5-Alpha-Reductase Deficiency 

Updated: Nov 11, 2016
Author: Anna H Isfort, MD; Chief Editor: Robert P Hoffman, MD 



5-alpha-reductase type 2 deficiency (5-ARD) is an autosomal recessive sex-limited condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT). Because DHT is required for the normal masculinization of the external genitalia in utero, genetic males with 5-alpha-reductase type 2 deficiency are born with ambiguous genitalia (ie. 46,XY disorder of sexual development (DSD)).[1]

Patients with 5-alpha-reductase type 2 deficiency classically present with striking ambiguity of the genitalia, with a clitoral-like phallus, bifid scrotum, pseudovaginal perineoscrotal hypospadias, and a rudimentary prostate. Occasionally, patients can appear more masculinized; they may lack a separate vaginal opening, and have isolated penile hypospadias[2] or even a penile urethra.[3]

The uterus and fallopian tubes are absent because of the normal secretion of the müllerian-inhibiting factor. Testes are intact and are usually found in the inguinal canal or scrotum; however, cryptorchidism is frequently described with testes occasionally located in the abdomen. Wolffian duct differentiation is normal with seminal vesicles, vasa differentia, epididymides, and ejaculatory ducts. The prostate is small, nonpalpable, and rudimentary in adulthood. Neither benign prostate hyperplasia (BPH) nor prostate cancer has been reported in these patients.[4]


The root cause of this disorder is a deficiency in the 5-alpha-reductase type 2 isoenzyme, which transforms testosterone to DHT. DHT is a more potent androgen than testosterone and is bound selectively to the androgen receptors in genital skin and fibroblasts. The 5-alpha-reductase type 2 isoenzyme is expressed in external genital tissues early in gestation, making its action necessary for the development of normal male external genital anatomy in the fetus.[3] As with most single enzyme disorders, 5-alpha-reductase type 2 deficiency is autosomal recessive and sex limited because it only causes a clinically significant disorder in genetic males, with very subtle phenotypic changes in homozygous females. See the image below.

Biochemical effects of 5-alpha-reductase type 2 de Biochemical effects of 5-alpha-reductase type 2 deficiency in testosterone biosynthesis. Typically levels of testosterone are elevated, whereas levels of dihydrotestosterone (DHT) are significantly decreased, leading to male undervirilization.

Three genes coding for 5-alpha-reductase have been identified, each for a slightly different isoenzyme. Only the genes coding for 5-alpha-reductase type 1 (SRD5A1) and 5-alpha-reductase type 2 (SRD5A2) are pertinent to the conversion of testosterone to DHT, whereas the gene coding 5-alpha-reductase type 3 is unrelated to any disorders of male sexual development, and may be implicated in a rare disorder of glycosylation.[5] Both of the pertinent genes, SRD5A1 and SRD5A2, contain five exons separated by four introns. A predominance of mutations have been observed in exons 1 and 4.[6, 7] The gene for 5-alpha-reductase type 2 has been determined to be on band 2p23. Lack of expression of this gene clinically correlates with the symptoms of 5-alpha-reductase type 2 deficiency. In adulthood, the 5-alpha-reductase type 2 isoenzyme is expressed in high levels in the prostate, genital skin, epididymis, seminal vesicle, and liver.[3]

The gene for 5-alpha-reductase type 1 is located on band 5p15. Its product is expressed only in nongenital skin and liver at low levels from the time the individual is aged 3 years until puberty, at which time enzyme expression is measurable in sebaceous glands and scalp. Linkage analysis has demonstrated that the type 1 enzyme is unrelated to the clinical syndrome of 5-alpha-reductase type 2 deficiency. Interestingly, partial virilization of males with 5-alpha-reductase type 2 deficiency occurs at puberty and may be attributable to the rise in type 1 enzyme activity or expression at that time.[4] An alternative mechanism for this virilization at puberty may be through binding of testosterone to the androgen receptor or by overcoming a partial enzyme deficiency with the increase in serum testosterone levels during puberty.[8]

