4. Disorders of Sexual Differentiation (DSDs)

·       5α-reductase deficiency.

    • Inability to convert testosterone to DHT
    • Ambiguous genitalia at birth; masculinization at puberty

·       Androgen insensitivity syndrome (AIS) ) or Male pseudo hermaphroditism

o   XY individual with non-functional androgen receptors → female external phenotype without uterus or fallopian tubes

·       Congenital adrenal hyperplasia (CAH) or Female pseudo hermaphroditism

o   XX individual with excess androgen production by the adrenal gland → virilized external genitalia.

·       Hermaphroditism or Ovotesticular DSD

o   a rare condition in which an individual possesses both ovarian and testicular tissue—either in the same gonad (ovotestis) or in opposite gonads.

§  46,XX testicular DSD: Translocation of SRY to X chromosome.

§  46,XY gonadal dysgenesis: Mutations in SRY or downstream genes.

Causes of DSDs

1.     Genetic Factors:

◦       Many DSDs have a genetic basis, involving mutations in genes responsible for sex determination and development. 

2.     Hormonal Factors:

◦       Imbalances or deficiencies in hormones like androgens or other sex hormones can lead to DSDs. 

3.     Environmental Factors:

◦       While less understood, environmental factors may also play a role in some cases.