5αRD2 and 17β-HSD3
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Intersex Variations
5-alpha Reductase 2 Deficiency and 17-beta hydroxysteroid Dehydrogenase 3 Deficiency
(5-alpha reductase deficiency is also known as 5αRD and 5αR2D. 17-beta hydroxysteroid dehydrogenase 3 deficiency is also known as 17β-HSD3.)
What are 5αRD2 and 17β-HSD3?
- Both 5αRD2 and 17β-HSD3 are genetic variations in people with a Y sex chromosome related to enzymes that impact sex hormones.
5-alpha-reductase – 5αRD2 impacts the body’s ability to convert testosterone to a stronger androgen dihydrotestosterone (DHT)
17-beta hydroxysteroid dehydrogenase – 17β-HSD3 helps the body convert the weaker androgen androstenedione to the stronger androgen testosterone. - Without the right balance of these hormones, bodies grow and develop little differently, including genital development which can be varied.
- The incidence of 5αRD2 and 17β-HSD3 are largely unknown.
5αRD2 and 17β-HSD3 share some similarities with Androgen Insensitivity Syndrome
Where do 5αRD2 and 17β-HSD3 Come From?
- Both variations are genetic and there are over 100 known genetic mutations across different genes that can result in 5αRD2 or 17β-HSD3.
- These genes can be inherited which is why 5αRD2 and 17β-HSD3 are more common in some families and communities.
- 5αRD2 and 17β-HSD3 may also occur from a genetic change during development, with no family history.
Recognising 5αRD2 and 17β-HSD3
5αRD2
- Genital differences including:
- female-appearing external genitalia,
atypical genitalia including clitoromegaly/microphallus and perineal urethral opening (pseudovaginal perineoscrotal hypospadias), or
male-appearing external genitalia with smaller penis, hypospadias and/or bifid scrotum. - Cryptorchidism including gonads (testes) located in the inguinal canals or in the labial folds.
- With no medical intervention secondary sex characteristics will masculinise at puberty (deepened voice, increased muscle mass and genital development).
- Absent or sparse body and facial hair post-puberty.
17β-HSD3
- Genital differences including:
female-appearing external genitalia with a vaginal pouch that does not connect to internal organs,
ambiguous genitalia (including fused labia and/or clitoromegaly) or
male-appearing external genitalia with smaller penis and/or hypospadias. - Cryptorchidism including gonads (testes) located in the inguinal canals, bifid scrotum, or in the labial folds.
- With no medical intervention secondary sex characteristics will masculinise at puberty (deepened voice, increased muscle mass, genital development and male pattern facial and body hair).
Health Considerations
- If you have not had your gonads removed, your body will start producing more testosterone at puberty. This will enhance masculine traits, including penile or clitoral growth. This may be positive or exciting, or it may bring up complex and challenging emotions.
- Low fertility or infertility may be experienced with these variations, though this varies from person to person and depends on the location of your testes and any previous medical interventions you may have had.
Treatment Considerations
Treatment and Gender
Some treatment pathways are predicated on the idea that it is preferable to make bodies fit stereotypical characteristics as much as possible.
Typical assumptions for ovotesticular variations are centred around the core idea that everyone identifies or understands themselves as a girl/woman or boy/man in line with their anatomy and sex of rearing. While this may be true for many, or even most people, and these assumptions exist, it is important to remember that people understand themselves in many different ways, and all understandings are equally valid.
Many people with ovotesticular variations do not identify as female despite their sex of rearing it is therefore important to take time to consider your options, feelings and identity before proceeding with any non-urgent medical options. Access to psychosocial support, peers and community can help you to understand these options.
Hormone Replacement Therapy
For Children and Adolescent
Children who need time to help make a decision can utilise puberty blockers to temporarily stop puberty from progressing, with few side effects. Puberty blockers allow children and adolescents to reflect and decide on how they want their body to appear and function, before undertaking either an irreversible masculinising puberty or irreversible medical intervention.
For people wanting a masculinising puberty, hormone blockers are not needed, or can be stopped to allow the body to develop in this way. Some people’s bodies may however, not produce enough hormones in which case they may need to utilise hormone supplementation with testosterone.
For people wishing to undergo a feminising puberty, hormone replacement with estrogen may be needed to support or induce the development of female secondary sex characteristics.
For Adults
If your body does not produce enough sex hormones such as estrogen or testosterone or if you have had surgery that has removed your gonads, you may need to start or continue hormone replacement therapy.
All bodies require a balance of estrogen and testosterone, and other sex hormones. Impacts of low sex hormones can include:
- Loss of bone density, which can lead to osteoporosis. Osteoporosis causes the bones to become brittle and more vulnerable to fractures and broken bones.
- Impaired cognition.
- Low mood.
- Low sex drive
- Fertility challenges, including low-no sperm count.
The benefits of hormonal therapy can include:
- Maintaining bone health and cognitive performance.
- Initiating, progressing or altering puberty.
