Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation

Premature ejaculation （PE） is the most common sexual disorder. It affects 20%-30% of adult men; the aetiology of this condition has not yet been elucidated. The aim of this study is to evaluate the efficacy, safety, tolerability, undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE. A total of 300 patients who presented with lifelong （primary） PE were included in this study. The study was performed for 28 weeks, in which placebo （starch tablet） was given for 4 weeks, and active ingredient （tramadol hydrochloride） was administered at different therapeutic dosages for 24 weeks. Patients were divided into three equal groups, each consisting of 100 patients. The first group （A） was given tramadol hydrochloride capsule 25 mg. The second group （B） was given tramadol hydrochloride capsule 50 mg. The third group （C） was given tramadol hydrochloride capsule 100 mg. All of the 300 participants included completed the study voluntarily. The age of the patients varied from 25 to 50 years. After the treatment period, the recorded data were collected for each group and analysed. The results showed a highly significant increase in the mean intravaginal ejaculatory latency time （IELT） in all groups compared to baseline data （P〈0.0001）. We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be souRht.

Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation

Aim: To assess the psychometric properties of the Chinese Index of Premature Ejaculation (CIPE). Methods: The sexual function of 167 patients with and 114 normai controls without premature ejaculation (PE) were evaluated with CIPE. All subjects were married and had regular sexual activity. The CIPE has 10 questions, focusing on libido, erectile function, ejaculatory latency, sexual satisfaction and difficulty in delaying ejaculation, self-confi dence and depression. Each question was responded to on a 5 point Likert-type scale. The individual question score and the total scale score were analyzed between the two groups. Results: There were no significant differences between the age, duration of marriage and educational level (P > 0.05) of patients with and vvithout PE and normai controls. The mean latency of patients with PE and normai controls were 1.6±1.2 and 10.2±9.5 minutes, respectively. Significant differences between patients with (26.7±4.6) PE and normai controls (41.9±4.0) were observed on the total score of CIPE (P < 0.01). Using binary logistic regression analysis, PE was significantly related to five questions of the original measure. They are the so-called the CIPE-5 and include: ejaculatory latency, sexual satisfaction of patients and sexual partner, difficulty in delaying ejaculation, anxiety and depression. Receiver Operat ing Characteristic (ROC) curve analysis of CIPE-5 questionnaire indicated that the sensitivity and specificity of CIPE were 97.60 % and 94.74 %, respectively. Employing the total score of CIPE-5, patients with PE could be divided into three groups: mild (>15 point) 19.8 %, moderate (10-14 point) 62.8 % and severe (< 9 point) 16.7 %. Conclusion: The CIPE-5 is a useful method for the evaluation of sexual function of patients with PE and can be used as a clinical endpoint for clinical trials studying the efficacy of pharmacologica] intervention.

Premature ejaculation： current and future treatments

Premature ejaculation （PE） is recognized to be the most common male sexual disorder. PE provides difficulties for professionals who treat this condition because there is neither a universally accepted definition nor a medication approved by the Food and Drug Administration （FDA）. Despite these shortcomings, physicians continue to diagnose their patients with PE according to major guidelines and treat them with either behavioral therapies or off-label medications. This review focuses on current and emerging treatment options and medications for PE. Advantages and limitations of each treatment option are discussed in the light of current published peer-reviewed literature.

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Comparative study of on-demand and daily use of sertraline in treatment of premature ejaculation:A randomized clinical trial

