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The Journal of Urology Jul 2022The Testicular Workup for Ischemia and Suspected Torsion (TWIST) score is a 7-point tool to evaluate acute scrotal pain. Parameters include testicular swelling (2... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The Testicular Workup for Ischemia and Suspected Torsion (TWIST) score is a 7-point tool to evaluate acute scrotal pain. Parameters include testicular swelling (2 points), hard testis (2), high-riding testis (1), absent cremasteric reflex (1) and nausea/vomiting (1). This review aimed to determine the diagnostic utility of TWIST and its role in risk stratification.
MATERIALS AND METHODS
A systematic review and meta-analysis of diagnostic test accuracy was conducted. Five risk stratification systems were explored, including the Barbosa (0-2, 3-4, 5-7) and Sheth (0, 1-5, 6-7) scoring systems, to obtain sensitivity, specificity and area under the receiver operating curve.
RESULTS
Thirteen studies were identified, 9 prospective studies proceeded to meta-analysis of diagnostic test accuracy and 5 pediatric studies (1,060 patients, 199 torsions) were included in the primary analysis. The most accurate risk stratification system was Barbosa (0-2, 3-4, 5-7), with an AUC of 0.924 (95% CI: 0.865, 0.956). Barbosa showed favorable sensitivity in low-risk patients (0.984), facilitating rule out of torsion, and favorable specificity (0.975) in high-risk patients, facilitating urgent surgical exploration. Sensitivity and specificity in intermediate-risk patients were 0.922 and 0.682, respectively, indicating a need for further workup with ultrasound. Using this stratification, 65.2% of patients were low-risk, 19.9% were intermediate-risk and 14.9% were high-risk. Per 100 presentations of acute scrotum, there was a missed torsion rate of 1.6/100, ultrasound rate of 19.9/100 and negative exploration rate of 2.5/100.
CONCLUSIONS
TWIST is an effective tool for suspected testicular torsion and is appropriate for widespread adoption. The Barbosa scoring system is reliable and reduces reliance on scrotal ultrasound.
Topics: Child; Humans; Male; Prospective Studies; Risk Factors; Scrotum; Spermatic Cord Torsion; Testis
PubMed: 35238603
DOI: 10.1097/JU.0000000000002496 -
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 -
The Journal of Urology Oct 2019With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility....
PURPOSE
With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility. We reviewed the literature regarding the effects of cannabis on male fertility.
MATERIALS AND METHODS
We performed a literature search using PubMed®/MEDLINE® to identify relevant studies of the effects of cannabis on male fertility. Relevant studies were identified and reviewed.
RESULTS
The strongest evidence of cannabis induced alterations in male fertility is in the category of semen parameters. Research supports a role for cannabis in reducing sperm count and concentration, inducing abnormalities in sperm morphology, reducing sperm motility and viability, and inhibiting capacitation and fertilizing capacity. Animal models demonstrate a role for cannabis in testicular atrophy, and reduced libido and sexual function but to our knowledge these results have not yet been replicated in human studies. Studies of hormonal changes suggest inconclusive effects on testosterone levels, lowered luteinizing hormone levels and unchanged follicle-stimulating hormone levels.
CONCLUSIONS
Current research suggests that cannabis may negatively impact male fertility. Further studies are needed to validate that robust findings in animal models will carry over into human experience. Clinicians should be aware of these potential effects when prescribing medical marijuana therapies to men of reproductive age, and they should consider the degree of cannabis use as a possible component of a complete male infertility workup.
Topics: Animals; Cell Survival; Disease Models, Animal; Fertility; Humans; Infertility, Male; Male; Medical Marijuana; Semen; Sperm Motility; Testis
PubMed: 30916627
DOI: 10.1097/JU.0000000000000248 -
Journal of Clinical Medicine Jan 2023Polyorchidism is a rare male urogenital tract anomaly characterized by at least one supernumerary testis in the scrotum or ectopically. According to data based on our... (Review)
Review
Polyorchidism is a rare male urogenital tract anomaly characterized by at least one supernumerary testis in the scrotum or ectopically. According to data based on our systematic review, 76% of the supernumerary testes (SNTs) were located in the scrotum, and 24% were extra-scrotal (p < 0.001). Among testes located outside the scrotum, 87% were found in the inguinal canal and 13% in the abdominal cavity. In 80% of cases, the diagnosis of SNT was made based on imaging tests, and the remaining 20% of cases were detected incidentally during surgery. The imaging tests performed (US or MRI) resulted in a significantly higher rate of patients who qualified for observation vs. surgical treatment (45% vs. 35%, p < 0.001). The most common conditions associated with SNT were ipsilateral inguinal hernia (15% of cases) and cryptorchidism (15% of cases). Surgery (orchidopexy/orchidectomy) was performed on 54% of patients with SNT, and the decision to observe the SNT was made in a total of 46% of patients (p = 0.001). The therapeutic approach depends on the location of the SNT and the presence of factors that raise suspicion of neoplastic proliferation.
