This Article Full Text Full Text (PDF) All Versions of this Article: 90/12/6516    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Swerdlow, A. J. Search for Related Content PubMed PubMed Citation Articles by Swerdlow, A. J. Related Collections Male Endocrinology

Mortality in Patients with Klinefelter Syndrome in Britain: A Cohort Study

Section of Epidemiology (A.J.S., C.D.H., M.J.S.), Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom; Cell and Molecular Genetics Section, Medical Research Council Human Genetics Unit (A.F.W.), Western General Hospital, Edinburgh EH4 2XU, United Kingdom; and Wessex Regional Genetics Laboratory (P.A.J.), Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom

Address all correspondence and requests for reprints to: Professor A. J. Swerdlow, D.Sc., Section of Epidemiology, Brookes Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom. E-mail: anthony.swerdlow{at}icr.ac.uk.

Context: Klinefelter syndrome is characterized by hypogonadism and infertility, consequent on the presence of extra X chromosome(s). There is limited information about long-term mortality in this syndrome because there have been no large cohort studies.

Objective: Our objective was to investigate mortality in men with Klinefelter syndrome.

Design and Setting: We obtained data about patients diagnosed with Klinefelter syndrome at almost all cytogenetics centers in Britain, as far back as records were available, and conducted a cohort study of their mortality, overall and by karyotype.

Patients: We assessed 3518 patients diagnosed since 1959, followed to mid-2003.

Outcome Measure: The outcome measure was standardized mortality ratio (SMR).

Results: A total of 461 deaths occurred. There was significantly raised mortality overall [SMR, 1.5; 95% confidence interval (CI), 1.4–1.7] and from most major causes of death including cardiovascular disease (SMR, 1.3; 95% CI, 1.1–1.5), nervous system disease (SMR, 2.8; 95% CI, 1.6–4.6), and respiratory disease (SMR, 2.3; 95% CI, 1.8–2.9). Mortality was particularly raised from diabetes (SMR, 5.8; 95% CI, 3.4–9.3), epilepsy (SMR, 7.2; 95% CI, 3.1–14.1), pulmonary embolism (SMR, 5.7; 95% CI, 2.5–11.3), peripheral vascular disease (SMR, 7.9; 95% CI, 2.9–17.2), vascular insufficiency of the intestine (SMR, 12.3; 95% CI, 4.0–28.8), renal disease (SMR, 5.0; 95% CI, 2.0–10.3), and femoral fracture (SMR, 39.4; 95% CI, 4.8–142.3). Mortality from ischemic heart disease was significantly decreased (SMR, 0.7; 95% CI, 0.5–0.9).

Conclusions: Patients diagnosed with Klinefelter syndrome have raised mortality from several specific causes. This may reflect hormonal and genetic mechanisms.

This article has been cited by other articles:

				M. Grossmann, M. C. Thomas, S. Panagiotopoulos, K. Sharpe, R. J. MacIsaac, S. Clarke, J. D. Zajac, and G. Jerums Low Testosterone Levels Are Common and Associated with Insulin Resistance in Men with Diabetes J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1834 - 1840. [Abstract] [Full Text] [PDF]

				D. J. Handelsman Update in Andrology J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4505 - 4511. [Abstract] [Full Text] [PDF]

				A. B. Araujo, V. Kupelian, S. T. Page, D. J. Handelsman, W. J. Bremner, and J. B. McKinlay Sex Steroids and All-Cause and Cause-Specific Mortality in Men Arch Intern Med, June 25, 2007; 167(12): 1252 - 1260. [Abstract] [Full Text] [PDF]

				E. Selvin, M. Feinleib, L. Zhang, S. Rohrmann, N. Rifai, W. G. Nelson, A. Dobs, S. Basaria, S. H. Golden, and E. A. Platz Androgens and Diabetes in Men: Results from the Third National Health and Nutrition Examination Survey (NHANES III) Diabetes Care, February 1, 2007; 30(2): 234 - 238. [Abstract] [Full Text] [PDF]

				K. Stochholm, S. Juul, K. Juel, R. W. Naeraa, and C. Hojbjerg Gravholt Prevalence, Incidence, Diagnostic Delay, and Mortality in Turner Syndrome J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3897 - 3902. [Abstract] [Full Text] [PDF]

				A. Bojesen, K. Kristensen, N. H. Birkebaek, J. Fedder, L. Mosekilde, P. Bennett, P. Laurberg, J. Frystyk, A. Flyvbjerg, J. S. Christiansen, et al. The Metabolic Syndrome Is Frequent in Klinefelter's Syndrome and Is Associated With Abdominal Obesity and Hypogonadism Diabetes Care, July 1, 2006; 29(7): 1591 - 1598. [Abstract] [Full Text] [PDF]

				D. J. Handelsman and P. Y. Liu Klinefelter's Syndrome--A Microcosm of Male Reproductive Health. J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1220 - 1222. [Full Text] [PDF]