Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy.
Linked to ROR, the Research Organization Registry
Abstract
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as urologic pain or discomfort in the pelvic region, associated with urinary symptoms and/or sexual dysfunction, lasting for at least 3 of the previous 6 months. The rate of symptoms related to prostatitis has a mean prevalence of 8-8.2%. CP/CPPS is most frequent in men younger than 50 years, among whom it is the most common urologic diagnosis. In the last decades, many studies have been published on CP/CPPS and its association with male infertility. The pathophysiologic relation between CP/CPPS and male infertility involves several aspects, which are not well studied yet. A reduction in semen parameters has been demonstrated in patients with CP/CPPS, and several mechanisms have been proposed to represent putative pathophysiological links between CP/CPPS and infertility, including male accessory gland inflammation, metabolic syndrome, inflammatory bowel disease, HPV co-infection and autoimmunity. In light of this evidence, a multidisciplinary approach is advocated for patients with known CP/CPPS, and particular attention is needed for male patients of infertile couples in order to evaluate male accessory glands correctly. In addition, it is advisable that future studies dealing with the treatment of CP/CPPS take into consideration all the different pathophysiological aspects implicated.
Grande G et al., 2026·The Journal of clinical endocrinology and metabolism·Free to read
Male factor infertility (MFI) is frequently labelled idiopathic when evaluation relies primarily on semen analysis, potentially overlooking endocrine and pathophysiological mechanisms relevant for targeted management.
To phenotypically define MFI and develop a pathophysiology-based classification aimed at reducing idiopathic infertility following comprehensive evaluation.
Prospective monocentric cohort study conducted at a tertiary referral academic centre.
Eight hundred male partners of infertile couples evaluated between October 2024 and January 2026 after exclusion of isolated female factor infertility.
Prevalence of MFI categories, hormonal patterns across phenotypes, and proportion of idiopathic infertility after comprehensive work-up.
All patients underwent standardized clinical evaluation, hormonal assessment (total testosterone, FSH, LH), testicular ultrasound, and complete semen analysis. Microbiological testing, transrectal ultrasound, and genetic analyses were performed according to guidelines.
Primary spermatogenic failure was the most prevalent category (56.0%), followed by infection/inflammation (22.4%) and hypogonadotropic hypogonadism (8.5%). Idiopathic infertility was identified in only 5.3% of cases. Distinct endocrine profiles were observed, with high-FSH spermatogenic failure representing the dominant phenotype.
Comprehensive phenotyping markedly reduces the proportion of patients classified as having idiopathic infertility and identifies clinically relevant subgroups. This prospective study provides validation of a pathophysiology-based classification and supports a shift toward endocrine-integrated diagnostic strategies in male infertility, with potential implications for targeted management.
Rocca MS et al., 2026·Journal of translational medicine·Free to read
Standard semen analysis has little prognostic value in distinguishing fertile from infertile men. Furthermore, in men with semen parameters within the reference ranges, it cannot distinguish fertile men from infertile men, i.e. partners of couples with idiopathic infertility. Oxidative stress, mitochondrial dysfunction, sperm telomere shortening, and DNA fragmentation have been proposed as contributors to impaired male fertility. However, these biomarkers have not been evaluated as a whole in subjects with normal semen parameters, partners of fertile and infertile couples.
To characterise a multidimensional panel of sperm biomarkers-including sperm telomere length (STL), mitochondrial DNA copy number (mtDNAcn), reactive oxygen species (ROS), lipid peroxidation (LP), sperm chromatin dispersion (SCD), and respiratory control ratio (RCR)-and to identify whether these parameters might discriminate, in men with normal semen parameters, infertile men from fertile controls.
A total of 150 men with semen parameters within the normal ranges were enrolled: 47 male partners of couples with idiopathic infertility and 103 fertile controls. STL and mtDNAcn were quantified by qPCR; ROS were assessed using OxiSperm®II with semiquantitative imaging; LP was measured spectrophotometrically in seminal plasma; SCD was used to determine DNA fragmentation; and mitochondrial function was evaluated by oxygen consumption and RCR. Correlations between biomarkers and semen parameters were analysed using Pearson or Spearman coefficients, and intergroup comparisons were adjusted for age.
Semen parameters did not differ significantly between male partners of fertile and infertile couples. compared to men of fertile couples, men of infertile couples exhibited significantly shorter STL (0.57 ± 0.59 vs 1.21 ± 1.13, p_adj = 0.001) and higher oxidative stress, with both ROS (8300.9 ± 4214.8 vs 6555.3 ± 3394.3, p_adj = 0.027) and LP (88.33 ± 55.50 vs 40.29 ± 46.98, p_adj < 0.001) markedly elevated. mtDNAcn, SCD, and RCR showed no difference between the groups. Across the entire cohort, STL correlated negatively with ROS and LP and positively with RCR. ROS correlated negatively with total sperm count, motility and RCR, and positively with LP. LP displayed the strongest pattern of associations, correlating negatively with concentration, total count, motility, STL and RCR, and positively with age and volume.
