Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.

G Rastrelli, S Cipriani, F Lotti, I Cellai, P Comeglio, S Filippi, V Boddi, P A Della Camera, R Santi, L Boni, G Nesi, S Serni, M Gacci, M Maggi, L Vignozzi

Journal: Journal of endocrinological investigation 2022;45(7):1413-1425

PMID: 35298833

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Plain Language Summary

Benign prostatic hyperplasia (BPH) — also called benign prostate enlargement — is frequent in aging populations, with a 40 – 50% prevalence in men aged 50–60 years and up to 90% in men older than 80 years. The aim of this study was to verify whether testosterone therapy (TTh) in men with BPH, metabolic syndrome (MetS) and low testosterone is able to improve lower urinary tract symptoms (LUTS) and intraprostatic inflammation. This study is a double blind, randomised 24-week clinical trial in men with low testosterone and MetS and a candidate for prostate surgery for BPH. Patients (n=144) were centrally randomised 1:1 to one of the two groups; TTh or placebo. Results show that TTh administered for 24 weeks is a safe option and it improves prostatic inflammatory features thus ameliorating one of the pathogenic components of BPH. However, there were no differences in improvements of the urinary symptoms between both groups (TTh and placebo). Authors conclude that decreased inflammation is not accompanied by a consistent improvement in urinary symptoms, and that their findings show the safety of TTh in subjects with BPH of surgical significance.

Abstract

PURPOSE

Benign Prostatic Hyperplasia (BPH) is a result of prostate inflammation, frequently occurring in metabolic syndrome (MetS). Low testosterone is common in MetS. A randomized clinical trial was designed to evaluate if 24 weeks of testosterone therapy (TTh) in BPH men with MetS and low testosterone improve urinary symptoms and prostate inflammation.

METHODS

One-hundred-twenty men with MetS waitlisted for BPH surgery were enrolled. They were categorized into normal testosterone (TT ≥ 12 nmol/L and cFT ≥ 225 pmol/L; n = 48) and testosterone deficient (TD) (TT < 12 nmol/L and/or cFT < 225 pmol/L; n = 72) then randomized to testosterone gel 2% (5 g/daily) or placebo for 24 weeks. At baseline and follow-up, questionnaires for urinary symptoms and trans-rectal ultrasound were performed. Prostate tissue was collected for molecular and histopathological analyses.

RESULTS

No differences in the improvement of urinary symptoms were found between TTh and placebo (OR [95% CI] 0.96 [0.39; 2.37]). In TD + TTh, increase in prostate but not adenoma volume was observed (2.64 mL [0.07; 5.20] and 1.82 mL [- 0.46; 0.41], respectively). Ultrasound markers of inflammation were improved. In a subset of 61 men, a hyper-expression of several pro-inflammatory genes was found in TD + placebo when compared with normal testosterone. TTh was able to counteract this effect. For 80 men, the inflammatory infiltrate was higher in TD + placebo than in normal testosterone (0.8 points [0.2; 1.4]) and TD + TTh men (0.9 points [0.2; 1.5]).

CONCLUSIONS

Twenty-four weeks of TTh in TD men with BPH and MetS improves ultrasound, molecular and histological proxies of prostate inflammation. This does not result in symptom improvement.

Address: Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy.; Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Neuroscience, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy.; Urology Unit, Azienda Ospedaliera Universitaria Careggi, Largo Piero Palagi, 1, 50139, Florence, Italy.; Pathological Anatomy Unit, Careggi University Hospital, Largo Piero Palagi, 1, 50139, Florence, Italy.; Unit of Clinical Epidemiology, IRCCS Policlinico San Martino, Largo Rosanna Benzi, 10, 16132, Genoa, Italy.; Department of Health Sciences, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy.; Istituto Nazionale Biostrutture e Biosistemi, Viale delle Medaglie d'Oro, 305, 00136, Rome, Italy.; Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy. [email protected].; Istituto Nazionale Biostrutture e Biosistemi, Viale delle Medaglie d'Oro, 305, 00136, Rome, Italy. [email protected].

DOI: 10.1007/s40618-022-01776-9

Patient Centred Factor

Mediators: Benign prostatic hyperplasia

Physical Environment

Xenobiotics

Clinical Imbalances

Hormonal Immune and inflammation

Laboratory Testing

Blood Imaging

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Inflammation Testosterone Cytokines Metabolic syndrome Blood pressure Benign prostatic hyperplasia Benign prostate enlargement Advanced glycated end-products Testosterone therapy

Bioactive Substances

Testosterone

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https://medlineplus.gov/enlargedprostatebph.html

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https://link.springer.com/article/10.1007/s40618-0...

MeSH Terms: Biomarkers, Humans, Inflammation, Lower Urinary Tract Symptoms, Male, Metabolic Syndrome, Prostatic Hyperplasia, Prostatitis, Testosterone