Complete androgen insensitivity syndrome (CAIS) is a rare condition where a person has XY (male) chromosomes and testicles, but the body cannot “hear” or use male hormones called androgens at all. Because the body cannot respond to androgens, the baby develops normal-looking female outer genitals, even though inside there are no ovaries or uterus, and the gonads are actually undescended testicles. CAIS usually shows up when a young person who looks like a girl does not start periods at puberty, or when a doctor finds a groin or labial hernia that contains a testicle.
Complete androgen insensitivity syndrome is a rare genetic condition where a person has male chromosomes (46,XY) and testes, but the body cannot respond to male hormones called androgens because the androgen receptor does not work properly. As a result, the baby is born with typical-looking female external genitalia, but has no uterus and usually has undescended testes inside the abdomen or groin. Puberty usually happens “automatically” through conversion of testosterone to estrogen, so breast development is normal, but there is no period and pregnancy is not possible.
CAIS is caused by a change (mutation) in the androgen receptor (AR) gene on the X chromosome. Because the receptor is faulty, testosterone and dihydrotestosterone cannot “switch on” their normal actions in the fetus and at puberty. The body therefore follows a mainly estrogen-driven path, giving a female external appearance even though the chromosomes and gonads are male. The testes often stay in the abdomen or groin and can slowly develop a small cancer risk with age. CAIS is usually inherited in an X-linked pattern, but many cases arise for the first time in a family.
CAIS happens because of a change (mutation) in the androgen receptor (AR) gene on the X chromosome, so cells cannot respond to testosterone or dihydrotestosterone at all, even though the body makes these hormones.
Other names
Doctors and older books use several other names for CAIS. The most correct and respectful term today is “complete androgen insensitivity syndrome.”
Older names you may still see include “complete androgen resistance syndrome,” “testicular feminization syndrome,” “Morris syndrome,” and “46,XY disorder of sex development due to androgen receptor defect.” These older terms are mostly historical now.
Types
Even though your topic is CAIS, doctors usually explain it as part of three main types of androgen insensitivity syndrome (AIS).
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Complete androgen insensitivity syndrome (CAIS)
In CAIS, the body cannot respond to androgens at all. External genitals look typically female, there is normal breast development at puberty, but there is no uterus, and the person has XY chromosomes and testicles. -
Partial androgen insensitivity syndrome (PAIS)
In PAIS, the body responds only partly to androgens. Genitals can look in between male and female, or more male or more female, depending on how strong the receptor works. This is not the same as CAIS but is part of the AIS spectrum. -
Mild androgen insensitivity syndrome (MAIS)
In MAIS, genitals usually look male at birth, but the person may have problems such as low sperm count or reduced body hair, because the androgen receptor works only a little. This is the mild end of the AIS spectrum.
Doctors may also describe CAIS types by age of diagnosis (found in infancy because of a hernia, or in teens because of no periods), or by where the testicles are located (inside abdomen, in inguinal canal, or in labia).
Causes of complete androgen insensitivity syndrome
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Mutation (change) in the androgen receptor (AR) gene
The main cause of CAIS is a harmful mutation in the AR gene on the X chromosome, so the receptor cannot bind androgen or cannot work inside the cell nucleus. -
X-linked recessive inheritance from the mother
Many people with CAIS inherit the AR gene mutation from their mother, who carries one changed copy of the gene but does not have CAIS herself because she also has one normal copy. -
De novo (new) mutation in the AR gene
Sometimes the AR mutation appears for the first time in the egg, sperm, or early embryo, with no family history before. This is called a de novo mutation and can still cause CAIS. -
Nonsense mutations that stop protein early
A nonsense mutation makes a “stop” signal in the AR gene, so the androgen receptor protein is cut short and cannot work, leading to complete loss of androgen response. -
Missense mutations that change key amino acids
A missense mutation swaps one amino acid for another in an important part of the receptor, such as the hormone-binding or DNA-binding region, which can totally block its function and cause CAIS. -
Splice-site mutations in the AR gene
Some mutations affect the “splicing” signals so exons are joined wrongly, creating an abnormal receptor that cannot move to the nucleus or bind DNA correctly, so androgen signals are lost. -
Large deletions in the AR gene
Sometimes one or more exons of the AR gene are missing, or the whole gene is deleted on the X chromosome, so the cell cannot make any functional androgen receptor at all. -
Insertions or frameshift mutations in AR
Extra DNA bases can be inserted, causing a frameshift that makes a long, abnormal receptor protein that is unstable or misfolded, again giving complete androgen insensitivity. -
Mutations in the ligand-binding domain of AR
Changes in the part of the receptor that grabs testosterone or dihydrotestosterone stop the hormone from binding, so the receptor never activates the target genes, leading to CAIS. -
Mutations in the DNA-binding domain of AR
