Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study

Objective: To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS). Design: In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population. Methods: Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer. Results: Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E-2) concentrations started to increase during puberty and inhibin B and anti-Mullerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P < 0.01), FSH (7.1 vs 2.5 U/l, P < 0.001), testosterone (18.7 vs 15.6 nmol/l, P < 0.01) and E2 (66 vs 46 pmol/l, P < 0.001) levels and lower AMH (33 vs 65 pmol/l, P < 0.01) and inhibin B (median 108 vs 187 pg/ml, P < 0.01) levels than the reference population. Conclusions: In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.