Testosterone and the child (0–12 years) with Klinefelter syndrome (47XXY): a review

Abstract

There is an absence of data that directly address the risks and benefits of testosterone therapy in prepubertal children with KS outside of the entity of microphallus. At this time, there is no other documented benefit for testosterone therapy in these children.

A qualitative exploration of mothers’ and fathers’ experiences of having a child with Klinefelter syndrome and the process of reaching this diagnosis

“…1 The majority exhibit a 47,XXY karyotype, although mosaicism or the presence of more than one supernumerary X chromosome are also observed. 2,3 The physical and non-physical features, as well as the comorbidities, are highly varied, [4][5][6][7][8][9][10] but most commonly include small testes, gynaecomastia, azoospermia, language and learning problems and behavioural and psychosocial difficulties. [11][12][13][14] In spite of its high incidence, 75% will remain undiagnosed throughout their lifetime 15,16 and only 10% will be diagnosed before puberty.…”

Advances in the Interdisciplinary Care of Children with Klinefelter Syndrome

“…108 Evidence to support this includes a higher prevalence of underdeveloped genitalia and cryptorchidism in infants, reduced germ cell number in testicular biopsies, smaller testicular size, and several studies suggesting a blunted testosterone surge during the mini-puberty period of infancy. 109–112 Some endocrinologists measure testosterone, LH, and FSH around 6–12 weeks of life during the mini-puberty period of infancy.…”

The role of hypogonadism in Klinefelter Syndrome

“…Beginning already in fetal life, a loss of germ cells that continues during infancy and accelerates through puberty leads to fibrosis and hyalinization of seminiferous tubules as well as hyperplasia of Leydig cells, which ultimately results in small firm testes (typically < 3 ml) seen in adults and azoospermia 13. At birth some KS boys may show signs of intrauterine hypogonadism such as micropenis or cryptorchism1415 and although anecdotal, testosterone injections may alleviate this problem 1416. Conflicting data regarding the surge in testosterone (mini-puberty) during the first 3 months has been published; demonstrating either low levels of testosterone,17 high-normal levels of testosterone18 or low-normal testosterone 19.…”

“…did find a better neuro-developmental outcome in KS boys ( n = 34) treated with testosterone in infancy (because of micropenis) compared with KS nontreated boys ( n = 67), but unfortunately, the treatment was not randomized or blinded, leaving the study with a great potential for selection bias. However, current knowledge does not support systematic treatment with testosterone in infancy except for cases of micropenis 16. Randomized controlled trials (RCTs) are needed to confirm a possible positive effect of testosterone treatment in infancy before treatment should be offered to all boys with KS.…”

“…A few studies have investigated the level of testosterone in KS neonates, but have been equivocal reporting either decreased or normal/high testosterone levels 1718. Some evidence for androgen deficits in KS prenatally has been indicated by the increased prevalence of microphallus and cryptorchidism16 seen in KS. Before any conclusion regarding the impact of testosterone deficiency in infancy on the cognitive and psychological phenotype can be drawn, more conclusive studies about testosterone levels in infants and follow up studies investigating the correlations between infant testosterone level and neuropsychological phenotype have to be performed.…”