Male factor has been considered a major contributory factor to infertility. Along with the conventional causes for male infertility such as varicocele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumors, a new, yet important cause has been identified: oxidative stress. Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body, which can lead to sperm damage, deformity and eventually male infertility. This involves peroxidative damage to sperm membrane and DNA fragmentation at both nuclear and mitochondrial levels. OS has been implicated as the major etiological factor leading to sperm DNA damage. OS-induced DNA damage can lead to abnormalities in the offspring including childhood cancer and achondroplasia. In this article, we discuss the need of ROS in normal sperm physiology, the mechanism of production of ROS and its pathophysiology in relation to male reproductive system. The benefits of incorporating antioxidants in clinical and experimental settings have been enumerated. We also highlight the emerging concept of utilizing OS as a method of contraception and the potential problems associated with it.

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Clinical relevance of oxidative stress in male factor infertility: an update.

Synopsis of Psychiatry

The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.

https://www.clevelandclinic.org/reproductiveresearchcenter/docs/agradoc343.pdf

Oxidative stress & male infertility

Current Concepts in the Etiology and Treatment of Behçet Disease

The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis.

https://www.fertstert.org/article/S0015-0282(08)03281-0/pdf

Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats.

Increased nitric oxide production in the spermatic vein of patients with varicocele

A placebo-controlled comparison of the efficiency of triple- and monotherapy in category III B chronic pelvic pain syndrome (CPPS).

The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB activity. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Body and testicular weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor.

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.108.006270

Chemoprotective Effect of a Nuclear Factor-κB Inhibitor, Pyrrolidine Dithiocarbamate, Against Cisplatin-Induced Testicular Damage in Rats

To evaluate the efficacy of oral sertralin in the treatment of premature ejaculation, out of 22 patients with premature ejaculation 16 received oral sertralin, 50 mg a day for at least 2 weeks. Four patients were lost to follow-up. Two patients interrupted treatment due to side effects of sertralin. Out of 16 patients who completed at least a two-week period of treatment 14 (87.5%) responded clinically. Clinical response was achieved in the first week of treatment in 11 of 16 responders (68.75%). We conclude that low dose oral sertralin may be useful with a reasonable side effect rate in the treatment of patients suffering from premature ejaculation.

Emin Özbek

Papers

Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats.

Increased nitric oxide production in the spermatic vein of patients with varicocele

A placebo-controlled comparison of the efficiency of triple- and monotherapy in category III B chronic pelvic pain syndrome (CPPS).

Chemoprotective Effect of a Nuclear Factor-κB Inhibitor, Pyrrolidine Dithiocarbamate, Against Cisplatin-Induced Testicular Damage in Rats

Treatment of premature ejaculation with sertralin.