If the receptor cannot attach to DNA at androgen-response elements, the signal cannot turn on needed genes, even if hormone is present, so tissues stay insensitive to androgens. -
Mutations affecting receptor nuclear transport
Some AR mutations stop the receptor from entering the cell nucleus after hormone binding, so gene activation fails and androgen effects do not occur, causing a complete phenotype. -
Mutations affecting receptor stability
Certain mutations make the receptor protein unstable and quickly broken down by the cell’s quality-control systems, leaving too little receptor for any androgen effect. -
Somatic mosaicism in AR gene
In some families, the mutation can be present in some of a parent’s germ cells but not all body cells, so one child develops CAIS due to a gonadal mosaic AR mutation. -
Germline mutation passed through multiple generations
CAIS can appear in several generations of a family, often in people assigned female at birth in the maternal line, due to a stable AR mutation passed from carrier mothers. -
Consanguineous (related) parents increasing chance of rare variants
In some regions, marriage between relatives can make rare X-linked mutations like those in the AR gene more likely to appear in children, including CAIS. -
AR mutations causing loss of co-factor binding
Some receptor changes disturb parts of the protein that link to helper proteins (co-activators), so even when hormone binds, the receptor cannot properly switch genes on. -
AR mutations that affect receptor folding
Misfolded receptor proteins cannot take the right 3-D shape, so they either stay in the cytoplasm or cannot bind hormone or DNA, resulting in absent androgen action. -
Rare promoter or regulatory region mutations
In a few cases, changes are not in the coding exons but in regulatory regions that control AR gene expression, so too little receptor is made and tissues behave as if there is no androgen signal. -
Unknown or undetected AR gene changes
In a small percentage of people with clear CAIS features, standard testing does not find a mutation, but experts still think the cause is a very subtle or hidden change in AR function. -
Very rare defects in AR-related pathways (CAIS-like)
Very rarely, conditions that mimic CAIS can come from defects in proteins that help AR work, but classic CAIS is almost always due to AR gene mutations on the X chromosome.
Symptoms and signs of CAIS
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Normal-looking female external genitals at birth
Babies with CAIS are usually born with a typical female-looking vulva, with no penis or scrotum, so doctors often assign them female at birth. -
No uterus and no upper vagina inside
Inside the pelvis there is no uterus and the upper part of the vagina is missing, because testicles make anti-Müllerian hormone that stops the uterus from forming. -
Short or shallow vaginal canal
The vagina is often shorter than average and may feel like a “pouch” or “dimple,” which can later affect comfort with penetrative sex unless dilatation or surgery is used if the person wants this. -
Undescended testicles (gonads) in abdomen or groin
The gonads are testicles, but they stay inside the abdomen, inguinal canal, or labia because the scrotum does not form correctly, and they may present as lumps or hernias. -
Primary amenorrhea (no first period)
Teens with CAIS often go to the doctor because they never start menstrual periods, since they have no uterus and therefore cannot build or shed a uterine lining. -
Normal or even prominent breast development
Breast development at puberty is usually normal or good, because the body converts testosterone from the testicles into estrogen, which stimulates breast tissue. -
Little or no pubic and underarm hair
Many people with CAIS have absent or very sparse pubic and axillary hair because hair follicles also depend on androgens, which cannot act on the skin. -
Normal female body shape at puberty
At puberty, the hips widen, breasts grow, and fat distribution looks typically female, because estrogen effects are working even though androgen effects are not. -
Infertility
People with CAIS cannot become pregnant because they do not have ovaries or a uterus and their testicles do not make usable sperm or have a normal outlet to the outside. -
Inguinal or labial hernia containing testis in childhood
In some children, a groin or labial swelling leads surgeons to discover a testicle in the hernia sac, which then prompts further studies and diagnosis of CAIS. -
Average or tall height compared with female peers
Many individuals with CAIS are as tall or slightly taller than average women, reflecting their XY karyotype and androgen-independent growth patterns. -
Possible feelings of difference about body or sexuality
When the diagnosis is shared, some people may feel confused, anxious, or different from others and can benefit from sensitive psychological support and peer groups. -
Risk of gonadal (testicular) tumors later in life
Undescended testicles have a higher risk of germ-cell tumors with age, so doctors discuss timing of removal (gonadectomy) and careful follow-up. -
Reduced bone mineral density
Some adults with CAIS have lower bone density, possibly because androgens help bones, and estrogen replacement after gonadectomy must be carefully managed. -
Generally normal life span and overall health
With good medical care and emotional support, most people with CAIS can live a full life, have satisfying relationships, and maintain good general health.
Diagnostic tests for CAIS
Below are tests grouped by type. Not every person needs all tests, but together they help confirm CAIS and rule out other conditions.
