ESPE Abstracts (2016) 86 RFC15.8

Replacement of Male Mini-Puberty

Dimitrios T. Papadimitrioua,b, Dionysios Chrysisc, Georgios Zoupanosa, Georgia Nyktaria, Eleni Liakoua & Anastasios Papadimitrioub


aAthens Medical Center, Athens, Greece; bAttikon University Hospital, Athens, Greece; cUniversity Hospital of Patras, Patras, Greece


Background: Hormonal replacement in boys with congenital HH remains a challenge. Micropenis has been traditionally successfully treated with 3 monthly injections of testosterone enanthate before the age of 2, but when bilateral cryptorchidism coincides, surgery is required. But even after a successful surgery, the hypoplastic testes with the deficient proliferation of immature Sertoli cells, due mainly to the lack of the male mini-puberty in the neonatal period as well as the subsequent midinfancy surge in pulsatile gonadotropin secretion, are condemned in azoospermia and the boys in infertility.

Objective and hypotheses: We investigated whether early postnatal daily injections of the commercially available recombinant LH/FSH preparation (Pergoveris®) could mimic the physiological male mini-puberty and successfully resolve bilateral cryptorchidism, repair micropenis, reinstate normal growth velocity and restore the responses of the Leydig and Sertoli cells.

Method: Five neonates and infants, all with bilateral cryptorchidism in intra-abdominal position and micropenis [≤ 2 cm, (−2 SDS)] with absence of neonatal male mini-puberty, were treated for 3 months with daily s.c. injections of the recombinant LH 75+FSH 150 IU preparation (Pergoveris®). Case 1 had CHARGE syndrome diagnosed before choanal atresia. Cases 2 and 4 had non syndromic Kallmann syndrome. Case 3 (septo-optic dysplasia) and 5 (aplastic pituitary) had panhypopituitarism diagnosed in the neonatal ICU before symptomatic hypoglycemia and/or cholestatic jaundice.

Results: Median LH from undetectable reached high normal 6.5 IU/L and FSH supranormal levels 88 IU/L. Inhibine b and AMH from subnormal, reached high normal levels: median 248 pg/ml and 1025 pmol/L respectively. Testosterone increased from undetectable to a median of 2.42 ng/ml. In all cases testes descended in scrotal position by the end of the 1st in one, 2nd in two and 3rd month in two patients with a volume between 1.5 and 2.5 ml. In 4 cases with a follow-up of 1–5 yrs testes have slightly regressed to 0.5–1.5 ml but are still in scrotal position. Penile length increased to a median of 4.5 cm. During therapy all infants initiated catch-up growth. None presented any adverse events or reactions.

Conclusion: The proposed regimen mimics neonatal male mini puberty repairing micropenis and cryptorchidism and inducing high-normal activation of Leydig and Sertoli cells.

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