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Central European Journal of Urology 2021The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce...
The effect of pharmacotherapy on prostate volume, prostate perfusion and prostate-specific antigen (prostate morphometric parameters) in patients with lower urinary tract symptoms and benign prostatic obstruction. A systematic review and meta-analysis.
INTRODUCTION
The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce prostate volume and prostate-specific antigen (PSA). This review assesses the effect of pharmacotherapy on prostate parameters effect on prostate parameters, namely total prostate volume (TPV), transitional zone volume (TZV), PSA and prostate perfusion.
MATERIAL AND METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting on morphometric parameters' changes after pharmacotherapy, as primary or secondary outcomes. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RCTs' quality was assessed by the Cochrane tool and the criteria of the Agency for Healthcare Research and Quality. The effect magnitude was expressed as standard mean difference (SMD). The study protocol was published on PROSPERO (CRD42020170172).
RESULTS
Sixty-seven RCTs were included in the review and 18 in the meta-analysis. The changes after alpha-blockers are comparable to placebo. Long-term studies reporting significant changes from baseline, result from physiologic growth. Finasteride and dutasteride demonstrated large effect sizes in TPV reduction ([SMD]: -1.15 (95% CI: -1.26 to -1.04, p <0.001, and [SMD]:-0.66 (95% CI: -0.83 to -0.49, p <0.001, respectively), and similar PSA reductions. Dutasteride's effect appears earlier (1 vs 3 month), the changes reach a maximum at month 12 and are sustained thereafter. Phosphodiesterase-5 (PDE-5) inhibitors have no effect on morphometric parameters. Phytotherapy's effect on TPV is non-significant [SMD]: 0.12 (95% CI: -0.03 to 0.27, p = 0.13). Atorvastatin reduces TPV as compared to placebo (-11.7% vs +2.5%, p <0.01). Co-administration of testosterone with dutasteride spares the prostate from the androgenic stimulation as both TPV and PSA are reduced significantly.
CONCLUSIONS
The 5-ARIs show large effect size in reducing TPV and PSA. Tamsulosin improves perfusion but no other effect is evident. PDE-5 inhibitors and phytotherapy do not affect morphometric parameters. Atorvastatin reduces TPV and PSA as opposed to testosterone supplementation.
PubMed: 34729231
DOI: 10.5173/ceju.2021.132.R1 -
Asian Journal of Urology Jan 2022Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride...
The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding. We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials (RCTs).
METHODS
A comprehensive literature search was performed through the electronic databases including Medline, Cochrane Library, Google Scholar, and ClinicalTrial.gov in October 2020. RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool. The heterogeneity was assessed using statistic. The measured outcomes were hemoglobin (Hb) levels, perioperative blood loss, blood transfusion, microvessel density (MVD), and operation time. Data were pooled as mean difference (MD) and odds ratio (OR).
RESULTS
A total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed. Patients that received dutasteride had less reduction in Hb levels (MD -1.10, 95% confidence interval [CI] -1.39 to -0.81, <0.00001). Dutasteride also significantly reduced the operation time (MD -1.79, 95% CI -2.97 to -0.61, =0.003) and transfusion rate after surgery (OR 0.34, 95% CI 0.15 to 0.77, =0.009) compared to the control group. However, the MVD (MD -3.60, 95% CI -8.04 to 0.84, =0.11) and perioperative blood loss in dutasteride administration for less than 4 weeks (MD 46.90, 95% CI -144.60 to 238.41, =0.63) and more than 4 weeks (MD -190.13, 95% CI -378.05 to -2.21, =0.05) differences were insignificant.
CONCLUSION
Preoperative administration of dutasteride is able to reduce bleeding during TURP, as indicated by less reduction in Hb level, lower transfusion rate, and less operation time.
PubMed: 35198393
DOI: 10.1016/j.ajur.2021.05.011 -
The Aging Male : the Official Journal... Sep 2016Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used... (Meta-Analysis)
Meta-Analysis Review
Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis.
Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used for LUTS/BPO may strongly affect sexual function and bother. The aim of this systematic review and meta-analysis was to evaluate the impact of combination therapy with alpha-blockers (AB), 5-alpha reductase inhibitors (5-ARI) on the risk of erectile dysfunction(ED) and libido alterations (LA) from randomized clinical trial (RCT). Based on the inclusion and exclusion criteria, five RCTs involving 6131 patients were included in the analysis. According to the analysis, the overall prevalence of ED and LA were significantly greater in the combination treatment group than in the AB group (7.93% versus 4.66%; OR 1.81; p < 0.0001 and 3.69% versus 2.36%; OR 1.58; p = 0.003, respectively). The combination therapy increased the risk of ED compared to monotherapy with 5-ARI (7.93% versus 6.47%; OR 1.25; p = 0.04) but not the risk of LA (3.51% versus 3.37; OR 1.03; p = 0.84). In our systematic meta-analysis, we demonstrated that combination therapy with ABs and 5-ARIs was associated with significantly higher risk of ED and LA compared with single monotherapy. Combination therapy showed similar risk of LA compared with 5-ARI monotherapy.
Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Drug Therapy, Combination; Erectile Dysfunction; Humans; Libido; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia
PubMed: 27310433
DOI: 10.1080/13685538.2016.1195361 -
Oncotarget May 2017High-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients.
METHODS
Literature searches were conducted in PubMed, EMBASE and Cochrane library according to Cochrane guidelines before January 31st, 2017. Direct meta-analysis were performed to summarize the efficacy of candidate chemopreventative agents Dutasteride, Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food products combination. Adjusted indirect meta-analyses were employed to compare the relative efficacy of these candidate chemoprevention agents head-to-head.
RESULTS
The overall incidence of prostate cancer in HGPIN was slightly decreased by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P = 0.183), with minor heterogeneity (I2 = 22.3%, ð2 = 15.08, P = 0.237), but without statistical significance. Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs 23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity (I2 = 47.9%, ð2 = 1.92, P = 0.166). The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355, 95% CI: 0.134-0.934).
CONCLUSION
The overall efficacy of chemoprevention agents in HGPIN patients is limited. But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients.
Topics: Anticarcinogenic Agents; Biological Products; Chemoprevention; Humans; Male; Odds Ratio; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Treatment Outcome
PubMed: 28415774
DOI: 10.18632/oncotarget.16230 -
Annals of the Academy of Medicine,... Dec 2022The oral antiviral agents nirmatrelvir-ritonavir (NMV/r) and molnupiravir are used to treat mild-to-moderate COVID-19 infection in outpatients. However, the use of NMV/r...
INTRODUCTION
The oral antiviral agents nirmatrelvir-ritonavir (NMV/r) and molnupiravir are used to treat mild-to-moderate COVID-19 infection in outpatients. However, the use of NMV/r is complicated by significant drug-drug interactions (DDIs) with frequently prescribed medications. Healthcare professionals should be aware of the possible risk of DDIs, given the emergence of COVID-19 variants and the widespread use of oral COVID-19 treatments. We reviewed available data on DDIs between NMV/r, molnupiravir and common dermatological medications; summarised the potential side effects; and suggest strategies for safe COVID-19 treatment.
METHOD
A systematic review using PubMed was conducted on data published from inception to 18 July 2022 to find clinical outcomes of DDIs between NMV/r, molnupiravir and dermatological medications. We also searched the Lexicomp, Micromedex, Liverpool COVID-19 Drug Interactions database and the National Institutes of Health COVID-19 Treatment Guidelines for interactions between NMV/r and molnupiravir, and commonly used dermatological medications.
RESULTS
NMV/r containing the cytochrome P-450 (CYP) 3A4 inhibitor ritonavir has DDIs with other medications similarly dependent on CYP3A4 metabolism. Dermatological medications that have DDIs with NMV/r include rifampicin, clofazimine, clarithromycin, erythromycin, clindamycin, itraconazole, ketoconazole, fluconazole, bilastine, rupatadine, dutasteride, ciclosporin, cyclophosphamide, tofacitinib, upadacitinib, colchicine and systemic glucocorticoids. With no potential DDI identified yet in in vitro studies, molnupiravir may be an alternative COVID-19 therapy in patients taking medications that have complicated interactions with NMV/r, which cannot be stopped or dose adjusted.
CONCLUSION
NMV/r has significant DDIs with many common dermatological medications, which may require temporary discontinuation, dosage adjustment or substitution with other anti-COVID-19 agents such as molnupiravir.
Topics: Humans; Ritonavir; COVID-19; SARS-CoV-2; Antiviral Agents; Drug Interactions
PubMed: 36592146
DOI: 10.47102/annals-acadmedsg.2022289 -
American Journal of Clinical Oncology Apr 2020To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). (Meta-Analysis)
Meta-Analysis
PURPOSE
To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
METHODS
The relevant randomized controlled trials were retrieved from PubMed and the Cochrane Library. Network meta-analyses were used to compare multiple drugs simultaneously for the outcomes of nmCRPC. Direct evidence in trials and indirect evidence across trials were combined by the network meta-analyses to estimate the treatment efficiency.
OUTCOME
Eight studies were included in our research. For prostate-specific antigen progression-free survival, the rate of progression was significantly decreased following apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide treatment compared with placebo. Compared with placebo treatment, metastases-free survival was significantly increased in patients who received apalutamide (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23-0.35), enzalutamide (HR: 0.29, 95% CI: 0.24-0.35), and darolutamide (HR: 0.42, 95% CI: 0.35-0.50). Direct comparison showed significant survival benefits in patients who received second-generation anti-androgen therapy (apalutamide, enzalutamide, and darolutamide: HR: 0.74, 95% CI: 0.61-0.91) compared with patients who received placebo. With respect to metastases-free survival, based on SUCRA analysis, there was 80% and 78% probability that apalutamide and enzalutamide were preferred treatment, while darolutamide was likely to be second-best choice. Compared with placebo, all agents were not associated with significantly higher likelihood of serious adverse events and grade 3 to 4 adverse events.
CONCLUSION
Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.