Physical examination tests
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General physical exam
The doctor looks at overall growth, height, weight, and puberty stage, and checks the chest, abdomen, and limbs to see if development matches the person’s age and assigned sex. -
External genital exam
The doctor gently examines the vulva, clitoris, and vaginal opening to see if the genitals look typically female, if the vagina is shallow, or if there are any unusual findings. -
Pubic and underarm hair assessment
The pattern and amount of pubic and axillary hair are checked because very little hair suggests lack of androgen effect and can point toward CAIS. -
Examination for groin or labial lumps
The doctor feels the groin and labial areas for hernias or firm lumps that might be undescended testicles, which are common in CAIS. -
Breast development assessment
Breast size and shape are checked and compared with hair pattern and menstrual history; good breast growth with no periods and little hair raises suspicion of CAIS.
Manual / bedside tests
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Gentle vaginal depth assessment (with finger or small dilator)
In a calm and consent-based exam, the clinician may gently check how deep the vaginal canal is; a short or blind-ending canal is typical in CAIS and helps guide imaging. -
Manual hernia examination
The doctor uses their hands to feel a groin hernia and may be able to tell that the lump is a testis, which then needs imaging and further work-up. -
Abdominal palpation for intra-abdominal gonads
By carefully feeling the abdomen, the clinician may detect deep masses that could be undescended testicles, prompting ultrasound or MRI. -
Manual puberty staging (Tanner staging)
Tanner staging of breasts and pubic hair is done with the eyes and hands to rate how far puberty has progressed and to see the mismatch between estrogen-driven breasts and androgen-dependent hair. -
Clinical family history review (pedigree drawing)
The clinician manually sketches a family tree and notes relatives with similar findings (such as primary amenorrhea or inguinal hernias) to support an X-linked pattern of inheritance.
Laboratory and pathological tests
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Karyotype (chromosome test)
A blood sample is used to look at chromosomes; CAIS shows a 46,XY karyotype, proving that the person is chromosomally male even though they look female externally. -
Serum testosterone level
Blood testosterone is usually in the normal or high male range for age, showing that the testicles make hormone but the body is not responding to it. -
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
LH is often elevated because the brain senses that androgen action is not working, so it drives the testicles harder; FSH may be normal or slightly raised. -
Estradiol (estrogen) level
Estradiol is often in the female range because some testosterone is changed into estrogen, supporting breast development despite androgen resistance. -
Anti-Müllerian hormone (AMH) level
AMH, made by Sertoli cells in testicles, is usually present, which explains why the uterus and upper vagina did not form. This helps distinguish CAIS from conditions with ovaries. -
Human chorionic gonadotropin (hCG) stimulation test
In some cases, doctors give hCG and then measure testosterone response; a good testosterone rise with no physical virilization supports androgen resistance rather than a problem with hormone production. -
Androgen receptor (AR) gene sequencing
Genetic testing of the AR gene looks for mutations that confirm CAIS; this is considered the gold standard, although a small number of people with CAIS features have no mutation found. -
Pathology of removed gonads (after gonadectomy)
When testicles are removed for cancer-risk management, a pathologist examines them to look for germ-cell tumors or early pre-cancer changes and to confirm testicular tissue.
Electrodiagnostic-type and monitoring tests
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Electrocardiogram (ECG) before and during hormone therapy
An ECG may be done before starting or changing hormone replacement therapy in adults with CAIS to make sure the heart rhythm is safe, especially if other risk factors exist. This does not diagnose CAIS but supports safe care. -
Bone density scan (DEXA) with possible software-based analysis
Bone mineral density is often checked with a DEXA scan, which uses low-dose X-rays and computer analysis; this helps monitor bone health in people with CAIS, especially after gonad removal and during estrogen therapy.
Imaging tests
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Pelvic ultrasound
Ultrasound of the pelvis is a painless imaging test that uses sound waves to look for a uterus (usually absent in CAIS) and to find gonads near the internal inguinal ring or in the pelvis. -
Inguinal and abdominal ultrasound
Focused ultrasound of the groin and abdomen helps locate undescended testicles inside a hernia sac or higher in the abdomen, guiding further surgery or follow-up. -
Magnetic resonance imaging (MRI) of pelvis and abdomen
MRI gives more detailed pictures of internal organs and gonads, helping confirm absence of uterus and showing the exact position and size of the testicles and any suspicious tumor areas. -
X-ray for bone age and bone health (if needed)
Simple X-rays can be used to assess bone age or look for signs of low bone density in some settings, though DEXA is better; this helps plan hormone treatment to protect bones. -
Laparoscopy (key-hole surgical inspection)
In some complex cases, doctors may do laparoscopy to directly see and sometimes remove the gonads and to confirm the internal anatomy when imaging is unclear. This is both a diagnostic and therapeutic procedure.
Non-pharmacological treatments (therapies and other approaches)
1. Multidisciplinary DSD team care
A person with CAIS benefits from a team that includes hormone specialists, surgeons, psychologists, and specialized nurses. This team helps coordinate decisions about hormone therapy, surgery, bone health, and fertility options. The purpose is to give consistent, accurate information and avoid rushed decisions. The mechanism of benefit is mainly through better communication, fewer medical errors, and a plan that respects the person’s own values and wishes.
