Substance abuse and male sexual dysfunction: what lies beneath?

INTRODUCTION: Substance abuse has become a worldwide health problem, leading to numerous consequences such as social problems among family members, abnormal behavior, adverse health effects, and psychological problems as well as economic consequences. OBJECTIVES: We sought to assess the relationship between substance abuse and male sexual health. METHODS: A search was carried out in the following databases: PubMed, MeSH (Medical Subject Headings), Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, and the Egyptian Knowledge Bank. The following keywords were used to assess the outcomes for relevant associations: illicit drugs, addiction, substance abuse, sexual health, erectile dysfunction, ejaculatory disorders, impotence, orgasm disorders, and sexual performance. RESULTS: The initial literature search identified a total of 148 articles in all searched databases. After removal of duplicate studies and application of inclusion/exclusion criteria, 75 reported studies were retained for review, including 38 case-control studies and 37 cross-sectional studies. These articles were classified into the following categories according to the type of abused substance addressed: cannabis/marihuana, 16 articles; opioids, 13 articles; heroin, 11 articles; cocaine, 5 articles; tramadol, 6 articles; ketamine, 2 articles; ecstasy, 4 articles; amphetamine, 2 articles; khat, 7 articles; androgen anabolic steroids, 2 articles; and polydrugs, 7 articles. Most of these recruited articles demonstrated a negative impact of the addressed substance on male sexual health, with variable levels. CONCLUSION: Substance abuse has negative impacts on male sexual health that should be addressed. More studies conducted with proper methodological and statistical approaches, including logistic regression analysis, are needed to predict the effects of specific substances, considering the rapidly growing effects of non-substance-use disorders on male sexual health.

Oral phosphodiesterase type 5 inhibitors and male reproductive potential: an overview.

BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5Is), due to their efficacy and tolerable profile for more than 2 decades,are considered a good addition to the available treatments in patients with erectile dysfunction (ED). AIM: We sought to assess the possible influence of oral PDE5Is on male human reproduction. METHODS: A literature review was performed in several databases, including the PubMed/Medline database, Scopus, Cochrane Library, EMBASE, Academic Search Complete, and Egyptian Knowledge Bank databases. The keywords/search terms were "PDE5Is," "sildenafil," "vardenafil," "tadalafil," or "avanafil," combining and crossing them with "male infertility," "semen," "reproductive hormones," or "sperm." RESULTS: Overall, 101 articles were selected. After removal of duplicates and animal studies, 75 articles were finally subjected to review covering the different items related to male human reproduction, including effects of PDE5Is on different parameters of semen or reproductive hormones, as uses of PDE5Is in cases related to distinctive male factor infertility, such as ED, temporary ED, or ejaculatory failure alongside assisted reproduction (AR) procedures, and ejaculatory dysfunction in spinal cord lesions. We found 26 articles that addressed the direct effects of PDE5Is on semen and reproductive hormonal profiles, 16 in vivo studies and 10 in vitro studies. Oral PDE5Is have in general a stimulatory effect on sperm motility, while other semen parameters and reproductive hormonal profiles showed varied outcomes. Such effects are more pronounced with a long-term daily regimen than with an on-demand regimen. However, it seems that the best-controlled studies suggested no change in the sperm quality of male reproductive potential. CONCLUSION: Oral PDE5Is have in general stimulatory effects on sperm motility, while other semen parameters and hormone profiles showed varied results. In addition, oral PDE5Is have played a useful role in conditions related to distinctive male factor infertility, such as ED, temporary ED, ejaculatory failure alongside AR, and ejaculatory dysfunction in spinal cord lesions.

Addiction and human male fertility: A systematic review and a critical appraisal.

