Infant boys born with a rare form of congenital hypogonadotropic hypogonadism, a condition associated with micropenis and undescended testes, experienced an improvement in symptoms after 3 months of combination treatment with two fertility hormones, according to findings published in the Journal of the Endocrine Society.
“Micropenis has been traditionally successfully treated, usually with 3 monthly injections of testosterone enanthate, ideally in the post-neonatal period or in early infancy, but when bilateral cryptorchidism coincides, two surgical operations are usually required,” Dimitrios T. Papadimitriou, MD, PhD, a pediatric endocrinologist and director of the department of pediatric-adolescent endocrinology and diabetes at Athens Medical Center in Greece, and colleagues wrote in the study background. “Even after successful surgery though, the hypoplastic testes with the deficient proliferation of immature Sertoli cells before and during puberty — 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 —result in azoospermia and infertility later in adult life.”
Papadimitriou and colleagues analyzed data from 10 infants with bilateral cryptorchidism and micropenis ( 2 cm) with absence of male mini-puberty, confirmed with at least three repeated measurements of undetectable levels of luteinizing hormone, follicle-stimulating hormone and testosterone between ages 2 weeks and 3 months. At a median age of 4 months, infants received daily subcutaneous injections of recombinant LH plus FSH (Pergoveris, Merck) for 3 months, receiving a total dose of 6,750 IU of LH and 13,500 IU of FSH. Parents were trained to administer injections at home, and infants were monitored monthly. Researchers assessed levels of LH, FSH, testosterone, anti-Müllerian hormone and serum inhibin-b. Primary outcomes were the resolution of bilateral cryptorchidism, repair of micropenis and restored Leydig and Sertoli cell function.
At the end of treatment, median LH and FSH levels for the cohort from undetectable levels at baseline to 4.45 IU/L and 83 IU/L, respectively. Median inhibin-b rose from 27.8 pg/mL at baseline to 365 pg/mL, whereas AMS rose from a median of 1.54 ng/mL at baseline to 150 ng/mL. Median testosterone rose from 0.02 ng/mL at baseline to 3.3 ng/mL at the end of treatment, according to researchers.
During treatment, researchers observed that all testes descended into the scrotal position by 3 months, with a median measurement of 1.5 mL in ultrasonography. Stretched penile length also increased from a median of 2 cm to 3.8 cm by 3 months.
After 3 to 10 years of follow-up, all testes remained in the scrotal position, the researchers noted; however, testes slightly regressed in size to a median of 1 mL. No children presented with signs of spontaneous pubertal maturation, according to researchers.
“Timely replacement of the neonatal male mini-puberty by daily [subcutaneous] injections of the commercially available [combination LH/FSH] for 3 months repairs even intra-abdominal cryptorchidism safely and cost-effectively, inducing high/normal activation of Sertoli and Leydig cells,” the researchers wrote. “This strategy corrects genital hypotrophy, restores testicular endocrine function and may improve the response to future treatments intended to induce fertility.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.