Objective:The intravaginal ejaculatory latency time(IELT)may increase less in on-demand compared to daily intake,but may fulfill a suitable treatment for specific patients.We decided to compare the efficacy and safety of on-demand and daily use of sertraline in order to find the most effective and least complicated method in treatment of premature ejaculation(PE).Methods:This study was parallel or concurrent control randomized clinical trial.Two hundred and forty patients with PE diagnosed by urologist in the two groups of 120 from July 2017 to February 2019 enrolled in the study.In the first group,it is prescribed 50 mg sertraline each 12 h daily and the second group received 50 mg 4 h before coitus for 4 and 8 weeks.The IELT before treatment and during all coitus after treatment were recorded by the patient’s wife with a stopwatch.Results:Mean IELT before,4 and 8 weeks after treatment in two groups were:On-demand group 101.62±65.44 s,208.75±128.02 s and 265.87±145.70 s;daily use group 102.50-81.22 s,276.87±181.08 s and 353.75±176.45 s,respectively.The ejaculation time increased significantly in both groups(p<0.05).However,increase in ejaculation time in daily use group was significantly higher than the on-demand group in 4 weeks(p=0.036),especially in 8 weeks(p=0.009).The percent of side effects in daily use group(26.7%)was higher than on-demand group(20%)(p<0.05).Drowsiness,diarrhea and vertigo were significantly higher in the daily use than on-demand(p<0.05).Conclusions:On-demand and daily use of sertraline are effective and usually have no serious complications,but the on-demand method is considerably more tolerable.In patients who did not tolerate to daily use of this drug,on-demand could be used as a salvage therapy.

A Double-Blind, Placebo-Controlled Study of the Effectiveness of Mate Endurance TM Dietary Supplement on Sexual Satisfaction, Ejaculatory Control, and Distress in Men with Premature Ejaculation

Background: To assess the efficacy of the dietary supplement Mate Endurance on sexual satisfaction, ejaculatory control, and sexually related personal distress in patients with premature ejaculation. Methods: In a double-blind, randomized, placebo-controlled study, 68 patients between 21 and 60 years old with premature ejaculation were randomized to receive either Mate Endurance or placebo treatment for three months. The patients were provided a questionnaire at the start of the study and again three months post commencement of the study. The questionnaires were comprised of the Index of Premature Ejaculation (IPE) and the PE Diagnostic Tool (PEDT). Results: Participants in the treatment group experienced a significant improvement in symptoms often associated with premature ejaculation versus those in the placebo group. The treatment was widely used with limited adverse effects. Conclusions: The results of the study demonstrate the effectiveness of the dietary supplement Mate Endurance in improving symptoms associated with premature ejaculation, including general sexual satisfaction and distress associated with sexual encounters.

New insights on premature ejaculation： a review of ：lefinition, classification, prevalence and treatmeni

There are ongoing debates about the definition, classification and prevalence of premature ejaculation （PE）. The first evidence-based definition of PE was limited to heterosexual men with lifelong PE who engage in vaginal intercourse. Unfortunately, many patients with the complaint of PE do not meet these criteria. However, these men can be diagnosed as one of the PE subtypes, namely acquired PE, natural variable PE or premature-like ejaculatory dysfunction. Nevertheless, the validity of these subtypes has not yet been supported by evidence. The absence of a universally accepted PE definition and lack of standards for data acquisition have resulted in prevalence studies that have reported conflicting rates. The very high prevalence of 20%-30% is probably due to the vague terminology used in the definitions at the time when such surveys were conducted. Although many men may complain of PE when questioned for a population-based prevalence study, only a few of them will actively seek treatment for their complaint, even though most of these patients would define symptoms congruent with PE. The complaints of acquired PE patients may be more severe, whereas complaints of patients experiencing premature-like ejaculatory dysfunction seem to be least severe among men with various forms of PE. Although numerous treatment modalities have been proposed for management of PE, only antidepressants and topical anaesthetic creams have currently been proven to be effective. However, as none of the treatment modalities have been approved by the regulatory agencies, further studies must be carried to develop a beneficial treatment strategy for PE.

