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European Urology Focus Jan 2024Male infertility has been associated with increased morbidity and mortality. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Male infertility has been associated with increased morbidity and mortality.
OBJECTIVE
To perform a systematic review and meta-analysis to provide the most critical evidence on the association between infertility and the risk of incident comorbidities in males.
EVIDENCE ACQUISITION
A systematic review and meta-analysis was performed according to the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and registered on PROSPERO. All published studies on infertile versus fertile men regarding overall mortality and risks of cancer, diabetes, and cardiovascular events were selected from a database search on PubMed, EMBASE, Google Scholar, and Cochrane. Forest plot and quasi-individual patient data meta-analysis were used for pooled analyses. A risk of bias was assessed using the ROBINS-E tool.
EVIDENCE SYNTHESIS
Overall, an increased risk of death from any cause was found for infertile men (hazard risk [HR] 1.37, [95% confidence interval {CI} 1.04-1.81], p = 0.027), and a 30-yr survival probability of 91.0% (95% CI 89.6-92.4%) was found for infertile versus 95.9% (95% CI 95.3-96.4%) for fertile men (p < 0.001). An increased risk emerged of being diagnosed with testis cancer (relative risk [RR] 1.86 [95% CI 1.41-2.45], p < 0.001), melanoma (RR 1.30 [95% CI 1.08-1.56], p = 0.006), and prostate cancer (RR 1.66 [95% CI 1.06-2.61], p < 0.001). As well, an increased risk of diabetes (HR 1.39 [95% CI 1.09-1.71], p = 0.008), with a 30-yr probability of diabetes of 25.0% (95% CI 21.1-26.9%) for infertile versus 17.1% (95% CI 16.1-18.1%) for fertile men (p < 0.001), and an increased risk of cardiovascular events (HR 1.20 [95% CI 1.00-1.44], p = 0.049), with a probability of major cardiovascular events of 13.9% (95% CI 13.3-14.6%) for fertile versus 15.7% (95% CI 14.3-16.9%) for infertile men (p = 0.008), emerged.
CONCLUSIONS
There is statistical evidence that a diagnosis of male infertility is associated with increased risks of death and incident comorbidities. Owing to the overall high risk of bias, results should be interpreted carefully.
PATIENT SUMMARY
Male fertility is a proxy of general men's health and as such should be seen as an opportunity to improve preventive strategies for overall men's health beyond the immediate reproductive goals.
Topics: Humans; Male; Men's Health; Infertility, Male; Prostatic Neoplasms; Health Status; Cardiovascular Diseases; Diabetes Mellitus
PubMed: 37573151
DOI: 10.1016/j.euf.2023.07.010 -
Toxicology and Applied Pharmacology Nov 2023Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The...
Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.
Topics: Adult; Male; Humans; Animals; Mice; Minoxidil; Finasteride; Alopecia; Administration, Oral; Prostatic Hyperplasia; Treatment Outcome
PubMed: 37805090
DOI: 10.1016/j.taap.2023.116710 -
Journal of Human Reproductive Sciences 2023Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive...
BACKGROUND
Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men.
OBJECTIVE
The objective of this study was to assess and systematically review the effects of AAS on male fertility parameters, spermiogram, testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) and to review reversibility and other morbidity impacting fertility.
METHODS
Eligibility criteria - We included studies mentioning data about adult males using supraphysiologic doses of AAS for sports performance or appearance enhancement, with comparison data from general population or matched controls if available reporting fertility parameters and sexual performance. Information sources - A systematic literature search was performed using PubMed, MEDLINE, EMBASE, Google Scholar and World of Science. Controlled clinical trials randomised or nonrandomised (if available), case series with or without matched controls, case reports, cross-sectional surveys, reports on follow-up of subjects caught in doping test and their fertility parameters when reported. Risk of bias/quality assessment - The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.
RESULTS
Included studies - Thirty-two studies were included. There were 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports. The study population comprised 9371 individuals, of which 2671 were AAS users. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population. These levels remained low for 3-6 months after stopping AAS. One year after stopping AAS, the users and naïve population had insignificant differences in FSH and LH values. The total testosterone (TT) levels were comparable in users and naïve populations at baseline, 3 months and 6 months after stopping, but at 1 year, TT values were lower in AAS users. Sperm concentration in AAS users and naïve population was similar, but sperm motility was lower in AAS users. The testicular size was lower in AAS users. The erectile function improved with AAS use, but on withdrawal, there was decreased libido and erectile dysfunction. Most AAS users need additional medications to mitigate detrimental effects on fertility. Description of the effect - AAS use negatively impacted the gonadotrophin levels and had lower sperm motility and testicular size. Strength - Comprehensive review of 32 publications, study population of 9371 individuals, of which 2671 were AAS users, meta-analysis of reproductive hormones, semen parameters and testis size.
LIMITATIONS
The limitations are small sample size of most of the studies, polypharmacy, lack of information on dosing and high heterogeneity.
INTERPRETATION
AAS use is detrimental for sperm motility and has a partially reversible negative impact on male fertility. Users must be cautioned about its negative impact on libido and erectile function. PROSPERO Registration No. CRD42023411294.
