Hypogonadism pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Overview

Pathophysiology

Pathogenesis

Hypogonadism in males

  • The hypogonadism pathogenesis in males depends mainly on the testosterone deficiency. Testosterone secretion occurs as the following:
    • Testosterone is secreted in response to stimulation signals from the brain cortex to the hypothalamus. The hypothalamus by its role secrets the gonadotropin releasing hormones (GnRH).
    • GnRH stimulates the pituitary gland which by its role secretes the gonadal hormones the Follicle Stimulating Hormone (FSH) and the Luteinizing Hormone (LH).
    • In males, LH stimulates the leydig cells in the testes which produce testosterone by converting the cholesterol to testosterone.
    • Production of testosterone from the testes gives negative feed back to the pituitary. This feedback inhibit the production of FSH and LH from the pituitary.
  • Testosterone deficiency can occur when different acquired or congenital disease affect the organs responsible for its secretion. So, pathogenesis of the hypogonadism in males depends on the underlying cause.[1]
  • GnRH deficiency has a main role in hypogonadism pathogenesis in males as it leads to decrease of the gonadal hormone and deficiency of testosterone eventually.[2]
  • It has been proved that GnRH deficiency is associated with most cases of idiopathic hypogonadotrophic hypogonadism in males.

Genetic

  • Gentic mutations have a big role in development of the hypogonadism especially congenital hypogonadotropic hypogonadism. There are more than 25 genes participate in the pathogenesis of hypogonadism.[3]
  • In this table number of genes with the associated diseases causing hypogonadism are enlisted:
Associated disease Genes Mutation
ANOS 1
SOX 10
SEMA3A
IL17RD

References

  1. Kumar P, Kumar N, Thakur DS, Patidar A (2010). "Male hypogonadism: Symptoms and treatment". J Adv Pharm Technol Res. 1 (3): 297–301. doi:10.4103/0110-5558.72420. PMC 3255409. PMID 22247861.
  2. Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF (1987). "The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations". J Clin Endocrinol Metab. 64 (2): 283–91. doi:10.1210/jcem-64-2-283. PMID 3098771.
  3. Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L; et al. (2015). "Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment". Nat Rev Endocrinol. 11 (9): 547–64. doi:10.1038/nrendo.2015.112. PMID 26194704.

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