BACKGROUND: Addiction is a global problem that has many negative consequences on human health as well as the quality of life. OBJECTIVES: This review aimed to assess the effect of addiction on human male fertility. METHODS: A systematic review was conducted on various electronic sites. RESULTS: The initial literature search identified a total of 5239 articles in all searched databases. After removing duplicates and application of inclusion/exclusion criteria, 177 were potential articles, 112 were omitted because no direct relevance was encountered. Finally, 65 studies were retained for review. They were classified according to the type of addiction into; opioids and cannabinoids (18 articles), alcohol (7 articles), cocaine (2 articles), Androgenic Anabolic steroids (AAS, 15 articles), tobacco (10 articles) and caffeine (13 articles). Most of these recruited articles demonstrated a negative impact of the addressed substance on male fertility with variable levels of evidence. CONCLUSIONS: It was concluded that addiction harms human male fertility that should be put into consideration. More future studies are needed after a proper methodological and statistical approach, including logistic regression analysis, to predict the effect of a specific substance on human male fertility.

Recreational Use of Oral PDE5 Inhibitors: The Other Side of Midnight.

BACKGROUND: Nowadays, Oral phosphodiesterase type 5 inhibitors (PDE5Is) are widely used for the treatment of erectile dysfunction (ED). However, these drugs have become abused among some men for recreational use to enhance their sexual performance. OBJECTIVE: To shed a light on the recreational use of oral PDE5Is. METHODS: A literature review was performed in the PubMed, Medline Medical Subject Heading, Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, Google scholar, Egyptian Knowledge Bank (EKB) databases, Medline, Embase, and Chem ID using the keywords; sexual health, erectile dysfunction, recreational use/abuse, phosphodiesterase type 5 inhibitors, sildenafil, tadalafil, vardenafil, avanafil, and adverse effects. RESULTS: Overall, 52 studies were retained for review out of 166 papers. Twenty-two studies that assessed the prevalence of the problem were investigated including 25,279 men from different countries. Most of these studies were cross-sectional studies that depend on multiple questionnaires representing the extent as well as the attitude of the recreational use of PDE5Is. CONCLUSION: Oral PDE5Is have become used among some men for recreational use to enhance their sexual performance. To counteract the possible side effects of such abuse, the media, as well as health authorities, should be aware of the potential adverse effects of such abuse and strengthen the regulatory activity to protect the customers from such risks. Mostafa T, Alghobary MF. Recreational Use of Oral PDE5 Inhibitors: The Other Side of Midnight. Sex Med Rev 2022;10:385-395.

Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal.

INTRODUCTION: Several treatment strategies are nowadays available for erectile dysfunction (ED) patients. Currently, oral phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line therapy for ED. However, they are effective in all treated cases with variable non-responsiveness. Many factors have been listed for this behavior, but the possibility of gene polymorphisms as an underlying cause has not been systematically investigated. OBJECTIVES: This review aimed to assess the possible involvement of gene polymorphisms affecting the response to PDE5Is in men with ED. METHODS: A systematic review was conducted based on a search of all relevant articles in various electronic sites such as PubMed, Medline Medical Subject Headings, Cochrane Library, Science Direct, Scopus, Embase, CINAHL, and Egyptian Knowledge Bank databases. Keywords used for relevant associations were sexual health, genes, variants, erectile dysfunction, polymorphisms, PDE5Is, and cavernous tissues. RESULTS: Several studies have been carried out to determine the contribution of different encoded genes to ascertain the association between different genotypes and ED men who were non-responders for PDE5Is. 11 studies were selected for this review. In these studies, 6 investigated eNOS genetic polymorphism with variable outcomes. Only 1 study was carried out for each of the following genetic polymorphisms: phosphodiestrase 5A, G-protein ß3 subunit, angiotensin converting enzyme, dimethylarginine dimethylaminohydrolase, arginase, and vascular endothelial growth factor with variable results. CONCLUSION: Despite the relative shortage of available studies and the varied methodologies used, most of the research articles demonstrated a significant association between genetic polymorphism and the response to PDE5Is, especially for endothelial nitric oxide synthase polymorphism. The limited number of studies that investigated the possible effect of genetic polymorphism and the response to PDE5Is are challenged by many factors, particularly for the definition of responders and non-responders. This should be a motivating factor for researchers to perform further studies with a standardized methodology to address the influence of genetic variations on the response to PDE5Is. Mostafa T, Hassan A, Alghobary MF, et al. Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal. J Sex Med 2020;8:573-585.

