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Immune checkpoint inhibitor drugs can trigger autoimmune endocrine reactions as a known side effect. Several cases of immunotherapy-induced autoimmune endocrinopathies have been described, but multiple sequential endocrine toxicities are a rare occurrence. A 39-year-old patient with metastatic melanoma started adjuvant therapy with pembrolizumab. One month later he presented with asymptomatic thyrotoxicosis and, within several weeks, overt hypothyroidism, for which he started levothyroxine therapy. Subsequently the patient developed central adrenal insufficiency due to probable hypophysitis, and steroid replacement therapy was started. Pembrolizumab therapy was then discontinued. After a few months, a full recovery of pituitary function was observed, but primary adrenal insufficiency occurred, requiring additional fludrocortisone therapy. The described clinical case is a very uncommon case of triple endocrinological toxicity from immunotherapy. The clinical and biochemical manifestations of immunotherapy-induced endocrinopathies can be variable and atypical; therefore, it is necessary to pay special attention to any clue of hormonal dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex ® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex ® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex ® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex ® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology.

Polyphenols are natural bioactives occurring in medicinal and aromatic plants and food and beverages of plant origin. Compared with conventional therapies, plant-derived phytochemicals are more affordable and accessible and have no toxic side effects. Thus, pharmaceutical research is increasingly inclined to discover and study new and innovative natural molecules for the treatment of several chronic human diseases, like type 2 diabetes mellitus (T2DM) and osteoporosis. These pathological conditions are characterized by a chronic inflammatory state and persistent oxidative stress, which are interconnected and lead to the development and worsening of these two health disorders. Oral nano delivery strategies have been used to improve the bioavailability of polyphenols and to allow these natural molecules to exert their antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic biological activities in in vivo experimental models and in patients. Polyphenols are commonly used in the formulations of nutraceuticals, which can counteract the detrimental effects of T2DM and osteoporosis pathologies. This review describes the polyphenols that can exert protective effects against T2DM and osteoporosis through the modulation of specific molecular markers and pathways. These bioactives could be used as adjuvants, in combination with synthetic drugs, in the future to develop innovative therapeutic strategies for the treatment of T2DM and osteoporosis.

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Introduction: This study aimed to investigate profiles of personality evaluated by temperament and character dimensions (TCI) in 638 adult and older adult patients (CP) who had recently been diagnosed with breast, colon, lung, and other kinds of cancer (female and male subjects were assessed). Tests: Temperament and Character Inventory (TCI). Statistical analysis: cluster K-means analysis for personality traits., Results: Two different personality profiles emerged: "Low self-determination and pessimism" (Profile 1) and "Self-determination and self-caring (medium)" (Profile 2). The following significant differences were observed in the TCI dimensions between the two profiles: Temperament-Novelty-Seeking (NS) ( p < 0.001); Harm-Avoidance (HA) ( p < 0.001); Reward-Dependence (RD) ( p < 0.001); Persistence (PS) ( p < 0.001); Character-Self-Directness (SD) ( p < 0.001); Cooperativeness (C) ( p > 0.001); Self-Transcendence (ST) ( p < 0.001). No differences in the two profiles were found between adult and elderly patients. Profile 1 - "Low self-determination and pessimism": Patients with this profile present low resistance to frustration, poor search for novelty and solutions (NS), anxiety and pessimism (medium HA), high social attachment and dependence on the approval of others (medium-high RD), and low self-determination (PS) as temperament dimensions; and medium-low self-direction, low autonomy and ability to adapt (SD-medium-low), medium cooperativeness (C), and low self-transcendence (ST) as character dimensions. Profile 2 - "Self-determination and self-caring (medium)": Patients with this profile have resistance to frustration, ability to search for novelty and solutions (medium-NS), low anxiety and pessimism (HA), low social attachment and dependence on approval (medium-low-RD), and determination (medium-high PS) as dimensions of temperament; and autonomy and capacity for adaptation and self-direction (SD), capacity for cooperation (high-CO), and self-transcendence (medium-high-ST) as character dimensions., Conclusion: Personality screening allows a better understanding of the difficulties of the individual patient and the planning of targeted psychotherapeutic interventions that promote quality of life and good adaptation to the disease course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Vespa, Giulietti, Fabbietti, Di Rosa, Gattafoni, Berardi, Arnaldi, Balercia and Spatuzzi.)

