Background: The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM).Objectives: The aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects.Materials and Methods: We have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks.Results: TRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non‐randomized clinical studies and observational studies. This is the case for the safety of a long‐term TRT in late‐onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure.Conclusion: Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.

Bisphenol A (BPA) represents the main chemical monomer of epoxy resins and polycarbonate plastics. The environmental presence of BPA is widespread, and it can easily be absorbed by the human body through dietary and transdermal routes, so that more than 90% of the population in western countries display detectable BPA levels in the urine. As BPA is qualified as an endocrine disruptor, growing concern is rising for possible harmful effects on human health. This review critically discusses the available literature dealing with the possible impact of BPA on male fertility. In rodent models, the in vivo exposure to BPA negatively interfered with the regulation of spermatogenesis throughout the hypothalamic–pituitary–gonadal axis. Furthermore, in in vitro studies, BPA promoted mitochondrial dysfunction and oxidative/apoptotic damages in spermatozoa from different species, including humans. To date, the claimed clinical adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA concentration and conventional semen parameters. These studies, however, produced controversial evidence due to heterogeneity in the extent of BPA exposure, type of population, and enrollment setting. Moreover, the cause–effect relationship cannot be established due to the cross-sectional design of the studies as well as the large spontaneous between- and within-subject variability of semen parameters. The best evidence of an adverse effect of BPA on male fertility would be provided by prospective studies on clinically relevant endpoints, including natural or medically assisted pregnancies among men either with different exposure degrees (occupational/environmental) or with different clinical conditions (fertile/subfertile).

The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between the mitochondrial membrane potential (ΔΨm) and motility of ejaculated spermatozoa cannot be explained convincingly by an impaired mitochondrial ATP generation only. Evidence has been produced suggesting that, in human sperm, dysfunctional mitochondria represent the main site of generation of reactive oxygen species (ROS). Furthermore, in these organelles, a complex bidirectional relationship could exist between ROS generation and apoptosis-like events that synergize with oxidative stress in impairing sperm biological integrity and functions. Despite the activity of enzymatic and non-enzymatic antioxidant factors, human spermatozoa are particularly vulnerable to oxidative stress, which plays a major role in male factor infertility. The purpose of this article is to provide an overview of metabolic, oxidative and apoptosis-like inter-linkages of mitochondrial dysfunction and their reflections on human sperm biology.

Background: An association between testicular microlithiasis (TM) and both carcinoma in situ (CIS) of the testis and testicular germ cell tumors (TGCTs) has been reported. Furthermore, TM seems to be significantly more prevalent in men with male-factor infertility, representing itself a risk factor for TGCT. Nevertheless, the evidence of the association of TM with a higher prevalence of testicular cancer in infertile men remains inconclusive. The aim of this study was to systematically evaluate whether, and to what extent, TM is associated to a significantly higher prevalence of testicular cancer in infertile males. Methods: A thorough search of MEDLINE, SCOPUS, CINAHL, WEB OF SCIENCE, and Cochrane Library databases was carried out to identify case-control studies comparing the prevalence of testicular cancer in infertile men with and without TM. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. In the absence of heterogeneity, odds ratios (ORs) with 95% confidence intervals (CIs) for testicular cancer were combined using a fixed effect model. Funnel plots and trim-and-fill analysis were used to assess publication bias. Results: Eight studies met the inclusion criteria and provided information on 180 infertile men with TM and 5,088 infertile men without TM. The pooled OR indicated that the presence of TM is associated with a ~18-fold higher odd for testicular cancer (pooled OR:18.11, 95%CI: 8.09, 40.55; P < 0.0001). No heterogeneity among the studies was observed (P_{for heterogeneity} = 0.99, I² = 0%). At the sensitivity analysis, similar pooled ORs and 95%CIs were generated with the exclusion of each study, indicating the high degree of stability of the results. The funnel plot revealed a possible publication bias and the trim-and-fill test detected two putative missing studies. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a still significantly higher odd for testicular cancer in the TM group (adjusted pooled OR: 16.42, 95%CI: 7.62, 35.37; P < 0.0001). Conclusions: In infertile men the presence of TM is associated to an ~18-fold higher prevalence of testicular cancer. Longitudinal studies are warranted to elucidate whether this cross-sectional association actually reflects a higher susceptibility of infertile men with TM to develop testicular cancer over time.

Introduction: Comparative studies on differences in sexual function outcomes between homosexual and heterosexual men are sparse and inconclusive. Aim: To systematically evaluate whether, and to what extent, a statistically significant difference exists in the odds of erectile dysfunction (ED) and premature ejaculation (PE) between homosexual and heterosexual men. Methods: A thorough search of Medline, SCOPUS, CINAHL, and Web of Science databases was carried out to identify case-control studies comparing the prevalence of ED and PE in homosexual and heterosexual men. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Odds ratios (ORs) of reporting ED and PE were combined using random effect models. The Cochrane Q and I2 tests were carried out to analyze the between-studies heterogeneity. Funnel plots and trim-and-fill analysis were used to assess publication bias. Main Outcome Measures: The relationship between sexual orientation and odds of ED and PE was assessed by calculating pooled ORs with a 95% CI. Results: 4 studies included in the quantitative analysis collectively provided information on 1,807 homosexual and 4,055 heterosexual men. The pooled ORs indicated that homosexual orientation was associated with 1.5-fold higher odds of reporting ED (OR = 1.49, 95% CI = 1.03–2.16; P = .04) and 28.0% lower odds of reporting PE in comparison to the heterosexual orientation (OR = 0.72, 95% CI = 0.52–1.00; P = .05). However, a significant heterogeneity among the studies was observed. Funnel plots revealed a possible publication bias only for the ED analysis, where the trim-and-fill test detected a putative missing study. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a significantly higher risk of ED in the homosexual group (adjusted OR = 1.60, 95% CI = 1.10–2.30; P = .01). Clinical Implications: These findings can drive future studies on sexual needs and concerns of homosexual men, which might not exactly match those of heterosexual individuals. Strength & Limitations: This is the first meta-analysis exploring the differences in the prevalence of ED and PE between homosexual and heterosexual men. However, the results should be interpreted with caution, because their generalization could be hindered by the non-probabilistic nature of the samples, and a measurement bias could result from the use of different non-standardized indicators of sexual dysfunctions. Conclusion: Homosexual orientation is associated with higher odds of ED and lower odds of PE compared with heterosexual orientation. Further studies are warranted to elucidate the clinical significance of these findings and whether they reflect differences in patterns of sexual lifestyle.