- Alleviating low mood or personal distress.
- Increasing sex drive (if this is beneficial for you).
People can respond in different ways to different hormone treatments. Therefore, you and your healthcare provider should understand and manage the side effects and consequences of undergoing hormone replacement.
Not all people with 5αRD2 or 17β-HSD3 want or need hormone replacement therapy. Counselling and peer support can help determine the best decision for you.
Surgical Interventions
Most people with 5αRD2 or 17β-HSD3 will not require surgical interventions. Where there are genuine health risks to an individual this should be addressed in an appropriate time frame as determined by the treating medical team/specialists.
The decision to pursue non-urgent surgical interventions should be thoroughly considered, and alternatives explored. This surgical decision making should be directed by the individual, with their full and informed consent. Where they are unable to provide informed consent, surgical interventions should be deferred. It is also important to consider when any proposed treatment should to occur. Many decisions can be delayed until an individual is old enough to participate fully in decision-making and make their own decisions about their body and healthcare.
Unnecessary surgery causes additional stress and may need to be followed by more treatments and surgeries later in life. These surgeries are intrusive and are often harmful to physical sensation and sexual enjoyment later in life and take away decision-making and options from the individual, who may grow up to understand their identity and values in ways that are incongruent with the proposed treatment/s. They may be illegal in some jurisdictions in Australia.
Genital surgery
Some surgeries may be suggested in infancy or childhood to change or alter genital appearance (such as clitoral surgeries and labiaplasties) or function to fit gender stereotypes (such as penile surgeries and vaginoplasties). These kinds of treatments are largely proposed for social reasons and do not address any medical need. Early surgeries take away decision-making and options from the individual, who may grow up to understand their identity and values in ways that are incongruent with proposed early treatments. Sometimes these surgeries may be described or referred to as a ‘correction’ or using other similar language. This presumes that something needs to be ‘fixed’ when in reality the tissue is healthy and functional. It is best to defer these decisions until an individual is old enough to be involved in decision-making and consent to treatment. They may be illegal in some jurisdictions in Australia.
Gonadal Surgery
In general, it is preferable to not remove gonads that have potential for future function, even if this may be incongruent with sex of rearing. Gonads have historically been removed to address potential cancer risks, but historical estimates are no longer thought accurate. A 2006 clinical statement recommends monitoring gonads. Recent clinical papers link gonad removal to female gender assignment.
Risk factors are individual and should be discussed and understood on a case-by case basis. It is always advisable to ask for more information from your care team when navigating these conversations. Potential cancer risks can be managed through routine monitoring and other non-surgical methods.
A gonadectomy is not only a sterilising procedure, but also creates the need for lifelong hormone replacement therapy, and comes with the associated risks of osteopenia and osteoporosis. These conditions can lead to increased fractures and broken bones and may be illegal in some jurisdictions in Australia.
It is therefore important to be guided by accurate, current and unbiased medical and scientific information in these conversations, and that input from the individual be centred in these conversations.
Reports also suggest that a significant proportion of people raised female with 5αRD or 17β-HSD3 will later live as men. Any identity is okay. It is important to ensure that early medical management leaves all options open for the future, irrespective of sex of rearing.
Undescended testes may be relocated to the scrotum if you have that anatomy. Relocating the testes can potentially improve fertility as the internal body temperature is much higher and associated with reduced fertility. In some cases, relocating the testes may also assist with testosterone production, however this is not guaranteed for people with 5αRD or 17β-HSD3. If you don’t have a scrotum or opt not to have your testes relocated outside the body you may choose to leave them where they are or choose to have them removed when you can provide fully-informed consent.
Fertility Treatment
Testosterone is the primary hormone involved in creating sperm, and where testosterone production or utilisation is impacted, so too is sperm production. As a result, many individuals with 5αRD or 17β-HSD3 experience impaired fertility or infertility. These can be challenging or distressing for many people with 5αRD or 17β-HSD3.
People with 5αRD or 17β-HSD3 also do not have a uterus which means that pregnancy is not possible and while sperm may be produced, it may be low in quantity or quality.
If having your own biological children is important to you, you may wish to consider options that utilise Assisted Reproductive Technologies.
Some options include:
- The use of donor sperm (if you have a partner with eggs and a uterus)
- The use of donor sperm and donor eggs (if you have a partner with a uterus)
- Surrogacy with donor sperm (if you have a partner with eggs)
- Surrogacy with donor eggs (if you have a partner with a sperm)
- Surrogacy with donor eggs and donor sperm or a donated embryo (if you do not have a partner, or your partner cannot or does not want to genetically contribute).
If your body can produce sperm some additional options may also include:
- Microscopic testicular retrieval of sperm (MicroTESE)
- Intracytoplasmic Sperm Injection (ICSI)
Fertility concerns should ideally be raised with a doctor early if you are considering having children. Where possible, your doctors can guide you through the steps and decisions you may need to make.