2. Psychological counseling
Ongoing counseling with a therapist who understands differences in sex development (DSD) can help with identity questions, anxiety, depression, and relationship worries. The purpose is to support mental health, self-esteem, and coping skills. The mechanism is by providing a safe space to talk, teaching cognitive and behavioral strategies to manage stress, and helping the person and family process complex feelings about diagnosis, fertility, and body image.
3. Peer and support-group contact
Meeting others with CAIS or other intersex variations, either in person or online, can reduce feelings of isolation and shame. The purpose is to normalize the experience and share practical tips about medical care, relationships, and everyday life. The mechanism is social support: hearing similar stories, sharing experiences, and seeing positive adult role models improves resilience and quality of life.
4. Family counseling and guided disclosure
Parents and caregivers often need help understanding CAIS and how, when, and what to explain to their child. The purpose is to promote honest but age-appropriate disclosure and avoid secrets that may damage trust later. The mechanism is structured conversations led by professionals so that the family can answer questions clearly, respect privacy, and support the child’s evolving understanding over time.
5. Education about CAIS and the body
Simple, repeated explanations about chromosomes, hormones, gonads, fertility, and bones help the person understand why treatment is recommended. The purpose is informed consent and self-management. Mechanistically, good health literacy improves adherence to hormone therapy, follow-up scans, and lifestyle advice, reducing long-term complications such as osteoporosis or late gonadal tumors.
6. Shared decision-making and delaying irreversible surgery
Modern guidelines encourage delaying irreversible genital surgery and gonadectomy until the person can participate in decisions, except when there is a clear medical emergency. The purpose is to respect bodily autonomy and reduce regret. The mechanism is ethical and psychological: involving the person in decisions can lower trauma, improve trust in doctors, and match treatments to their own gender identity and life plans.
7. Bone-health monitoring and exercise programs
People with CAIS, especially after gonadectomy, have lower bone mineral density and higher risk of osteopenia or osteoporosis. The purpose of regular DEXA scans plus weight-bearing and resistance exercise is to maintain bone strength. The mechanism is mechanical loading of bone and muscle, which stimulates bone formation, and early detection of bone loss so that hormones and supplements can be adjusted.
8. Nutrition counseling for bone and heart health
Dietitians can help build a meal plan rich in calcium, vitamin D, protein, and plant foods, while limiting excess salt, sugary drinks, and unhealthy fats. The purpose is to support bone mineralization, healthy weight, and cardiovascular health. The mechanism is through supplying the right building blocks for bone (calcium, vitamin D, protein) and reducing risk factors such as high blood pressure or insulin resistance.
9. Pelvic floor and sexual-function physiotherapy
Physiotherapists with expertise in pelvic health can teach relaxation, stretching, and strengthening exercises. The purpose is to improve comfort with sexual activity, reduce pain, and support bladder and bowel control. The mechanism is local muscle training and nervous-system desensitization, which can lower pain and improve blood flow and function in the pelvic region.
10. Non-surgical vaginal dilation (if desired)
Some adults with CAIS choose non-surgical vaginal dilation to increase vaginal length using gradually larger dilators. The purpose is to allow comfortable penetrative sex if the person wants that. The mechanism is gentle, regular mechanical pressure that stretches tissues over time; it is now preferred over early surgery because it is non-invasive and high success has been reported.
11. Sexual counseling and relationship support
Specialized sex therapists can help the person and their partner talk about intimacy, pleasure, and worries about “difference.” The purpose is to build satisfying, consensual sexual relationships. The mechanism is by improving communication, teaching techniques to manage anxiety or pain, and reframing sex as something flexible and not limited by anatomy alone.
12. Fertility and family-building counseling
Because people with CAIS do not have a uterus and cannot carry a pregnancy, early honest discussion about alternative family-building options (adoption, fostering, partner’s pregnancy, assisted reproduction using partner or donor gametes) is important. The purpose is to reduce shock later and help long-term planning. The mechanism is providing realistic options and emotional support, rather than leaving a painful “silence” around fertility.
13. Genetic counseling for the person and family
Genetic counselors explain how the AR mutation is inherited, what the recurrence risk is in future pregnancies, and what testing is available for relatives if they wish. The purpose is informed reproductive choices and family understanding. Mechanistically, this reduces confusion, guilt, and blame and supports respectful family decision-making.
14. Transition planning from pediatric to adult care
A structured plan for moving from children’s services to adult endocrine and gynecology care helps prevent gaps in hormone prescriptions and monitoring. The purpose is continuity of care. The mechanism is scheduling joint visits, preparing the young person to speak for themselves, and making sure bone scans and labs continue regularly.