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice., Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured., Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%)., Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3-36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [-0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], p = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition., Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method., Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated., Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Night shift work is related to sleep disorders, disruption of circadian rhythm and low serum levels of vitamin D. It is known that all these conditions can adversely affect bone mass. The rate of bone turnover can be assessed through the measurement of molecules called bone turnover markers, including C-terminal telopeptide fragment of type I collagen (CTX) and procollagen type I N-terminal propeptide (P1NP). In this study, we evaluated the serum levels of CTX, P1NP and 25-Hydroxy Vitamin D in 82 male subjects (42 daytime workers and 40 night shift workers) to assess the possible risk of osteoporosis in male shift workers. Serum levels of CTX and P1NP were found to be higher in night shift workers than in daytime workers. No significant difference was found in vitamin D levels between night shift and daytime workers. The increased CTX and P1NP levels reveal a higher rate of bone turnover in night shift workers and thus a possible increased risk of osteoporosis in this category of workers compared with daytime workers. In view of this, our results highlight the importance of further studies investigating the bone health in male night shift workers.

Purpose: Thyroid dysfunction in patients with Klinefelter syndrome (KS) remains an unresolved issue. Although low free thyroxine (FT4) levels within the normal range and normal thyroid stimulating hormone (TSH) levels have been reported, there is currently no data on nodular thyroid disease in this population. This study aims to evaluate the results of thyroid ultrasound (US) examinations in KS patients compared with healthy controls., Methods: A cohort of 122 KS and 85 age-matched healthy male controls underwent thyroid US screening and thyroid hormone analysis. According to US risk-stratification systems, nodules ≥1 cm were examined by fine needle aspiration (FNA)., Results: Thyroid US detected nodular thyroid disease in 31% of KS compared to 13% of controls. No statistical differences in the maximum diameter of the largest nodules and in moderate and highly suspicious nodules were found between patients and the control group. Six KS patients and two controls with nodules underwent FNA and were confirmed as cytologically benign. In line with published data, FT4 levels were found significantly near the lower limit of the normal range compared to controls, with no differences in TSH values between the two groups. Hashimoto's thyroiditis was diagnosed in 9% of patients with KS., Conclusions: We observed a significantly higher prevalence of nodular thyroid disease in KS compared to the control group. The increase in nodular thyroid disease is likely linked to low levels of FT4, inappropriate TSH secretion, and/or genetic instability., (© 2023. The Author(s).)

