Efficacy and safety of tadalafil vs tamsulosin in lower urinary tract symptoms (LUTS) as a result of benign prostate hyperplasia (BPH)-open label randomised controlled study.

INTRODUCTION & AIM: Several newer medications have emerged for the management of lower urinary tract symptoms secondary to benign prostate hyperplasia (BPH). The efficacy/safety of PDE-5 inhibitors (Tadalafil 5 mg) in BPH-lower urinary tract symptoms (LUTS) has been sparingly assessed in the published English literature as compared with their established role in erectile dysfunction. We aim to assess the efficacy/safety of tadalafil vs tamsulosin in symptomatic patients of BPH in a tertiary care teaching institution. METHODS: After obtaining an informed written consent and institutional ethics clearance, 100 patients of BPH with an IPSS score of more than 7, without any complications of the disease were computer randomised to receive therapy with either tamsulosin 0.4 mg or tadalafil 5 mg once daily for a period of 2 months. They were evaluated for its efficacy (IPSS, Peak flow rate, IIEF-5, quality of life index [QOL] and PVR) and safety (side effect profile) with monthly visit assessments for 2 months. Data were analysed statistically using ANOVA and unpaired t-tests.The protocol was registered with the CTRI/2018/03/012825. RESULTS: Patients in both groups were comparable on basis of their demographic data, renal function, PSA and baseline efficacy parameters. Significant improvements were visualised amongst/within both groups for IPSS, however the intergroup improvement was not significant (P = .096). Similar trends were seen with peak flow rate and PVR with intergroup improvement differences not being significant (P = .552 and P = .131, respectively).Improvements in QOL index were more significant in the tamsulosin group (mean difference -2.3 vs -3.06 P = .010).The adverse effects were minor and were managed symptomatically without any drug discontinuity. CONCLUSIONS: In summary, therefore, we may conclude that that once daily monotherapy with tadalafil 5 mg or tamsulosin 0.4 mg was equally efficacious in the management of moderate to severely bothersome LUTS in majority of patients as a result of BPH. The role of Tadalafil monotherapy in BPH patients with predominant storage LUTS merits further evaluation with larger trials.

Mesenchymal stem cells and the embryonic reawakening theory of BPH.

The prostate is the only organ in a man that continues to grow with age. John McNeal proposed, 40 years ago, that this BPH is characterized by an age-related reinitiation of benign neoplastic growth selectively in developmentally abortive distal ducts within the prostate transition-periurethral zone (TPZ), owing to a reawakening of inductive stroma selectively within these zones. An innovative variant of this hypothesis is that, owing to its location, the TPZ is continuously exposed to urinary components and/or autoantigens, which produces an inflammatory TPZ microenvironment that promotes recruitment of bone marrow-derived mesenchymal stem cells (MSCs) and generates a paracrine-inductive stroma that reinitiates benign neoplastic nodular growth. In support of this hypothesis, MSCs infiltrate human BPH tissue and have the ability to stimulate epithelial stem cell growth. These results provide a framework for defining both the aetiology of BPH in ageing men and insights into new therapeutic approaches.

Review of Prostate Anatomy and Embryology and the Etiology of Benign Prostatic Hyperplasia.

Prostate development follows a common pattern between species and depends on the actions of androgens to induce and support ductal branching morphogenesis of buds emerging from the urogenital sinus. The human prostate has a compact zonal anatomy immediately surrounding the urethra and below the urinary bladder. Rodents have a lobular prostate with lobes radiating away from the urethra. The human prostate is the site of benign hyperplasia, prostate cancer, and prostatitis. The rodent prostate has little naturally occurring disease. Rodents can be used to model aspects of human benign hyperplasia, but care should be taken in data interpretation and extrapolation to the human condition.

DNA methylation as a dynamic regulator of development and disease processes: spotlight on the prostate.

Prostate development, benign hyperplasia and cancer involve androgen and growth factor signaling as well as stromal-epithelial interactions. We review how DNA methylation influences these and related processes in other organ systems such as how proliferation is restricted to specific cell populations during defined temporal windows, how androgens elicit their actions and how cells establish, maintain and remodel DNA methylation in a time and cell specific fashion. We also discuss mechanisms by which hormones and endocrine disrupting chemicals reprogram DNA methylation in the prostate and elsewhere and examine evidence for a reawakening of developmental epigenetic pathways as drivers of prostate cancer and benign prostate hyperplasia.

Prostate development and growth in benign prostatic hyperplasia.

The etiology of benign prostatic hyperplasia [BPH] in elderly men has intrigued anatomists, pathologists and scientists for centuries. Studies of morbid anatomy, clinical observations and contemporary cellular biology have contributed to an evolving interpretation of the causality of the disease. Insights into the detailed microanatomy and ductal architecture of the prostate during stages of fetal and early postnatal development suggest that mechanisms involved in the early growth period become aberrantly expressed in elderly men. Age, hormones and epithelial-mesenchymal interactions are all contributing factors to the pathogenesis of BPH. Control of the microenvironment in normal and abnormal growth is a multifactorial process. Susceptibility to the disease may include clinical comorbid diseases, region-specific changes in cell-cell interactions and a variety of signaling pathways including a novel hypothesis regarding the role of the primary cilium as a regulator of signal transduction mechanisms. Recent work in animal models has shown that there are region-specific differences within the prostate that may be significant because of the dynamic and intricate interplay between the epithelium and mesenchyme. Because of the focal nature of BPH a closer examination of normal morphogenesis patterns, which defines the gland's architecture, may facilitate a detailed understanding of the atypical growth patterns.

Glandular epithelial induction by embryonic mesenchyme in adult bladder epithelium of BALB/c mice.

Tissue recombinants prepared with epithelium of the urinary bladder of adult mice and mesenchyme of the embryonic urogenital sinus were grown as renal capsular grafts in adult male hosts. Under these conditions the bladder epithelium, which is derived embryologically from the urogenital sinus, was induced to form prostate-like acini. The relevance of this observation to McNeal's (1978) hypothesis, that the formation of prostatic acini during the development of human benign prostatic hyperplasia may be a reexpression of the embryonic inductive capacity of the prostatic stroma, is discussed.