More than 60 different mutations of the gene for 5-alpha-reductase type 2 have been reported in people with clinical and biochemical evidence of the enzyme deficiency. The occurrence of identical mutations in individuals with widely divergent geographic and ethnic backgrounds suggests the existence of mutational hot spots.[9] Patients with a heterozygous mutation have been shown to have a wider phenotypic spectrum; however, correlation between the severity of the syndrome and a particular gene defect has not been observed.[3] There is also a lack of phenotype/genotype relationship in patients carrying the same mutation, which suggests that factors other than 5-alpha-reductase enzyme activity contribute to phenotype.[10]



United States

The carrier frequency and number of individuals with this disorder are not established.


Although frequencies for various countries are not established, increased frequency is reported in the Dominican Republic, some highland tribes in New Guinea, and in Turkey. The high frequency in these areas represents the effect of consanguinity in specific kindreds.[3] Overall, more than 50 families with this disorder have been described in several parts of the world. In a few patients with 46,XY DSD due to 5-alpha-reductase type 2 deficiency diagnosed by clinical and hormonal findings, no mutations were identified in the SRD5A2.[11] In general, disorders of sexual differentiation as a whole are uncommon, with an overall incidence of 1:5500.[12]


This enzyme deficiency is not life threatening; however, if intra-abdominal testes are retained, an increased risk of gonadoblastoma is noted. Secondary issues include a risk of osteoporosis if hormone replacement therapy is not initiated in the patient with a gonadectomy. Psychological morbidity is not uncommon, with occasional asynchrony of assigned gender and sexual identity (see Treatment).


Clinical 5-alpha-reductase type 2 deficiency is limited to genetic males. Although the enzyme deficiency can be documented in homozygous females, no clinical or developmental need for DHT is documented in women, who are likely asymptomatic.


Most individuals with 5-alpha-reductase type 2 deficiency are identified in the neonatal period with ambiguous genitalia.[13] However, some of these children are misdiagnosed as having partial or complete androgen insensitivity syndrome (AIS), which can produce almost identical phenotypes. As noted above, some patients with 5-alpha-reductase type 2 deficiency present with more masculinized genitalia including isolated hypospadias or penile urethra with micropenis, which can lead to a delay in diagnosis.[3] Delayed diagnosis can also occur in patients with isolated clitoromegaly and otherwise normal female-appearing external genitalia. In patients with this phenotype, diagnosis is often delayed until the time of puberty, when they present with primary amenorrhea and virilization.[9, 14] Preliminary data suggest the incidence of 5-alpha-reductase deficiency in elite female athletes that screen positive for hyperandrogenemia may be more than 200 times that of the general population.[15]

Medical/Legal Pitfalls

The clinical heterogeneity resulting in unpredictable and varying outcomes for patients with a DSD, particularly those associated with abnormalities in androgen response or synthesis, places an ethical, and potentially legal, burden on the treatment team. The team is responsible for ensuring education of the parent, and, when appropriate, the patient, regarding the diagnosis and obtaining informed consent prior to medical or surgical intervention. This is especially important in the setting of gonadectomy and/or genitoplasty, which are irreversible procedures that result in potential loss of fertility and have lifelong impact on gender satisfaction.

The healthcare team needs to clearly communicate to the parent of the patient and the patient, when appropriate, that available research is insufficient to absolutely predict adult gender satisfaction, irrespective of initial medical or surgical treatment. Early genitoplasty with or without gonadectomy does not appear to be associated with increased gender assignment satisfaction or a decrease in the potential for gender role change. On the other hand, although delaying these procedures provides a greater opportunity for the patient's involvement in the decision process, this alternative approach is not without risk. Some data suggest negative consequences of delayed repair of ambiguity on the development of self-esteem and gender satisfaction within cultures with low incidence of disease.[16, 17, 18]

The more contemporary approach, to delay definitive therapy, has developed over the last 2 decades as adult DSD patients and advocates have voiced their dissatisfaction with life-changing procedures performed prior to their ability to consent.

