Androgens During Infancy, Childhood, and Adolescence: Physiology and Use in Clinical Practice

Abstract

We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.

Hormonal Effects on Hair Follicles

“…The sources of androgen are the adrenal glands, the gonads (ovaries, testes), the brain, and the placenta in pregnant women. Androgens exert their action through intracellular receptors [ 3 ]. The adrenal glands are the source of DHEA and DHEA-S, which are relatively weak androgens.…”

“…This review provides a comprehensive up-to-date understanding of the subject of the hormonal effects on the hair follicle. This review also highlights the significant progress in research that has been made in recent years on the effects of hormonal changes on hair at different stages of the life of women [ 3 ].…”

GnRH Deficient Patients With Congenital Hypogonadotropic Hypogonadism: Novel Genetic Findings in ANOS1, RNF216, WDR11, FGFR1, CHD7, and POLR3A Genes in a Case Series and Review of the Literature

“…Regarding the reproductive phenotype, male KS patients with ANOS1 variants display a complete penetrance of CHH and their pre- and postnatal gonadotropin deficit is severe with a high frequency of micropenis, cryptorchidism and complete absence of gonadal development ( 15 , 16 ).…”

“…Current research regarding the pathophysiology of CHH provides evidence that genetic abnormalities play a key role in the development of the disease and is estimated that a genetic cause is apparent in almost 50% of CHH cases ( 1 , 6 ). Up-to-date there have been reported more than 60 putative loci for CHH, 17 of which have been linked with KS ( 1 , 6 , 13 – 16 ).…”

Editorial: New Aspects in Hypogonadism

“…Testosterone and estradiol play critical, wide-ranging roles during development, before and beyond the traditional notion of a reproductive lifespan. In fetal life, testosterone is crucial for sexual differentiation and the proper development of male external genitalia ( 1 ). During late pregnancy and the first 6 months of neonatal life (i.e., minipuberty), testosterone and follicle-stimulating hormone play a major role in priming the male reproductive axis for fertility potential in later life ( 2 ).…”