World Journal of Mens Health最新文献

There is a natural balance between the major sex steroids, testosterone and estradiol, controlled by gonadal secretion and peripheral conversion by aromatase. This balance is impacted by a variety of inborn and acquired conditions, and, more recently, by a growing use of exogenous testosterone therapy and off-label aromatase use under the guise of "men's health." We summarize reported testosterone:estradiol ratios, both naturally occurring and with pharmacologic manipulation and consider the ramifications of significant changes in these ratios. However, significant limitations exist in terms of steroid separation and measurement techniques, timing of samples, and lack of consistency from one assay to another, as well as definition of normative data. Limited data on the testosterone:estradiol ratio in men exists, particularly due to the scan data on concurrent estradiol values in men receiving testosterone therapy or aromatase inhibitors. Nonetheless, there seems to be a range of apparently beneficial values of the testosterone: estradiol radio at between 10 and 30, calculated as: testosterone in ng/dL/estradiol in pg/mL. Higher values appear to be associated with improved spermatogenesis and reduced bone density while lower values are associated with thyroid dysfunction. While there is growing awareness of the significance of the testosterone:estradiol ratio, and a sense of a desired range, the optimal value has not yet been determined. Further work is needed to clarify the measurement strategies and clearly-defined outcome measures related to the testosterone:estradiol ratio.

Purpose: To investigate the dietary factors affecting male lower urinary tract symptoms (LUTS).

Materials and methods: This retrospective study analyzed men who underwent health check-ups. The men who completed the International Prostate Symptom Score (IPSS) and a dietary questionnaire with 19 items were included in the study. Men with a history of medication for LUTS were excluded from the study. The influences of each dietary habit on total IPSS, voiding symptoms, storage symptoms and quality of life were evaluated separately. Dietary risk group was defined by the number of significant dietary risk factors.

Results: The mean age of 28,463 men was 52.2±8.7 years. After adjusting for age and other conditions, 13 dietary habits (for examples; overeating, preference for salty food, frequently eating sweets, and infrequently eating vegetables, etc.) were the significant risk factors related to worse total IPSS scores. For voiding symptoms, storage symptoms, and quality of life scores, 14, 12, and 12 dietary habits were identified as independent risk factors, respectively. Drinking four or more cups of water per day was related to worse storage symptoms (odds ratio [OR]=1.12, 95% confidence interval [95% CI]=1.09-1.22), but better voiding symptoms (OR=0.90, 95% CI=0.86-0.95). The newly developed dietary risk group showed that total and subtotal IPSS scores increased by the number of bad dietary habits in all age groups, respectively.

Conclusions: This study showed that dietary habits had a significant impact on LUTS. The amount of water consumed had a differential influence on each subdomain symptom.

The Korean Society of Men's Health and Aging (KSMHA) acknowledges the necessity for an updated statement on testosterone therapy driven by evolving clinical practices and new research findings. The primary purpose of this position statement is to provide a tailored, evidence-based framework that aligns with international best practices while addressing the unique needs of the Korean population. Additionally, this statement addresses the growing recognition of both organic and functional hypogonadism, particularly given the rising rates of obesity and metabolic syndrome, which affect testosterone levels and overall health. The position statement addresses key areas, including the clinical and laboratory diagnosis of male hypogonadism, with a focus on appropriate cut-off values for testosterone levels in Korean men, and provides guidance on assessing treatment outcomes. In this statement, we present an objective position on testosterone therapy based on recent studies that have carefully evaluated its effectiveness and safety. By providing a tailored framework for the management of male hypogonadism, KSMHA aims to enhance patient care and align Korean practices with global standards.

Purpose: To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus-induced erectile dysfunction (DMED).

Materials and methods: DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose (HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins.

Results: Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and that the TGF-β pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-β signaling, as well as the overexpression of collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs.

Conclusions: TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile dysfunction by inhibiting the TGF-β/SMAD pathway.

