The Metabolic Syndrome Is Frequent in Klinefelter’s Syndrome and Is Associated With Abdominal Obesity and Hypogonadism

Abstract

OBJECTIVE—Klinefelter’s syndrome is associated with an increased prevalence of diabetes, but the pathogenesis is unknown. Accordingly, the aim of this study was to investigate measures of insulin sensitivity, the metabolic syndrome, and sex hormones in patients with Klinefelter’s syndrome and an age-matched control group. RESEARCH DESIGN AN METHODS—In a cross-sectional study, we examined 71 patients with Klinefelter’s syndrome, of whom 35 received testosterone treatment, and 71 control subjects. Body composition was evaluated using dual-energy X-ray absorptiometry scans. Fasting blood samples were analyzed for sex hormones, plasma glucose, insulin, C-reactive protein (CRP), and adipocytokines. We analyzed differences between patients with untreated Klinefelter’s syndrome and control subjects and subsequently analyzed differences between testosterone-treated and untreated Klinefelter’s syndrome patients. RESULTS—Of the patients with Klinefelter’s syndrome, 44% had metabolic syndrome (according to National Cholesterol Education Program/Adult Treatment Panel III criteria) compared with 10% of control subjects. Insulin sensitivity (assessed by homeostasis model assessment 2 modeling), androgen, and HDL cholesterol levels were significantly decreased, whereas total fat mass and LDL cholesterol, triglyceride, CRP, leptin, and fructosamine levels were significantly increased in untreated Klinefelter’s syndrome patients. In treated Klinefelter’s syndrome patients, LDL cholesterol and adiponectin were significantly decreased, whereas no difference in body composition was found in comparison with untreated Klinefelter’s syndrome patients. Multivariate analyses showed that truncal fat was the major determinant of metabolic syndrome and insulin sensitivity. CONCLUSIONS—The prevalence of metabolic syndrome was greatly increased, whereas insulin sensitivity was decreased in Klinefelter’s syndrome. Both correlated with truncal obesity. Hypogonadism in Klinefelter’s syndrome may cause an unfavorable change in body composition, primarily through increased truncal fat and decreased muscle mass. Testosterone treatment in Klinefelter’s syndrome only partly corrected the unfavorable changes observed in untreated Klinefelter’s syndrome, perhaps due to insufficient testosterone doses.

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

“…It is this amplification and extension of the injurious oxidative environment that may be responsible for the damage seen in the previously mentioned studies. The proposition is supported by Bojesen et al (2006) who concluded that in Klinefelter's syndrome it was the increased prevalence of diabetes (i.e. hyperglycaemia) rather than hypogonadism or the combination of conditions constituting MetS that is likely to play a role in jeopardising spermatogenesis.…”

Testosterone Deficiency Linked to Lower Urinary Tract Symptoms

“…The basis of this concept came from increased insulin resistance found in both hypergonadotropic and hypogonadotropic hypogonadism. Patients of un-treated Klinefelter's syndrome, compared with control subjects, showed a significantly higher prevalence of metabolic risk factors (Bojesen et al, 2006). GnRH agonist-treated men with prostate cancer also showed significantly decreased insulin sensitivity (Smith et al, 2006).…”

Metabolic syndrome and the older male population

“…Recently, a number of studies in men have suggested that low testosterone may be associated with insulin resistance and testosterone replacement may enhance insulin action [21,22,23,24,25]. A recent study has shown that males with prostate cancer treated with a GnRH agonist are at increased risk of diabetes mellitus [26,27].…”