Benign prostatic hyperplasia and metabolic syndrome: the expanding evidences of a new disease of aging male

Metabolic syndrome (MetS) is a complex and widespread epidemic disorder with a high socio-economic impact, due to its association with increased morbidity and mortality. A significant amount of epidemiological evidence have underlined the emerging link between MetS, benign prostatic enlargement secondary to benign prostatic hyperplasia (BPH) and related lower urinary tract symptoms (LUTS) [1–3].

Among these features, the presence of hyperinsulinemia has been taken into account as the most important key factor. Hyperinsulinemia is in fact associated with an increase in the activity of the sympathetic nervous system and this may contribute to the increased muscle tone of the prostate, resulting in more severe LUTS independently from prostate enlargement [4]. In fact, accumulating evidence indicates that glucose homeostasis, hyperinsulinemia, and insulin resistance may increase the risk of BPH [5–7].

Among MetS features, reduced HDL and increased triglyceride levels were significantly related to higher prostatic inflammation by secreting IL-8 in response not only to oxidated LDL, but also to insulin [8], indicating that different MetS features could synergistically boost inflammation and tissue-remodeling in BPH/LUTS [9,10].

In addition to age, LUTS and MetS also share a variety of other risk factors, such as obesity, high fasting plasma glucose levels, hypertension, androgen deficiency, depression, and smoking, thus indicating that metabolic syndrome might play a key role in the pathogenesis of LUTS [11]. Taken into account these premises, it should be noted that all previous pathogenetic mechanisms are known to increase cardiovascular disease (CVD) risk [12].

In a recent cross-sectional study in a cohort of patients with BPH/LUTS, it has been demonstrated an increase of more than 5-fold of having a Framingham risk score ≥10% in men with moderate–severe LUTS [13].

Although a direct link between LUTS/BPH occurrence and increased CVD-risk cannot be directed linked, it may be postulated as common pathogenic pathways between both diseases. In this pathological circle, non-alcoholic fatty liver disease (NAFLD) has been proposed as the hepatic manifestation of the MetS, with IR as the common path physiological factor.

Insulin resistance is the underlying mechanism of metabolic syndrome and is also the most prevalent risk factor for NAFLD, a condition strongly associated with hepatic and adipose tissue insulin resistance, as well as reduced whole-body insulin sensitivity

Interestingly, MetS induced inflammation within the liver, also known as steato-hepatitis, has been very recently elucidated in an experimental study in the rabbit [14]. Surprisingly, a recent cross-sectional study showed a new link between the presence of BPH/LUTS, MetS and NAFLD, demonstrating a 2.0-fold risk of having moderate–severe LUTS in men with both manifestation (OR = 2.10, p < 0.01) [15]. All these findings suggest that the MetS-related BPH/LUTS should be considered as potentially targeted therapy in order to counteract the resulting prostate overgrowth.

BPH/LUTS is often considered as a normal consequence of the aging men leading to medical and therefore surgical intervention [16]. We would breakdown this view and unveil that the progression of this condition could be prevented by modifying previous metabolic factors. In our point of view, BPH/LUTS may be considered as a complex disorder that can also be discovered in the earlier stage.

Primum non- “nocere” (first do no harm) should always be kept in mind, and therefore the counteraction of previous metabolic alterations should be the milestone of BPH/LUTS treatment. The next challenges of urologists should be the contrast of early onset of BPH/LUTS and the development of new target therapies in men at risk.

Declaration of interest

The authors report no declarations of interest.