Purpose: Evidence of an association between leukocyte telomere length (LTL) and prostate cancer (PCa) is accumulating; however, their shared genetic basis remains unclear.

Materials and methods: Using summary statistics obtained from the genome-wide association study (GWAS), we quantified the global and local genetic correlations between two traits. Subsequently, we identified potential pleiotropic loci, common tissue-enriched regions, and risk gene loci while inferring assumed causal relationships.

Results: Our study demonstrated a global genetic correlation between LTL and PCa (genetic correlation=0.066, p=0.017), which was further confirmed in local genomic regions. Cross-trait GWAS meta-analysis revealed 44 shared loci, including 10 novel pleiotropic single nucleotide polymorphisms appearing concurrently in significant local genetic correlation regions. Notably, two new loci (rs9419958; rs3730668) were additionally validated to co-localize. For the first time, we identified a significant shared genetic enrichment of both traits in the small intestine tissue at the terminal ileum, with functional genes in this region affecting both LTL and PCa. Concurrently, Mendelian randomization analysis indicated a positive causal relationship between LTL and PCa.

Conclusions: In conclusion, our study makes a significant contribution to the ongoing debate concerning the potential association between longer LTL and a higher risk of PCa. Additionally, we provide new evidence for the development of therapeutic targets for PCa and propose new directions for future risk prediction in this regard.

Purpose: Ferroptosis is a type of iron-dependent regulated cell death characterized by increased bioavailability of redox-active iron, loss of GPX4 antioxidant capacity, and oxidation of polyunsaturated fatty acid-containing phospholipids mediated by reactive oxygen species (ROS). The aim of this study was to evaluate the effect of oxidative stress induced by arachidonic acid (AA) on ferroptotic cell death in human spermatozoa.

Materials and methods: Spermatozoa from normozoospermic donors were exposed to AA (5, 25, and 50 µM) for 1 hour at 37 ℃, including an untreated control. Oxidative stress was confirmed by evaluation of cytosolic and mitochondrial ROS production, viability, mitochondrial membrane potential (ΔΨm) and motility. Subsequently, molecular markers of ferroptosis including iron content, levels of GPX4, SLC7A11, ACSL4, IREB2 and lipid peroxidation were evaluated. The analyses were carried out using either flow cytometry, a microplate reader or confocal laser microscopy.

Results: AA-induced oxidative stress showed increased cytosolic and mitochondrial ROS production accompanied by impaired ΔΨm, viability and motility in human spermatozoa. These results were associated with biochemical and molecular markers related to ferroptotic cell death including an increase in iron content in the form of ferrous (Fe²⁺) ions, SLC7A11, ACSL4, IREB2, a decrease in the level of GPX4, and an increase in the level of lipid peroxidation compared to the untreated control.

Conclusions: This study revealed that AA-induced oxidative stress induces cell death with biochemical characteristics of ferroptosis in human spermatozoa, demonstrating another mechanism of alteration of sperm function induced by oxidative stress and could establish new therapeutic objectives to prevent the decrease in sperm quality mediated by oxidative stress.

Purpose: To assess the effects of testosterone replacement therapy (TRT) compared to placebo or other medical treatments in men with sexual dysfunction.

Materials and methods: We performed a comprehensive search with no restrictions on publication language or status up to 29 August 2023. We only included randomized controlled trials (RCTs).

Results: We identified 43 studies with 11,419 randomized participants. We found that TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference [MD]: 2.37, 95% confidence interval [CI]: 1.67 to 3.08; I²=0%; 6 RCTs, 2016 participants; moderate-certainty evidence) compared to placebo. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD: -2.31, 95% CI: -3.63 to -1.00; I²=0%; 5 RCTs, 1,030 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio: 0.83, 95% CI: 0.21 to 3.26; I²=0%; 10 RCTs, 3,525 participants; moderate-certainty evidence) compared to placebo. TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or lower urinary tract symptoms.