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations., Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus., Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing., Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Exposure to extremely low frequency magnetic fields (ELF-MF) may have different effects on spermatozoa depending on the waveform, magnetic flux density, frequency of ELF-MF, and duration of exposure. In this study, we investigated the possible role of ELF-MF (50 Hz; 1 mT) exposure in altering sperm parameters. In this study we found that exposure to ELF-MF at the frequency of 50 Hz (1 mT) for two hours induces statistically significant alterations in progressive motility, morphology and reactive oxygen species (ROS) production of human spermatozoa, suggesting a role of ELF-MF in altering reproductive function of spermatozoa. Our results represent an important discovery in the field since occupational exposure to the sine waveform 1 mT 50 Hz ELF-MF used in our study is possible in workplace. Moreover, these electromagnetic fields are product by many electronic devices and household appliances. Thus, alterations of progressive motility and morphology of spermatozoa would be important consequences of human exposures to ELF-MF., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen ® , Mivell, Italy) synergistically decreases expression levels of the pro-inflammatory gene SEMA3E in insulin-resistant HepG2 cells and synergistically decreases DPPIV activity in insulin-resistant Hep3B cells, indicating that the combination of these five phytochemicals is able to inhibit pro-inflammatory and insulin resistance molecular mechanisms and could represent an effective innovative complementary approach to T2DM pharmacological treatment.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility., Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field., Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available., Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Background: The environment plays a key role in male infertility, changing the incidence in various populations, and pesticides are one of the most studied hazards. The use of the latter has never decreased, jeopardizing the safety of workers and the general population., Objective: Our purpose was to summarize the results of studies discussing the association between pesticides and male fertility., Methods: A comprehensive literature search was performed through MEDLINE via PubMed, Scopus, and Web of Science. Only human studies were considered. Semen parameters and DNA integrity were considered to evaluate the effect of pesticides on men., Results: A total of 64 studies that investigated their impact in terms of semen parameters (51 studies) and chromatin and DNA integrity (25 studies) were included. The most frequently affected parameters were total sperm count, sperm motility, and sperm morphology, although a reduction in ejaculate volume and concentration occur in several cases. A tangible worsening of semen quality was associated with organochlorines and organophosphates. Furthermore, pesticide exposure, especially pyrethroids, was related to a higher DNA fragmentation index and chromosome aneuploidy in most articles., Conclusion: The epidemiological evidence supports the association between pesticides and male fertility for workers and the exposed population in terms of semen quality, DNA fragmentation, and chromosome aneuploidy., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: So far, male genital tract color-Doppler ultrasound (MGT-CDUS) was not standardized. Recently, the European Academy of Andrology (EAA) published the results of a multicenter study assessing the CDUS characteristics of healthy-fertile men (HFM) to obtain normative parameters., Objectives: To report the EAA US study (i) standard operating procedures (SOPs) for assessing MGT-CDUS, (ii) main MGT-CDUS normative parameters, and (iii) compare the EAA and previously published "normal" CDUS values., Methods: A cohort of 248 HFM (35.3 ± 5.9 years) was studied, evaluating MGT-CDUS before and after ejaculation following SOPs., Results: SOPs for MGT-CDUS assessment are summarized here. All subjects underwent scrotal CDUS and 188 men underwent transrectal ultrasound before and after ejaculation. The main CDUS reference ranges and characteristics of the HFM-MGT are reported here. The mean testicular volume was ∼17 mL. The lower limit for right and left testis was 12 and 11 mL, defining testicular hypotrophy. The upper limit for epididymal head, body, tail, and vas deferens was 11.5, 5, 6, and 4.5 mm, respectively. Testicular and epididymal arterial reference ranges are reported. The EAA varicocoele classification is reported. CDUS-varicocoele was detected in ∼37% of men. Prostate mean volume was ∼25 mL, while lower and upper limits were 15 and 35 mL, defining hypotrophy and enlargement, respectively. Prostate arterial reference ranges are reported. Prostate calcifications and inhomogeneity were frequent; midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. The upper limit for periprostatic venous plexus was 4.5 mm. Lower and upper limits of seminal vesicles (SV) anterior-posterior diameter were 6 and 16 mm, defining hypotrophy or dilation, respectively. Seminal vesicle volume and ejection fraction reference ranges are reported. SV-US abnormalities were rare. Deferential ampullas upper limit was 6 mm. A discussion on the EAA and previously published "normal" CDUS values is reported here., Conclusions: The EAA findings will help in reproductive and general male health management., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) disease that has rapidly spread worldwide, causing hundreds of thousand deaths. Normal placentation is characterized by many processes strictly regulated during pregnancy. If placentation is impaired, it can lead to gestational disorders, such as preeclampsia that is a multisystem disorder that occurs in 2-8% of pregnancies worldwide., Methods: We performed a systematic search to understand the potential involvement of SARS-CoV-2 in preeclampsia onset using the databases, PubMed and Web of Science until 31 January 2022., Results: SARS-CoV-2 infection not only causes damage to the respiratory system but also can infect human placenta cells impairing pivotal processes necessary for normal placenta development. The inflammatory response trigged by COVID-19 disease is very similar to that one found in preeclampsia pregnancies suggesting a possible link between SARS-CoV-2 infection and preeclampsia onset during pregnancy., Conclusion: Some studies showed that pregnancies affected by COVID-19 had higher incidence of preeclampsia compared with SARS-CoV-2-negative ones. However, increased blood pressure found in COVID-19 pregnancies does not allow to associate COVID-19 to preeclampsia as hypertension is a common factor to both conditions. At present, no diagnostic tools are available to discriminate real preeclampsia from preeclampsia-like syndrome in patients with SARS-CoV-2 infection. Thus, new specific diagnostic tools are necessary to assure an appropriate diagnosis of preeclampsia in these patients, especially in case of severe COVID-19 disease., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy-fertile men (HFM) to establish normative parameters., Objectives: To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters., Methods: 188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures., Results: TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior-posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed., Conclusions: The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice., Materials and Methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries., Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions., Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

Acromegaly is a rare pathology characterized by chronic hypersecretion of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) that causes somatic, metabolic, and systemic changes. The somatotropic axis acts physiologically favoring gonadal function, but when GH is produced in excess it has deleterious effects on many aspects of male sexuality. It is widely demonstrated, in fact, that acromegaly induces hypogonadism through different mechanisms, both through direct mass effect on gonadotropic cells and through increased plasma levels of prolactin. Moreover, hypogonadism is also one of the factors linking acromegaly to erectile dysfunction (ED), but also metabolic complications of acromegaly and, probably, GH itself contribute to the genesis of this disorder. There are few data in the literature on the impact of the disease on fertility and testicular volume. Finally, knowledge of the role of GH hypersecretion on the occurrence of prostatic diseases such as benign prostatic hypertrophy and prostatic cancer appears to be of fundamental clinical importance in the long-term management of these patients., (© 2022. The Author(s).)