The consequence is that the parents of the newborn with a 46,XY DSD are placed in a difficult situation. They must adapt to the diagnosis, acutely acquire an understanding of the issues of gender as well as the risks, benefits, and potential complications of treatment and non-treatment options. This education process, ultimately concluded with a statement of informed consent, should satisfy a "reasonable patient" standard: "a doctor must disclose those risks, benefits, and alternatives that a reasonable person in the patient's position would be likely to consider significant in deciding whether or not to undergo treatment, including diagnosis and prognosis, common risks of the proposed procedure, remote risks with grave consequences, probable outcomes and expected posttreatment course, and the risks, benefits and unknowns of alternative treatments and non-treatment."[17]




Diagnosis of 5-alpha-reductase type 2 deficiency (5-ARD) is usually made in the newborn period when the infant presents with ambiguous genitalia.[13] No risk factors or clinical markers in pregnancy are known. Genital ambiguity is occasionally diagnosed prenatally when an infant who is demonstrated by amniocentesis or chorionic villus sampling to have XY karyotype fails to have a demonstrable penis on ultrasonography.

If 5-alpha-reductase deficiency is considered in a newborn, a broad approach to ambiguous genitalia should be taken.[1, 12] The utmost care should be taken not to assign a gender to the child before evaluation and consultation with an experienced, multidisciplinary team. The first words spoken to the parents are likely to be remembered and should focus on the overall health of the infant. A sensitive discussion about the uncertainty of the child's gender and explanation of the child's genital anatomy can be aided by online developmental Web sites, such as the ones available on the Sick Kids and DSD Guidelines sites. See Ambiguous Genitalia and Intersexuality for more in depth discussion

Initial evaluation should begin with a careful history.[1] Assess prenatal and maternal past medical and family history. Specific questions should be asked regarding relatives with disorders of sexual development (DSDs), neonatal deaths, amenorrhea, or infertility and consanguinity. Parental consanguinity increases the child's risk for autosomal recessive disorders including 5-alpha reductase type 2 deficiency.


Workup of ambiguous genitalia must include careful physical examination to characterize the degree of virilization on the Prader scale (see the image below), presence of palpable gonadal tissue, and overall health of the child.[12]

Prader scale reflecting the degree of virilization Prader scale reflecting the degree of virilization of the external genitalia. The internal genitalia reflect the changes in the urogenital sinus in response to the presence or absence of mullerian inhibiting hormone (MIH)

Neonatal presentation

Phenotypic findings in a newborn are limited to the genitalia.[13, 19] The spectrum of findings ranges from minimal undervirilization presenting with normal male anatomy, except for isolated micropenis or hypospadias, to severe undervirilization presenting as normal female external genitalia with mild clitoral enlargement as the only physical finding. In a study published in 2011, a cohort of 55 patients with 5-alpha-reductase type 2 deficiency displayed widely varied phenotypes in the neonatal period. In this cohort, clitoromegaly was the most common phenotype in 49% of patients, followed by microphallus with varying degrees of hypospadias in 33% of patients.[20]

Most commonly, the external genitalia exhibit labial appearance to the labioscrotal folds with some mild rugation or pigmentation present in some patients.

The phallus is often indeterminate in size and morphology. Its length falls between 1 cm (ie. usual maximum for a clitoris) and 2 cm (ie. lower limit of normal for a penis).

The urethra may empty anywhere from the tip of the phallus to the perineum, with the latter observed more frequently.

The testes are usually in the inguinal canals bilaterally; however, in some individuals with 5-alpha-reductase type 2 deficiency, the testes can be found in the labioscrotal folds or retained in the abdomen.

A pseudovaginal blind-ending introitus may be present with a normal hymen.

The uterus and cervix are absent on imaging and by examination.

The rest of the examination findings are within normal limits.