PubMed: 36675578
DOI: 10.3390/jcm12020649 -
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 -
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 -
Environmental Research Feb 2023Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are... (Review)
Review
INTRODUCTION
Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.
AIM
To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.
METHODS
A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.
RESULTS
Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).
CONCLUSIONS
The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.
Topics: Male; Female; Humans; Endocrine Disruptors; Endocrine System; Pesticides; Testis; Metals, Heavy
PubMed: 36460069
DOI: 10.1016/j.envres.2022.114869 -
Biological Trace Element Research Jul 2021It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process...
It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process are not clear. Besides, the relationship between dose, route, and time of exposure and injuries remains poorly understood. Thus, we aimed to assess whether cadmium exposure in any dose, route, and time of exposure causes significant alteration in the testicular tissue of murine models, as well as the main mechanisms involved. We performed a structured search on the Medline/PubMed and Scopus databases to retrieve studies published until September 2018. The results were organized into an Adverse Outcome Pathway (AOP) framework. Also, a bias analysis of included studies was performed. We included 37 studies, and most of them identified significant histopathologies in both tubule and intertubule regarding routes, in a dose- and time-dependent manner. The damages were observed after the first hours of exposure, mainly vascular damages suggesting that vasculature failure is the primary mechanism. The AOP showed that potential molecular initiating events may mimic and interfere with essential elements disrupting proteins (structural and antioxidants), change in the oxidative phosphorylation enzyme activities, and gene expression alteration, which lead to reproductive failure (adverse outcome). Analysis of methodological quality showed that the current evidence is at high risk of bias. Despite the high risk of bias, cadmium triggers significant lesions in the testis of murine models, regarding routes, in a dose- and time-dependent manner, mainly due to vascular changes. Therefore, cadmium is a risk factor for male reproductive health.
Topics: Animals; Antioxidants; Cadmium; Disease Models, Animal; Male; Mice; Testis
PubMed: 32951117
DOI: 10.1007/s12011-020-02389-0 -
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 -
European Urology Focus Nov 2021Acute testicular torsion is a common urological emergency. Accepted practice is surgical exploration, detorsion, and orchidopexy for a salvageable testis. (Review)
Review
CONTEXT
Acute testicular torsion is a common urological emergency. Accepted practice is surgical exploration, detorsion, and orchidopexy for a salvageable testis.
OBJECTIVE
To critically evaluate the methods of orchidopexy and their outcomes with a view to determining the optimal surgical technique.
EVIDENCE ACQUISITION
This review protocol was published via PROSPERO [CRD42016043165] and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). EMBASE, MEDLINE, and CENTRAL databases were searched using the following terms: "orchidopexy", "fixation", "exploration", "torsion", "scrotum", and variants. Article screening was performed by two reviewers independently. The primary outcome was retorsion rate of the ipsilateral testis following orchidopexy. Secondary outcomes included testicular atrophy and fertility.
EVIDENCE SYNTHESIS
To our knowledge, this is the first systematic review on this topic. The search yielded 2257 abstracts. Five studies (n = 138 patients) were included. All five techniques differed in incision and/or type of suture and/or point(s) of fixation. Postoperative complications were reported in one study, and included scrotal abscess in 9.1% and stitch abscess in 4.5%. The contralateral testis was fixed in 57.6% of cases. Three studies reported follow-up duration (range 6-31 wk). No study reported any episodes of ipsilateral retorsion. In the studies reporting ipsilateral atrophy rate, this ranged from 9.1% to 47.5%. Fertility outcomes and patient-reported outcome measures were not reported in any studies.
CONCLUSIONS
There is limited evidence in favour of any one surgical technique for acute testicular torsion. During the consent process for scrotal exploration, uncertainties in long-term harms should be discussed. This review highlights the need for an interim consensus on surgical approach until robust studies examining the effects of an operative approach on clinical and fertility outcomes are available.
PATIENT SUMMARY
Twisting of blood supply to the testis, termed testicular torsion, is a urological emergency. Testicular torsion is treated using an operation to untwist the cord that contains the blood vessels. If the testis is still salvageable, surgery can be performed to prevent further torsion. The method that is used to prevent further torsion varies. We reviewed the literature to assess the outcomes of using various surgical techniques to fix the twisting of the testis. Our review shows that there is limited evidence in favour of any one technique.
Topics: Abscess; Atrophy; Humans; Male; Orchiopexy; Spermatic Cord Torsion; Testis
PubMed: 32863201
DOI: 10.1016/j.euf.2020.07.006