What Is 5-Alpha-Reductase Deficiency?

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The congenital condition of 5-alpha-reductase deficiency affects male development. It affects XY individuals and is considered an intersex condition or a disorder of sexual differentiation.

Individuals with this condition have testes do not make sufficient dihydrotestosterone to cause the genitals to virilize, or masculinize, prior to puberty. Therefore, infants are born with what appears to be a clitoris and a vagina, and they are often assigned female at the time of birth.

At puberty, the body starts making more testosterone. At that time, the testicles descend, the penis enlarges, and the rest of the body starts to reshape to have a more masculine appearance.

In one community in the Dominican Republic where this condition is found, individuals with 5-alpha-reductase deficiency are reportedly known as Guevedoces—meaning penis at 12.

Group of pre-teens sitting on a fence.

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5-Alpha-Reductase Deficiency Symptoms

In infancy, the symptoms of 5-alpha reductase deficiency are not necessarily recognizable. They are XY infants with testes, but they are not born with a penis and scrotum. Instead, they are born with what appears to be a clitoris, labia, and vagina.

The extent to which the structures appear one way or the other varies from individual to individual. Some individuals will have bodies that are more in between.

The testes are generally found either in the inguinal sac or the abdomen rather than the scrotum, but they contain all the normal testicular structures. They are capable of making testosterone. However, most individuals with 5-alpha-reductase deficiency are infertile.

At puberty, individuals who maintain their testes will likely see growth of the clitorophallic complex. The testes may descend into the unfused labia. (The structures that become the scrotum are the same as the structures that become the labia—but they fuse during development.)

They may start growing facial hair and experience deepening of the voice. However, males with 5-alpha-reductase will usually have less facial and body hair than their peers.

Causes

5-alpha-reductase deficiency is caused by an autosomal recessive mutation. This means that individuals only develop the condition if they have two copies of the mutated gene (one from each genetic parent). There are more than 40 identified mutations that can cause 5-alpha-reductase deficiency.

This deficiency is relatively rare in White people. It is still rare, but more common, in populations where there is a lot of intermarriages. The most well-known clusters of cases occurred in the Dominican Republic. However, cases have been identified around the world.

Diagnosis

How and when 5-alpha-reductase deficiency is diagnosed is highly dependent on whether an infant is born with visibly ambiguous genitalia. If not, and there was no fetal genetic analysis that identified that the apparently female infant was XY, it is possible the condition might not be diagnosed until they experienced virilization at puberty.

If a child is born with ambiguous genitalia, 5-alpha-reductase deficiency is one condition doctors may look for. This could involve gene sequencing. It could also involve looking at the testosterone/dihydrotestosterone ratio after stimulation with hCG.

Treatment

Treatment for 5-alpha-reductase deficiency varies significantly from area to area. Gender assignment at the time of birth is generally based on the size and appearance of the external genitalia.

This is because the appearance of genitalia correlates to the efficacy of testosterone and DHT exposure prior to birth, which may also be related to gender identity formation. However, the process is complex and uncertain.

Historically gender assignment has often been followed by genital surgery. However, in the United States, there is a recent, but growing, recognition that it is unethical to perform non-medically necessary genital surgeries on infants.

Therefore, some of the traditional treatment options—including reducing the size of the clitoris if it was thought to be too small for a male gender assignment—are being banned by certain high profile children's hospitals.

Enough individuals with 5-alpha-reductase deficiency develop male gender identities that early surgery to make the genitals appear feminine is deeply problematic.

Individuals with 5-alpha-reductase deficiency who are raised as girls should be educated about their condition and given the option of having their testes removed before they hit puberty.

That way, those who are comfortable with their feminine gender assignment will not experience unwanted virilization. Those who feel uncomfortable with the female gender assignment can maintain their testes and experience virilization at puberty.

Individuals who are raised as boys may undergo surgery to correct hypospadias. This is usually done early in life, if it is needed. No other treatment is widely recommended. However, fertility treatment may be an option for some men who wish to have genetic children.

Girls with 5-alpha-reductase deficiency who continue to assert a female identity may also choose to undergo vaginoplasty in order to create a functional vagina once they reach adolescence or adulthood.

Coping

Children with 5-alpha-reductase deficiency don't necessarily have any noticeable symptoms until puberty.

When they are young, the condition can be more of a coping concern for their parents. They may feel significant anxiety about what the condition means for their child's future, their treatment options, or their choices regarding gender of raising.

As a child approaches puberty, and moves through adulthood, they may benefit from formal supports. Understanding the changes they experience in their body can be confusing. In addition, for those raised as female, it can be difficult to make informed decisions about orchiectomy without additional support.

If you or your child has been diagnosed with 5-alpha-reductase deficiency, it may be useful to reach out to reputable intersex groups for information. The organization InterACT was developed to advocate for Intersex youth and has a library of resources, including links to other groups that provide support.

It is also helpful for youth and their parents to talk to doctors and therapists who have expertise in the field. Getting multiple opinions can help make better decisions. Different doctors have very different philosophies of care.

A Word From Verywell

5-alpha-reductase deficiency is an interesting condition both in its own right and because of what it teaches us about gender identity. Researchers have hypothesized that androgen exposure in the brain during fetal development may affect gender identity. Indeed, there is a great deal of data supporting this assertion.

However, it's unclear how it interacts with what we know about the gender identity of individuals with 5-alpha reductase deficiency.

While the majority of individuals 5-alpha-reductase assigned as female at the time of birth identify as female through adulthood, a far greater percentage than in the general population develop a male gender identity. Many of those transition to live as male.

It is plausible that the increased likelihood of developing a male identity is related to differences in testosterone exposure in the brain, but there's no definitive answer. It could also reflect other factors like culture, the desirability of male gender, and the way people were raised.

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