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Frontiers in Endocrinology 2023Benign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Benign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational studies exploring the association between thyroid function and BPDs have hitherto yielded inconsistent results. In this study, we explored whether there is a causal genetic association between them using Mendelian randomization (MR) analysis.
METHODS
We used publicly available summary statistics from the Thyroidomics Consortium and 23andMe on thyrotropin (TSH; 54,288 participants), thyroxine [free tetraiodothyronine (FT4); 49,269 participants], subclinical hypothyroidism (3,440 cases and 49,983 controls), overt hypothyroidism (8,000 cases and 117,000 controls), and subclinical hyperthyroidism (1,840 cases and 49,983 controls) to screen for instrumental variables of thyroid function. Results for BPD such as prostatic hyperplasia (13,118 cases and 72,799 controls) and prostatitis (1,859 cases and 72,799 controls) were obtained from the FinnGen study. The causal relationship between thyroid function and BPD was primarily assessed using MR with an inverse variance weighted approach. In addition, sensitivity analyses were performed to test the robustness of the results.
RESULTS
We found that TSH [OR (95% CI) = 0.912(0.845-0.984), =1.8 x 10], subclinical hypothyroidism [OR (95% CI) = 0.864(0.810-0.922), =1.04 x 10], and overt hypothyroidism [OR (95% CI) = 0.885 (0.831-0. 944), =2 x 10] had a significant effect on genetic susceptibility to BPH, unlike hyperthyroidism [OR (95% CI) = 1.049(0.990-1.111), =1.05 x 10] and FT4 [OR (95% CI) = 0.979(0.857-1.119), = 7.59 x 10] had no effect. We also found that TSH [OR (95% CI) =0.823(0.700-0.967), = 1.8 x 10] and overt hypothyroidism [OR (95% CI) = 0.853(0.730-0.997), = 4.6 x 10] significantly influenced the prostatitis, whereas FT4 levels [OR (95% CI) = 1.141(0.901-1.444), = 2.75 x 10], subclinical hypothyroidism [OR (95% CI) =0. 897(0.784- 1.026), = 1.12 x 10], and hyperthyroidism [OR (95% CI) = 1.069(0.947-1.206), = 2.79 x 10] did not have a significant effect.
CONCLUSION
Overall, our study results suggest that hypothyroidism and TSH levels influence the risk of genetically predicted BPH and prostatitis, providing new insights into the causal relationship between thyroid function and BPD.
Topics: Humans; Male; Hyperthyroidism; Hypothyroidism; Prostatic Hyperplasia; Prostatitis; Quality of Life; Thyrotropin
PubMed: 37143736
DOI: 10.3389/fendo.2023.1163586 -
Urologie (Heidelberg, Germany) Jun 2023Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as chronic pain or discomfort in the pelvic region for at least 3 of the past 6 months. It is... (Review)
Review
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as chronic pain or discomfort in the pelvic region for at least 3 of the past 6 months. It is variably associated with lower urinary tract symptoms, psychosocial consequences, and sexual dysfunction. Specific test systems or biomarkers for a definitive diagnosis are still not available. The purposes of the basic diagnostic assessment are to determine the individual spectrum of symptoms and to rule out differential diagnoses of pelvic pain. Patient-reported outcome measures (PROMs) like the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) are valuable instruments for the initial diagnostic assessment and to evaluate treatment response. Classification systems like UPOINTS (urinary, psychosocial, organ specific, infection, neurologic/systemic, tenderness of skeletal muscles, sexual dysfunction) are valuable tools to determine the individual spectrum of symptoms, to guide the adapted diagnostic assessment, and to identify relevant targets for a multimodal and tailored treatment. Close urological monitoring of CP/CPPS patients is usually necessary, especially to minimize the unwarranted use of antibiotics in the case of undulating complaints.
Topics: Male; Humans; Prostatitis; Chronic Disease; Chronic Pain; Sexual Dysfunction, Physiological; Pelvic Pain
PubMed: 37120786
DOI: 10.1007/s00120-023-02089-2 -
BMJ (Clinical Research Ed.) Nov 2023
Topics: Male; Humans; Prostatitis; Chronic Disease; Pelvic Pain; Chronic Pain
PubMed: 37977592
DOI: 10.1136/bmj-2023-073908 -
International Urology and Nephrology Apr 2021Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has uncertain etiology and lacks effective treatment. Autoimmunity is an important pathogeny, and experimental... (Review)
Review
PURPOSE
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has uncertain etiology and lacks effective treatment. Autoimmunity is an important pathogeny, and experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. This review presents the detailed current knowledge of EAP models based on evaluation criteria aspects to provide a tool for model selection in pathogenesis studies and therapeutic drug screening.
METHODS
We extensively searched the published literature on CP/CPPS and different antigen-induced EAP models focusing on the histopathology, clinical-related phenotypes, and biochemical indicators. We also cover the changes in the prostate function and other organs in EAP. Finally, we try to get some insights about antigen-based therapeutic approaches for CP/CPPS.