Conclusions: TRT for men with sexual dysfunction showed no difference in erectile function, sexual quality of life, or cardiovascular mortality compared to placebo. Furthermore, it also appears to no difference in treatment withdrawals due to adverse events, prostate-related events, or lower urinary tract symptoms.

Environmental endocrine disruptors, as exogenous chemicals that interfere with hormonal behavior, are known to cause testicular Leydig cell death and senescence. The incidence of diseases of the male reproductive system has been increasing over the past half-century. Genetic defects alone cannot explain the rapid increase in incidence, and there is growing evidence that environmental factors or lifestyle changes are responsible for the high incidence in recent years. Testicular Leydig cells occupy an important role in the male reproductive system. In this study, we review the mechanisms by which environmental endocrine disruptors promote both death and senescence of testicular Leydig cells, refine the former into two programmed death modes, apoptosis, and autophagy, and further explore the interactions among them, thus summarizing the advances of the toxic effects of environmental endocrine disruptors on testicular Leydig cells, and expecting to provide a new therapeutic idea.

To provide an evidence based consensus on the diagnosis and management of premature ejaculation (PE). The British Society for Sexual Medicine (BSSM) takes issue with the advice to use off label treatments, such as daily selective serotonin reuptake inhibitors treatment, favoring on-demand dapoxetine. There is increasing evidence for the use of PDE5 inhibitors which are superior to a placebo for the treatment of PE. A recent meta-analysis of international PE guidelines supports the need for research to investigate the association of PE with erectile dysfunction (ED), prostatitis and thyroid disease, and supports the early use of PDE5 inhibitors either alone or in combination with dapoxetine or psychosexual interventions. Topical agents and non-pharmacological treatments also have a place, with new agents in the pipeline. The United Kingdom (UK) lacks formal guidance from the National Institute of Clinical Excellence (NICE) on any of the common male sexual dysfunctions, namely ED, PE, ejaculatory disorders, and male hypogonadism. As a result, general practitioners in the UK have relied on local guidance, and international guidelines which are heterogeneous, indicating diagnostic and therapeutic approaches that are often inconsistent. The aim of this position statement is to improve the management of PE in the UK.

Leukocytospermia, defined as a leukocyte concentration in semen exceeding 1×10⁶ leukocytes/mL, significantly impacts male reproductive health by affecting sperm functionality and fertility outcomes. This condition arises from various etiological factors, including infections, autoimmune responses, lifestyle factors, and other physiological conditions. Adverse effects on sperm associated with leukocytospermia include acrosome damage and abnormalities in the sperm midpiece and tail. The review explores the complex interplay between leukocytospermia and oxidative stress, emphasizing the harmful effects on sperm DNA integrity and overall sperm quality. Due to the multifactorial nature of leukocytospermia, diagnosing this condition presents several challenges. Effective management strategies discussed include the use of antibiotics, anti-inflammatory agents, and assisted reproductive technologies. Diagnostic methods range from traditional peroxidase staining to more advanced techniques such as immunocytochemistry and flow cytometry, which offer higher sensitivity and specificity. Infections of the male genital tract, particularly male accessory gland infection and male genital tract infection, play a significant role in the etiology of leukocytospermia. These infections lead to an inflammatory response, resulting in leukocyte infiltration into the semen. Systemic conditions like diabetes mellitus and autoimmune disorders also contribute to leukocytospermia by provoking inflammatory responses that facilitate leukocyte presence in semen. This review underscores the importance of a comprehensive diagnostic approach that includes patient history, physical examination, and advanced laboratory tests. Treatment is tailored to the identified underlying cause, whether infectious or non-infectious. Lifestyle modifications, such as reducing stress, improving diet, and avoiding environmental toxins, are also recommended to enhance semen quality. For clinicians, this review provides a concise yet thorough overview of leukocytospermia, integrating the latest research findings and clinical insights to aid in the effective management of this condition, ultimately aiming to improve patient care in male reproductive health.