Replacement of male mini-puberty

Abstract

Context: Clinical management of congenital hypogonadotropic hypogonadism (CHH) remains a challenge in pediatric endocrinology. Objective: To investigate whether daily subcutaneous injections of the recombinant human LH/FSH preparation could mimic the physiological male mini-puberty. Design and Setting: The REMAP (REplacement of MAle mini-Puberty) study with up to 10 years of follow-up. Patients and Intervention: Ten neonates or infants, all with bilateral cryptorchidism in intraabdominal/inguinal position and micropenis with the absence of neonatal male mini-puberty, received daily subcutaneous injections of Pergoveris® (LH/FSH 75/150 IU) for 3 months. Main Outcome Measures: Restoration of bilateral cryptorchidism/micropenis and the Leydig/Sertoli cells function. Results: At the end of treatment, median LH and FSH, both undetectable before treatment, reached high normal levels of 4.45 IU/L and supranormal levels 83 IU/L, respectively; median inhibin-b and anti-Mullerian hormone levels increased from subnormal (27.8 and 1.54 ng/mL, respectively) to normal levels (365 and 150 ng/mL, respectively); median testosterone increased from just detectable (0.02 ng/mL) to normal levels (3.3 ng/mL). Stretched penile length increased from a median of 2 to 3.8 cm. During therapy, all testes descended to the scrotal position (by the end of the first month in three patients, the second month in four patients, and the third month in three patients), measuring 1.5 mL and appearing normal in ultrasonography. Three infants received additional treatment with testosterone enanthate. In two infants, one of two testes regressed in the low inguinal area; both infantswere successfully treated surgically. After 1 to 10 years of follow-up, all testes are still in scrotal position and have slightly regressed in size. Conclusions: The proposed regimen mimics neonatal male mini-puberty and successfully treats infants with micropenis and cryptorchidism in CHH.