Among men with normal semen analysis, partners of couples with idiopathic infertility exhibit a distinct sperm molecular profile characterised by telomere shortening and oxidative imbalance. STL, ROS and LP emerged as age-independent biomarkers associated with infertility status and showed promising discriminatory ability in this cohort, supporting their integration as second-level tests to complement routine semen analysis in cases of normozoospermia.
Ponce MR et al., 2026·Andrology·Free full text on PubMed Central
Transgender individuals assigned male at birth (AMAB) may choose to preserve their fertility prior to starting gender-affirming hormone therapy (GAHT). However, limited data exist regarding the baseline reproductive and hormonal characteristics of this population before and after GAHT.
To characterize semen quality and hormonal profiles in transgender AMAB individuals prior to GAHT and compare findings with cisgender men and with transgender individuals who discontinued GAHT for at least 3 months.
This retrospective study included transgender AMAB individuals from two tertiary andrology centers who underwent sperm cryopreservation before GAHT initiation (treatment-naïve group). Clinical evaluation included anthropometric measures, testicular volume assessment, varicocele detection, and sex hormone measures. Semen parameters were analyzed according to WHO criteria and compared with those of cisgender men and previously treated transgender individuals.
Thirty-two treatment-naïve transgender AMAB individuals were included. Hormonal parameters were generally within reference ranges. Only 46.9% of treatment-naïve individuals met WHO criteria for normozoospermia, compared with 75.5% of cisgender controls. Compared with nine previously treated individuals, estradiol levels were higher and seminal volume lower. A higher frequency of seminal abnormalities was observed, although not statistically significant.
A substantial proportion of treatment-naïve transgender AMAB individuals exhibited impaired semen parameters prior to GAHT initiation. Prior GAHT exposure showed a trend toward poorer semen quality. These findings support early fertility counseling and preservation in transgender individuals prior to GAHT initiation.
Delbarba A et al., 2026·Reviews in endocrine & metabolic disorders·Free full text on PubMed Central
Male hypogonadism is associated with significant alterations in body composition, including reduced lean body mass (LBM), increased fat body mass (FBM), particularly visceral adiposity, and impaired muscle function, contributing to frailty and cardiometabolic risk. These changes reflect the disruption of a complex endocrine crosstalk among bone, muscle, and adipose tissue, mediated by cytokines such as osteokines, myokines, and adipokines. This dysregulation promotes the development of osteosarcopenic obesity, a condition characterized by the coexistence of low bone mass, sarcopenia, and excess adiposity. Testosterone (T) plays a central role in maintaining body composition by stimulating muscle protein synthesis, inhibiting adipogenesis, and preserving bone health. Its deficiency, irrespective of etiology, leads to rapid impairment of anabolic pathways, resulting in decreased lean mass and increased fat accumulation. Evidence from clinical and experimental models demonstrates that these alterations are partially reversible with T replacement therapy (TRT), although variability exists depending on the underlying cause of hypogonadism. Dual-energy X-ray absorptiometry (DXA) represents the gold standard for assessing bone mineral density (BMD) and a key tool for evaluating body composition through a three-compartment model. It allows precise quantification of fat and lean mass, as well as their regional distribution, with minimal radiation exposure. In this review, we provide a comprehensive and clinically oriented overview of body composition alterations in male hypogonadism, focusing on underlying pathophysiological mechanisms and the practical application of DXA across different clinical scenarios. We discuss evidence from conditions such as Klinefelter syndrome, Kallmann syndrome, androgen deprivation therapy, HIV infection, and transgender care, aiming to offer a pragmatic framework for integrating body composition assessment into routine practice and improving patient management.
Kulishova TV et al., 2018·Urologiia (Moscow, Russia : 1999)
The aim of the study was to increase the efficiency of complex treatment of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with the combined effect of magnetolaser therapy (MLT) and red light. We examined and included in the study 120 men with a verified diagnosis of CP/CPPS (III B), at the stage of exacerbation. By envelope method, patients were divided into two randomized groups. The main group consisted of 60 patients who received a basic treatment complex, including medicamentous therapy, prostate massage, diet therapy, a complex of therapeutic gymnastics, and the combined effect of MLT and red light of 10 procedures per course. The comparison group consisted of 60 patients who received only a basic therapeutic complex. Evaluation of the effectiveness of treatment was carried out in dynamics before complex treatment, immediately after the course of treatment and 6 months later for analysis of long-term results using the questionnaire "System of summary evaluation of chronic prostatitis symptoms", dopplerography of urethral arteries of the prostate, laser Doppler flowmetry in the prostate. In the main group of patients with CP/CPPS immediately after complex treatment and after 6 months, a positive therapeutic effect was noted in the form of relief of pain syndrome, dysuria, improving the quality of life, improvement of blood circulation in the urethral arteries of the prostate and microcirculation. In the comparison group, the positive effects from the complex baseline treatment were less pronounced. Comparative analysis of the results of the study between the main group of patients with CP/CPPS and comparison group showed the presence of statistically significant differences in all indicators of clinical symptoms of the disease, dopplerography in the urethral arteries of the prostate and microcirculation in the prostate, both immediately after treatment and after 6 months of follow-up. The method of complex treatment of patients with CP/CPPS with the combined effect of MLT and red light has greater immediate and remote efficacy in comparison with baseline treatment.
