The Impact of Androgens on Abnormalities of Male Genital Development and Size

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From Conception to Adulthood: The Impact of Androgens on Abnormalities of Male Genital Development and Size (2022)
Sarah A. Holzman, Carol A. Davis-Dao, and Antoine E. Khoury


Abstract

Androgens play a critical role in male development starting in utero. In a 46XY male patient, testosterone plays a significant role in the development of the internal genitalia while external genitalia formation is largely dependent on the conversion of testosterone to dihydrotestosterone (DHT). Testosterone is important for testicular descent and later, the onset of puberty. Defects in the production of testosterone, the conversion of testosterone to DHT, or within the androgen receptor can lead to a variety of pediatric urological conditions including micropenis, cryptorchidism, hypospadias, and disorders of sexual differentiation. Supplementation with testosterone is the standard of care for the treatment of micropenis and is used to increase glans size and reduce complications before hypospadias repair. Unfortunately, patients with a 5-alpha reductase deficiency will respond suboptimally to testosterone supplementation and instead may benefit from DHT supplementation.




Introduction

Androgens play an important role in male development and impact many common pediatric urological conditions. In utero, testosterone is critical for male internal genitalia development including testicular descent, and conversion of testosterone to dihydrotestosterone (DHT) is responsible for the development of external male genitalia. Postnatally, androgens lead to increased penile length during mini-puberty. During puberty, testosterone is responsible for the development of secondary sex characteristics.

Defects in testosterone production, its conversion to DHT, and the androgen receptor (AR) are the source of many of the common urological pathologies with phenotypes ranging from female in complete androgen insensitivity syndrome (CAIS) to male with hypospadias and/or micropenis. In addition, testosterone supplementation is useful in the treatment of micropenis during childhood. In this study, we discuss the involvement of testosterone and DHT in normal development and the impact of androgens in the development of common pediatric urological conditions. We also discuss the use of testosterone and DHT to treat micropenis with and without associated hypospadias.





Part I: Testosterone in normal development Prenatal.


Postnatal development

-Neonatal period and mini-puberty
-Puberty





Part II: Testosterone in pathological states AR gene mutations

-Micropenis
-5-Alpha reductase deficiencies
-Testosterone and DHT supplementation





Conclusions

Androgens play a critical role in the development of both internal and external male genitalia. Androgen abnormalities affect numerous pediatric urologic conditions and can have a wide range of phenotypes. Testosterone supplementation is useful in micropenis management as well as preoperative management of boys with hypospadias and small glans. More recently, DHT transdermal gel supplementation can be used for boys with micropenis and 5-alpha reductase deficiency and potentially as an option for boys with micropenis and/or preoperative hypospadias treatment.
 

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