Considerations for androgen therapy in children and adolescents with Klinefelter syndrome (47, XXY).

The goals of androgen therapy for adolescents are to promote linear growth and secondary sexual characteristics, at the same time as to permit the normal accrual of muscle mass, bone mineral content and the adult regional distribution of body fat. Secondary goals are mainly in the psychosocial sphere, in which pubertally delayed boys feel that they look too young, are not considered a 'peer' in their age group and have difficulty competing in athletic endeavors. Puberty often starts normally in adolescents with KS corresponding to the peer group with genital enlargement and pubic hair growth. The testes start to enlarge, but rarely expand beyond 6 mL, leaving a discordance between the degree of sexual development and the size of the testes. Androgen therapy is considered mainly supplemental and one usually begins with the long acting esters, testosterone enanthate or cypionate because the other forms patches and gels--are metered for full male replacement. The dose of testosterone is escalated until the lower range of the adult dose is reached and then a choice among the various forms can be made. Treatment-emergent adverse events often represent the pharmacodynamic effects of an androgen oily skin and acne, but as the dose is escalated more effects may be noted in the behavioral sphere, especially in adolescents with Klinefelter syndrome compared to those who receive replacement therapy with testosterone for other purposes, for example, constitutional delay of growth and puberty.