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus infectious disease (COVID-19) and has rapidly spread worldwide, causing serious problems to the healthcare systems of many countries and hundreds of thousand deaths. In this review we discuss data from the literature to understand whether the various districts of the male reproductive system may represent another vulnerable target for SARS-CoV-2. Studies were searched from electronic databases such as Google Scholar, PubMed, Scopus, and COVID-19 specific databases such as LitCovid, until July 31, 2021. It appears that SARS-CoV-2 virus infection not only causes damage to the respiratory system, but could have a serious impact on the reproductive system of male patients modulating many physiological processes. Like some other infections, SARS-CoV-2 also leads to a worsening of semen quality and an increase in oxidative stress (OS) levels. However, due to the limited number of studies, it is unclear whether this deterioration in semen parameters is temporary or lasts over time. It is certainly important that patients' reproductive function is monitored after coronavirus infection to avoid problems in reproductive health in the future., (© 2022 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.)

Introduction: Hyperhomocysteinemia may contribute to the development of endothelial dysfunction and, consequently, atherosclerosis, a systemic disease involving the vessels that may affect the cavernous arteries leading to vasculogenic erectile dysfunction. Our study aims therefore to explore the relationship between homocysteine levels and velocimetric parameters detected by basal penile duplex ultrasound such as peak systolic velocity and flaccid penile acceleration in patients with erectile dysfunction., Methods: A cross-sectional study was conducted collecting clinical, metabolic, hormonal, and instrumental (basal penile duplex ultrasound) data in patients affected by vasculogenic erectile dysfunction., Results: Data of 126 subjects affected by erectile dysfunction were collected. Mean age was 52.1 ± 12.6 years, whereas mean body mass index was 25.6 ± 4.0 kg/m 2 . Basal penile duplex ultrasound showed peak systolic velocity values of 13.1 ± 2.9 cm/s and mean flaccid penile acceleration of 2.28 ± 0.70 m/s 2 , with a strong correlation among these two parameters (r = 0.690; p < 0.001). Frankly pathological values of peak systolic velocity and flaccid penile acceleration were detected in 39.7% and 4.8% of the subjects examined, respectively. Mean homocysteine levels were 14.9 ± 9.5 μmol/l. Homocysteine values >15 μmol/l were found in 26% of the subjects with erectile dysfunction. Peak systolic velocity values and homocysteine levels showed an inverse correlation (r = -0.213; p = 0.03). Similarly, flaccid penile acceleration values were inversely correlated to homocysteine levels (r = -0.199; p = 0.05). In addition, an inverse correlation was found between both peak systolic velocity and flaccid penile acceleration and body mass index, atherogenic lipid pattern, and age. Homocysteine and metabolic parameters showed no significant correlations., Conclusion: Hyperhomocysteinemia is highly prevalent in erectile dysfunction patients. The results of our study show that homocysteine levels correlate with velocimetric parameters assessed by basal penile duplex ultrasound, confirming the role of hyperhomocysteinemia in the genesis of erectile dysfunction of arterial origin., (© 2022 American Society of Andrology and European Academy of Andrology.)

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)

We conducted a survey during the first pandemic wave of coronavirus disease 2019 (COVID-19) on a large group of osteoporotic patients to evaluate the general conditions of osteoporotic patients and the impact of the pandemic on the management of osteoporosis, finding high compliance to treatments and low COVID-19 lethality., Introduction: During the first pandemic wave of coronavirus disease 2019 (COVID-19), 209,254 cases were diagnosed in Italy; fatalities were 26,892 and were overwhelmingly older patients. The high prevalence of osteoporosis in this age group suggests a potential relationship between SARS-CoV-2 infection and bone metabolism., Methods: In a telephone survey conducted from April to May 2020, patients from the Osteoporosis Center, Clinic of Endocrinology and Metabolic Diseases of Umberto I Hospital (Ancona, Italy), were interviewed to evaluate the general clinical conditions of osteoporotic patients, compliance with osteoporosis medications, COVID-19 prevalence, hospitalization rate, COVID-19 mortality, and lethality., Results: Among the 892 patients interviewed, 77.9% were taking osteoporosis treatment and 94.6% vitamin D supplementation as prescribed at the last visit. COVID-19-like symptoms were reported by 5.1%, whereas confirmed cases were 1.2%. A total number of 33 patients had been in hospital and the hospitalization rate of those who had not discontinued vitamin D supplementation was less than 4%. There were eight deaths, two with a concomitant COVID-19 diagnosis. The prevalence of severe osteoporosis was 50% in total COVID-19 patients and 87.5% in deceased COVID-19 patients. The overall COVID-19 mortality was 0.2%; lethality was 20%, lower than the national rate of the same age group., Conclusions: This large group of osteoporotic patients showed high compliance and lower COVID-19 lethality compared to patients of the same age. Novel approaches such as telemedicine can provide critical support for the remote follow-up of patients with chronic diseases also in the setting of routine care., (© 2022. The Author(s).)