The possible role of NF-κB1 Rs28362491 polymorphism in male fertility of Egyptian population.

Male reproductive impairment is responsible for at least 50% of cases of couple infertility. Nuclear factor-kappa B (NF-κB) has been functionally linked to germ cell apoptosis, which may affect human fertility. The aim of this study was to determine the association between the rs28362491 SNP of the NF-κB1 gene and infertility in Egyptian men. In this case-control study, semen and blood samples of 247 infertile men, constituting the case group, and of 113 fertile healthy men as the control group were analysed. All study participants were genotyped for polymorphism of the NF-κB1 gene (rs28362491) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Heterozygous I/D genotype of the NF-κB1 rs28362491 polymorphism was associated with a significantly lower risk of poor semen quality, including asthenozoospermia, astheno-teratozoospermia, and oligo-astheno-teratozoospermia, when compared to I/I genotype (odds ratio = 0.25, 0.26, 0.18, p < .0005, <.0005, <.0005) respectively. Overall, the presence of the D allele was associated with a significantly decreased risk of poor sperm quality as compared to the I allele (odds ratio = 0.56, 0.64, 0.49, p = .050, .038, .001). In conclusion, these results suggest that heterozygosity of the NF-κB1 gene may play a protecting role against male infertility in Egyptians.

Oral dapoxetine versus topical lidocaine as on-demand treatment for lifelong premature ejaculation: A randomised controlled trial.

This trial aimed to assess the efficacy of on-demand oral dapoxetine versus topical lidocaine treatments for lifelong PE. Cases with lifelong PE were randomised to start treatment by oral dapoxetine 60 mg or topical lidocaine 10% spray. The intravaginal ejaculatory latency time (ILET), validated Arabic Index for PE (AIPE), Sexual Health Inventory for Men (SHIM) and frequency of intercourse/week were recorded at the baseline and after 12 weeks treatment period of the first medication before two weeks washout period and then crossing over to the other one for another 12 weeks. Results showed that both medications significantly increased both IELT and AIPE scores compared with the baseline being significantly better with topical lidocaine (63.44 s, 179.4 s versus 21.87 s, p < .05). Significant decrease of SHIM score was recorded with lidocaine but not with dapoxetine. Global Efficacy Question for the patient's assessment of the effectiveness of drugs showed that lidocaine was described as being effective by 43 cases and ineffective by 12 cases, oral dapoxetine was described as being effective by 16 cases and ineffective by 39 cases. From these accumulated data, it is concluded that topical lidocaine is more effective on-demand therapy for lifelong PE compared with oral dapoxetine.

Evaluation of cannabinoid receptors Type 1 and Type 2 mRNA expression in mature versus immature spermatozoa from fertile and infertile males.

The expression of the main cannabinoid receptors (CBR1 and CBR2) was investigated to evaluate the possible association with the sperm maturation from fertile and infertile individuals. One hundred subjects were classified into fertile (n = 50) and infertile groups (n = 50). Fresh semen samples were collected. Computer-assisted semen analysis and acrosin activity test were done. RNA was extracted from mature and immature sperm pellets. Reverse transcriptase reaction and real-time PCR were done to assess the levels of both CBR1 and CBR2 genes expression in all samples. Mature spermatozoa from both groups showed significantly higher levels of both CBR1 and CBR2 compared with the immature spermatozoa (p < .05). This increment was significantly more important in the fertile group (p < .05). In mature spermatozoa, CBR1 expression was significantly related to variation in sperm morphology, and CBR2 was significantly related to both sperm morphology and linearity index. In conclusion, CBR1 and CBR2 mRNA expression may closely direct the sperm maturation at different steps of the reproductive process.

Keloidectomy with core fillet flap and intralesional verapamil injection for recurrent earlobe keloids.

