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Clinical Practice Operations · Care Team and Roles

Improving care for individuals with gender incongruence: Establishing a multidisciplinary approach in Italy

Scala A, Ceolin C, Miscioscia M, Basso D, Campello E, Camozzi V, Cattelan A, Gatta M, Giannini S, Iafrate M, Musso G, Meneguzzo P, Ottaviano G, Perilli R, Rosin R, Ruzza I, Saccardi C, Sasset L, Sergi G, Tascini B, Vezzaro T, Vianello F, Simioni P, Ferlin A, Garolla A, Interdisciplinary Group for Gender Incongruence (GIIG)

Published June 6, 2025 Journal of endocrinological investigation
DOI 10.1007/s40618-025-02580-x PMID 40478402 PMC PMC12313810

Abstract

Purpose

To present a multidisciplinary care model designed to provide personalized gender-affirming care and assess general health for transgender and gender-diverse (TGD) individuals.

Methods

Drawing from our experience in a tertiary center in Padua (Italy), the Interdisciplinary Group for Gender Incongruence (GIIG) model employs a multidisciplinary approach to provide diverse gender-affirmation services. Mental health support, gender-affirming medical and surgical treatments (GAMST), screening programs, and regular follow-up ensure treatment safety and efficacy. The GIIG model promotes collaboration among specialists, primary health services, and LGBTQ + associations. Furthermore, it advocates for training healthcare professionals and raising awareness in the population.

Results

The GIIG involves mental health professionals, endocrinologists, surgeons (plastic, urological, and gynaecological), voice specialists, internists, and associations. Associations serve as a point of reference for the community and offer psychological and legal services. Initial contact at the Center is made with MHP, who provide a safe space to explore gender identity, receive information, and support mental well-being. Endocrinologists prescribe hormone therapy and monitor its potential risks and overall health. Surgical interventions include chest, genital, and laryngeal surgery. Internists and other specialists assess osteo-muscular, hemo-coagulative, oncological, and infectious risks.

Conclusions

Our experience emphasizes the need for personalized care tailored to individuals' desires while ensuring the safety of gender-affirming treatments. By adhering to the Standards of Care and offering comprehensive services, our center aims to serve as a model for modern transgender care.

Topics

By this author

Semen Analysis · Sperm Function Testing

Preimplantation genetic testing for male factor infertility: lights and shadows

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.

Male Factor Causes · Hormonal Causes

Pathophysiology-Based Classification of Male Infertility: Evidence from an 800-patient Prospective Cohort

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.

Neoplastic Risk in Patients With Klinefelter Syndrome

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.

Male Endocrine and Genetic Factors · Genetic Causes of Male Infertility

Impact of FSHB and FSHR Genes Polymorphisms on Hormonal Profile and Sperm Retrieval Outcome in Men With Klinefelter Syndrome: A Clinical-Genetic Predictive Study

Graziani A et al., 2026 Andrology Free to read

Genetic variability within the follicle-stimulating hormone (FSH)-related genes might contribute to phenotypic heterogeneity in patients with Klinefelter syndrome (KS), yet its clinical impact on sperm retrieval remains unclear. To investigate the association between FSHB c.211 G > T and FSHR polymorphisms (c.2039 A > G and c.29 G > A) and hormonal parameters, as well as their potential role in predicting sperm retrieval rate (SRR) in patients with KS undergoing testicular sperm extraction (TESE). A retrospective cohort of patients with KS was analyzed. Only subjects not receiving testosterone replacement therapy were included (n = 417). Hormonal, anthropometric, and clinical variables were compared across genotypes using nonparametric tests. Additive genetic models were applied to evaluate allele-dose effects. Multivariable logistic regression was performed to identify independent predictors of SRR. Predictive performance of clinical and combined clinical-genetic models was assessed using ROC curve analysis. FSHB and FSHR genes polymorphisms were associated with variations in serum FSH concentrations, confirming a modulatory role of the FSH-related genes. In additive modeling, the FSHR c.29 G > A polymorphism emerged as an independent predictor of SRR (adjusted OR: 0.29; 95% CI, 0.09-0.97), whereas FSHB c.211 G > T showed a nonsignificant trend. The inclusion of genetic variants modestly improved predictive accuracy compared with clinical variables alone, as demonstrated by ROC analysis. Genetic variants within the genes involved in FSH action might contribute incremental information for the prediction of sperm retrieval in patients with KS. While the overall predictive gain remains moderate, additive genetic modeling highlights a potential allele-dose effect of FSHR c.29 G > A on reproductive outcome, supporting a role for integrated clinical-genetic assessment in this population, although external validation remains required.

Related research

Hormonal Agents · Estrogen Preparations

Risk and management of congenital thrombophilia in transgender individuals undergoing gender-affirming hormone therapy

Campello E et al., 2026 International journal of transgender health Free full text on PubMed Central

Gender-affirming hormone therapy (GAHT), particularly estrogen-based regimens, is associated with an increased risk of venous thromboembolic events (VTE), which may be exacerbated in individuals with hereditary thrombophilia. Despite this risk, the prevalence and clinical implications of hereditary thrombophilia in transgender individuals remain underexplored. We screened 114 transgender individuals (54 AMAB, 60 AFAB) at the University Hospital of Padua (Italy) for hereditary thrombophilia, including factor V Leiden (FVL), prothrombin G20210A (PT20210A), antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, as well as antiphospholipid antibodies. Hereditary thrombophilia was identified in 9.6% of participants, including two cases of severe thrombophilia. No participants tested positive for antiphospholipid antibodies. Individuals with thrombophilia had a higher prevalence of personal and family history of VTE. Three thrombotic events were recorded prior to one transgender woman (heterozygous FVL) with unprovoked lower limb VTE, one transgender man (PC deficiency) with neonatal cerebral ischemia, and one transgender man (heterozygous FVL) with subclavian VTE during chemotherapy. A multidisciplinary approach involving coagulation specialists and endocrinologists was implemented to optimize risk reduction strategies, including tailored GAHT regimens and anticoagulation when necessary. No VTE occurred during a 15-month follow up. These findings highlight the importance of thrombophilia screening to enable individualized care and enhance the safety of GAHT protocols.

Clinical Practice Operations › Care Team and Roles › Collaborative and Shared Care · Therapeutics › Hormonal Agents › Estrogen Preparations · Ethics and Policy › Reproductive Ethics › LGBTQ Rights
Marina Miscioscia, Daniela Basso, Annamaria Cattelan, Michela Gatta, Giulia Musso, Paolo Meneguzzo, Giancarlo Ottaviano, Rossella Perilli, Roberta Rosin, Ilaria Ruzza, Carlo Saccardi, Lolita Sasset, Benedetta Tascini, Tommaso Vezzaro, Fabrizio Vianello
M Miscioscia, D Basso, A Cattelan, M Gatta, G Musso, P Meneguzzo, G Ottaviano, R Perilli, R Rosin, I Ruzza, C Saccardi, L Sasset, B Tascini, T Vezzaro, F Vianello
PMID 40478402 40478402 DOI 10.1007/s40618-025-02580-x 10.1007/s40618-025-02580-x Scala et al. 2025, Scala 2025

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