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Effects of an Early Postnatal Treatment of Hypogonadotropic Hypogonadism with a Continuous Subcutaneous Infusion of Recombinant Follicle-Stimulating Hormone and Luteinizing Hormone

Department of Pediatric Endocrinology (P.B., M.F., L.P., D.R., C.B.) and Pediatric Hormone Laboratory (N.L.), Hôpital Saint Vincent de Paul, Pôle d’Endocrinologie Cochin, University René Descartes, F-75014 Paris, France; Serono France (E.D.) 92658 Boulogne Cedex, France

Address all correspondence and requests for reprints to: P. Bougnères, Pediatric Endocrinology, Hôpital Saint Vincent de Paul, Pôle d’Endocrinologie Cochin, University René Descartes, F-75014 Paris, France. E-mail: bougneres{at}paris5.inserm.fr.

Background: The neonatal-midinfancy surge in pulsatile gonadotropin secretion is attributable to an increase in GnRH pulse amplitude and is associated with a rapid expansion of Leydig and Sertoli cell populations with concomitant surges in testosterone, inhibin, and anti-Mullerian hormone production as well as an increase in testicular volume. Boys with congenital hypogonadotropic hypogonadism (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: The objective of the study was to investigate whether early postnatal continuous sc infusion 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 microorchidism were treated for 6 months with high doses of recombinant LH and FSH (a gift of Luveris and Gonal-F from Serono, Lyon, France) delivered sc with an insulin pump.

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

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