Complete Androgen Resistance Syndrome

Complete androgen resistance syndrome means the body cannot “hear” or use male sex hormones (androgens) at all, even though these hormones are present in normal or high amounts. [1] In almost all cases, the person has male chromosomes (46,XY) and has testes that make testosterone, but the cells of the body cannot respond to this hormone because the androgen receptor is not working. [1][2] As a result, the baby develops normal-looking female external genitals, even though the chromosomes are male. [3] Most people are raised as girls and feel like girls. [2][4] They do not have a uterus or periods, and they cannot get pregnant, because the inner female organs did not form. [1][3] This condition is rare and is passed down in families as an X-linked genetic condition, or it can happen for the first time in a family due to a new gene change. [1][2][5]

Complete androgen resistance syndrome is usually called Complete Androgen Insensitivity Syndrome (CAIS). In simple words, it is a genetic condition where a person has one X and one Y chromosome (46,XY) and internal testes, but the body cannot respond to male hormones (androgens) at all. Because the androgen receptor does not work properly, the external body develops along a typical female pattern: the person looks female, has breasts at puberty, but usually has no periods, no uterus, and cannot become pregnant. [GeneReviews]

CAIS is inherited in an X-linked way, meaning the change in the androgen receptor (AR) gene is carried on the X chromosome. The testes make normal or high levels of testosterone, but the tissues “do not hear” the signal, so the body cannot use these hormones. This mismatch between chromosomes, hormones, and body response is why CAIS is classified as a difference of sex development (DSD). [Orphanet summary]

Other names

Many different names have been used for the same condition over time. [1][4] Some older names are no longer preferred, but you may still see them in books or on reports. [4][6]

• Complete androgen insensitivity syndrome (CAIS)

• Androgen insensitivity syndrome, complete type

• Testicular feminization syndrome (older term)

• Morris syndrome (older term based on the name of the doctor who first described it)

• 46,XY disorder (or difference) of sex development due to androgen receptor defect

• X-linked androgen receptor defect with complete resistance

• Complete androgen receptor (AR) deficiency

These all describe the same basic problem: a 46,XY person whose body cannot respond to androgens at all, so the outside of the body looks typically female. [2][4]

Types

Doctors often talk about “types” of androgen insensitivity syndrome based on how much the body can respond to androgens. [2][7] In that system, complete androgen resistance syndrome is one end of a spectrum. [2][7]

• Complete androgen insensitivity syndrome (complete androgen resistance) – no meaningful response to androgens

• Partial androgen insensitivity syndrome – some weak response to androgens

• Mild androgen insensitivity syndrome – mostly male body pattern but with mild problems such as breast growth or infertility

Within complete androgen resistance itself, doctors sometimes also describe people by: [3][8]

• Age at diagnosis (found in infancy, childhood, or at puberty because periods never start)

• Where the testes are located (inside the abdomen, in the groin, or in the labia)

• How long the vagina is (short, blind-ending vagina vs near-normal length)

These “types” are mostly used for medical planning and research, not as separate diseases. [3][8]

Causes of complete androgen resistance syndrome

Here “causes” means different gene problems and biological reasons that lead to the same final result: the androgen receptor does not work. In real life, almost all causes are changes in the androgen receptor (AR) gene on the X chromosome. [1][2][4]

1. Missense mutation in the AR gene – One “letter” in the AR gene code is changed. The receptor protein is made, but its shape is slightly wrong, so it cannot bind hormone or cannot work correctly. [2][4][9]

2. Nonsense mutation in the AR gene – A change in the gene creates a “stop” signal too early. The receptor protein is cut short and cannot work at all, leading to complete resistance. [1][2]

3. Frameshift mutation – One or more DNA letters are added or deleted. This shifts the reading frame and usually produces a completely abnormal protein that is quickly destroyed. [2][17]

4. Splice-site mutation – Changes at the borders of gene segments (introns and exons) interfere with normal RNA processing. The final AR message is wrong, so the receptor is faulty or missing. [1][2]

5. Large deletion of part of the AR gene – A big piece of the gene is missing. No full receptor can be made, so the cells have no working androgen receptor. [4][9]

6. Deletion of the whole AR gene – Rarely, the entire AR gene is lost from the X chromosome. In this case, there is complete absence of the receptor, and androgens have no effect. [4]

7. Mutation in the ligand-binding domain of AR – The receptor is present but cannot grab onto testosterone or dihydrotestosterone. The hormone is there, but the “lock” cannot hold the “key.” [7][16]

