5α-Reductase deficiency

5α-Reductase deficiency is an autosomal recessive intersex condition caused by a mutation of the 5α-reductase type II gene. 5α-Reductase deficiency is an autosomal recessive intersex condition caused by a mutation of the 5α-reductase type II gene. Individuals with 5-ARD are born with male gonads, including testicles and Wolffian structures. They can have normal male external genitalia, ambiguous genitalia, or normal female genitalia, but usually tend towards a female appearance. The development of the genital tubercle tissue (which by week 9 of a fetus' gestation becomes either a clitoris or a penis) tends towards a size qualifying it as an ambiguous macroclitoris/micropenis (large clitoris/small penis), and the urethra may attach to the phallus. If the condition has not already been diagnosed, it usually becomes apparent at puberty around age twelve with primary amenorrhoea and virilization. This may include descending of the testes, hirsutism (facial/body hair considered normal in males – not to be confused with hypertrichosis), deepening of the voice, and enlargement of the clitoris into what would then be classed as a penis. In adulthood, individuals do not experience male-pattern baldness. As dihydrotestosterone (DHT) is a far more potent androgen than testosterone alone, virilization in those lacking DHT may be absent or reduced compared to males with functional 5-AR. It is hypothesized that rising testosterone levels at the start of puberty are able to generate sufficient levels of DHT either by the action of 5α-reductase type I (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5α-reductase type II in the testes. 5-ARD is associated with an increased risk of cryptorchidism and testicular cancer. Since the gonad tissue develops into testes rather than ovaries, they are thus unable to create ova but may be able to create sperm. Male fertility can still be possible if viable sperm is present in the testes and is able to be extracted. In general, individuals with 5-ARD are capable of producing viable sperm. Although the external genitalia can sometimes be completely female, the vagina consists of only the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch. Because of normal action of Müllerian inhibiting factor produced by the testes in utero, individuals with 5-ARD lack a uterus and Fallopian tubes. Thus, they would not physically be able to carry a pregnancy in any event. Even with treatments such as surrogate motherhood, female infertility is caused by the lack of any ova to implant in a surrogate mother. In individuals with an ambiguous genital resulting in a macroclitoris/micropenis, the genital may be capable of ejaculations as well as erections, but may be of insufficient size for penetrative sexual intercourse.