5-Alpha-Reductase Deficiency

5-alpha-reductase deficiency is a rare inherited condition that affects sexual development before birth and during puberty. People with the condition have one X and one Y chromosome and have testes, and they produce testosterone normally. What they cannot do normally is convert that testosterone into dihydrotestosterone (DHT), the more potent androgen that external genital development before birth depends on.

The cause is a change in the SRD5A2 gene, which carries the instructions for the enzyme steroid 5-alpha reductase 2 — the enzyme that performs the conversion. Inheritance is autosomal recessive: both copies of the gene carry a variant, and parents who carry one altered copy typically have no signs of the condition themselves. Someone with two variant copies and two X chromosomes is not physically affected, because female development does not depend on DHT.

How it presents

Appearance at birth varies considerably. External genitalia may appear female, may be male-typical with a small penis and hypospadias, or may not look clearly male or female. At puberty, rising testosterone produces some secondary sex characteristics — increased muscle mass, a deeper voice, pubic hair and a growth spurt — and the penis and scrotum may grow. Facial and body hair tend to remain sparse. MedlinePlus records that most affected people are infertile and cannot have biological children without assisted reproduction.

The condition is rare and its exact incidence is not known. Large affected families have been described in several countries, among them the Dominican Republic, Papua New Guinea, Turkey and Egypt.

How it is evaluated

Because the problem is a conversion step rather than a missing hormone, no single hormone measurement identifies it. Testosterone can be normal or raised while DHT is low, so what carries the information is the relationship between the two. Both laboratories that run the dihydrotestosterone assay name evaluating a possible 5-alpha-reductase deficiency as an intended use of the test, and point to the testosterone-to-DHT ratio rather than DHT alone. Genetic testing of SRD5A2 identifies the underlying change.

A DHT result on its own, without a testosterone beside it, does not establish this diagnosis — and a low DHT is not evidence of it, since a 5-alpha-reductase inhibitor such as finasteride or dutasteride lowers DHT by design.

Getting care

This is a condition of sex development, and evaluation belongs with a specialist team — typically paediatric endocrinology and genetics — who can take the whole picture into account. Decisions about care are individual, and they are made with that team rather than from a laboratory result.