Metabolic syndrome and urologic diseases

Abstract

Metabolic syndrome (MetS) is a complex entity consisting of multiple interrelated factors including insulin resistance, central adiposity, dyslipidemia, endothelial dysfunction and atherosclerotic disease, low-grade inflammation, and in males, low testosterone levels. MetS has been linked to a number of urologic diseases including nephrolithiasis, benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, male infertility, female incontinence, and prostate cancer. This article reviews the relationships between MetS and these entities. Urologists need to be cognizant of the impact that MetS has on urologic diseases as well as on overall patient health.

Keywords: Benign prostatic hyperplasia; Cardiovascular disease; Endothelial dysfunction; Hypogonadism; Insulin resistance; Lower urinary tract symptoms; Metabolic syndrome; Nephrolithiasis; Obesity.

Figure 1

Possible mechanisms of nephrolithiasis in metabolic syndrome (MetS). Several lithogenic factors are noted in MetS including increased uric acid (UA), oxalate, and calcium (Ca²⁺) excretion as well as decreased citrate excretion. Renal lipotoxicity may be a cause of elevated net acid excretion (NAE) in addition to decreased ammonia (NH3) synthesis and ammonium (NH₄⁺) excretion, leading to lower urinary pH. These abnormalities respectively contribute to elevated UA, Ca²⁺, and mixed stones.

Figure 2

Possible mechanisms of benign prostatic hyperplasia, lower urinary tract symptoms (LUTS), and erectile dysfunction (ED) in metabolic syndrome (MetS). Features that may be seen in MetS, including pelvic atherosclerosis and ischemia, decreased nitric oxide (NO) availability, elevated sympathetic activity, low-grade inflammatory state, and elevated estrogen/testosterone ratio can contribute to benign prostatic hyperplasia (BPH), LUTS, and ED. Lower NO availability and elevated sympathetic activity can stimulate RHO-kinase activity, further exacerbating the process.

Figure 3

Possible mechanisms of female incontinence in metabolic syndrome (MetS). Features of MetS including diabetes and obesity may contribute to stress urinary incontinence (SUI). In addition, diabetes (DM) and other possible MetS components such as elevated sympathetic activity and pelvic ischemia may further lead to overactive bladder (OAB) and urinary urge incontinence (UUI) via the denoted pathways. M receptor, muscarinic receptor.

Figure 4

Possible mechanisms of male infertility in metabolic syndrome (MetS). Several features of MetS may contribute to male infertility. Obesity might lead to scrotal lipomatosis and elevated scrotal temperatures, depressing sperm quality. This may be further augmented by dyslipidemia, hyperglycemia, and a proinflammatory state contributing to reactive oxygen species (ROS) formation and sperm damage. Other contributors may include elevated estrogen/testosterone ratio (E/T), erectile dysfunction (ED) and ejaculatory dysfunction (EjD). LPO, lipid peroxidation. Data from Kasturi SS et al.

Figure 5

Possible mechanisms of prostate cancer (PCa) in metabolic syndrome (MetS). Features of MetS such as elevated BMI, hypertension (↑BP), and low HDL levels may increase risk of PCa. Hyperinsulinemia (↑insulin) and low testosterone levels are interrelated and may further contribute. Increases in proinflammatory cytokines might lead to prostatic malignancy via increased NF-κB (↑NF-κB) activity. However, lower IGF-1 activity seen in MetS may decrease risk of PCa. Additionally, lower PCa levels in late T2DM may be secondary to a hypoinsulinemic state.