15. Structured exercise and lifestyle coaching
Programs that combine aerobic, resistance, and balance training support bone, heart, and mental health. The purpose is to counteract bone loss, weight gain, and mood problems that can accompany hormonal changes. The mechanism is improved bone remodeling, better insulin sensitivity, and increased endorphins and serotonin that lift mood.
16. Sleep and stress-management training
Techniques such as sleep-hygiene routines, breathing exercises, mindfulness, and relaxation can reduce stress hormones that affect mood and bone. The purpose is to improve daily functioning and support hormone balance. The mechanism is lowering chronic activation of the stress (HPA) axis, which can otherwise worsen anxiety and possibly bone turnover.
17. Educational and workplace support
Some people benefit from school or work adjustments (flexible appointments, privacy for medical visits, or support for mental-health days). The purpose is to reduce academic or job stress and stigma. The mechanism is practical: fewer conflicts between care and responsibilities, and better understanding from teachers or managers leads to improved adherence and wellbeing.
18. Reliable written and online information
Providing evidence-based patient leaflets and trusted websites about CAIS helps people avoid misinformation and harmful “cures” advertised online. The purpose is safe self-education. The mechanism is giving vetted resources produced by specialist centers and peer-reviewed groups instead of random internet content.
19. Regular long-term follow-up visits
Even when someone feels well, regular reviews of hormones, bones, and general health are needed for life. The purpose is to adjust hormone doses, check side effects, and detect any bone or heart issues early. The mechanism is simple: structured surveillance improves outcomes and allows early intervention for problems.
20. Advocacy and legal support if needed
In some settings, people with CAIS may face discrimination or may need help with documentation or insurance. The purpose is to protect rights and access to care. The mechanism is support from advocacy organizations, legal advice where necessary, and policies recognizing intersex/DSD conditions in healthcare and social systems.
Medicines and hormone treatments
Important reality note: there are not 20 different drugs approved only for CAIS. In real clinical practice, doctors use standard estrogen (and sometimes testosterone) hormone-replacement medicines plus usual bone-health drugs, based on FDA-approved products and specialist guidelines.
Below are key medicine types commonly used; doses are examples only from labels and literature, not personal medical advice. Always follow your own doctor’s prescription.
1. Transdermal estradiol patches (e.g., Alora, Minivelle, Estraderm, Climara, Menostar)
Estradiol patches deliver estrogen through the skin at a steady rate, avoiding first-pass metabolism in the liver. Typical delivery rates range from about 0.025–0.1 mg/day, with patches changed once or twice weekly depending on the brand. These products are labeled for hypoestrogenism and menopause, but in CAIS they are widely used off-label to maintain breast development, bone health, and wellbeing after gonadectomy. Main side effects include breast tenderness, headache, spotting (if a uterus were present), and small risks of blood clots and stroke, especially with other risk factors.
2. Oral estradiol tablets
Oral micronized estradiol is a synthetic version of the main natural estrogen. Doses for hypogonadism or HRT often range around 1–4 mg once daily, typically given at bedtime or in the evening. In CAIS it is used to induce or maintain puberty and adult estrogen levels after gonadectomy, supporting bone mineral density and secondary sexual characteristics. Because it passes through the liver, it may have a slightly higher impact on clotting and lipids than patches, so clinicians weigh benefits and risks for each person.
3. Estradiol transdermal gels and sprays
These preparations deliver estradiol through the skin using a daily gel or spray. Typical doses (for hypogonadism and menopause) are chosen to match patch doses and are titrated based on symptoms and blood levels. In CAIS they provide flexible dosing and may be preferred by some adults who dislike patches. Side effects are similar to other estrogen products, and users must avoid skin-to-skin transfer to others immediately after application.
4. Conjugated estrogen tablets
Conjugated estrogens are mixtures of estrogen compounds historically used in postmenopausal hormone therapy. In CAIS they are less commonly chosen today, but may be considered when local practice favors them. They are usually taken once daily in low doses, with side effects similar to estradiol and small but real risks of thrombosis and breast cancer with long-term high-dose use in some populations.
5. Testosterone gel (off-label option in some CAIS care)
Some adults with CAIS prefer low-dose testosterone gel alone or combined with estrogen, reporting improved energy, libido, and sense of wellbeing. Guidelines and patient leaflets from specialist centers describe this as an individualized choice, not a standard requirement. Doses are usually much lower than those used for hypogonadal cis men. Possible side effects include acne, oily skin or hair, mood changes, and raised red-blood-cell counts; virilizing effects are often minimal in CAIS due to the receptor defect but must still be monitored.
6. Calcium with vitamin D preparations (as “drugs” on prescription)
Although often thought of as supplements, in many countries calcium and vitamin D combinations are prescribed as medicines to protect bone in hormone-related bone loss. In CAIS they are recommended when bone density is low or dietary intake is inadequate. Typical doses might be around 1000–1200 mg elemental calcium and 800–1000 IU vitamin D3 per day, adjusted for diet. Side effects can include constipation and, rarely, high calcium levels if overdosed or combined with other high-dose products.
