Testicular function in Klinefelter syndrome

Abstract

Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism, but the phenotype becomes evident only after puberty. During childhood, and even during early puberty, pituitary-gonadal function in 47,XXY subjects is relatively normal, but from midpuberty onwards, FSH and LH levels increase to hypergonadotropic levels, inhibin B decreases to undetectable levels, and testosterone after an initial increase levels off at a low or low-normal level. Hence, most adult KS males display a clear hypergonadotropism with a varying degree of androgen deficiency; subsequently, testosterone substitution therapy is widely used to prevent symptoms and sequels of androgen deficiency. Testicular biopsies of prepubertal KS boys have shown preservation of seminiferous tubules with reduced numbers of germ cells, but Sertoli and Leydig cells have appeared normal. The testes in the adult KS male are, however, characterized by extensive fibrosis and hyalinization of the seminiferous tubules, and hyperplasia of the interstitium, but the tubules may show residual foci of spermatogenesis. Introduction of testicular sperm extraction in combination with intracytoplasmic sperm injection techniques has allowed non-mosaic KS males to father children.