Morbidity in Klinefelter syndrome and the effect of testosterone treatment

Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):344-355. doi: 10.1002/ajmg.c.31798. Epub 2020 Jun 4.


Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosome abnormality in males (150 per 100,000 males). The condition leads to hypergonadotropic hypogonadism and ever since the condition was described approximately 80 years ago, testosterone treatment has been the cornerstone in care for individuals with KS. However, KS is associated with an array of health-related and socioeconomic challenges and it is becoming progressively clear that proper care for boys and men with KS reaches far beyond simply supplementing with testosterone. There are no widely implemented guidelines for KS care, and studies investigating crucial aspects of testosterone treatment in individuals with KS, including both beneficial and potentially adverse effects, have only begun to emerge during the last decades. For this descriptive review, we present an overview of literature describing health-related outcomes of testosterone treatment in KS and outline the clinical applications of testosterone treatment in KS. Collectively, beneficial effects of testosterone treatment on overall health in KS are described with few apparent adverse effects. However, larger randomized studies in adult and pediatric patients are warranted to elucidate key aspects of treatment. We stress the implementation of centralized multidisciplinary clinics and the need for a dedicated international guideline to ensure optimal care of boys and men with KS.

Keywords: Klinefelter syndrome; hypogonadism; review article; testosterone treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Body Composition
  • Humans
  • Hypogonadism / drug therapy*
  • Hypogonadism / metabolism
  • Hypogonadism / pathology
  • Klinefelter Syndrome / drug therapy*
  • Klinefelter Syndrome / metabolism
  • Klinefelter Syndrome / pathology
  • Male
  • Morbidity
  • Testosterone / metabolism
  • Testosterone / therapeutic use*


  • Testosterone