Foresta C, Ferlin A, Lenzi A, Montorsi P, Italian Study Group on Cardiometabolic Andrology
Andrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications.
Mazzilli R et al., 2026 · Journal of endocrinological investigation
Male factor could contribute, alone or in combination with female factor, to the inability to conceive in a couple in more than half of cases. The effect of male factor infertility (MFI) on embryological assisted reproductive technology (ART) outcomes remains an ongoing discussion. to evaluate the impact of MFI on embryo aneuploidy rates, to better understand the role and possible indication for Preimplantation genetic testing for aneuploidies (PGT-A), considering the role of sperm characteristics, paternal age, sperm DNA fragmentation and sperm aneuploidies. this narrative review included all available articles, published up to January 2026. Available evidence, often based on heterogeneous and old-fashioned methodologies, suggests that MFI may impair embryonic development, particularly in terms of fertilization rate and blastulation rate, more than embryo euploidy; however, a comprehensive evaluation of MFI should be integrated into clinical practice in the context of couple infertility, to also optimize the efficiency and outcomes of ART. Promising results emerged from sperm DNA fragmentation as a tool to predict embryo euploidy, but further investigations involving larger sample sizes and improved standardization are required.
Graziani A et al., 2026 · Andrology · Free to read
Besides gonadal involvement (hypogonadism, male factor infertility, and testicular hypotrophy), patients with Klinefelter syndrome (KS) may suffer from several extra-gonadic complications, including neoplastic events. The aim of this review is to summarize all major clinical evidence dealing with the association between KS and neoplastic diseases and provide practical suggestions for the management of patients with KS regarding neoplastic risk. This narrative review was conducted through a comprehensive search of the PubMed database, using combinations of the following keywords: "Klinefelter syndrome," "cancer," "neoplasm," "breast cancer," "germ cell tumor," "lymphoma," and "testosterone replacement therapy". KS is associated with a higher risk of breast cancer and mediastinal germ cell tumors and an apparent higher risk of hematological malignancies, in particular non-Hodgkin lymphoma and leukemia. Evidence on testicular cancer is limited, with no clear increase in risk attributable to KS, while prostate cancer has a lower risk and lower mortality rate. Given the complexity of the syndrome and the limited available evidence, regular clinical follow-up with targeted investigations when clinically indicated may facilitate early diagnosis and management of associated comorbidities.
Scala A et al., 2026 · Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · Free full text on PubMed Central
In transgender adults, reference-gender choice alters Z-scores and fracture-risk estimates. Z-scores differ by 0.4-0.6 SD, with male references identifying more individuals with low BMD for age, especially in those assigned male at birth. Dual-reference reporting is advisable until further evidence becomes available. Transgender individuals, especially those assigned male at birth (AMAB), exhibit lower bone mineral density (BMD) compared with the cisgender population. Interpretation of densitometric data is challenging, as the choice of reference gender can significantly influence Z-scores and fracture risk scores. This study aims to evaluate the impact of the gender reference database (male or female) on the assessment of BMD and fracture risk in transgender adults prior to gender-affirming hormone therapy (GAHT). We conducted a cross-sectional analysis of 249 transgender individuals (153 assigned female at birth - AFAB and 96 AMAB) aged 18-43 years, recruited in the Hospitals of Padua and Brescia (Italy). Z-scores were calculated using both male and female reference databases and FRAX scores were computed using both gender inputs. Associations with anthropometric, biochemical, and hormonal parameters were explored. Z-scores differed systematically depending on the reference gender, with mean ΔZ ranging 0.4-0.6 SD across skeletal sites. Switching reference databases frequently led to reclassification of BMD status. AMAB individuals showed a higher prevalence of low BMD for age, particularly when assessed against male references (27.1%), whereas AFAB participants generally maintained normal BMD. However, FRAX scores remained low. BMI and 25-OH vitamin D levels were independent predictors of BMD and Z-scores in AMAB individuals. The choice of reference gender significantly influences densitometric interpretation in young transgender adults. Until further evidence becomes available, calculating Z-scores using both male and female reference databases is advisable. Early preventive interventions remain essential to preserve bone health.
De Toni L et al., 2026 · Journal of endocrinological investigation · Free full text on PubMed Central
Varicocele is a recognized male factor of infertility. Surgical/microsurgical correction represents a therapeutical option to improve fertility outcomes but predictive parameters for the identification who can actually benefit from varicocele correction are under investigated. Here we aimed to identify baseline predictors of semen outcome improvement after varicocele treatment by scleroembolization approach. 85 patients receiving varicocele treatment by anterograde scleroembolization (ASE, N = 42) or retrograde scleroembolization (RSE, N = 43) were retrospectively recruited. Basal and 6-months follow-up evaluation of semen, hormonal and ultrasound parameters (US) were performed to address the respective effect of varicocele treatment. In addition, basal parameters were assessed as clinical outcome predictors. Varicocele grade reduction was observed in more than 90% of patients (P < 0.001). Compared to basal, significant increase of sperm concentration (10.0 ± 9.2 × 106cells/mL vs. 23.4 ± 26.9 × 106cells/mL; P < 0.001), total sperm count (TSC 39.0 ± 54.5 × 106cells vs. 70.3 ± 90.6 × 106cells, P < 0.001) and total motile sperm count (TMS, 9.8 ± 12.8 × 106cells vs. 36.7 ± 58.1 × 106cells, P < 0.001), was observed, with no differences between RSE or ASE. All US parameters were also improved (all P < 0.001). Logistic regression analysis of basal semen and ultrasound parameters showed that basal sperm motility and left testis-mean transit time (L-MTT) were associated with TSC and TMS doubling at follow-up. However, Receiver Operating Characteristic curve analysis showed that only basal L-MTT basal sperm was consistently associated with TSC and TMS doubling at follow-up (respectively: AUC = 0.834, CI: 0.747-0.921 and AUC = 0.805, CI: 0.708-0.901; both P < 0.001). Baseline sperm count and US parameters represent useful clinical descriptors to address those subjects eligible for varicocele correction.