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Efficacy and safety of local anaesthetics for prematurejaculation： a systematic review and meta-analysis

To assess the efficacy and safety of local anaesthetics for premature ejaculation （PE）, a systematic review of the literature was performed using the Cochrane Library, PUBMED and EMBASE. We screened and retrieved the randomized controlled trials on the treatment of PE with local anaesthetics. End points included intravaginal ejaculation latency time （IELT）, patient-reported outcome assessments and adverse events. Meta-analyses were conducted with Stata 11.0. In total, seven publications involving 566 patients with local anaesthetics and 388 with placebos strictly met our eligibility criteria. Meta-analyses showed that after the patients were treated with the local anaesthetics, the value of the standardized mean difference of the changes in IELT was 5.02 （95% Ch 3.03- 7.00）. A higher rate of adverse events occurred compared with placebos （odds ratio： 3.30, 95% Ch 1.71-6.36）, but these events were restricted to local side effects. In addition, significantly greater improvement was observed in patient-reported outcomes. In summary, local anaesthetics can prolong IELT and improve ejaculatory control and sexual satisfaction.

Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation （PE）, Our objective in this study was to characterize the efficacy of on-demand dapoxetine （30 and 60 mg） and daily paroxetine （20 mg） usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine （30 mg）, Group 2 with on-demand dapoxetine （60 mg） and Group 3 with daily paroxetine （20 rag）, Our outcome measurement was increased from baseline intravaginal ejaculatory latency time （IELT） after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group （P 〈 0,01）, 30 mg dapoxetine group （P 〈 0,01） and 60 mg dapoxetine group （P 〈 0.01）, respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups （P 〉 0,05）, while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine （P〈 0.05） and paroxetine （P〈 0.01） groups, Dapoxetine （60 mg） 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.

A new potential risk factor in patients with erectile dysfunction and premature ejaculation： folate deficiency

We investigated serum folic acid （FA） levels in patients with erectile dysfunction （ED） and/or premature ejaculation （PE）. Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time （IELT） was measured during a 4 weeks baseline period. Levels of sex hormones （follicle-stimulating hormone, luteinizing hormone, total testosterone）, homocysteine （Hcys）, and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation （CIPE）. The abridged Intemational Index of Erectile Function-5 （IIEF-5） questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED （7.61 ~ 3.97 ng ml-1）, PE （9.37 ＋ 3.40 ng ml-1）, and ED/PE （8.84 ＋ 4.28 ng m1-1） patients than in healthy men （12.23 ~ 5.76 ng ml-z, P〈 0.05）. No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls （P 〉 0.05）. There were positive correlations between serum FA concentrations and ClPE scores （r= 0.530, P〈 0.01）, IIEF-5 scores （r= 0.589, P〈 0.01）, and IELT （r= 0.445, P〈 0.01）; negative correlations with Hcys concentrations （r= -0.487, P〈 0.01） were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.

Prevalence of premature ejaculation in young and middle-aged men in Korea： a multicenter intemet-based survey from the Korean Andrological Society

In this study, we aimed to investigate the prevalence and perception of premature ejaculation （PE） in young and middle-aged Korean men. The study was conducted using an Internet-assisted questionnaire. A total of 2 037 Korean male adults, aged 20 years or older, were randomly sampled based on age and residency. The questionnaire developed by the PE Study Group of the Korean Andrological Society includes four categories （overall sexual function, symptoms, distress and treatment） with a total of 16 questions. For each question, symptoms were evaluated by a scale ranging from 0 to 10. Intravaginal ejaculation latency time was ‘5-10 min＇ in 38.6%, followed by ‘longer than 10 min＇ in 2919%, ‘2-5 min＇ in 23.6%, ‘1-2 min＇ in 5.4% and ‘shorter than 1 min＇ in 2.5%. In our series, 27.5% of respondents reported having PE. Control over ejaculation within a recent 3-month period was 6.2 points on average. Respondent complaints of PE-related stress averaged 7.1 points and stress-related complaints from sexual partners averaged 7.1 points. The effect of PE on sexual life was 6.8 points. Of the respondents determined as having PE, 42.6% responded that they were inclined to receive treatment. Results from this study suggest that the prevalence of PE diagnosed by the respondent on his own was approximately 27.5% in young and middle-aged men in Korea. PE-related stress had a significant effect on the stress, sexual activity and quality of life of the respondent and his sexual partner.

