Partial androgen insensitivity may be the reason for impaired fertility in men with Noonan Syndrome
Jovanna Dahlgren, Carina Ankarberg-Lindgren & Otto Westphal
Background: Some previous reports point out undescended testes (UT) to be the main course of impaired fertility in males with Noonan syndrome (NS). Whether abnormities in gonadal function are present during prepuberal years or appear during pubertal development has not been investigated previously.
Objective: To study the gonadal development during prepubertal and pubertal years in NS males.
Patients: Twelve short NS males were followed from prepubertal years (median age 11, range 1012) throughout puberty until adulthood (median age 21 years, range 1829). Bilateral UT was found in four and unilateral UT in one male. All of these except one were surgical treated before start of puberty. The NS group was compared with an age-matched male reference population.
Methods: Gonadotrophins, testosterone, estradiol and inhibin B concentrations were determined by immunoassays and testicular volume by orchidometer.
Results: Only one of four adult NS males who underwent bilateral surgical treatment of UT had normal testicular volumes. All males with bilateral UT had at adult age elevated LH and FSH levels compared with the spontaneous descended group (median 10.9 and 25.8 U/l vs 4.4 and 5.1 U/l, P<0.01) and compared with the reference population (4.0 and 2.5 U/l, P<0.05). Inhibin B reached a peak level during early to mid-puberty in all NS males, but to a lower level in the bilateral UT-group compared to descended group (116 vs 227 pg/ml, P<0.01), and declined to subnormal concentrations at adulthood (23 vs 139 pg/ml, P<0.001).
Conclusion: As previously reported, bilateral UT was found to be the main factor contributing to impaired gonadal function in a substantial minority (30%) of NS males. Interestingly, this was unrelated to whether surgery was performed at a young age and to the achievement of normal testicular volume.