Benign prostatic hyperplasia: a new metabolic disease?

Background Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are conditions extremely prevalent in the aging male. Although androgens are involved in prostate growth during developmental age, their role in the pathogenesis of BPH/LUTS is debated. Recent data indicate that low testosterone and high estradiol favor disease progression. In addition, the role of other determinants, such as metabolic syndrome or prostate inflammation, is emerging. Aim We reviewed the evidence regarding the pathogenesis of BPH/LUTS with particular attention to metabolic influence. Materials and methods A review of published evidence was performed using Medline. Results Available evidence shows that a three-hit hypothesis can be drawn. An overt, or even a subclinical, bacterial or viral infection could induce prostatic inflammation (first hit) that could be autosustained or exacerbated by the presence of an altered metabolism and in particular by hypercholesterolemia (second hit). Hypogonadism and/or hyperestrogenism could act as a third hit, favoring the maintenance of this inflammatory state. The combined action of all three hits, or even two of them, may result in overexpression of Toll-like receptors (TLRs), transformation of prostatic cells into antigen-presenting cells and activation of resident human prostate-associated lymphoid tissue ending in overproduction of growth factors which, in turn, will induce prostate remodeling and further prostate enlargement. The mechanical obstruction, along with the direct action of the unfavorable metabolic and hormonal milieu on the bladder neck, helps in generating LUTS. Conclusion Inflammation, dyslipidemia and altered sex-steroid milieu mutually concur in determining BPH/LUTS.