7. Bisphosphonates (e.g., alendronate, risedronate) for osteoporosis when needed
For adults with CAIS and established osteoporosis or fragility fractures, bone-specialist teams may consider bisphosphonates used in standard osteoporosis care. These drugs bind to bone and slow down bone breakdown by osteoclasts, increasing bone mineral density and lowering fracture risk. They are usually taken weekly or monthly with strict instructions (fasting, staying upright) to protect the esophagus. Side effects include digestive upset, rare jaw osteonecrosis, and atypical femoral fractures with long use.
8. Other osteoporosis medicines (denosumab, teriparatide, etc.) in selected cases
If osteoporosis is severe or bisphosphonates cannot be used, bone specialists may consider other standard osteoporosis medicines. Denosumab is an antibody given by injection every 6 months that blocks RANKL and reduces bone resorption; teriparatide is a parathyroid hormone analog that stimulates new bone formation, usually for up to 2 years. These drugs are not specific to CAIS, but may be used when bone fragility is significant despite optimal estrogen therapy.
(Because of space and scientific honesty, I have focused on the main medicine families actually used in CAIS rather than inventing 20 separate “disease-specific” drugs.)
Dietary molecular supplements
1. Calcium
Calcium is the main mineral in bone. Adults with low bone density or low dietary calcium are often advised to aim for about 1000–1200 mg elemental calcium per day from food plus supplements if needed. The purpose is to provide raw material for bone mineralization. Mechanistically, adequate calcium reduces secondary hyperparathyroidism and bone resorption, helping maintain bone mineral density in CAIS when combined with estrogen and exercise.
2. Vitamin D3 (cholecalciferol)
Vitamin D3 helps the gut absorb calcium and supports normal bone remodeling. Typical maintenance doses range from 800–2000 IU daily, but higher short-term doses may be used under medical supervision if deficiency is present. The purpose is to keep blood vitamin D at a healthy level, usually above 20–30 ng/mL depending on the guideline. Mechanistically, this optimizes calcium balance and bone mineralization and may support muscle function, reducing falls and fractures.
3. Vitamin K2
Vitamin K2 is involved in activating osteocalcin, a protein that helps bind calcium in bone. Some studies suggest it may improve bone quality when combined with vitamin D and calcium, although evidence is still evolving. A typical supplemental dose may be around 45–180 mcg per day in products marketed for bone health. The purpose is to support proper placement of calcium into bone rather than blood vessels.
4. Magnesium
Magnesium is a cofactor for many enzymes in bone and vitamin D metabolism. Insufficient magnesium can impair parathyroid hormone function and bone mineralization. Supplemental doses often range from 200–400 mg elemental magnesium per day, depending on diet and kidney function. The purpose is to support healthy bone, nerve, and muscle function; mechanism is enzymatic co-factor activity and improved vitamin D activation.
5. Omega-3 fatty acids (EPA/DHA)
Omega-3 fats from fish oil or algae may have modest positive effects on inflammation, cardiovascular risk, and possibly bone metabolism. Common doses are around 250–1000 mg EPA+DHA daily in supplements, in addition to fatty fish in the diet. The purpose is overall cardiometabolic support, especially important if estrogen therapy affects lipids. Mechanistically, omega-3s influence inflammatory mediators, endothelial function, and may modestly influence bone turnover.
6. Vitamin B12
Vitamin B12 deficiency can contribute to anemia, fatigue, and possibly reduced bone density. In people with low B12 levels, oral doses around 250–1000 mcg per day or intermittent injections may be used, depending on cause. The purpose is healthy red blood cells and nerve function. Mechanistically, B12 is needed for DNA synthesis and homocysteine metabolism, both relevant to bone and vascular health.
7. Folate (folic acid)
Folate works with B12 in DNA synthesis and homocysteine regulation. Adequate intake may support cardiovascular and possibly bone health. Typical supplemental doses in multivitamins are 400–800 mcg daily, unless higher doses are prescribed for specific reasons. The purpose is to prevent deficiency and support cell division and tissue repair.
8. Iron (if deficient)
Iron deficiency is not specific to CAIS but can worsen fatigue and quality of life. If blood tests show low iron or anemia, supplements (for example 30–60 mg elemental iron daily) may be advised for a limited period. The purpose is to restore iron stores and hemoglobin. Mechanistically, iron is essential for oxygen transport and many enzymes in energy metabolism.
9. Zinc
Zinc plays a role in immune function, wound healing, and bone formation. Mild deficiency is common with limited diets. Typical supplemental doses for adults range around 8–15 mg per day in multivitamins. The purpose is general immune and tissue health; mechanistically, zinc acts as a co-factor in many enzymes and may support osteoblast function.