Presentation of 46XY males at puberty

Clear signs of virilization predominate at puberty. The escutcheon is male in distribution. The phallus exhibits definite enlargement. The shoulders are relatively broad and the hips are narrow.

Muscularity and body hair may increase. Generally, no breast development is present. A prominentia laryngea (Adam's apple) may start to develop. In addition, facial hair develops and the child's voice may begin to deepen.

The mucosa of the vaginal introitus remains atrophic in appearance (remaining red) rather than the thickened pink of estrogen-stimulated mucosa.

Presentation of 46XX females

Females homozygous for 5-alpha-reductase type 2 deficiency have very subtle manifestations, such as delayed menarche, minimal acne, and minimal body hair.[21] Fertility is normal in females.


The cause of 5-alpha-reductase type 2 deficiency is the deficiency of the type 2 isozyme of 5-alpha-reductase.

As with most single enzyme disorders, 5-alpha-reductase type 2 deficiency is an autosomal recessive trait and sex limited because the clinical syndrome only affects genetic males, with very subtle phenotypic findings in homozygous females.[22]





Laboratory Studies

General laboratory evaluation for all newborns with ambiguous genitalia should begin with the following:

  • Karyotype with specific X and Y probes.

  • 17-hydroxyprogesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dihydrotestosterone (DHT), anti-Müllerian hormone (AMH), electrolytes, and urinalysis

  • Abdominopelvic ultrasound to assess for presence of internal male/female structures

Results should be expedited, ideally available within 48-72 hours.

In neonates with Y material (46,XY or fluorescent in situ hybridization [FISH] results positive for sex-determining region [SRY]) and ambiguous genitalia, 5-alpha-reductase type 2 deficiency should be considered.

Elevated serum testosterone-to-DHT ratio (T/DHT) is the hallmark of 5-alpha-reductase type 2 deficiency. Typically, testosterone levels are normal to modestly elevated and DHT levels are low to undetectable. Levels are detectable to diagnostic levels during the physiologic testosterone surge that occurs between birth and age 1-3 months. Basal unstimulated T/DHT levels are not usually high enough to make a definitive diagnosis, especially in a prepubertal patient over 3 months of age.

Human chorionic gonadotropin (hCG) stimulation is needed after the early infant period of minipuberty in order to obtain adequate levels of testosterone and DHT for diagnosis. Multiple protocols, both short-term and long-term, have been established with varying sensitivities. Three common protocols include the following: (1) 1500 IU intermuscularly (IM) on days 1, 3, and 5 (short test); (2) 1500 IU IM every other day for 7 injections (prolonged test); or (3) 5000 IU/m2 IM as a single dose. Baseline laboratory results are established prior to hCG administration, and stimulated laboratory studies are drawn 24 hours after the last dose for the multi-day tests, or 72 hours after the single-dose test. The reference ranges for expected stimulated values were obtained using the short test as described above, and may be applied to the other testing methods, however values have not been validated in these other testing methods.

In normal prepubertal males, the mean T/DHT ratio following hCG stimulation is 10.7, with ranges from 3.5-14. In male infants, the stimulated ratio is somewhat lower and is usually less than 10. The T/DHT ratio in prepubertal patients with 5-alpha-reductase-2 deficiency generally exceeds 30. In adults, the discriminatory value of the post hCG T/DHT ratio is even higher. Normal patients respond with ratios from 8-16, while patients with 5-alpha-reductase-2 deficiency exhibit T/DHT ratios from 35-84.[23]

Mutation analysis of the 5-alpha-reductase type 2 gene (SRD5A2) is now available commercially through GeneDx (www.genedx.com). Testing is performed via exon array comparative genomic hybridization (CGH) or by direct gene sequencing. Utility of this testing includes confirmation of a clinical diagnosis; differentiation of 5-alpha-reductase type 2 deficiency from other causes of 46,XY DSD; prenatal diagnosis for known familial mutations; and carrier testing for at-risk relatives.

Imaging Studies


Although not diagnostic for 5-alpha-reductase type 2 deficiency, ultrasonography of the pelvis is useful.

