Paediatric and adult-onset male hypogonadism

Abstract

The hypothalamic–pituitary–gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of coordinated activities is carried out leading to sustained testicular endocrine function, with gonadal testosterone production, as well as exocrine function, with spermatogenesis. Conditions impairing the hypothalamic–pituitary–gonadal axis during paediatric or pubertal life may result in delayed puberty. Late-onset hypogonadism is a clinical condition in the ageing male combining low concentrations of circulating testosterone and specific symptoms associated with impaired hormone production. Testosterone therapy for congenital forms of hypogonadism must be lifelong, whereas testosterone treatment of late-onset hypogonadism remains a matter of debate because of unclear indications for replacement, uncertain efficacy and potential risks. This Primer focuses on a reappraisal of the physiological role of testosterone, with emphasis on the critical interpretation of the hypogonadal conditions throughout the lifespan of the male individual, with the exception of hypogonadal states resulting from congenital disorders of sex development.

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Fig. 1: The hypothalamic–pituitary–gonadal axis.
Fig. 2: Anatomical changes and serum hormone levels associated with male sex determination and maturation.
Fig. 3: Pathophysiology of hypogonadism.
Fig. 4: Pathophysiology of congenital secondary hypogonadism.
Fig. 5: Relationship between age, BMI and reproductive hormones.
Fig. 6: Diagnostic algorithm for hypogonadism in pubertal age.

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Introduction (A.S.); Epidemiology (G.R. and G.H.); Mechanisms/pathophysiology (S.B.S. and I.T.H.); Diagnosis, screening and prevention (R.A.R. and W.J.G.H.); Management (M.R.P., G.C. and G.R.D.); Quality of life (M.K.); Outlook (Y.-M.C. and M.M.); Overview of Primer (A.S.).

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Correspondence to Andrea Salonia.

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Salonia, A., Rastrelli, G., Hackett, G. et al. Paediatric and adult-onset male hypogonadism. Nat Rev Dis Primers 5, 38 (2019). https://doi.org/10.1038/s41572-019-0087-y

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