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Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jamshidi, P, Farsi, Y, Nariman, Z, Hatamnejad, MR, Mohammadzadeh, B, Akbarialiabad, H, Nasiri, MJ, Sechi, LA
International journal of molecular sciences. 2023;24(19)
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Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder the cause of which is not yet fully elucidated. Probiotics, prebiotics and dietary changes have been shown to mitigate IBS symptoms whilst the results from studies of faecal microbiota transplants (FMT) have been inconsistent. The aim of this systematic review and meta-analysis of double-blind, randomised controlled trials (RCT) was to evaluate the efficacy and safety of FMT in IBS. 7 RCTs with a low risk of bias and no publication bias were included in the meta-analysis. Overall, no statistically significant effect was observed. A subgroup analysis by treatment modality showed that benefits were seen with lower GI administration of a single dose of multiple-donor FMT. Abdominal pain, nausea, diarrhoea and bloating were the most common adverse events, with no severe or critical adverse events reported. The authors call for larger and longer clinical trials to fill existing knowledge gaps.
Abstract
Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
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Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials.
Mitra, AK, Asala, AF, Malone, S, Mridha, MK
Diseases (Basel, Switzerland). 2023;11(4)
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Gastroenteritis is a major cause of morbidity and mortality globally and symptoms can range from mild to life-threatening. Some studies have suggested benefits of probiotics in the treatment of gastroenteritis in children whilst in adults, results are inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics on acute and chronic gastroenteritis in adults. 35 clinical trials were included in the systematic review and 22 in the meta-analysis. Of these, 23 dealt with inflammatory bowel disease, 5 with pouchitis, 3 with antibiotic-induced diarrhoea, 2 with Helicobacter pylori infection and one each with diverticulitis and acute watery diarrhoea. 27 (77%) of studies showed some benefits of probiotic administration. The meta-analysis of 22 studies did not show a statistically significant benefit of probiotics. Although statistical analysis showed the studies to be homogenous, the authors point out that studies differed widely in aetiologies and probiotics used. A subgroup analysis of 8 studies in patients with ulcerative colitis also showed no benefit. In all studies, probiotics were well tolerated and no adverse side effects were reported. The authors concluded that further research is needed to help identify the most appropriate use of probiotics for the different types of gastroenteritis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For chronic inflammatory gastroenteritis conditions in adults, probiotics were effective in treating and preventing relapse
- In ulcerative colitis, probiotics were not effective and adverse events outweighed the benefits
- No safety concerns were found for probiotic use in any studies
- Aetiologies, disease severity and duration as well as the type of probiotics used were widely diverse.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
To date, evidence has been mixed for probiotic effectiveness in gastrointestinal syndromes associated with gastroenteritis. The aim of this study was to review current evidence on the effect of probiotics on gastroenteritis in adults.
Methods
This was a systematic review (n=35; total sample size 4577, median 44) and meta-analysis (n=22) of randomised controlled trials. Quality was assessed using CADIMA as per a rating scale (0 to 4) and standards of critical appraisal.
Results
All 35 studies on gastroenteritis included participants with chronic diarrhoea of diverse aetiologies such as IBD, antibiotic-associated, except one which had acute watery diarrhoea.
51% (n=18) of studies assessed the effects of probiotics in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). 60% (n=21) used multiple strains of probiotics while the rest used single strains. Lactobacilli, Bifidobacteria, Escherichia and Streptococcus were the most common and only a few studies administered probiotics with another conventional treatment.
19 studies (55%) rated highly in terms of quality while 15 (43%) scored moderately. The majority (63%) of the 27 studies where probiotics were shown to be effective were of high quality.
Systematic review results:
- 27/53 studies (77%) showed a favourable response after using probiotics (resolution, improvement, remission or no relapse), mostly in patients with IBDs
- 7 studies (20%) found probiotics to be ineffective
- 1 study was inconclusive
- Multiple strain probiotics (VSL #3) was found to be most effective in IBD
- All administered probiotics were well tolerated with no adverse side effects although caution in immunocompromised patients was mentioned in several studies.
The meta-analysis results:
- Overall effectiveness for 22 studies (p=0.37) highlighted there was not enough evidence that the intervention was more protective than controls.
- Probiotics were not effective in UC (p = 0.28), and adverse events caused by probiotics may outweigh the benefits in studies with UC patients.
Conclusion
While benefits of effectiveness were found for probiotic use in gastroenteritis in adults, results from the systematic review and meta-analysis showed a mixed effect.
Clinical practice applications:
- Based on the systematic review, probiotics may be an effective treatment or adjuvant treatment for gastroenteritis but ineffective for around 20% of patients
- It is worth noting that combined therapy with standard treatment showed effective results
- Beneficial effects of probiotics in other key clinical outcomes including disease prevention, relapse, quality of life, morbidity were found
- While the results are interesting it is difficult to apply them in practice as the type of probiotics used were widely different as were the causes, severity and duration of gastroenteritis.
