Andrology · 2026
Multidimensional Determinants of Quality of Life in Men With Klinefelter Syndrome: A Narrative Review of Workshop Evidence.
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Allosso Francesca, Digitale Selvaggio Lucia, Pasquali Daniela
Аннотация
BACKGROUND: Klinefelter syndrome (KS), typically characterized by a 47, XXY karyotype, is the most common sex chromosomal aneuploidy in males, with a prevalence of approximately one in 600-660 individuals. Despite its frequency, the syndrome remains significantly underdiagnosed, with 50%-75% of affected individuals never receiving a clinical diagnosis. While the classic phenotype includes hypergonadotropic hypogonadism and infertility, recent evidence highlights a lifelong burden of neurocognitive, psychological, and socioeconomic challenges.
OBJECTIVES: This study synthesizes current evidence regarding the determinants of quality of life (QoL) in men with KS, specifically contextualizing the registry data and clinical trajectories discussed during the fourth International Workshop on Klinefelter Syndrome.
MATERIALS AND METHODS: To perform a narrative review, a literature search was conducted across major electronic databases, including PubMed/MEDLINE, Scopus, and the Cochrane Library. The search focused on peer-reviewed articles published up to March 2026, utilizing primary keywords such as "Klinefelter Syndrome," "47, XXY, " "Quality of Life, " "Socioeconomic Status, " and "Testosterone Replacement Therapy."
RESULTS: Affected individuals consistently report lower QoL across physical, psychological, and social domains compared to healthy controls, with social relationship scores often reaching levels observed in psychiatric reference populations. Key drivers of reduced well-being include lower educational achievement, precarious employment, chronic health comorbidities, and experienced discrimination.
DISCUSSION: While testosterone replacement therapy is essential for physical virilization, it is frequently insufficient to normalize QoL or alleviate deep-seated psychological distress, highlighting the impact of unmitigated developmental hurdles, metabolic burdens, and infertility-related psychological trauma.
CONCLUSION: A multidisciplinary approach-integrating endocrinology with specialized psychological, fertility, and educational support-is strictly required to address the complex, multidimensional needs of this population across the lifespan.
OBJECTIVES: This study synthesizes current evidence regarding the determinants of quality of life (QoL) in men with KS, specifically contextualizing the registry data and clinical trajectories discussed during the fourth International Workshop on Klinefelter Syndrome.
MATERIALS AND METHODS: To perform a narrative review, a literature search was conducted across major electronic databases, including PubMed/MEDLINE, Scopus, and the Cochrane Library. The search focused on peer-reviewed articles published up to March 2026, utilizing primary keywords such as "Klinefelter Syndrome," "47, XXY, " "Quality of Life, " "Socioeconomic Status, " and "Testosterone Replacement Therapy."
RESULTS: Affected individuals consistently report lower QoL across physical, psychological, and social domains compared to healthy controls, with social relationship scores often reaching levels observed in psychiatric reference populations. Key drivers of reduced well-being include lower educational achievement, precarious employment, chronic health comorbidities, and experienced discrimination.
DISCUSSION: While testosterone replacement therapy is essential for physical virilization, it is frequently insufficient to normalize QoL or alleviate deep-seated psychological distress, highlighting the impact of unmitigated developmental hurdles, metabolic burdens, and infertility-related psychological trauma.
CONCLUSION: A multidisciplinary approach-integrating endocrinology with specialized psychological, fertility, and educational support-is strictly required to address the complex, multidimensional needs of this population across the lifespan.