Published studies relating to the usefulness of diagnostic and operative laparoscopy in women with chronic pelvic pain (CPP) were reviewed. This revealed that approximately 40 per cent of all laparoscopies were done for CPP. However, the definition of CPP was found to be nebulous and inconsistent, and that muddled definitive conclusions about patient diagnoses and treatments. The following definition of CPP was proposed: nonmenstrual pain of 3 or more months duration that localizes to the anatomic pelvis and is severe enough to cause functional disability and require medical or surgical treatment. A survey of published reports showed laparoscopically diagnosable abnormalities in 61 per cent of patients, compared with abnormalities in 28 per cent of women without CPP. Studies in adolescents were also reviewed and showed that adolescents with CPP also had significant laparoscopically diagnosed abnormalities, with 78 per cent showing some pathology, especially endometriosis (40 per cent). Endometriosis, pelvic adhesions, chronic pelvic inflammatory disease, and ovarian cysts were the diagnoses most commonly made via laparoscopy in CPP patients. The potential roles of each of these abnormalities in CPP were discussed, as well as the results of laparoscopic treatment of each disease. Laparoscopy was also found to have a limited role in women with CPP after hysterectomy or bilateral salpingo-oophorectomy, with usefulness in diagnosing and treating adhesions and residual ovary syndrome, although its role in ovarian remnant syndrome was uncertain. Overall, the data showed that less than 50 per cent of women with CPP were helped by diagnostic and operative laparoscopy, stressing the need for both physicians and patients to recognize that laparoscopy is neither the ultimate evaluation nor the panacea for CPP.
Nowosielski K et al., 2015·International Journal of Gynecology & Clinical Practices·Free to read
The presences of sexual dysfunctions in women were not a subject of scientific debate until the 21st century. At the beginning of the new millennium interdisciplinary groups of scientists agreed that female sexuality and sexual dysfunctions have to be taken seriously and analyzed independently of male sexuality. Finally, Rosemary Basson's description of the cyclic model of sexual response resulted in abandon of the linear model, which was characteristic for male sexual response, and creating circular models of female sexual response. The researchers are still studying the nature of sexual pain in women. The aim of this article is to interest physicians, especially gynaecologists, in aetiology and treatment options for chronic pelvic pain syndrome (CPPS). The causes of CPPS may lie in sexual disorders which were until recently classified by the American Psychiatric Association in DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) as dyspareunia and vaginismus and changed in DSM-5 to Genito-Pelvic Pain/Penetration Disorder (GPPD). The DSM-5 classification emphasizes treatment focusing on elimination fear and anxiety more than on relaxation of vaginal muscles. Therapeutic experience confirms that such an approach is well-grounded; a therapy focusing on non-organic factors gives excellent and promising results. If we point to the necessity of introducing changes in the approach to treatment of GPPD, then we also have to allow for the role of fear and anxiety in the aetiology of these disorders. The Fear-Avoidance Model - FAM – presented in this article gives a scientific bases for psychological treatment of CPPS.
Thomson JC et al., 2005·The Journal of reproductive medicine
To determine the prevalence of chronic inflammation of the pelvic peritoneum, systemic inflammation and autoimmunity in chronic pelvic pain and to explore the significance of these findings and assess the response to treatment with immune modification. Prospective, observational clinical studies from 2 centers were performed on 3,238 women presenting with pelvic pain to determine the prevalence of chronic inflammation by biopsy when endometriosis was absent. A second study included 40 women with chronic pelvic pain not resulting from endometriosis; immunologic investigations were carried out and therapy instituted. Chronic inflammation of the peritoneum, while not evident in the absence of pelvic pain, was present in 15.7% of women with chronic pelvic pain. In the second group, 10% had histologic evidence of chronic inflammation, 55% demonstrated evidence of systemic inflammation, and 37.5% were found to have autoimmune disorders. Chronic inflammation of the vagina was found in 42.5% and polycystic ovary syndrome in 22% of those with systemic inflammation. Twelve of the 40 were subsequently treated, with considerable success, with immune-modifying drugs, hydroxychloroquine and methotrexate. Chronic pelvic pain is frequently associated with systemic inflammation, including autoimmune diseases. Peritoneal chronic inflammation is sometimes also associated. It is often successfully treated with immune-modifying drugs.
Male Fertility › Male Factor Causes › Lifestyle and Environment
Giordana Ferraioli, Elena Colonnello, Fabrizio Dal Moro
G Ferraioli, E Colonnello, F Moro
PMID 37629557 37629557 DOI 10.3390/life13081700 10.3390/life13081700 Graziani et al. 2023, Graziani 2023
00240q980