Testicular function during puberty and young adulthood in patients with Klinefelter's syndrome with and without spermatozoa in seminal fluid

Patients with Klinefelter's syndrome experience progressive testicular degeneration resulting in impaired endocrine function and azoospermia. What proportion of adolescents develop testosterone deficiency during puberty and how many have spermatozoa in their semen is unclear to date. We aimed to investigate testicular function during puberty and young adulthood in patients with Klinefelter's syndrome and to assess testosterone effects in target tissues. The clinical data of 281 patients with non-mosaic Klinefelter's syndrome aged 10-25 years without previous testosterone replacement were reviewed. In late pubertal adolescents, semen analyses were evaluated, and testicular volumes, hormone and haemoglobin (Hb) levels, the number of CAG repeats and final height data were compared to those of 233 age-matched controls with pubertal gynaecomastia. Spontaneous pubertal virilisation to Tanner stages IV-V occurred. Serum T levels >= 10 nmol/L were reached in 62% of patients with Klinefelter's syndrome and in 85% of controls at ages 15-25 (T-KFS: 12.2 +/- 5.4 vs. TC: 16.6 +/- 7.2 nmol/L). LHKFS levels were elevated >= 10 U/L in 84%, and normal in all controls (LHKFS: 18.6 +/- 12.2 vs. LHC: 3.5 +/- 1.6 U/L). In nine of 130 (7%) adolescents with Klinefelter's syndrome, spermatozoa (oligozoospermia) were found in semen; all had T levels >7 nmol/L and eight of nine had LH levels <= 18 U/L, while their hormone levels, number of CAG repeats and testicular volumes were not different from those of adolescents with azoospermia. Controls had normal sperm concentrations in 73% (46/63). Semen volumes(KFS) were normal in 55% vs. 78% in controls; Hb(KFS) was normal in 89% (Hb(C): 97%). Mean final height(KFS) was 185 +/- 8 cm vs. 181 +/- 7 cm in controls. Hypergonadotropic hypogonadism develops during early puberty in adolescents with Klinefelter's syndrome and remains compensated in over 60% during ages 15-25, with sufficient testosterone secretion for spontaneous accomplishment of pubertal development. Spermatozoa in semen are rare and associated with T levels >7 nmol/L. Parameters reflecting androgen deficiency in target tissues may help to optimise timing of testosterone substitution, which should preferably not be initiated before fertility status has been clarified.