Ultrasonography can verify the location of the testes and other wolffian structures as well as the absence of müllerian structures, to include the cervix and uterus.

The ultrasonographer, and other members of the radiographic and laboratory evaluation team, should be cognizant of the suspected diagnosis and be trained on how to properly discuss findings with gender-neutral terms.


A genitogram (ie. dye introduced into the urogenital (UG) sinus via small catheter or feeding tube) is a useful tool to assess urethral anatomy, UG sinus length, or evidence of müllerian remnants.

This study can verify that no fistulous connections are present between the urinary tract and UG sinus.

CT and MRI

CT or MRI are usually not necessary but may be useful to more accurately assess internal anatomy.

Histologic Findings

The testes exhibit Leydig cell hyperplasia and decreased spermatogenesis. However, testicular biopsy is not part of the routine evaluation.



Medical Care

Caring for patients with 46,XY DSD requires parental and, when appropriate, patient, education regarding the specific developmental abnormalities found on the physical examination of the patient, contrasted with normal sexual development. This education should include an open and frank discussion of what is known, and not known, about long-term effects of gender assignment, including gender identity, gender role, and sexual satisfaction. These discussions need to begin as soon as the patient is discovered to have ambiguous genitalia, and is ideally performed by a multidisciplinary team that includes representation from pediatric endocrinology, pediatric urology or surgery, genetics, and mental health.

Although everyone agrees that an expeditious and thorough assessment in regard to the diagnosis is critical, decisions with lifelong impact, such as surgical intervention should not be rushed. Families must be afforded time to digest the information, adjust to the implications of the diagnosis, and be provided open and ready access to members of the treatment team as they work through the decision process.

Full disclosure of the diagnosis, prognosis (gender identity outcome as well as potential for fertility and sexual function), rationale with risks and benefits for proposed procedures, alternative treatments, and local clinical experience must be shared under the standard of informed consent.

Gender assignment

Multiple factors must be considered in recommending gender assignment for children born with ambiguous genitalia. These include diagnosis, genital appearance, surgical options for both cosmetic and functional outcome, potential for fertility, potential need for lifelong hormone replacement therapy, and the particular social, religious, and cultural context of the family.

The ultimate medical goal of treatment is to restore external genitalia as close to a nonambiguous appearance as possible while retaining full sensation, the ability for sexual satisfaction (to include penetrative intercourse), and ideally, fertility. In conditions where androgen response or synthesis leads to a DSD, such as partial androgen insensitivity syndrome (PAIS), 17-beta-hydroxysteroid dehydrogenase deficiency, and 5-alpha-reductase deficiency (5-ARD), attaining all of these goals is unlikely. Conveying this to the parents and/or patient while being empathetic to their anxiety is essential.

Affording the child the best opportunity for a healthy long-term psychosocial development is the foundation for recommendations of gender assignment. In select cultures with high prevalence of 5-alpha-reductase deficiency, such as the Dominican Republic and Papua New-Guinea, gender role change is an accepted part of culture. Unfortunately, for most other cultures, a third gender is not accepted, suggesting that a decision for gender assignment should occur before the patient is able to make an individual choice. Although gender assignment in the newborn period may not be ideal, this well-intended, and perhaps justifiable approach is undertaken due to social as well as developmental concerns because children typically develop a sense of gender identity by age 3 years.

Proponents of early surgery for female gender assignment suggest that early gonadectomy increases the likelihood of gender satisfaction and stability and that surgical outcome is improved due to increased tissue plasticity. Opponents point out the increased likelihood of repeat surgical intervention, the irreversible nature of the procedure made at a time when patient consent is not attainable, and the high incidence of gender dysphoria and sexual dissatisfaction.