Considerations for future research:
- Further and larger studies would be beneficial to understand the benefits of probiotics in terms of single therapy or in combination with standard treatment particularly for UC, CDs, gastroenteritis not due to viral infection
- Individual-level data instead of aggregated data could give a better idea of effectiveness of probiotics in the future
- In this study aetiologies and the type, dosage, duration of probiotics used were widely diverse therefore systematic reviews and meta-analysis on specific conditions, specific probiotic strains and combinations would be beneficial.
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet).
Nabrdalik, K, Drożdż, K, Kwiendacz, H, Skonieczna-Żydecka, K, Łoniewski, I, Kaczmarczyk, M, Wijata, AM, Nalepa, J, Holleman, F, Nieuwdorp, M, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;168:115650
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Metformin has been the number one drug of choice for the management of type 2 diabetes, however there is a proportion of individuals who suffer from stomach issues and discontinue therapy. This may be due to the possibility that metformin impacts gut microbiota composition. This randomised control trial of 82 individuals with metformin intolerance aimed to determine the effect of a multi-strain probiotic in conjunction with metformin administration. The results showed that whilst on probiotics, there was a significant improvement in symptoms, with reduced incidence and severity of nausea, reduced frequency and severity of stomach pain and bloating and self-assessed improvement of tolerability of metformin. Nausea was also decreased, but only when the probiotic was allowed time to act. It was concluded that probiotic supplementation improves gastrointestinal side effects associated with metformin intolerance. This study could be used by healthcare professionals to understand that individuals who are on metformin may experience gastrointestinal side effects, which may be relieved with a multi-strain probiotic.
Abstract
BACKGROUND For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. METHODS AND ANALYSIS This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. RESULTS 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). CONCLUSION A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.
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Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.
Muehlenbein, M, Gassen, J, Nowak, T, Henderson, A, Morris, B, Weaver, S, Baker, E
American journal of men's health. 2023;17(2):15579883221130195
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A growing body of research finds that in men, testosterone levels may be prognostic of clinical outcomes related to coronavirus disease 2019 (COVID-19 disease). The presence of pre-existing chronic conditions in many patients with COVID-19 disease further complicates the relationship among testosterone and severe outcomes. The aim of this study was to examine whether pre-existing conditions for severe COVID-19 disease were related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This study obtained data from men (n = 142) who participated in the longitudinal study Waco COVID Survey. All data included in the study was collected as part of the initial intake survey and first laboratory appointment. Results show that serum-free testosterone levels decreased as a function of age. In fact, greater burden of pre-existing conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. Furthermore, in men older than 40 years of age the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Authors conclude that their findings add important insights into the complex role of androgens in chronic and infectious diseases and contribute to the growing body of literature on the relationship between chronic disease and men’s testosterone levels.
Abstract
Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.
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Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial.
Dierikx, T, Berkhout, D, Eck, A, Tims, S, van Limbergen, J, Visser, D, de Boer, M, de Boer, N, Touw, D, Benninga, M, et al
Gut. 2022;71(9):1803-1811
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Early-life microbiome acquisition and development can be compromised by external perturbations such as delivery via caesarean section (CS), formula feeding and antibiotics. Currently, based on revised international guidelines, all infants born by CS are exposed to broad-spectrum antibiotics via the umbilical cord. Even though there was not an increase in the incidence of neonatal sepsis, the effects on the gut microbiota colonisation and long-term health consequences remain largely unknown. The hypothesis for this study was that exposure to antibiotics in children delivered by CS, related to the revised international guidelines, influences the microbial colonisation process and may impact health outcome. This study is a randomised controlled trial on the microbiome and health state of infants up to 3 years of age. The study enrolled women delivering via CS who received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20) and women who had a vaginal delivery (n=23). Results show that CS delivery in general leads to a profound impact on the initial microbial colonisation. Furthermore, maternal antibiotic administration prior to CS does not lead to a ‘second hit’ on the already compromised microbiome in CS born infants. Authors conclude that early-life microbiome development is strongly affected by mode of delivery.
Abstract
OBJECTIVE Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.
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Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.
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Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis.
Sari Motlagh, R, Abufaraj, M, Karakiewicz, PI, Rajwa, P, Mori, K, Mun, DH, Shariat, SF
World journal of urology. 2022;40(4):907-914
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The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is equal in both sexes; however, disease severity and progression rates are approximately three times higher in the male gender. Androgen deprivation therapy (ADT) and the second-generation androgen receptor targeting therapy were developed to suppress the androgen-activated intracellular cascade that leads to tumour progression and aggressive tumour growth. The aim of this study was to assess the risk of SARS-CoV-2 infection and the severity of disease in prostate cancer (PCa) patients treated with ADT. This study is a systematic review and meta-analysis of six cohort studies. The study results show that there is not a significant association between ADT use and the severity of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) in PCa patients. However, results also show that ADT does not worsen COVID-19 risk and trajectory. Authors conclude that ADT, as a cancer treatment, might be safely administered to patients during the COVID-19 pandemic.