Caretta N et al., 2016 · Endocrine
Diabetes is an established risk factor for erectile dysfunction (ED). The pathophysiology of ED in diabetic men is multifactorial, but it mainly involves a vascular disorder related to a reduction of endothelial function. Recently, several studies have correlated ED risk factors with vitamin D deficiency. In this study, we evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] levels, erectile dysfunction, and vascular disease, in type 2 diabetes mellitus men (T2DM). In this observational study, 92 T2DM males (58.83 ± 9.73 years) underwent medical history collection, International Index of Erectile Function (IIEF-5) questionnaire, that allows the identification and grading of DE, physical examination, biochemical/hormonal blood tests, and penile echo-color Doppler ultrasonography. T2DM patients with lower 25(OH)D levels (<25 nmol/l) showed higher penile IMT (p < 0.05), waist circonference (p < 0.05), glucose concentrations (p < 0.05), and lower IIEF-5 score (p < 0.005), testosterone concentrations (p < 0.05), and cavernous peak systolic velocity (PSV) (p < 0.05), compared to patients with 25(OH)D >50 nmol/l. 25(OH)D levels were directly correlated with IIEF-5 (R = 0.39; p = 0.0001), testosterone (R = 0.24; p = 0.02), and PSV (R = 0.24; p = 0.04) and inversely with waist (R = -0.33; p = 0.002), HbA1c (R = -0.22; p = 0.03), triglyceride (R = -0.21; p = 0.06), and penile IMT (R = -0.30; p = 0.009). At multivariate analysis, 25(OH)D deficiency remained an independent predictor of DE. We demonstrate a significant association between 25(OH)D deficiency and erectile dysfunction in T2DM men. This association may be due to the influence of 25(OH)D deficiency on cardiovascular risk factor (glycaemia, HDL cholesterol, and triglycerides), testosterone plasma levels and endothelial dysfunction.
Graziani A et al., 2026 · Journal of clinical medicine · Free full text on PubMed Central
Erectile dysfunction (ED) is increasingly recognized as an early manifestation of systemic vascular disease and might represent a window for cardiovascular risk assessment. Dynamic penile colour Doppler ultrasound (PCDU) provides quantitative arterial and venous parameters that could reflect subclinical vascular impairment. We investigated the association between PCDU parameters and estimated cardiovascular risk in men with ED. In this single-center retrospective observational study, 275 men undergoing PCDU for ED were evaluated. Clinical characteristics, biochemical data, and QRISK3 10-year cardiovascular risk scores were collected. Mean peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were analyzed. Correlation analyses, logistic regression using a QRISK3 ≥ 10% threshold, linear regression models, age-stratified analyses, and receiver operating characteristic (ROC) curve analyses were performed. Patients with impaired PSV (<35 cm/s) were older and exhibited higher QRISK3 scores and a greater prevalence of diabetes mellitus and previous cardiovascular events. Mean PSV was inversely correlated with QRISK3 (r = -0.203, p < 0.01) and was associated with higher cardiovascular risk categories in unadjusted logistic regression (β = -0.016, p = 0.048), but not after adjustment for age and diabetes mellitus. ROC analysis showed modest discrimination of increased cardiovascular risk (AUC = 0.60). The addition of PSV to a model including age and diabetes resulted in minimal improvement in discrimination (AUC 0.966 vs. 0.968). Age-stratified analysis demonstrated a significant association between lower PSV and higher cardiovascular risk only in patients ≤60 years. A progressive increase in QRISK3 was observed according to the number of abnormal Doppler parameters (p = 0.013). PCDU parameters reflect the overall cardiovascular risk burden in men with ED. Although not independent predictors beyond traditional risk factors, penile Doppler abnormalities might identify a vascular phenotype associated with higher estimated cardiovascular risk, particularly in younger individuals. These findings support the role of comprehensive vascular assessment in selected patients with ED.
Corona G et al., 2023 · Journal of endocrinological investigation · Free full text on PubMed Central
Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.
Caretta N et al., 2023 · Journal of endocrinological investigation · Free full text on PubMed Central
To evaluate in men with type 2 diabetes the association of cardiometabolic indices [Visceral Adiposity Index (VAI), Triglyceride Glucose Index (TyG), and lipid accumulation product (LAP)] with total testosterone (TT) levels, and their predictive cut-off values in identifying hypogonadism. 265 consecutive men aged 40-70 years with type 2 diabetes performed an andrological evaluation; metabolic parameters and TT were determined. Receiver operating characteristic (ROC) curves were used to identify cut-off values of cardiometabolic indices in predicting low testosterone (TT < 12 nmol/l). VAI, TyG, and LAP were negatively associated with TT levels. The prevalence of hypogonadism in men in the fourth quartiles of VAI, TyG, and LAP was ~ 70.0-75.0% compared to ~ 10.0-17.0% in men in the first quartiles (p < 0.001). The sensitivity and specificity of the three cardiometabolic indices in predicting TT < 12 nmol/l were significantly higher concerning BMI, waist circumference, lipid profile and HbA1c. Cut off values of VAI ≥ 3.985, TyG ≥ 4.925, and LAP ≥ 51.645 predict hypogonadism with good sensitivity and specificity. This is the first study evaluating the association of VAI, TyG, and LAP with hypogonadism in men with type 2 diabetes. Alterations in these indices should direct the patients to andrological evaluation.