The most important message from the surgical literature is that the timing of the surgery appears to be of lesser importance than ensuring that the surgery be performed by a surgeon with extensive experience in caring for patients with DSD.[12]

Medical care

Medical care is dictated by gender assignment and surgical intervention

Hormone replacement therapy should be considered in patients raised in the male gender and is required in patients raised in the female gender that have undergone gonadectomy

In patients with 5-alpha-reductase deficiency who are raised as male, testosterone or dihydrotestosterone (DHT) therapy may increase penile length. Two doses of testosterone ester (125 mg per dose), given 3 weeks apart has been used in prepubertal children to increase penile length, and should be considered prior to hypospadias repair.[24] Higher dose therapy (250-500 mg 1-2 times per week given for 6-36 mo) has been used in pubertal or postpubertal patients.[24, 25, 11]

If testosterone is used in a prepubertal patient for a prolonged course of therapy, parents should be counseled over the potential to decrease final adult height secondary to androgen associated skeletal advancement

In patients with 5-alpha-reductase deficiency who are raised female, estrogen replacement therapy should be initiated at a bone age of 12 years or once an increase in gonadotropins is observed. The dose is tailored to reach adult replacement levels over a 3-4 year range. Progesterone or cycling of estrogen therapy is not required due to the absence of a uterus.

Decreased bone mineral density may be a complication for female patients who are not initiated or not maintained on appropriate estrogen replacement therapy but does not appear to be a problem for male patients with intact gonads.[26]

Surgical Care

Female gender assignment[11]

In patients with near complete enzyme dysfunction, infants have pseudovaginal perineoscrotal hypospadias, severely bifid scrotum, small phallic structure (microphallus or clitoromegaly, description designated based on gender assignment), and urogenital sinus (blind vaginal pouch).

Feminizing genitoplasty is a broad term to describe potential surgical interventions, and may include gonadectomy (removal of the testes), restructuring of the labioscrotal folds into labia, and reduction or recession of the phallus to provide a more clitoral appearance. Recent advances in surgical techniques have focused on procedures that spare the clitoral enervation; however, no long-term studies have assessed the success of these procedures.

Specific surgeries include gonadectomy, clitoroplasty with preservation of the clitoral glans and sensory input, separation of the urethra from the vagina, and construction (eg. Y-V vaginoplasty, colovaginoplasty).

Laparoscopic gonadectomy is recommended, if available. Proponents of female gender assignment recommend early gonadectomy to lessen the exposure to androgen, allowing for development of a more stable female gender identity and to avoid the associated virilization that occurs with puberty.

Although some centers advocate for a single-stage procedure, others delay vaginal reconstruction surgery until puberty when the patient is better able to perform required postsurgical care (dilatation).

Complications include the following:

  • Urinary tract complications

  • Decreased clitoral sensation

  • Vaginal and/or introital stenosis

Estrogen replacement therapy is required for the initiation of puberty. This therapy is typically started after the patient has attained a bone age of 12 years or once an increase in gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) is noted.

Postoperative care for vaginoplasty involves the use of vaginal dilatation with molds and for patients that underwent prepubertal vaginoplasty may require repair of introital and/or vaginal stenosis and vaginal lengthening.

Once gonadectomy has been performed, fertility is not possible, even if the patient decides on a gender-role change during adolescence or adulthood. Childbirth is not possible because no müllerian structures are present due to the presence of müllerian inhibiting substance during fetal development.

Male gender assignment[11, 27]

The same clinical description and timing considerations apply as is described for female gender assignment above.

The surgical correction of hypospadias, chordee, and/or cryptorchidism is required in most cases. The technique is determined by severity. Approaches include the following:

  • Urethroplasty (Perineoscrotal hypospadias repair is typically a multistage procedure.)

  • Repair of bifid scrotum

  • Chordee repair

  • Orchiopexy

Complications include the following:

  • Urethral fistula

  • Urethral stenosis

Micropenis is an anticipated clinical feature, defined by stretched penile length of less than 2.5 cm in a term newborn or a length of less than 7 cm in an adult male.[28, 29]

Testosterone or DHT therapy has been reported to increase penile size and virilization. The nonaromatizable nature of DHT decreases the chance for developing iatrogenic gynecomastia. However, neither DHT gel nor a long-acting injectable form of DHT are FDA approved or currently available in the United States.