10. Probiotics (selected strains)
Some research suggests that certain probiotic strains may modestly support bone health and inflammation by interacting with the gut–immune–bone axis. Doses vary widely depending on product, often billions of CFU per day. The purpose is not to “treat CAIS” directly, but to support gut health, nutrient absorption, and possibly bone metabolism. Mechanistically, probiotics may influence calcium absorption and inflammatory signaling.
Immunity booster / regenerative / stem cell drugs – what is realistic?
At present there are no FDA-approved stem cell or regenerative drugs that treat CAIS itself or repair the androgen receptor. Management is supportive: sex-steroid replacement, bone-health medicines, and psychological care.
Some adults with severe osteoporosis may receive anabolic bone drugs (like teriparatide) under standard osteoporosis indications, and almost all will need good estrogen replacement plus calcium and vitamin D. These treatments help the skeleton but do not change the underlying genetic condition. Experimental gene or cell therapies for DSD are still research topics and not available as routine care.
Surgeries (procedures and why they are done)
1. Gonadectomy (removal of testes)
Gonadectomy removes the intra-abdominal or inguinal testes to lower the risk of gonadal tumors that rises with age in CAIS. Many modern teams recommend delaying this until after puberty so that spontaneous estrogen production can drive natural breast development and growth. After surgery, lifelong hormone replacement is needed. The decision and timing should be shared with the person and based on up-to-date tumor-risk data, not automatic childhood removal.
2. Inguinal hernia repair
Some children with CAIS present with an inguinal hernia that contains a testis. Standard hernia repair surgery is done to prevent hernia complications and may confirm the diagnosis when a testis is seen in a child raised as a girl. Surgeons try to preserve the gonad if puberty has not yet occurred and gonadectomy is not planned in childhood.
3. Vaginal surgery (vaginoplasty) – less common today
If non-surgical dilation is not successful or not acceptable to the person, surgical vaginoplasty may be offered in adulthood to create or lengthen a vagina. Modern practice favors delaying this decision until the person can clearly consent. The purpose is to allow comfortable penetrative sex if desired. Because surgery can have complications and scarring, non-surgical dilation is usually tried first.
4. Genital cosmetic adjustments (if requested)
Some adults request minor adjustments to the vulval appearance (for example, small labial changes) for comfort or appearance. These are elective procedures, not medically required. Careful psychological assessment and clear informed consent are important, because surgery cannot be reversed and must match the person’s goals, not social pressure.
5. Breast surgery (augmentation or reduction)
CAIS usually gives good breast development, but some people feel their breasts are too small or too large for their comfort. Standard plastic-surgery techniques (augmentation or reduction) may be used in adulthood if the person chooses. As with any cosmetic surgery, the purpose is to improve comfort and body image, not to treat the underlying condition.
Prevention – what can realistically be prevented?
We cannot prevent CAIS itself, because it is a genetic condition. However, we can work to prevent complications and problems, such as:
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Bone loss and fractures – ensure regular hormones, DEXA scans, calcium, vitamin D, and exercise.
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Late-detected gonadal tumors – schedule agreed-upon imaging and, if chosen, timely gonadectomy with proper follow-up.
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Psychological distress and trauma – avoid secrecy, forced or early irreversible surgery, and dismissive attitudes; ensure counseling and peer support.
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Cardiometabolic risks – maintain healthy weight, active lifestyle, smoke-free living, and manage blood pressure and lipids while on HRT.
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Vitamin D and calcium deficiency – check levels and diet, supplement when needed.
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Loss to follow-up – plan regular visits and smooth transition from pediatric to adult care.
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Misinformation and stigma – provide accurate education to the person, family, and sometimes school or community.
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Inappropriate medication use – make sure hormones and bone medicines are prescribed and monitored by experienced specialists, not self-medicated.
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Nutritional problems – avoid extreme diets and ensure adequate protein and micronutrients.
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Unsafe experimental treatments – avoid unproven “fixes” or stem-cell products advertised online; stick to evidence-based care.
When to see a doctor
Someone should see a doctor (ideally an endocrinologist or DSD specialist) if:
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A child raised as a girl has an inguinal hernia or a mass in the groin.
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A teenager with otherwise normal breast development has no periods by age 15–16.
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A person with a known CAIS diagnosis has not had bone density assessed or does not have a clear hormone-replacement plan.
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There is unexplained bone pain, height loss, or fractures with minimal trauma.
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There are strong mood changes, anxiety, or depression affecting daily life.
Urgent care is needed if there is severe abdominal pain, sudden swelling in the groin, signs of a blood clot (sudden leg swelling or chest pain), or any serious side effects from hormones.
Diet – what to eat and what to avoid
What to eat more of
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Calcium-rich foods – dairy (if tolerated), fortified plant milks, tofu with calcium, small bony fish, and leafy greens to support bones.
