Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: What Is the Role and Significance of Inflammation?
- 137 Downloads
Purpose of Review
The purpose of this review is to summarize the role and significance of inflammation as a putative additional factor contributing to lower urinary tract symptoms and the progression of benign prostatic hyperplasia. We review (1) the histologic definition of prostatic inflammation and its prevalence, (2) the effects inflammation in the prostate including on risk of acute urinary retention, and (3) the effects of systemic inflammation on the prostate and on voiding.
Inflammation is a highly prevalent finding in the prostate, both on a histological and biochemical level. Men with inflammation have higher IPSS scores and increased prostate size; however, these differences appear to be imperceptibly small. Men with inflammation do experience a significantly increased risk of developing acute urinary retention, an event that is associated with significant morbidity. Recently, attempts have been made to identify more specific biochemical markers of local inflammation, and to identify regional patterns of inflamed tissue within the prostate which may be associated with higher IPSS scores, accelerated progression, and AUR. The effects of systemic inflammatory states, most notably MetS, and their role in LUTS have also been examined.
Inflammation is a common finding in prostates of aging men, but its contribution to lower urinary tract symptoms and benign prostatic hyperplasia progression appears to be small when considered as a clinically relevant entity. Advances in the understanding of different forms of inflammation, and their impact when experienced in different locations within the prostate, may refine this knowledge. Systemic inflammation affects voiding, including in the absence of a prostate, but again significant effects of systemic inflammation on the prostate itself are also difficult to demonstrate. Prostatic inflammation is associated with a significantly increased risk of acute urinary retention.
KeywordsProstatic inflammation Benign prostate hyperplasia Lower urinary tract symptoms Inflammation
This work was also supported by grants NIH U54 DK104310 and R01 ES01332 (WAR).
Compliance with Ethical Standards
Conflict of Interest
Granville L. Lloyd, Jeffrey M. Marks, and William A. Ricke each declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 6.Cornu JN, Ahyai S, Bachmann A, de la Rosette J, Gilling P, Gratzke C, et al. A systematic review and meta-analysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic obstruction: an update. Eur Urol. 2015;67:1066–96.CrossRefGoogle Scholar
- 12.••Inamura S, Ito H, Shinagawa T, Tsutsumiuchi M, Taga M, Kobayashi M, et al. Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia. The Prostate. 2018;78:743–52 The authors retrospectively analyzed the prostate specimens of 179 men undergoing BPH surgery. Uniquely, they found that stromal inflammation was associated with a significant increase in prostate volume (63 mL vs 53 mL) and the existence of acute urinary retention (36.1% vs 11.4%). CrossRefGoogle Scholar
- 13.••Torkko KC, Wilson RS, Smith EE, Kusek JW, van Bokhoven A, Lucia MS. Prostate biopsy markers of inflammation are associated with risk of clinical progression of benign prostatic hyperplasia: findings from the MTOPS study. J Urol. 2015;194:454–61 980 men in the MTOPS study were part of a subset requiring baseline biopsy. Men diagnosed with cancer were excluded. Inflammatory markers (CD-4, CD-8, CD-45, CD-68) in the transition zone biopsy cores were analyzed and compared with their prospectively collected clinical variables. CD-4 was associated with BPH progression as defined by IPSS progression of 4 points (HR = 1.86 (1.16, 2.98)). CD-4, CD-8, and CD-68 was associated with an increased risk of developing acute urinary retention. CrossRefGoogle Scholar
- 20.Barry MJ, Williford WO, Chang Y, Machi M, Jones KM, Walker-Corkery E, et al. Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients? J Urol. 1995;154:1770–4.CrossRefGoogle Scholar
- 21.Cantiello F, Cicione A, Salonia A, Autorino R, Ucciero G, Tucci L, et al. Metabolic syndrome correlates with peri-urethral fibrosis secondary to chronic prostate inflammation: evidence of a link in a cohort of patients undergoing radical prostatectomy. Int J Urol Off J Jpn Urol Assoc. 2014;21:264–9.Google Scholar
- 30.•Hughes FM, Hill HM, Wood CM, Edmondson AT, Dumas A, Foo W-C, et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J Urol. 2016;195:1598–605 This rat model elucidates the inflammatory mechanism by which bladder outlet obstruction leads to histologic changes in the bladder. Bladder outlet obstruction led to an increase in the NLRP3 inflammasome. This was associated with increased inflammation and bladder hypertrophy. Targeted inhibition of the inflammasome led to improvements in urodynamics and bladder hypertrophy. CrossRefGoogle Scholar
- 33.Schenk JM, Calip GS, Tangen CM, Goodman P, Parsons JK, Thompson IM, et al. Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2012;176:156–63.CrossRefGoogle Scholar
- 35.Sutcliffe S, Grubb Iii RL, Platz EA, Ragard LR, Riley TL, Kazin SS, et al. Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the prostate, lung, colorectal, and ovarian cancer screening trial. BJU Int. 2012;110:1050–9.CrossRefGoogle Scholar
- 43.Tarhan H, Ekin RG, Can E, Cakmak O, Yavascan O, Mutlubas Ozsan F, et al. C-reactive protein levels in girls with lower urinary tract symptoms. J Pediatr Urol. 2016;12(105):e1–4.Google Scholar
- 44.Peixoto CA,dos Gomes SFO. The role of phosphodiesterase-5 inhibitors in prostatic inflammation: a review. J Inflamm Lond Engl [Internet]. 2015 [cited 2019 Mar 10];12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570643/
- 45.Zhang W, Zang N, Jiang Y, Chen P, Wang X, Zhang X. Upregulation of phosphodiesterase type 5 in the hyperplastic prostate. Sci Rep [Internet]. 2015 [cited 2019 Mar 10];5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674741/
- 50.•Yamaguchi H, Kurita M, Okamoto K, Kotera T, Oka M. Voiding behavior and chronic pelvic pain in two types of rat nonbacterial prostatitis models: attenuation of chronic pelvic pain by repeated administration of tadalafil. The Prostate. 2019;79:446–53 Using rat non-bacterial prostatitis models, the authors demonstrated that chronic pelvic pain was increased after induction of the model. However, bladder function as measured by cystometric changes was not affected. Six-week administration of tadalafil attenuated the chronic pelvic pain. CrossRefGoogle Scholar
- 51.Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61:994–1003.CrossRefGoogle Scholar
- 58.•Rył A, Rotter I, Grzywacz A, Małecka I, Skonieczna-Żydecka K, Grzesiak K, et al. Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017;14 This study analyzed the relationships between the incidence of metabolic diseases and the genotypes of the 5훂-reductase enzyme polymorphisms in patients with BPH. 299 patients who presented for TURP had their blood drawn preoperatively. This found that certain polymorphisms of the SDR5A2 loci were associated with MetS. Google Scholar
- 66.••Vignozzi L, Gacci M, Maggi M. Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol. 2016;13:108–19 This review explores the pathogenic relationships between LUTS, metabolic syndrome and its components, inflammation, and sex steroid imbalance in men. They conclude that various metabolic insult lead to inflammation and alter the natural history of BPH and LUTS. More studies are needed to investigate lifestyle modifications to mitigate to progression of this disease process. CrossRefGoogle Scholar