Michael Zitzmann1, Lise Aksglaede2, Giovanni Corona3, Andrea M Isidori4, Anders Juul2, Guy T'Sjoen5, Sabine Kliesch1, Kathleen D'Hauwers6, Jorma Toppari7, Jolanta Słowikowska-Hilczer8, Frank Tüttelmann9, Alberto Ferlin10. 1. Center for Reproductive Medicine and Andrology/Clinical and Surgical Andrology, University Hospital of Münster, Münster, Germany. 2. Rigshospitalet, Department of Growth and Reproduction, University of Copenhagen, Copenhagen, Denmark. 3. Medical Department, Endocrinology Unit, Maggiore Bellaria Hospital, Azienda Usl, Bologna, Italy. 4. Department of Experimental Medicine, Advanced Endocrine Diagnostics Unit, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy. 5. Department of Endocrinology and Center for Sexology and Gender, Ghent University and Ghent University Hospital, Ghent, Belgium. 6. Department of Urology, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands. 7. Department of Pediatrics, Institute of Biomedicine, Research Centre for Integrated Physiology and Pharmacology and Centre for Population Health Research, University Hospital, University of Turku, Turku, Finland. 8. Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland. 9. Institute of Human Genetics, University of Münster, Münster, Germany. 10. Department of Clinical and Experimental Sciences, Unit of Endocrinology and Metabolism, University of Brescia and ASST Spedali Civili Brescia, Brescia, Italy.
Abstract
BACKGROUND: Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS. OBJECTIVE: To create the first European Academy of Andrology (EAA) guidelines on KS. METHODS: An expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RESULTS: Clinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone-related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility. CONCLUSION: These guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.
BACKGROUND: Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS. OBJECTIVE: To create the first European Academy of Andrology (EAA) guidelines on KS. METHODS: An expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RESULTS: Clinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone-related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility. CONCLUSION: These guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.
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