Horm Metab Res
DOI: 10.1055/a-2343-4696
Original Article: Endocrine Care

Investigational Treatment of Congenital Hypogonadotropic Hypogonadism in Infants

Xiaoya Ren
1   Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
,
Yi Wang
1   Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
,
Ying Liu
2   Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
,
Chunxiu Gong
1   Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
› Institutsangaben

Abstract

The aim of the study was to investigate whether the administration of gonadotropins to mimic the physiological development of infants with congenital hypogonadotropic hypogonadism (CHH) after birth can facilitate testicular descent, penile growth, and ultimately preserve fertility. This study included eight infants with CHH who received a gonadotropin-releasing hormone (GnRH) pump or human chorionic gonadotropin (HCG) combined with human menopausal gonadotropin (HMG) therapy at Beijing Children's Hospital from August 2018 to March 2023. The age of the infants ranged from 6 months to 2 years. 2. For literature review, a search was conducted in the PubMed database using the keywords “congenital hypogonadotropic hypogonadism,” “infants,” and “mini-puberty” up until June 2023. After 1–3 months of treatment, significant increases were observed in PL and TV. The testes descended from the inguinal region to the scrotum. Serum T and INH-B levels increased from being undetectable to 737.1±409.5 ng/dl and from 47.88±23.03 to 168.94±59.34 pg/ml, respectively. In a comparative literature review of 22 infants with CHH, the age at treatment initiation ranged from 0.5 to 7.9 months. Treatment involved various dosages and durations, ranging from 2 to 6 months of subcutaneous injections of LH and FSH. Both therapies successfully improved PL, TV, and testicular descent; reduced the need for surgery; and were safe. This is the first report of the use of a GnRH pump for the treatment of infant CHH.



Publikationsverlauf

Eingereicht: 13. März 2024

Angenommen nach Revision: 06. Juni 2024

Artikel online veröffentlicht:
09. Juli 2024

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  • References

  • 1 Bouvattier C, Maione L, Bouligand J. et al. Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism. Nat Rev Endocrinol 2011; 8: 172-182
  • 2 Main KM, Schmidt IM, Skakkebaek NE. A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab 2000; 85: 4905-4907
  • 3 Braslavsky D, Grinspon RP, Ballerini MG. et al. Hypogonadotropic hypogonadism in infants with congenital hypopituitarism: a challenge to diagnose at an early stage. Horm Res Paediatr 2015; 84: 289-297
  • 4 Liu Y, Ren XY, Peng YG. et al. Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism. Chin Med J 2021; 134: 1152-1159
  • 5 Boukari K, Meduri G, Brailly-Tabard S. et al. Lack of androgen receptor expression in Sertoli cells accounts for the absence of anti-Mullerian hormone repression during early human testis development. J Clin Endocrinol Metab 2009; 94: 1818-1825
  • 6 Bergadá I, Milani C, Bedecarrás P. et al. Time course of the serum gonadotropin surge, inhibins, and anti-Müllerian hormone in normal newborn males during the first month of life. J Clin Endocrinol Metab 2006; 91: 4092-4098
  • 7 Rey RA, Musse M, Venara M. et al. Ontogeny of the androgen receptor expression in the fetal and postnatal testis: its relevance on Sertoli cell maturation and the onset of adult spermatogenesis. Microsc Res Tech 2009; 72: 787-795
  • 8 Winter JS, Hughes IA, Reyes FI. et al. Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. J Clin Endocrinol Metab 1976; 42: 679-686
  • 9 Forest MG, Cathiard AM, Bertrand JA. Evidence of testicular activity in early infancy. J Clin Endocrinol Metab 1973; 37: 148-151
  • 10 Boas M, Boisen KA, Virtanen HE. et al. Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys. Eur J Endocrinol 2006; 154: 125-129
  • 11 Cortes D, Müller J, Skakkebaek NE. Proliferation of Sertoli cells during development of the human testis assessed by stereological methods. Int J Androl 1987; 10: 589-596
  • 12 Koskenniemi JJ, Virtanen HE, Wohlfahrt-Veje C. et al. Postnatal changes in testicular position are associated with IGF-I and function of Sertoli and Leydig cells. J Clin Endocrinol Metab 2018; 103: 1429-1437
  • 13 Russell LD, Ren HP, Sinha Hikim I. et al. A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell. Am J Anat 1990; 188: 21-30
  • 14 Toulis KA, Iliadou PK, Venetis CA. et al. Inhibin B and anti-Mullerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies. Hum Reprod Update 2010; 16: 713-724
  • 15 Hatipoğlu N, Kurtoğlu S. Micropenis: etiology, diagnosis and treatment approaches. J Clin Res Pediatr Endocrinol 2013; 5: 217-223
  • 16 Ren X, Tian Y, Feng G. et al. Hormonal changes throughout puberty in boys: an observational study on the treatment outcome of congenital hypogonadotropic hypogonadism. Chin Med J 2021; 135: 362-364
  • 17 Bougnères P, François M, Pantalone L. et al. Effects of an early postnatal treatment of hypogonadotropic hypogonadism with a continuous subcutaneous infusion of recombinant follicle-stimulating hormone and luteinizing hormone. J Clin Endocrinol Metab 2008; 93: 2202-2205
  • 18 Sarfati J, Bouvattier C, Bry-Gauillard H. et al. Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life. Orphanet J Rare Dis 2015; 10: 71
  • 19 Stoupa A, Samara-Boustani D, Flechtner I. et al. Efficacy and safety of continuous subcutaneous infusion of recombinant human gonadotropins for congenital micropenis during early infancy. Horm Res Paediatr 2017; 87: 103-110
  • 20 Main KM, Schmidt IM, Toppari J. et al. Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH. Eur J Endocrinol 2002; 146: 75-79
  • 21 Kohva E, Huopio H, Hietamäki J. et al. Treatment of gonadotropin deficiency during the first year of life: long-term observation and outcome in five boys. Hum Reprod (Oxford, England) 2019; 34: 863-871
  • 22 Lambert AS, Bougneres P. Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion. Int J Pediatr Endocrinol. 2016 13. DOI: 10.1186/s13633-016-0031-9
  • 23 Rohayem J, Alexander EC, Heger S. et al. Mini-puberty, physiological and disordered: consequences, and potential for therapeutic replacement. Endocr Rev 2024; 00: 1-33
  • 24 Quinton R, Mamoojee Y, Jayasena CN. et al. Society for endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty. Clin Endocrinol (Oxf) 2017; 86: 305-306