If testosterone is administered to prepubertal children for a prolonged course of therapy, advancing skeletal age that ultimately results in decreased final height is a risk.

In patients with 5-alpha-reductase deficiency, limited data suggest that high-dose testosterone may increase penile shaft length and circumference, increase erectile potency and ejaculatory volume, increase facial hair and muscularity, and improve a sense of well-being.[25, 24]

Various penile enhancement procedures are available and are directed at increasing penile length or circumference. Unfortunately, limited standardization of procedures and disappointing short-term and long-term patient satisfaction are reported.[29]

Significant complications associated with the surgical procedures include penile deformity, paradoxical shortening, scarring and granuloma formation, and sexual dysfunction.[29] The average increase in penile length for either medical or surgical intervention is 1-2 cm.

Patients with 5-alpha-reductase deficiency who have not undergone feminizing procedures may be fertile; however, most of this subpopulation require in vitro fertilization or other assisted-fertilization techniques.[30, 31] Sperm counts are typically very low, with abnormal spermatogenesis and thick ejaculate.


Pediatric endocrinologist

The pediatric endocrinologist is responsible for coordinating the laboratory and radiologic evaluation, reviewing the results to determine the etiology of the clinical findings from the other potential diagnoses in the differential, to include defects in gonadal development (Denys-Drash syndrome and others), testosterone production (3-beta-hydroxysteroid dehydrogenase, 17-beta-hydroxysteroid dehydrogenase), and testosterone response (partial androgen insensitivity) and for ensuring that parents feel informed and are educated leaders of the decision-making team.

In addition, the pediatric endocrinologist is responsible for instituting and following hormone replacement when clinically indicated. Many pediatric endocrine offices offer a multidisciplinary team approach, which may assist the family as the child matures.

Pediatric surgeon or pediatric urologist

The pediatric surgeon or pediatric urologist assesses the potential for surgical reconstruction as either male or female based on physical examination, laboratory, and radiologic information. This assessment has significant impact on helping the family make a gender assignment choice. No matter the choice, surgery is likely to be part of the treatment plan, and coordination of the timing and staging for the initial and/or subsequent procedures should be a part of the initial discussion. Surgical planning should begin at birth, but time is available to decide on the appropriate procedure based on family comfort, decreased anesthesia risk, and other issues.


The geneticist is responsible for verifying the karyotype and discussing with the family the male-limited autosomal recessive inheritance pattern for the disorder, to include the recurrence risk of 1:8 for each subsequent pregnancy. Due to a higher incidence in consanguinity, the geneticist is best prepared to interview families for this potential and to provide appropriate counseling. In families with no known genetic risk, many parents have a feeling of guilt at the birth of a child with the disorder. In this situation, emphasize to the family that nothing was missed or could have been done differently during the pregnancy to alter the outcome, but that prenatal diagnosis is an option in future pregnancies.

Child psychiatrist or pediatric psychologist

The child psychiatrist or pediatric psychologist should be involved from the beginning. These mental health professionals can help the family work with psychological issues (eg. any feelings of guilt or blame) that accompany the birth of a child with 5-alpha-reductase type 2 deficiency and help facilitate communication between the family and the medical consultants.

A child psychiatrist or pediatric psychologist with experience working with disorders of sexual development can provide emotional support for the family, can help the family formulate questions, and can be the counselor for the family and patient for issues regarding gender identity, gender role, gender satisfaction and potential change in gender role. A long-term relationship with such a support system may ensure that information about the diagnosis and treatment is provided in an age-appropriate fashion, hopefully decreasing fears and misconceptions.



Medication Summary

Because of recent data, reconsidering the past policies of raising children with 46,XY, such as those with 5-alpha-reductase type 2 deficiency (5-ARD) with ambiguous genitalia and small phalli as females may be appropriate.

