Background: The neonatal-mid-infancy surge in pulsatile gonadotropin secretion is attributable to an increase in GnRH pulse amplitude and is associated with 1) a rapid expansion of Leydig and Sertoli cell populations with concommittant surges in testosterone, inhibin and AMH production; and 2) an increase in testicular volume. Boys with congenital HH do not activate these processes. A potential cause for azoospermia and infertility in adult life is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH.

Objective: To investigate whether early postnatal continuous subcutaneous infusion (CSI) of gonadotropins could mimic the physiological growth of testes and to evaluate responses of the Leydig and Sertoli cells to early gonadotropin replacement.

Design and Methods: Two neonates (P1 with hypotuitarism and P2 with HH) with micropenis and micro-orchidism were treated for 6 months with high doses of recombinant LH and FSH (a gift of Luveris and Gonal-F, from Serono) delivered subcutaneously with an insulin pump.

Results: Gonadotropin CSI increased mean serum LH and FSH to normal or supranormal levels. Mean testosterone increased from undetectable levels to 7.6 and 5.2 nmol/L, respectively in P1 and P2. Inhibin B and anti-Müllerian hormone (AMH) increased to normal levels. Mean testicular volume increased from 0.45–0.57 ml at birth to 2.10 ml at 7 months. Stretched penile length increased from 8 to 30 mm (P1) and from 12 to 48 mm (P2).

Conclusions: The present regimen induced physiological postnatal testes growth and high-normal activation of Leydig and Sertoli cells.