The Coronavirus-19 (COVID-19) pandemic, which began in December 2019 in Wuhan, China, has spread rapidly worldwide, affecting mostly frail individuals and resulting in high lethality among people with chronic conditions. The management of chronic endocrine disorders during the pandemic period proved particularly challenging, as they require close physician-patient contact for proper long-term management. In addition, acute endocrinologic conditions that presented during the COVID-19 period required timely management in an unusual clinical setting, providing an ongoing challenge for clinicians. This article summarizes the most recent guidance on the management and therapy of frequent conditions such as diabetes and osteoporosis and less common endocrine disorders (e.g., adrenal insufficiency) in this setting.

Introduction: The "lost penis syndrome" (LPS) is a term often used in non-clinical settings to describe the subjective perception of the loss of cutaneous and proprioceptive feelings of the male organ during vaginal penetration. Although deserving clinical attention, this syndrome did not receive any consideration in the medical literature. Notwithstanding, it represents a relatively unexceptional condition among patients in sexual medicine clinics, and it is often reported together with other sexual dysfunctions, especially delayed ejaculation, anejaculation, male anorgasmia and inability to maintain a full erection., Objectives: To draft a new conceptual characterization of the LPS, defined as a lack of penile somesthetic sensations during sexual penetration due to various causes and leading to several sexual consequences in both partners., Methods: Based on an extensive literature review and physiological assumptions, the mechanisms contributing to friction during penovaginal intercourse, and their correlation to LPS, have been explored, as well as other nonanatomical factors possibly contributing to the loss of penile sensations., Results: Efficient penile erection and sensitivity, optimal vaginal lubrication and trophism contribute to penovaginal friction. Whenever one of these processes does not occur, loss of penile sensation defined as LPS can occur. Sociocultural, psychopathological and age-related (ie, couplepause) factors are also implicated in the etiology. Four types of LPS emerged from the literature review: anatomical and/or functional, behavioral, psychopathological and iatrogenic. According to the subtype, a wide variety of treatments can be employed, including PDE5i, testosterone replacement therapy and vaginal cosmetic surgery, as well as targeted therapy for concomitant sexual comorbidity., Conclusion: We held up the mirror on LPS as a clinically existing multifactorial entity and provided medical features and hypotheses contributing to or causing the occurrence of LPS. In the light of a sociocultural and scientific perspective, we proposed a description and categorization of this syndrome hypothesizing its usefulness in daily clinical practice. Colonnello E, Limoncin E, Ciocca G, et al. The Lost Penis Syndrome: A New Clinical Entity in Sexual Medicine. Sex Med Rev 2022;10:113-129., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate personality traits associated with depression in breast cancer women (BCW)., Methods: Sample: 236 BCW recently diagnosed (early stages). Tests: SASB-Structural-Analysis of Social-Behavior; IPAT-CDQ-Depression . Statistical analysis: cluster K-Means analysis to explore SASB personality-traits considering the 8 SASB clusters (Cl); CDQ scores dichotomized by 50th percentile cutoff (high/low); Pearson's chi square test to compare CDQ levels and SASB traits., Results: Cluster analysis results supported two distinguishable SASB personality traits (for all SASB Cl-Scales P < .001) classified as "Love and Autonomy" (62.2%) and "Control and Hate" (37.8%). Patients with Love/Autonomy traits are spontaneous, accept their deepest feelings and desire to be close to other people (Cl1, Cl2, Cl3, Cl4). They show a medium value of self-control and a low tendency to self-abusive and self-critical behaviors (Cl5, Cl6). They pay attention to themselves and to their needs at emotional and physical levels also if may be occasionally engaged in self-destructive behaviors (Cl7, Cl8). Women with Control/Hate traits are not spontaneous and do not always express emotions (C1, Cl2, Cl3, Cl4) and flexibility in their relationship with others (Cl5, Cl6). In stressful situations, they may ignore the option of choices for self-growth and neglect their needs and those of others (Cl7, Cl8). BCWs with Control/Hate traits scored higher in depression ( P <.001) than those with the Love/Autonomy profile., Conclusions: Healthcare professionals should be aware of these personality traits and their association with depression to identify the psychologically most vulnerable BCW and improve the care they provide them. The psychotherapeutic intervention should be planned to face on the personality problems.