You may also wish to explore alternate family-building options. Parenting takes many shapes and forms such as adoption, step-parenting, foster care, parenting pets, being a godparent or playing an active role with nieces, nephews or cousins. Life is rich with opportunities to nurture, care for and provide guidance to others. Our families can be the ones we are born with but also the ones we choose for ourselves. This can include choosing to have a family without children.
When making any decisions about starting a family, take time to consider your view on your role you want to play in your family and acknowledge the impact of social pressures to conform to traditional ideals about parenthood.
Health Monitoring and Other Treatments
Dilation
For some people with 5αRD or 17β-HSD3, a non-surgical treatment called dilation may be suggested. Dilation is a process of gradually stretching and opening the vaginal canal with a series of insertable cylinder or tube-shaped devices called dilators.
It is important that dilation is only undertaken by choice when you are old enough to make an informed decision that this is something that you want to do and that is important to you. Dilation is mainly intended to help people who wish to receive penetrative intercourse where this may be uncomfortable, painful, or otherwise limited. For people who have had a vaginoplasty this is an important element of post-operative care and treatment, though it is also chosen even without surgery. It can be quite a long-term and involved process. Dilating can be as clinical or informal as is most comfortable for you.
Examinations and Photography
You may need to undergo regular examinations to understand how your body is functioning. This includes genital examinations. Ask how these can be reduced in number, or if they need to go ahead at all.
If you are a parent or carer, you may be asked if photographs can be taken of your child’s genitals, this is not usually necessary, so it is important to ask why it is being suggested. This is sometimes done to minimise the need for future genital examinations, however, should be fully considered due to the distress they can cause the individual later in life. These photographs will not be distributed without your explicit consent as the parent/individual. If you’re uncomfortable with a decision your parents made, you can ask for the photographs to be destroyed.
You can choose not to have genital examinations, or photography altogether, and may wish to ask whether the doctor is able to get the same information another way. As an adult, your permission must be sought to be examined by doctors, or medical students for education purposes. You should not feel compelled to agree. More guidance on paediatric genital examinations and photography is available at View Link
Ongoing Care
You may see many different kinds of doctors and health workers. Some people that may be involved in your care may include:
- A psychologist or psychiatrist, who can help you consider your own treatment options, your wishes and support you and your family.
- A social worker, peer navigator and peer support workers who can help you navigate health systems, connect you with community, and address any challenges.
- Your general practitioner or family doctor.
- An endocrinologist (to help with any hormonal management).
- A gynaecologist (for anything to do with your anatomy, menstruation or sex).
- A urologist (for anything to do with your anatomy, bladder or urination).
- Surgeons involved in your care.
- Fertility specialists (for any fertility support or assisted reproduction).
- Sexual health specialists.
- Pelvic health physiotherapists.
- Sexologists and sexological bodyworkers.
You can ask your regular doctor about creating a care plan, and for referrals to community/peer support organisations. Other people have been through these circumstances before, and they can help you navigate medical and support systems.
If you are maintaining healthy hormone levels, and your body is functioning and developing in ways you are happy with, there is likely no need for any medical interventions. As always you should ask for written copies of the latest reports on outcomes so that you can access all the information about your body and health if and when you need access to it. It’s important for everyone to have adequate information about their body, in order to best manage your physical and mental health. Finding health professionals who are knowledgeable about 5αRD or 17β-HSD3 and understand the person’s emotional needs is vital for the general practitioner who might know that you are perfectly healthy in general, but might lack the awareness of the psychological impact.
When seeking medical care you may be confronted by medical professionals who lack awareness of 5αRD or 17β-HSD3 and/or show a lack of interest in doing additional research to address their knowledge gap. This can make the patient feel discouraged or compelled to educate the professional who is supposed to be looking after them. Experiences like this can be traumatic, creating distrust when asking for help and barriers to accessing medical care. Finding referrals to knowledgable services from your peer network can help you avoid being repeatedly disappointed.
Working with a doctor is important to understand which of these health concerns are relevant to your body. Learning how to monitor and manage these conditions is an important aspect of living with 5αRD or 17β-HSD3.
Community and Other Supports
Connecting with community – including family, friends and peers is important for your mental health and wellbeing. Creating or finding a space where it is safe to explore or express what it means to you to have MRKH can be rewarding and empowering. Connecting your experiences to others’ can also give you more tools to look after your physical health. Seeing, being and interacting with people with similarly diverse bodies can help you make informed decisions free from external pressure from families, doctors or societal norms.
Supports Available for Individuals and Families in Australia
- InterLink psychosocial support service – https://ilink.net.au
- InterAction for Health and Human Rights – https://interaction.org.au/
- IPSA Intersex Peer Support Australia (formerly AISSGA) – https://isupport.org.au/
- +61 7 3017 1724
- info@ilink.net.au
- PO Box 1372 Eagle Farm QLD 4009
InterLink is a program of InterAction for Health and Human Rights. We respect your rights when using our services.
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