, the participants with comorbidities that can affect metabolic profile parameters were included in this study, although there were no statistically significant differences between groups. Accordingly, further longitudinal studies are needed to elucidate the relationship between MetS and BPH.

Nonetheless, we believe that obesity management and prevention may be a novel target for the prevention of BPH. Previous literature has indicated that the detrimental effect of obesity is reversible and long-term weight loss was shown to have a significant effect on bladder pressure and urinary incontinence [19,30]. Moreover, a meta-analysis of 11 published studies concluded that moderate to vigorous physical activity was associated with a 25% lower risk for BPH or LUTS [31]. This indicates that physical activity and lifestyle modification may have a therapeutic effect in men with BPH. These data show that many of the metabolic disturbances associated with cardiovascular disease and their modulating lifestyle factors may be associated with BPH onset and progression. Therefore, urologists should consider the effect of obesity on urological health as well as overall public health.