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Morbidity in Klinefelter Syndrome: A Danish Register Study Based on Hospital Discharge Diagnoses

Medical Department M (Diabetes and Endocrinology), Aarhus Sygehus (A.B., C.H.G.), and Department of Pediatrics, Skejby Hospital (N.H.B.), Aarhus University Hospital; and Institute of Public Health, Department of Epidemiology, Aarhus University (S.J.), DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Dr. Anders Bojesen, Medical Department M (Diabetes and Endocrinology), Aarhus Sygehus, Aarhus University Hospital, Noerrebrogade 42–44, DK-8000 Aarhus C, Denmark. E-mail: anders.bojesen{at}dadlnet.dk.

Background: Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder in man; it affects approximately one in 660 men and is a common cause of hypogonadism and infertility. Our current knowledge of morbidity in KS is based on observational studies and case reports and therefore is limited.

Design: We used Danish registers to obtain dates of hospital admissions and discharge diagnoses in a cohort of all males diagnosed with KS in Denmark and a randomly selected, age-matched control group. Our cohort consisted of 832 KS subjects and 4033 control subjects, contributing with a total of approximately 100,000 person years. We used stratified Cox regression analysis on main groups of diagnoses. Where significant results were found, subsequent analyses were performed on subgroups of diagnoses.

Results: We found a significantly increased risk of being hospitalized among the KS subjects [hazard ratio (HR), 1.69; 95% confidence interval, 1.54–1.86]. The increased admission risk was present in all but one of the main diagnosis groups, with the highest HRs for congenital malformations (HR, 10.7), psychiatric disorders (HR, 3.7), and endocrine and metabolic disorders (HR, 3.2). We compared hospitalization rates before and after the diagnosis of KS and found that the increased rate was present even before the diagnosis of KS.

Conclusions: Males suffering from KS experienced an increased hospitalization rate from a variety of disorders. Some are likely to be caused by hypogonadism, and some may be linked to the syndrome per se, whereas others are not readily explained. However, other factors, e.g. socioeconomic, may be involved.

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