PubMed: 38322636
DOI: 10.4103/jhrs.jhrs_90_23 -
International Journal of Molecular... Oct 2023Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to... (Meta-Analysis)
Meta-Analysis Review
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
Topics: Male; Rats; Animals; Melatonin; Vitamins; Molecular Docking Simulation; Semen; Benzhydryl Compounds; Reproduction; Receptors, Estrogen; Vitamin A; Vitamin K; Testosterone; Endocrine Disruptors
PubMed: 37834378
DOI: 10.3390/ijms241914930 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
American Journal of Men's Health 2023Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the... (Meta-Analysis)
Meta-Analysis Review
Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the effects of varicocele surgical repair on serum hormones and inhibin B levels in patients with varicocele. A literature search was performed in August 2022, and no language or geographic region restrictions were applied. The search included the following databases: PubMed, Embase, and Medline. A literature review was performed to identify all published clinical trials assessing serum hormone and inhibin B levels before and after varicocele surgical repair. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Eight articles were selected from 162 articles, including 452 patients. The combined analysis showed that after surgical treatment, mean serum testosterone, inhibin B, and sperm concentration levels increased compared with preoperative levels ( .05). After surgical treatment, mean serum follicle-stimulating hormon (FSH), and Luteinizing hormone (LH) levels decreased compared with preoperative levels ( .05). This meta-analysis demonstrates that varicocele surgical repair can improve testicular function, increase serum testosterone, and inhibin B levels and decrease serum FSH and LH levels in patients with varicocele. This might be related to the improvement of infertility. A large-scale multicenter randomized controlled study is needed for further confirmation.
Topics: Humans; Male; Follicle Stimulating Hormone; Luteinizing Hormone; Varicocele; Testosterone; Semen; Multicenter Studies as Topic
PubMed: 37694823
DOI: 10.1177/15579883231199400 -
European Urology Oncology May 2024Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear.... (Review)
Review
CONTEXT
Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC.
OBJECTIVE
To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments.
EVIDENCE ACQUISITION
A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC.
EVIDENCE SYNTHESIS
From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel.
CONCLUSIONS
Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients.
PATIENT SUMMARY
Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.
PubMed: 38704358
DOI: 10.1016/j.euo.2024.04.011 -
Urologia Nov 2023Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and... (Review)
Review
Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.
Topics: Humans; Male; Fertility Preservation; Androgens; Infertility, Male; Testicular Neoplasms; Urologic Neoplasms
PubMed: 37491831
DOI: 10.1177/03915603221146147 -
Journal of Clinical Medicine Aug 2023Approximately one-third of renal cell carcinoma (RCC) is recognized in its metastatic stage. This systematic review aimed to summarize knowledge on the occurrence and... (Review)
Review
Approximately one-third of renal cell carcinoma (RCC) is recognized in its metastatic stage. This systematic review aimed to summarize knowledge on the occurrence and treatment of testicular RCC metastasis. The literature search was performed by two authors independently, with the use of main electronic medical databases (Science Direct, Web of Science, and PubMed) until March 2023 to identify relevant articles that could potentially contribute to this review. Neither language nor publication dates were set as limits. Although we found a total of 51 case reports, only 31 of them contained all the required information. Testicular metastasis in patients with RCC suggests a late stage of the disease. Moreover, it usually does not present typical systemic or specific symptoms except for swelling and enlargement of the affected testis. Knowledge of the possibility of such variants of RCC metastases will allow a clinician to make an appropriate diagnosis and implement adequate treatment without delay, which is crucial in the management of neoplastic disease.
PubMed: 37685703
DOI: 10.3390/jcm12175636 -
Robot-assisted retroperitoneal lymph node dissection: a systematic review of perioperative outcomes.BJU International Jul 2023To assess the safety and feasibility of robot-assisted retroperitoneal lymph node dissection (R-RPLND) and to compare the perioperative outcomes of R-RPLND with open... (Review)
Review
OBJECTIVE
To assess the safety and feasibility of robot-assisted retroperitoneal lymph node dissection (R-RPLND) and to compare the perioperative outcomes of R-RPLND with open RPLND (O-RPLND), as RPLND forms an integral part of the management of testis cancer and R-RPLND is a minimally invasive treatment option for this disease.
MATERIALS AND METHODS
The PubMed , Scopus , Cochrane Central Register of Controlled Trials, and Web of Science™ databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND.
RESULTS
The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4222 patients (single-arm studies, n = 459; comparative studies, n = 3763). Of 459 patients in the single-arm studies, 271 underwent primary R-RPLND and 188 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175 to 540 min and the major complication rate was 4.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134 to 550 min and the major complication rate was 8.5%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 9.0% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, P < 0.001) and a lower complication rate (18.5% vs 7.8%, P = 0.002).
CONCLUSION
Robot-assisted RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated.
Topics: Male; Humans; Robotics; Retroperitoneal Space; Neoplasms, Germ Cell and Embryonal; Lymph Node Excision; Testicular Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 36754376
DOI: 10.1111/bju.15986