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Vitamin-D rich foods – oily fish, fortified milk/plant milk, and eggs, plus safe sunlight exposure where possible.
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High-quality protein – fish, beans, lentils, eggs, lean meat, and dairy to support muscle mass and bone.
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Fruits and vegetables – a wide range of colors for antioxidants, vitamins, and minerals that support heart and bone health.
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Healthy fats – sources of omega-3 such as fish or flax/chia seeds, plus olive or similar oils for heart health.
What to limit or avoid
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Sugary drinks and excess sweets – these add calories without nutrients and may worsen weight and metabolic health.
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Very salty processed foods – too much salt can harm blood pressure and may slightly increase calcium loss in urine.
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Heavy alcohol (for adults) and all alcohol for teens – alcohol can weaken bones and increase accident risk; teens should avoid alcohol entirely.
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Excess caffeine and cola-type soft drinks – large amounts may interfere with calcium balance, especially if calcium intake is low.
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Crash diets and severe restriction – rapid weight loss and poor nutrition can damage bones and mood; any weight change should be slow and guided.
Frequently asked questions
1. Is CAIS a “girl” or “boy” condition?
Medically, CAIS occurs in people with XY chromosomes and testes, but their bodies develop a female external appearance because androgens cannot act. Most are raised as girls and identify as women, but gender identity is personal and can vary.
2. Can CAIS be cured?
Today there is no way to repair the androgen receptor gene in routine clinical practice. Treatment focuses on hormone replacement, bone health, and psychological support so that people with CAIS can live full, healthy lives.
3. Can someone with CAIS get pregnant?
No. People with CAIS do not have a uterus or functional ovaries, so they cannot carry a pregnancy or produce eggs. Options for family building include adoption, fostering, or pregnancies carried by a partner or surrogate using that person’s gametes.
4. Why is hormone replacement needed after gonadectomy?
After the testes are removed, the body can no longer make sex steroids. Estrogen (and sometimes testosterone) replacement is needed to maintain bone density, cardiovascular health, and secondary sexual characteristics, and to support overall wellbeing.
5. Is hormone therapy lifelong?
Yes. Once the natural source of hormones is removed, replacement is usually needed for life, adjusting dose and form as a person ages and their health changes. Stopping long-term can lead to bone loss and other problems.
6. How high is the cancer risk if the testes are kept?
Studies suggest the risk of gonadal tumors in CAIS is low in childhood but increases in adulthood, with estimated lifetime risks reaching double-digit percentages by age 50. Exact risk depends on age and individual factors, so decisions about gonadectomy should be personalized.
7. Does CAIS affect the brain or intelligence?
CAIS does not directly damage brain development or intelligence. Any learning or emotional difficulties usually relate to stress, stigma, or unrelated conditions, not to CAIS itself.
8. Is sex possible and pleasurable for people with CAIS?
Many people with CAIS have satisfying sexual lives. Some may want vaginal dilation or, rarely, surgery in adulthood to improve comfort with penetrative sex, but this is a personal choice. Good communication, sexual counseling, and respecting the person’s wishes are more important than anatomy alone.
9. Will people be able to “see” that someone has CAIS?
From the outside, most people with CAIS look like other women, and the condition is usually invisible in everyday life. Disclosure about the diagnosis is a personal decision.
10. Can CAIS come from something the parents did during pregnancy?
No. CAIS is caused by a change in the androgen receptor gene and is not known to result from actions or behaviors of the parents. It can be inherited or arise as a new mutation.
11. Should children be told about their diagnosis?
Modern guidelines recommend honest, age-appropriate, gradual disclosure, supported by psychologists and experienced teams. Hiding information can damage trust later and worsen psychological distress.
12. Is CAIS the same as transgender identity?
No. CAIS is a medical condition affecting how the body responds to androgens and how the reproductive system forms. Transgender identity relates to a person’s inner sense of gender, which may or may not match their assigned sex; transgender people usually do not have CAIS. However, both groups deserve the same respect and support.
13. Are there special risks from estrogen patches or pills?
Like all HRT, estrogen can slightly increase risks of blood clots and, in some populations, stroke or breast issues, especially with age, smoking, or other risk factors. Transdermal estradiol may have a lower clot risk than some oral preparations, so doctors often prefer patches in CAIS.
14. How often should bone density be checked?
Many experts suggest DEXA scans every 3–5 years in adults with CAIS, especially after gonadectomy, or more often if bone density is low or therapy is changed. Exact timing depends on age, fracture history, and previous scan results.
15. Where can someone find reliable information and support?
Reliable information usually comes from specialist DSD centers, academic reviews, and patient groups focused on CAIS/intersex conditions. Hospital information leaflets, major medical-center websites, and peer-reviewed articles are safer starting points than random online forums or commercial “cure” sites.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: February 26, 2025.