Current therapeutic strategies for premature ejaculation and future perspectives

Premature ejaculation （PE） is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ＇off-label＇, some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE.

A research on the relationship between ejaculation and serum testosterone level in men

The purpose of this study is to gain understanding of the relationshi p between ejaculation and serum testosterone level in men. The serum testosteron e concentrations of 28 volunteers were investigated daily during abstinence peri ods after ejaculation for two phases. The authors found that the fluctuations o f testosterone levels from the 2nd to 5th day of abstinence were minimal. On the 7th day of abstinence, however, a clear peak of serum testosterone appeared, re aching 145.7% of the baseline (P<0.01). No regular fluctuation was observed foll owing continuous abstinence after the peak. Ejaculation is the precondition and beginning of the special periodic serum testosterone level variations, which wou ld not occur without ejaculation. The results showed that ejaculation-caused va r iations were characterized by a peak on the 7th day of abstinence; and that the effective time of an ejaculation is 7 days minimum. These data are the first to document the phenomenon of the periodic change in serum testosterone level; the correlation between ejaculation and periodic change in the serum testosterone le vel, and the pattern and characteristics of the periodic change.

Frequency of Monthly Ejaculation at Sexual Intercourse, DNA Fragmentation Index and Fertilization Rate among Sperm Donors and Fertility-Challenged Men in Sub-Saharan Africa: Paper 1

Introduction: In humans, the ideal ejaculation frequency depends on age, exercise and sexual potential. Natural ejaculation frequency balances the testosterone levels in the body. Materials and Methods: Semi-structured questionnaire was used to collect information from subjects. Semen samples were collected from sperm donors and sub-fertile men who presented for infertility challenges. Processing and analysis of semen samples were done according to World Health Organization guidelines. Sperm DNA fragmentation was evaluated using the Halosperm&#174;?kit. Results: A total of 114 subjects, including 19 sperm donors and 95 sub-fertile males were studied. There was a significant difference (t =?&#8722;5.96, P-value = 0.00001) in the mean [±sd] age of sperm donors (30.8 [8.1]) and that of sub-fertile men (42.3 [76]). There was a significant difference (t=?&#8722;4.10, P-value = 0.0005) in the mean monthly ejaculation during sexual intercourse (MESI) among sperm donors with DNA fragmentation index &#8722;2.20, P-value = 0.02) in MESI among sub-fertile men aged ≥40 years (8.9 [4.6]) than among those aged &#8722;0.67, SE = 0.28, t = &#8722;2.40, P-value = 0.02, 95% CI: &#8722;1.24,?&#8722;0.10). Conclusion: In men < 40 years, fewer MESI did not worsen the DFI. A higher number of professionals such as doctors, lawyers and engineers, reported lower monthly frequency of sexual ejaculations compared to entrepreneurs. Entrepreneurs and non-smokers had the highest frequencies of MESI.

Prevalence of Premature Ejaculation among Patients with Type 2 Diabetes in a Tertiary Health Institution: A Cross-Sectional Study

Background: Premature ejaculation (PE) is one of the sexual dysfunctions commonly present among patients with diabetes mellitus (DM), but rarely reported and not commonly investigated compared to erectile dysfunction. In this study, we aimed to investigate the prevalence of PE in a group of patients with type 2 DM and explore possible determinants of its occurrence and its association with erectile dysfunction. Methods: This was a cross-sectional study of subjects recruited from the Diabetes clinic and whose sexual function was assessed using the premature ejaculation diagnostic tool (PEDT) and erection hardness score (EHS), who were in heterosexuals relationship and resides together with their wives and had no major organ failure or acute infection within the last 1 month. Other socio-demographic history and diabetes-related questions were assessed. Results: A total of 69 subjects were recruited. The prevalence of PE was 27.5% in the study. There was a significant inverse relationship between the prevalence of premature ejaculation and frequency of sexual intercourse. Almost half 14/30 (46.7%) of those with erectile dysfunction had premature ejaculation. Diabetic patients with erectile dysfunction (ED) showed a significantly higher incidence of PE with significantly lower values of EHS. Higher level of fasting blood glucose was associated with higher prevalence of erectile dysfunction. Conclusions: The prevalence of PE was relatively high at 19/69 (27.5%) among our type 2 diabetic patients. Hence, health care giver should always endeavour to ask about it even when patients do not volunteer the information.