BACKGROUND: Earlobe keloids are usually recalcitrant to treatment and have a high rate of recurrence. Verapamil is a calcium channel antagonist that has been shown to inhibit the synthesis/secretion of extracellular matrix molecules and increase collagenase. OBJECTIVES: This prospective study was designed to evaluate the results of treatment of recurrent earlobe keloids using keloidectomy with core fillet flap and intralesional verapamil injection. METHODS: Nineteen keloids in 16 patients were treated using this technique with intralesional verapamil injection given intraoperatively, then every 2 weeks for 3 months, with postoperative follow-up for 18 months. RESULTS: Fourteen patients completed the study. Ten patients (71.4%) showed response to treatment. Four (28.6%) cases showed recurrence, two (14.2%) at the wound bed and another two (14. 2%) at the incision line. Eighty percent of responders were highly satisfied with their treatment. CONCLUSION: Keloidectomy with core fillet flap and intralesional verapamil injection is a reliable and cost-effective method in the treatment of recurrent earlobe keloids with a low rate of recurrence and high patient satisfaction.

Androgen receptor expression relationship with semen variables in infertile men with varicocele.

PURPOSE: Androgen receptor, a member of the nuclear receptor superfamily, has important roles in male reproductive function. It is required for sexual differentiation, pubertal development, spermatogenesis regulation, meiosis completion and spermatocyte transition to haploid round spermatids. We assessed the association of androgen receptor expression and semen variables in infertile men with varicocele. MATERIALS AND METHODS: A total of 299 men were grouped into healthy, fertile controls, infertile men without varicocele and men with infertility associated with varicocele. A history was obtained, clinical examination and semen analysis were done and reproductive hormones were estimated. Androgen receptor expression and the acrosome reaction were determined in recovered spermatozoa. RESULTS: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile controls. Androgen receptor correlated positively with sperm count, motility, normal forms, velocity, linear velocity, acrosome reaction and α-glucosidase. It correlated negatively with serum follicle-stimulating hormone and estradiol. Multiple stepwise regression analysis of androgen receptor expression revealed that the sperm acrosome reaction and linearity index were the most affected independent variables. CONCLUSIONS: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile men. Androgen receptor expression correlated positively with sperm count, motility, normal forms, velocity, linear velocity and acrosome reaction.

Evaluation of tramadol on demand vs. daily paroxetine as a long-term treatment of lifelong premature ejaculation.

INTRODUCTION: Premature ejaculation (PE) is the most common male sexual dysfunction with many lines of treatment that show conflicting results. Paroxetine and tramadol were both reported to be effective in treatment of PE. AIM: To investigate the effectiveness of long-term daily paroxetine vs. on-demand tramadol HCl in treatment of PE. MAIN OUTCOME MEASURES: Intravaginal ejaculatory latency time (IELT) and Arabic Index of PE (AIPE) were used to assess the efficacy of investigated drugs. METHODS: Thirty-five cases with lifelong PE were enrolled in this study. Baseline recording of IELT using a stop watch and AIPE was done. Patients were randomized to take tramadol HCl on-demand or daily paroxetine. Reassessment was done after 6 and 12 weeks. A wash-out period for 2 weeks was given before cross-over to the other medication. Assessment of the effect of the second medication after 6 and 12 weeks was done. RESULTS: Tramadol and paroxetine increased IELT significantly after 6 weeks by seven- and 11-folds, respectively, compared with baseline. After 12 weeks, a decline of IELT to fivefolds was recorded with tramadol whereas further increase of IELT to 22-folds was recorded with paroxetine compared with baseline (P < 0.05). Tramadol improved AIPE score significantly after 6 weeks but not after 12 weeks vs. baseline, whereas paroxetine increased the AIPE score after 6 and 12 weeks vs. baseline (P < 0.05). CONCLUSIONS: Daily paroxetine is more effective than on-demand tramadol for treatment of lifelong PE. Tramadol is not recommended as a long-term treatment of lifelong PE.