RESULTS
Several inciting autoantigens were reported in EAP, including male accessory gland extracts, prostate extracts (PE), prostatic steroid-binding protein, prostatic spermine-binding protein (p25), prostatic acid phosphatase, seminal vesicle secretory protein 2, and T2 peptide. All of these models mimicked histological prostatitis, however only p25- and T2-induced models developed both pelvic pain and voiding behaviors. PE immunization is the most widely used method. Diminished fertility and mental health disorders can be found in PE model. Oral and intravenous T2 peptide have been studied for antigen-specific therapy and achieved preliminary progress in EAP models.
CONCLUSIONS
PE-induced model is the most commonly used, while T2- or p25-model could serve as a promising CP/CPPS model. Antigen-specific therapy in CP/CPPS deserves further study.
Topics: Animals; Antigens; Autoantigens; Autoimmune Diseases; Chromobox Protein Homolog 5; Disease Models, Animal; Humans; Male; Prostatitis
PubMed: 33200334
DOI: 10.1007/s11255-020-02703-8 -
Journal of Immunology Research 2022Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder. Although ferroptosis is closely associated with inflammation, oxidative...
PURPOSE
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder. Although ferroptosis is closely associated with inflammation, oxidative stress, and neuropathic pain, its role in CP/CPPS has not yet been elucidated. Therefore, we sought to explore the role and mechanism of ferroptosis in the prostatitis development.
METHODS
The experimental autoimmune prostatitis (EAP) was established through intradermal immunization of prostate extract. Iron chelator deferoxamine (DFO) and free radical scavenger edaravone (EDA) were applied to evaluate the effects of ferroptosis inhibition on oxidative stress, ferroptosis, inflammation, fibrosis, and mast cell activation in the context of CP/CPPS.
RESULTS
Increased generation of lipid peroxidation products (ROS and MDA) and decreased activities of antioxidant enzymes (SOD and CAT) suggested an aberrant oxidative stress status in EAP model. Elevated iron concentration was observed in the EAP model. Meanwhile, we discovered significant biological performances associated with ferroptosis in CP/CPPS, including the downregulation of the system Xc/GPX4 axis and the upregulation of the ACSL4/LPCAT3 axis. EAP rats performed serious leukocyte infiltration, advanced inflammatory grade, and abnormal expression of inflammatory mediators. Abundant collagen deposition, enhanced RhoA, ROCK1, and -SMA protein levels indicated that EAP rats were prone to suffer from stromal fibrosis compared with control group. An elevated number of degranulated mast cells and corresponding marker TPSB2 represented that mast cell-sensitized pain was amplified in the EAP model. Furthermore, reduction of NRF2/HO-1 indicated a vulnerability of EAP towards ferroptosis response. However, application of DFO and EDA had partially reversed the adverse influences mentioned above.
CONCLUSION
We first demonstrated that ferroptosis might be a crucial factor of chronic prostatitis progression. Inhibition of ferroptosis using DFO and EDA represented a promising approach for treating prostatitis by ameliorating inflammation, fibrosis, and mast cell activation.
Topics: Animals; Autoimmune Diseases; Chronic Disease; Chronic Pain; Disease Models, Animal; Ferroptosis; Fibrosis; Humans; Inflammation; Male; Mast Cells; Pelvic Pain; Prostatitis; Rats; rho-Associated Kinases
PubMed: 35755168
DOI: 10.1155/2022/6833867 -
Critical Reviews in Food Science and... 2023Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant... (Review)
Review
Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.
Topics: Male; Humans; Aged; Prostate; Prostatic Neoplasms; Prostatic Hyperplasia; Prostatitis
PubMed: 35021909
DOI: 10.1080/10408398.2021.2013158 -
The Prostate Oct 2023Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety,...
BACKGROUND
Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety, and prostatitis remains controversial. Therefore, we aimed to use two-sample Mendelian randomization (MR) to assess the causal effects of MDD and anxiety on prostatitis.
METHODS
We conducted univariable and multivariable MR analyses using summary statistics from publicly available genome-wide association studies to estimate the causal relationships between MDD, anxiety, and prostatitis risk. In the main MR analysis, the inverse-variance weighted (IVW) method was used, while secondary methods included the weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual and outlier (MR-PRESSO) tests to detect and correct for the presence of pleiotropy.
RESULTS
MDD had 97 independent instrumental variables (IVs) and anxiety had 15 IVs. Univariable MR analysis showed that genetically determined MDD had a detrimental causal effect on prostatitis (IVW: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.005), while no causal relationship was found between anxiety and prostatitis (IVW: OR = 0.25, 95% CI = 0.02-2.82, p = 0.26). More convincingly, after adjusting for confounding factors such as body mass index, alcohol consumption, and smoking, the genetic liability for MDD remained associated with prostatitis risk, with no strong evidence of anxiety affecting prostatitis incidence.