Treatment of Functional Retrograde Ejaculation with Acupuncture and TCM Herbal Drugs

Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed effective for functional retrograde ejaculation in 25 cases. The total effective rate of 68.0% was significantly better than imipramine used in the control group (P<0.05).

Male masturbation device for the treatment of delayed ejaculation: A case report

Delayed ejaculation is a rare condition with different etiologies. Majority of cases of delayed ejaculation have a strong psychological/behavior component. A 48-year-old male with a diagnostic of delayed ejaculation acquired was encouraged to make an exercise protocol using a masturbation device for 8 wk, the percentage of intercourse successful a month after finish protocol exercise was 81%.

Evaluation of Sperm Parameters of Infertile Men with Retrograde Ejaculation

Objective To investigate sperm parameters of infertile men with retrograde ejaculation. Methods Twelve infertile men with retrograde ejaculation （group A） were enrolled into this study. Sperm samples were obtained from the postejaculation urine. After sperm recovery and washing procedure, sperm parameters were assessed. Twelve semen samples from normospermic donors were Used as the control （group B）. Results In all retrograde cases, motile sperm with forward movement were observed in the medium. Motility of group A was significantly lower than that of group B （P〈0.01）. In group A, sperm motility ranged from 11% to 56%, sperm with intact both head and tail membranes was 42.2 ±12.3%, sperm count ranged （13-85）×^ 106/ml, and the sperm survival time was highly shortened. Sperm with normal morphology and intact acrosome were observed in retrograde specimens. Conclusion Sperm parameters recovered from retrograde specimens were highly variable between subjects. The toxicity of urine caused deleterious to sperm functions. Motile sperm could be collected by sperm recovery procedure. Sperm parameters could meet the requirement for the use of assisted reproductive techniques for treating infertile men with retrograde ejaculation.

Frequency of Monthly Ejaculation at Sexual Intercourse, DNA Fragmentation Index and Fertilization Rate among Sperm Donors and Fertility-Challenged Men in Sub-Saharan Africa: Paper 2

Introduction: Heterogenous sexual intercourse often produces a powerful orgasm that stimulates the pituitary function. Studies have suggested ejaculation frequency based on age. Materials and Methods: Semi-structured questionnaires were used to collect information from subjects. Semen samples were collected from sperm donors and sub-fertile men who presented for infertility challenges. Processing and analysis of semen samples were done according to World Health Organization (WHO) guidelines. Sperm deoxyribonucleic acid (DNA) fragmentation was evaluated using the Halosperm kit. Results: Among sperm donors, those aged χ2 = 0.09, P-value = 0.81, OR = 3.2, 95% CI: 0.23, 45.19) while among sub-fertile men those aged ≥40 years were approximately 2.3 times more likely to have very low frequency of MESI compared to aged χ2 = 2.11, P-value = 0.51, OR = 2.27, 95% CI: 0.74, 9.92). The frequency of all categories of MESI was highest among sub-fertile men aged χ2 = 0.03, P-value = 0.57, OR = 2.42, 95% CI: 0.41, 14.46). Sub-fertile men aged ≥40 with diastolic hypertension (≥90 mmHg) were approximately 6 times more likely to have a low (6 - 10) frequency of MESI compared to those aged χ2 = 1.97, P-value = 0.16, OR = 6.22, 95% CI: 0.69, 55.77). Overall mean fertilization rate was significantly higher (t-test = 2.44, P-value = 0.01) among sub-fertile men aged Conclusion: Cigarette smoking, more than alcohol consumption, appears to be a major factor that significantly affects the frequency of MESI among sub-fertile men in all age groups. Frequency of MESI negatively but insignificantly correlated with systolic blood pressure.