Hormone therapy

Class Summary

Testosterone therapy has been reported to increase penile size and cause virilization in some patients with 5-alpha-reductase type 2 deficiency, and may be used in prepubertal males prior to surgical intervention, or at pubertal onset. Some males with 5-alpha-reductase type 2 deficiency respond with an increase in penile size when 2% dihydrotestosterone (DHT) cream is applied as reported internationally and in research settings. Maximum penile enlargement is achieved after 6 months of treatment. Treatment with DHT is not currently FDA approved for use in the United States.

Children reared as girls require estrogen replacement therapy in adolescence. Progestins are not required due to the absence of a uterus.

Testosterone enanthate or cypionate (Delatestryl)

Promotes and maintains secondary sex characteristics in males with androgen deficiency. Limited data suggest that testosterone therapy may increase penile shaft length and circumference, increase erectile potency and ejaculatory volume, increase facial hair and muscularity, and improve a sense of well-being in patients with 5-alpha-reductase deficiency. The goal of adult dosing is to get the DHT level into the normal range.

Dihydrotestosterone, DHT cream 2%

Promotes and maintains secondary sex characteristics in androgen-deficient males.

Estrogens, conjugated (Premarin)

Used as hormone replacement in patients reared as female. Promotes development of secondary sex characteristics.

Ethinyl estradiol (Estinyl)

Used as hormone replacement in patients reared as female. Promotes development of secondary sex characteristics.



Further Outpatient Care

Outpatient care may be fairly regular during the first 2 years of life during the education and decision phase of gender assignment. Subsequent to this decision, outpatient care generally revolves around mental health support until the time of puberty. Even if the family adjusts well, providing ongoing support to answer questions as they arise is important. As noted above, these answers should be medically accurate and appropriate to the child's level of understanding (see Consultations).

Further Inpatient Care

After the newborn period, further inpatient care of 5-alpha-reductase type 2 deficiency (5-ARD) is only necessary at the time of surgery.


Currently, the only methods of prevention if both parents are carriers of the 5-alpha-reductase type 2 gene mutation are avoidance of future pregnancies or selective termination of affected pregnancies detected by prenatal mutation analysis. The latter presents significant ethical issues.


Psychosexual dysfunction may occur in the presence of genital malformation with or without surgical intervention. Appropriately timed consultations for patient and family to mental health professionals experienced in working with patients with DSD is important.

A mental health professional, preferably a child psychiatrist or pediatric psychologist, should be available to the patient and family due to the emotional loading of some of these issues. In addition to emotional support, they can help facilitate communication between the medical team, the patient, and the family.

Patient Education

Questions about gender and sexuality are extremely anxiety provoking and emotionally upsetting. Ensuring that the family feels informed and involved in the entire decision-making process is important. The family should leave the first session with a sense that all members of the team are in place to support them and should be provided the contact information that allows them to readily access any and all members of the treatment team.

Counseling is a lifelong process because of the variability of family dynamics, childhood development, and unforeseeable developments in medical and surgical treatment options. As the child grows, they must also feel a sense of comfort in accessing the team members to discuss age-appropriate developmental concerns to ultimately include intimacy with partners, sexual function and satisfaction, and potential fertility.

Education is a key part of the care plan for individuals with 5-alpha-reductase type 2 deficiency. Providing patients (and their families) with accurate, complete, and unbiased information about the diagnosis and the treatment options is an absolute requirement. This approach should include an honest discussion on the unpredictability of choosing gender identity and gender satisfaction.

Currently no group is specific to individuals with 5-alpha-reductase type 2 deficiency, but the androgen insensitivity syndrome (AIS) support group may be a reasonable surrogate. It has branches in several countries and maintains an active web site (see Androgen Insensitivity Syndrome Support Group: www.aissg.org). Members have made the group available to individuals with 46,XY DSD other than AIS.

Lastly, several Web sites may provide further information, including the following:

  • Kid's Health

  • DSD Guidelines

  • US National Library of Medicine sponsored Genetics Home Reference