Background: Hormonal replacement in boys with congenital Hypogonadotrophic Hypogonadism (HH) as well as hormonal repair of bilateral cryptorchidism and micropenis remain a challenge in pediatric endocrinology.
Methods: In the «REMAP» study ISRCTN13007297 eight neonates and infants, all with bilateral cryptorchidism in intra-abdominal position and micropenis (≤2 cm), with absence of neonatal male-mini puberty were treated for 3 months with daily subcutaneous injections of the recombinant LH 75 plus FSH 150 IU preparation (Pergoveris®) from 2009 to 2018. One had CHARGE syndrome diagnosed before choanal atresia. Three had non-syndromic and one syndromic Kallmann syndrome diagnosed in the neonatal period. Two had septo-optic dysplasia with panhypopituitarism and one aplastic pituitary all diagnosed in the neonatal ICU before symptomatic hypoglycemia and/or cholestatic jaundice.
Results: Median LH and FSH, from undetectable reached high normal levels 6.4 IU/l and FSH supranormal levels 86 IU/l. Inhibine b and AMH from subnormal, reached high normal levels: median 241 pg/ml and 1034 pmol/l respectively. Testosterone levels increased from undetectable to a median of 2.20 ng/ml. In all cases testes descended in scrotal position by the end of the 1st in two, 2nd in three and 3rd month in three patients with a volume ranging between 1.5 and 2.5 ml. Penile length increased to a median of 4.3 cm In one case with septo-optic dysplasia one of the two testes needed surgical stabilization as 6 months after completion of treatment it regressed in low inguinal position. The same boy needed a supplementary treatment with 3 monthly I.M. injections of 50 mg testosterone enanthate increase penile length from 3.5 to 5 cm (50th percentile for age). In all cases with a follow-up up to 8 years testes have slightly regressed to 0.5 1.5 ml but are still in scrotal position. During therapy, all infants seemed to have initiated catch-up growth. All testes had a normal ultrasonography after treatment completion. None presented any adverse events or reactions local or systemic.
Conclusions: In our series, the total dose administered to each patient was 6,750 IU of LH and 13,500 IU of FSH, analogous to that of Bougneres et al. JCEM 2008;93:22025, which is the work of reference. The proposed regimen mimics neonatal male mini puberty successfully repairing micropenis and cryptorchidism in HH. This strategy corrects genital hypotrophy, restores testicular endocrine function, and may improve the response to future treatments intended to restore fertility.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology