Testosterone protects the lower urinary tract from metabolic syndrome-induced alterations

Abstract

Epidemiological studies document a positive and independent association between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS). In the male, the pathogenesis of MetS-related LUTS involves a complex interplay among pathophysiological mechanisms mainly affecting the prostate and the bladder. Recently, hypogonadism has been recognized as a key factor bridging MetS and LUTS. Preclinical data have evidenced that MetS-induced hypogonadism is associated with alterations not only of the prostate but also of the bladder, and testosterone supplementation can counteract both. Interestingly, testosterone also shows a marked effect on the bladder, preventing the MetS-related RhoA/ROCK hyperactivation, which drives the pathogenesis of bladder overactivity and LUTS. The precise mechanisms through which testosterone exerts its protective action on the LUT remains to be fully elucidated; however, indirect (through improved cardiometabolic status) and direct (through local androgen receptor-mediated pathways) actions are both likely to play a role.

Benign prostatic enlargement is not associated with diabetes: a population-based study

“…A previous in vitro study found that oxidized low‐density lipoprotein can induce and sustain inflammatory response in human prostatic cells through the secretion of interleukin 6 (IL‐6), IL‐8, and basic Fibroblast growth factors (bFGF; Vignozzi et al ., ). Other studies further reported that IL‐8 and bFGF can recruit CXCR1‐ and CXCR2‐positive leukocytes and CD15+ neutrophils and lead to prostate cell hyperplasia (Penna et al ., ; Vignozzi et al ., ,b, ).…”

“…Several studies have shown a significant association of MetS with BPH (Vignozzi et al ., , ,b; Corona et al ., ; Vignozzi et al ., ; Gacci et al ., , ; Yin et al ., ). In particular, the association between hyperlipidemia and BPE has proven to be very significant and has drawn much attention (Gacci et al ., , ).…”

“…Chi‐squared tests were performed to examine differences in sociodemographic characteristics and medical comorbidities (hypertension, coronary heart disease (CHD), hyperlipidemia, obesity, tobacco use disorder (ICD‐9‐CM code 305.1), and alcohol abuse/alcohol dependence syndrome) between cases and controls. These medical comorbidities were selected because they were the potential risk factors for BPE (Vignozzi et al ., , ,b; Corona et al ., ; Vignozzi et al ., ; Gacci et al ., , ; Yin et al ., ). Sociodemographic characteristics included monthly income (NT0–15840, NT 15 841–25 000, and ≥NT$ 25 001), geographical location (Northern, Central, Eastern, and Southern Taiwan), and urbanization level of the patient's residence (five levels with 1 as the most urbanized and five as the least).…”

Hypogonadal men with moderate-to-severe lower urinary tract symptoms have a more severe cardiometabolic risk profile and benefit more from testosterone therapy than men with mild lower urinary tract symptoms

“…Generally, BPH is considered a common etiology of LUTS but this is not an inevitable correlation. The association between LUTS and obesity, metabolic syndrome (MetS), and erectile dysfunction is established at epidemiological level [ 4 5 ]. As potential biological mechanism prostatic inflammation resulting from the immunologic response of pathogenic noxae is discussed to be involved in the development and progression of chronic prostatic diseases such as BPH [ 6 7 ].…”

The influence of asymptomatic inflammatory prostatitis on the onset and progression of lower urinary tract symptoms in men with histologic benign prostatic hyperplasia

“…Recent meta-analysis reveals that the metabolic syndrome was associated with a greater prostate volume increment [16] . In addition, other report suggests that patients with metabolic syndrome presented higher obstructive urinary symptoms score and lower uroflowmetric parameters as compared with those without metabolic syndrome [17] , [18] . In this context, oxidized low-density lipoprotein led to the high secretion of IL-6, IL-8, and bFGF, which are surrogate markers of prostate inflammation on human prostatic myofibroblastic cells [19] .…”