Abstract
PURPOSE Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
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Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.
Rastrelli, G, Cipriani, S, Lotti, F, Cellai, I, Comeglio, P, Filippi, S, Boddi, V, Della Camera, PA, Santi, R, Boni, L, et al
Journal of endocrinological investigation. 2022;45(7):1413-1425
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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.
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Combination therapy with tamsulosin and traditional herbal medicine for lower urinary tract symptoms due to benign prostatic hyperplasia: A double-blinded, randomized, pilot clinical trial.
Lee, CL, Shin, HK, Lee, JY, Kwon, O, Seo, CS, Kim, AR, Seo, BN, Yang, SW, Song, KH, Lim, JS, et al
International journal of urology : official journal of the Japanese Urological Association. 2022;29(6):503-509
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Plain language summary
Benign prostatic hyperplasia (BPH) is a common diagnosis of progressive enlargement of the prostate in older men and the prevalence increases with an aging population. BPH is one of the leading causes of lower urinary tract symptoms (LUTS), causing significant morbidity and decreasing the quality of life of older men. The aim of this study was to describe the efficacy and safety of combination therapy with tamsulosin, and two traditional herbal medicines - Hachimijiogan (HJG) and Ryutanshakanto (RST) in patients with LUTS due to BHP. This study is a double-blind randomised controlled trial. Participants (n= 44) were randomly assigned to one of the three groups: control (tamsulosin and placebo), RST (tamsulosin and RST) or HJG (tamsulosin and HJG) group. Results show that: - in all three groups, prostate volume increased after treatment compared to that before treatment. The HJG and RST combination do not exhibit inferior efficacy to alpha‐blocker monotherapy. - patients in all three groups showed significant improvement in international prostate symptom score (IPSS) and quality of life index without significant differences among the groups. - there weren’t significant differences in the laboratory tests results among the groups before and after treatment. Authors conclude that HJG and RST in conjunction to tamsulosin can be safe supplements for patients with adverse events on taking other medications or high operation risk.
Abstract
OBJECTIVES To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.
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The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.
Fotovat, A, Samadzadeh, B, Ayati, M, Nowroozi, MR, Momeni, SA, Yavari, S, Nasseri, A, Sharifi, L
Urology journal. 2022;19(5):406-411
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Free full text
Plain language summary
Benign prostatic hyperplasia (BPH) is a common issue in men older than 40. BPH is accompanied by irritating and obstructive symptoms that sometimes lead to surgery due to lack of recovery. Tamsulosin is an alpha-receptor blocker that is considered a standard treatment for patients. The aim of this study was to investigate the effect of melatonin [a hormone secreted by the pineal gland at night that regulates the sleep-wake cycle] along with standard treatment on improving the BPH urinary symptoms as well as patients’ quality of life due to their urinary problems. This study is a single centre, parallel group randomised, double-blind clinical trial with balanced randomisation. Patients (n = 108) were randomly allocated to one of the two groups. Results show the combination of melatonin and tamsulosin was significantly effective in treating the symptoms of frequency and nocturia in patients with BPH. Authors conclude that their findings can be used to pave the way to improving the symptoms of patients with BPH.
Abstract
PURPOSE to investigate the effect of melatonin along with tamsulosin in improving BPH urinary symptoms. MATERIALS AND METHODS A total of 108 men with BPH symptoms, age of ≥ 50 years, and International Prostate Symptom Score (IPSS) ≥ 8 entered into the parallel group randomized, double-blind clinical trial with balanced randomization. The treatment group received of 3mg melatonin plus 0.4mg tamsulosin and the control group received placebo plus 0.4mg tamsulosin. Patients and physicians were concealed by sealed and opaque envelopes. Symptoms were assessed at baseline and 1 month after treatment. Finally all scores at the initial and end of the study were compared and analyzed using SPSS software. RESULTS This study showed that adding melatonin to the classic treatment of BPH patients with tamsulosin could significantly reduce the likelihood of nocturia by 2.39 times (95% CI: 1.07-5.32, OR = 2.39, p = 0.033) and could also reduce the frequency of urination by 2.59 times (95% CI: 1.15-5.84, OR = 2.59, p = 0.021). There was no statistically significant difference between the two groups in IPSS, intermittency, incomplete emptying, straining, urgency, and weak stream. CONCLUSION Melatonin plus tamsulosin treatment is associated with a significant improvement of nocturia and frequency in patients with benign proststic hyperplasia. However, it is necessary to do more studies.