Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Andrea Salzano, Roberta D’Assante, Liam M. Heaney, Federica Monaco, Giuseppe Rengo, Pietro Valente, Daniela Pasquali, Eduardo Bossone, Daniele Gianfrilli, Andrea Lenzi, Antonio Cittadini, Alberto M. Marra, Raffaele Napoli

Research output: Contribution to journalReview articlepeer-review


Purpose: Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Methods: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. Results: Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. Conclusion: Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

Original languageEnglish
Pages (from-to)194-203
Number of pages10
Issue number2
Publication statusPublished - Aug 1 2018


  • Cardiovascular diseases
  • Diabetes mellitus
  • Insulin resistance
  • Klinefelter syndrome
  • Metabolic syndrome
  • Testosterone therapy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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