CONCLUSION
This study supports the notion that MDD has a detrimental effect on prostatitis risk, and strategies focused on addressing MDD may be one of the cornerstones for treating prostatitis. The potential preventive value of treating MDD for prostatitis should be further investigated in future research.
Topics: Male; Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Prostatitis; Anxiety; Polymorphism, Single Nucleotide
PubMed: 37504798
DOI: 10.1002/pros.24601 -
International Journal of Urology :... May 2023Prostatitis is classified into four categories according to the National Institutes of Health Consensus Classification. The largest category, Category III chronic... (Review)
Review
Prostatitis is classified into four categories according to the National Institutes of Health Consensus Classification. The largest category, Category III chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), has a wide range of symptoms and is difficult to diagnose because diagnosis is based on exclusion. Although many treatment modalities, including both pharmacological and non-pharmacological treatments, have been tried, definitive treatment methods have not yet been established, and many urologists struggle with the daily treatment of these conditions. The reasons for the failure of treatment are not only the wide variety of symptoms, but also the wide variety of causes. Therefore, the UPOINTS system is widely used, in which treatment methods are divided or combined according to symptoms and causes. This article summarizes the reports on treatment and reviews treatment findings for CP/CPPS in accordance with the UPOINTS system.
Topics: Male; Humans; Prostatitis; Chronic Disease; Pelvic Pain; Chronic Pain
PubMed: 36788717
DOI: 10.1111/iju.15149 -
Parasites, Hosts and Diseases Feb 2023Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in... (Review)
Review
Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in most infected men but can lead to chronic infection. The inflammatory response to chronic T. vaginalis infection may contribute to prostatic diseases, such as prostatitis and benign prostatic hyperplasia (BPH); however, studies on the relationship between T. vaginalis infection and prostate diseases are scarce. In this review, we discuss evidence from our studies on the involvement of T. vaginalis in the pathogenesis of prostate diseases, such as prostatitis and BPH. Studies of prostatitis have demonstrated that the attachment of T. vaginalis trophozoite to prostate epithelial cells (PECs) induces inflammatory cytokine production and inflammatory cell migration, leading to prostatitis. T. vaginalis also causes pathological changes, such as inflammatory cell infiltration, acinar changes, interstitial fibrosis, and mast cell infiltration, in prostate tissues of infected rats. Thus, T. vaginalis is considered an infectious agent that triggers prostatitis. Meanwhile, studies of prostatic hyperplasia revealed that mast cells activated by T. vaginalis-infected prostate cells secreted inflammatory mediators, such as β-hexosaminidase and tryptase, which promoted proliferation of prostate stromal cell (PSC). Moreover, interleukin-6 produced by proliferating PSCs induced the multiplication of BPH-1 epithelial cells as a result of stromal-epithelial interaction, suggesting that the proliferation of T. vaginalis-infected prostate cells can be induced through crosstalk with mast cells. These collective findings suggest that T. vaginalis contributes to the progression of prostatitis and prostatic hyperplasia by creating an inflammatory microenvironment involving PECs and PSCs.
Topics: Male; Humans; Rats; Animals; Trichomonas vaginalis; Prostatitis; Prostatic Hyperplasia; Trichomonas Infections; Prostate
PubMed: 37170459
DOI: 10.3347/PHD.22160 -
The Prostate Sep 2023The expression of programmed cell death ligand protein (PD-L1) is weakly investigated in non-tumoral and inflammatory prostatic pathology. The diagnosis of granulomatous...
BACKGROUND
The expression of programmed cell death ligand protein (PD-L1) is weakly investigated in non-tumoral and inflammatory prostatic pathology. The diagnosis of granulomatous prostatitis (GP) rests on the recognition of localized or diffuse epithelioid granulomatous inflammation in prostatic tissue which is frequently difficult by conventional histological observation alone. PD-L1 expression in GP is not well studied so far.
METHODS
We studied PD-L1 expression in 17 GP cases (9 nonspecific GP, 5 Bacillus Calmette-Guérin induced prostatitis, 1 prostatic tuberculosis, and 3 cases of postsurgical prostatic granulomas). The control group included 10 radical prostatectomies of patients with high Gleason score prostate adenocarcinoma (PCa) and National Institutes of Health-category IV prostatitis (high-grade histologic prostatitis; HG-HP).
RESULTS
All of the GP cases showed easily visible strong membranous PD-L1 expression (high levels of combined positive score) in localized and diffuse epithelioid granulomatous prostatic inflammation. None of the control cases showed the presence of significant PD-L1 expression in inflammatory infiltrates in HG-HP, tumor parenchyma, and stroma in PCa.
CONCLUSIONS
The study presents the first attempt to examine PD-L1 expression in GP. Granulomatous inflammation in GP is easily identified when stained with PD-L1.
Topics: Male; Humans; Prostatitis; B7-H1 Antigen; Diagnosis, Differential; Prostatic Neoplasms; Granuloma; Inflammation
PubMed: 37357498
DOI: 10.1002/pros.24590