What Is 5-Alpha Reductase Deficiency?

A Genetic Disorder That Delays Male Genital Development

Medically reviewed by Anju Goel, MD, MPH

5-alpha-reductase deficiency is a congenital condition that affects male sexual development. Children born with 5-alpha-reductase deficiency may appear to be biologically female at birth but they are genetically male and will develop male genitals during puberty.

5-alpha reductases are a group of enzymes that help regulate sex hormones in the body. This includes female hormones like estrogen and male hormones like testosterone that influence the development of a fetus as well as sexual development and function in later life.

5-alpha-reductase deficiency is considered a disorder of sexual differentiation, which some people describe as being intersex. Intersex refers to individuals with reproductive organs and/or external sexual characteristics that are both male and female.

People with 5-alpha-reductase deficiency are often assigned female at birth. In some cases, they will undergo gender reassignment during or after puberty when their body changes.

This article looks at the symptoms and causes of 5-alpha-reductase deficiency. It also describes how this rare congenital disorder is diagnosed and how it may be treated.

5-Alpha-Reductase Deficiency Symptoms

During infancy, the symptoms of 5-alpha-reductase deficiency are often not recognizable. Some babies will appear biologically female with what appears to be a clitoris, labia, and vagina. Others may have an underdeveloped penis or genitals that are sexually ambiguous.

Infants with 5-alpha-reductase deficiency are born with a bifid scrotum. This is because the structures that become the scrotum when exposed to testosterone during fetal development are the same structures that become the labia when exposed to estrogen.

Although newborns with 5-alpha-reductase deficiency have normal testes (testicles), the organs will be buried within the abdomen or in a passage called the inguinal canal.

It is only during puberty that a child with 5-alpha reductase deficiency will develop secondary male characteristics as testosterone levels are increased.

However, males with 5-alpha-reductase deficiency will tend to have less facial and body hair than their peers and will usually have infertility.

Causes

5-alpha-reductase deficiency is a rare hereditary disorder caused by the mutation of the SRD5A2 gene. It is an autosomal recessive mutation, meaning that you can only get it if both of your parents pass an SRD5A2 gene mutation to you. There are more than 60 different mutations that can cause this.

Under normal circumstances, 5-alpha reductase converts testosterone into a hormone known as dihydrotestosterone (DHT). DHT is important as it is responsible for sexual differentiation of the male genitals during fetal development.

DHT is also responsible for the maturation of the penis and scrotum during puberty as well as the growth of facial and body hair, the deepening of the voice, the increase in height and muscle mass, and the development of the prostate gland.

With 5-alpha-reductase deficiency, the SRD5A2 mutation impairs the conversion of testosterone into DHT during fetal development. It is only during puberty, where testosterone levels spike, that the person's testicles will descend, the penis will enlarge, and the body will develop secondary male characteristics (a process referred to as virilization).

5-alpha-reductase deficiency can occur in females, but the condition has no effect on either their genitals, sex characteristics, or reproductive function.

The frequency of 5-alpha-reductase deficiency is unknown. It is more often seen in populations where intermarriage is common. Families with the disorders have been found in places like Papua New Guinea, Turkey, Egypt, and the Dominican Republic (where the condition is referred to as guevedoces, meaning "penis at 12").

Diagnosis

The diagnosis of 5-alpha-reductase deficiency is dependent on whether an infant is born with genitals that are distinctly "female" or genitals that are sexually ambiguous.

If the genitals appear female, the condition may not be diagnosed until puberty. On the other hand, if a child is born with ambiguous genitals, 5-alpha-reductase deficiency is one of the first conditions a healthcare provider might consider.

To confirm the suspicion, the following tests may be performed:

• Ultrasound of the pelvis or abdomen to check for undescended testicles or the presence of a prostate gland

• Blood tests to measure the ratio of testosterone to DHT in the body

• Chromosome analysis to see if the child has XX (female) chromosomes or XY (male) chromosomes

• Gene sequencing to check for known mutations of SRD5A2
  

Treatment

The treatment for 5-alpha-reductase deficiency differs based on when the condition is identified.

One of the more common—and controversial—practices is gender assignment. In the past, this often meant surgery to assign a child with either a "male" or "female" identity. Today, there are ethical concerns about performing non-essential genital surgery on infants, effectively assigning them a gender for which they may not identify in later life.

Even if surgery is not pursued, children with 5-alpha-reductase deficiency are often "raised as female." and may be faced with the challenge of either adopting a "male" identity or continuing to live as "female" during or after puberty.

If they choose to identify as "female," they would need life-long hormonal therapy to maintain their secondary female characteristics. They may also decide to undergo gender-affirming surgery (including vaginoplasty) to align their body with their gender identity.

Individuals who choose to live as "male" may not need any treatment, although assistive fertility may be needed if they choose to have children. Those with a penile deformity such as hypospadias (in which the opening of the penis is not at the tip) may need corrective surgery.

Coping

Children with 5-alpha-reductase deficiency may not have any noticeable symptoms until puberty. In fact, when children are young, their condition can be more of a concern for their parents.

Parents will often feel anxiety about what the condition means for their child's future, including how the child will eventually identify.

It is often helpful for children with 5-alpha-reductase deficiency and/or their parents to speak with a doctor or therapist who has expertise in the field. This can help them make more informed choices or come to terms with concepts (like gender fluidity) that may be foreign to them.

As the child approaches puberty, counseling may be needed to help them understand not only their physical changes but also the psychological or social challenges. This is especially true of adolescents, teens, or adults who may be considering gender-affirming surgery.

It may also be useful to reach out to reputable intersex organizations like InterACT that provide support, information, and referral to intersex or questioning youth.

Related:Gender vs. Sex: Meaning, Differences, Healthcare

Summary

5-alpha-reductase deficiency that a congenital disorder that affects male sexual development. People with 5-alpha-reductase deficiency may appear to be biologically female at birth but will develop male genitals during puberty. It is a rare inherited condition caused by the mutation of the SRD5A2 gene.

5-alpha-reductase deficiency can be diagnosed with various blood tests and an ultrasound examination of the internal reproductive organs, though a definitive diagnosis is via a genetic analysis. The treatment can vary based on when the condition is diagnosed or whether the individual chooses to live as "female" or "male."

A Word From Verywell

While many people with 5-alpha-reductase who were "raised as female" continue to identify as female after puberty, others may choose to identify as male. Neither is right or wrong.

What is arguably more important is that you embrace the gender identity (or identities) that align with how you see yourself internally. In some cases, the choice may be to embrace no gender.

Today, an increasing number of people identify as intersex or non-binary rather than choosing between "male" or "female." For people with 5-alpha-reductase deficiency, this can affirm that their condition is neither abnormal nor one for which they have to "choose sides."

Frequently Asked Questions

What happens in 5-alpha-reductase deficiency?

With 5-alpha-reductase deficiency, a gene mutation impairs the conversion of testosterone into dihydrotestosterone (DHT). Without DHT, the development of male sexual organs is impaired. When this happens, the child may appear to be biologically female at birth and only develop male genitals during puberty.

Are people with 5-alpha reductase deficiency fertile?

Most males with 5-alpha-reductase deficiency are infertile because 5-alpha reductase is involved with the normal development of the male reproductive system. Females with 5-alpha reductase deficiency are unaffected and do not experience infertility as a result of the disorder.