Efficacy and Safety of Continuous Subcutaneous Infusion of Recombinant Human Gonadotropins for Congenital Micropenis during Early Infancy

Abstract

Background: Early postnatal administration of gonadotropins to infants with congenital hypogonadotropic hypogonadism (CHH) can mimic minipuberty, thereby increasing penile growth. We assessed the effects of gonadotropin infusion on stretched penile length (SPL) and hormone levels in infants with congenital micropenis. Methods: Single-center study including 6 males with micropenis in case of isolated CHH (n = 4), panhypopituitarism (n = 1), and partial androgen insensitivity syndrome (PAIS; n = 1). Patients were evaluated at baseline, monthly and at the end of the study through a clinical examination (SPL, testicular position and size), serum hormone assays (testosterone, luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-Müllerian hormone [AMH]), and ultrasound of penis/testes. Results: In CHH, significant increases occurred in serum testosterone (from undetectable level to 3.5 ± 4.06 ng/mL [12.15 ± 14.09 nmol/L]), SPL (from 13.8 ± 4.5 to 42.6 ± 5 mm; p < 0.0001), inhibin B (from 94.8 ± 74.9 to 469.4 ± 282.5 pg/mL, p = 0.04), and AMH (from 49.6 ± 30.6 to 142 ± 76.5 ng/mL, p = 0.03). Micropenis was corrected in all patients, except one. On treatment, in the patient with PAIS, SPL was increased from 13 to 38 mm. Conclusions: Early gonadotropin infusion is a safe, well-tolerated and effective treatment. The effect in PAIS has not been reported previously. Long-term follow-up is needed to assess the impact, if any, on future fertility and reproduction.

Correlation of anti‐Mullerian hormone with humanchorionic gonadotropin test in the evaluation of testicular function of children with 46 XY male hypogonadism: Use of anti‐Mullerian hormone as abiomarker

“…It was found that AMH values higher than 125 pmol/L and hCG responses higher than 238 pmol/L, as well as AMH values higher than 110 pmol/L and hCG responses higher than 189 pmol/L, could be used as diagnostic values to differentiate between UT and micropenis, respectively. There are AMH values different from those stated here that are related to cryptorchidism and micropenis in the literature . Some studies indicate that AMH values vary depending on testis localisation .…”

“…There are AMH values different from those stated here that are related to cryptorchidism and micropenis in the literature. 19,20 Some studies indicate that AMH values vary depending on testis localisation. 21,22 A more primary localisation of the testis means lower values of AMH.…”

Male Central Hypogonadism in Paediatrics – the Relevance of Follicle-stimulating Hormone and Sertoli Cell Markers

“…Similar results were observed in patients receiving continuous subcutaneous infusion of rh gonadotropins. 46 Even though long-term follow-up is needed to fully evaluate the outcomes of this therapeutic approach, these results suggest that subcutaneous gonadotropin infusion is able to induce not only Sertoli cell proliferation and function but also testis descent in patients with congenital central hypogonadism, thus avoiding surgical treatment. 47 …”

Ontogeny of Hypothalamus-Pituitary Gonadal Axis and Minipuberty: An Ongoing Debate?

“…However, targeted neonatal treatment for cryptorchid boys with absent minipuberty might reveal significantly higher success rates (75,76). Table 1 summarizes available studies on gonadotropin treatment in order to replace minipuberty in infants with congenital hypogonadotrophic hypogonadism (77)(78)(79)(80)(81)(82)(83). In patient with congenital central hypogonadism, the impairment of HPG axis ontogeny results in a profound perturbation of germ cell-specific gene expression during late gestation with cryptorchidism at birth, and abnormal germ cell development and differentiation during minipuberty (31).…”