Klinefelter syndrome (KS) (47, XXY) is the most abundant
sex-chromosome disorder, and is a common cause of
infertility and
hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from
hypogonadism and
azoospermia, most men with KS suffer from some degree of
learning disability and may have various kinds of psychiatric problems. The effects of long-term
hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone
mineral mass, as well as increased risk of metabolic consequences, such as
type 2 diabetes and the
metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases.
Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of
hypogonadism in KS and the rationale for
testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.