Topics: Humans; Male; Network Meta-Analysis; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31972568
DOI: 10.1097/COC.0000000000000660 -
Sexual Medicine Reviews Jan 2019Many studies have reported that 5α-reductase inhibitors (finasteride and dutasteride) raise serum testosterone (T) levels, yet there is lack of consistency among... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many studies have reported that 5α-reductase inhibitors (finasteride and dutasteride) raise serum testosterone (T) levels, yet there is lack of consistency among studies on this point.
AIM
To review and meta-analyze available studies reporting changes in serum T concentrations in men treated with 5α-reductase inhibitors (5α-RIs).
METHODS
A Medline search using PubMed and EMBASE was performed including the following key words: "finasteride," "dutasteride," "testosterone and 5α-reductases."
MAIN OUTCOME MEASURE
Relevant studies were extracted, evaluated, and analyzed. Of these, 40 studies were analyzed qualitatively and 11 were included in the meta-analysis. A random effects model was used to conduct the meta-analysis.
RESULTS
In 11 studies comprising 1,784 patients with age ranging between 18 and 83 years and average treatment follow-up of 17 months, meta-analytic estimate of the mean baseline change was 27 (95% confidence interval 1-54). The meta-analysis did not demonstrate unequivocal significant increase in serum T levels. The increase was not uniform among all studies reported. Sensitivity analysis showed that no single study contributed decisively to the outcome or could be attributed to drug action. The reported increases in T levels with finasteride or dutasteride in men with low baseline serum T may be attributed, in part, to increased trapping of T by unsaturated sex hormone binding globulin (SHBG) due to dissociation of 5α-dihydrotestosterone. In men with high baseline T levels, there appears to be no change in serum T levels. 10 studies reported luteinizing hormone, follicle-stimulating hormone, SHBG, and estradiol values and none reported significant changes in their levels, suggesting that observed changes in serum T levels are unlikely mediated by gonadotropins levels or peripheral conversion of T to estradiol.
CONCLUSION
5α-RI therapy is not associated with consistent and significant increases in serum T levels. Traish AM, Krakowsky Y, Doros G, et al. Do 5α-reductase inhibitors raise circulating serum testosterone levels? A comprehensive review and meta-analysis to explaining paradoxical results. Sex Med Rev 2019;7:95-114.
Topics: 5-alpha Reductase Inhibitors; Clinical Trials as Topic; Dutasteride; Finasteride; Humans; Luteinizing Hormone; Male; Observational Studies as Topic; Testosterone
PubMed: 30098986
DOI: 10.1016/j.sxmr.2018.06.002 -
JAMA Surgery Feb 2019A growing number of transgender patients are receiving gender-affirming hormone treatments. It is unclear whether the evidence supports the current practice of routinely...
IMPORTANCE
A growing number of transgender patients are receiving gender-affirming hormone treatments. It is unclear whether the evidence supports the current practice of routinely discontinuing these hormones prior to surgery.
OBJECTIVE
To determine how medications used in cross-sex hormone treatment (CSHT) affect perioperative risk.
EVIDENCE REVIEW
A series of searches were carried out in PubMed and Excerpta Medica Database to identify articles using each of the terms testosterone, estrogen, estradiol, oral contraceptive, spironolactone, cyproterone acetate, finasteride, dutasteride, leuprolide, goserelin, and histrelin, in combination with the terms surgery, perioperative, thrombosis, thromboembolism, and operative. The search was not restricted to perioperative outcomes in transgender populations because many surgeons routinely discontinue hormone use prior to surgery in this population, which makes it impossible to study how hormones affect outcomes. Additional sources were also identified from the texts of reviewed articles. Articles were excluded if they were animal studies or case reports, did not explicitly discuss surgical outcomes, or were restricted to removal of hormonally sensitive tissues.
FINDINGS
Eighteen articles addressing perioperative outcomes were identified by this systematic review, including 1 on CSHT, 12 on estrogens and progesterones, 1 on testosterone, and 4 on spironolactone and antiandrogens. Data were limited, but use of exogenous testosterone was not found to be associated with an increased risk of venous thromboembolism or other complications during surgery. Moderate evidence suggests that spironolactone is not associated with negative surgical outcomes. The data linking estrogen use and thrombosis is inconsistent in the perioperative period and does not address the types of estrogens most often used for CSHT.
CONCLUSIONS AND RELEVANCE
Current evidence does not support routine discontinuation of all CSHT prior to surgery, particularly given the lack of information on risks associated with resuming these medications after they have been stopped. Evidence suggests there is no need to discontinue either testosterone or spironolactone, although their association with perioperative outcome quality has not been studied in depth. Most of the evidence that supports discontinuation of estrogen prior to surgery is based on oral estrogen regimens that are not typically used in transgender patients, and even with those formulations, there are conflicting reports on perioperative risk. Further research is needed to determine the safety of continuing hormone treatment and elucidate risks of short-term discontinuation.
Topics: Drug Substitution; Female; Gender Dysphoria; Gonadal Steroid Hormones; Humans; Intraoperative Complications; Male; Observational Studies as Topic; Practice Patterns, Physicians'; Preoperative Care; Transgender Persons; Transsexualism
PubMed: 30516808
DOI: 10.1001/jamasurg.2018.4598