8. Mutation in the DNA-binding domain of AR – The receptor can bind hormone but cannot attach to DNA in the nucleus. It cannot turn target genes on, so androgen signals are blocked. [7]

9. Mutation in the N-terminal activation domain – This part helps the receptor start gene transcription. Damage here can severely reduce androgen response, leading to complete resistance in some cases. [2]

10. Defects in AR nuclear transport signals – The receptor may fail to move from the cell fluid into the nucleus, where DNA is stored. If it stays in the wrong place, it cannot act on genes. [7]

11. Abnormal AR interaction with co-regulator proteins – Even if the receptor itself is mostly normal, changes that prevent it from working with helper proteins can stop androgen-driven gene activity. [7][16]

12. X-linked recessive inheritance from carrier mother – A person inherits the changed AR gene from their mother, who carries one normal and one changed copy. Sons with 46,XY who get the changed copy can develop complete resistance. [1][6][18]

13. De novo (new) mutation in the AR gene – The gene change happens for the first time in the child, either in the egg, the sperm, or very early after fertilization. No one else in the family had it before. [1][2]

14. Germline mosaicism in a parent – A parent has some egg or sperm cells with the AR mutation and some without. They may look healthy but can have more than one child with the condition. [1]

15. Somatic mosaicism in the child – The AR mutation occurs after fertilization, so some cells have the mutation and some do not. If most relevant cells are affected, the child may show complete resistance. [1][2]

16. Complex or combined AR mutations – Some people have more than one AR change (for example, a missense plus a splice defect), which together remove all receptor function. [9][16]

17. Promoter or regulatory region mutations – Changes in parts of the DNA that switch the AR gene on and off can greatly reduce how much receptor is made in key tissues. Low receptor levels can behave like full resistance. [16][17]

18. Epigenetic silencing of the AR gene (rare / theoretical) – Chemical changes to DNA or chromatin (such as abnormal methylation) might “turn off” the AR gene, although this is less clearly proven in classic CAIS.

19. Very rare defects in AR mRNA stability or processing – Abnormalities that make AR messenger RNA unstable can mean the message is destroyed before protein is made.

20. Very rare combined AR defect with other sex-development genes – In a few complex cases, AR mutations may occur together with changes in other genes for sex development, further blocking androgen action and reinforcing complete resistance. [17][20]

All these different genetic problems lead to the same end result: androgens are present, but the body cannot use them to guide sexual development. [2][4][17]

Symptoms and clinical features

1. Female-appearing external genitals in a person with 46,XY chromosomes – The baby’s genitals look typically female (clitoris, labia, small vaginal opening), so the baby is usually registered and raised as a girl. [3][6][22]

2. Short, blind-ending vagina – The vagina may be shorter than average and does not lead to a cervix or uterus. During exam, the doctor may feel that the vaginal canal stops early. [3][12]

3. Absence of uterus and fallopian tubes – The child has no womb or fallopian tubes because the testes make anti-Müllerian hormone, which stops these structures forming. This is usually found on imaging. [2][6]

4. Undescended testes in abdomen, pelvis, or groin – Instead of ovaries, there are testes. They often sit in the abdomen, pelvis, or in the groin hernia sac, not in a scrotum. [3][12]

5. Primary amenorrhea (no periods by the usual age) – Many people are diagnosed when a teenager comes to the clinic because breast development has started, but periods never begin. [2][6][22]

6. Normal or even large breast development at puberty – Estrogen is made from testosterone in the body. Because androgens cannot act, more is turned into estrogen, so the breasts often develop well. [2][7]

7. Little or no pubic and underarm hair – Hair follicles need androgens to grow sexual hair. Because the body cannot respond to androgens, pubic and axillary hair is sparse or absent. [2][7]

8. Female gender identity and typical female behavior in most cases – Most people with complete androgen resistance feel themselves to be girls or women and live in that gender role. [2][4]

9. Inguinal hernia in infancy or childhood – A groin hernia that contains testes is a common way the condition is first found in babies who are thought to be girls. [3][8]

10. Infertility – There are no ovaries or uterus, so pregnancy is not possible. Testes are often under-developed and cannot make functional sperm. [2][12]

11. Possible groin or abdominal pain from gonads – Some people feel discomfort where the testes are located, especially during puberty when they grow or if there are cysts or tumors.

12. Higher risk of testicular (gonadal) tumors over time – Long-term undescended testes have an increased risk of certain tumors, especially in adulthood, which is why many doctors recommend later removal. [2][7][14]

13. Low or absent acne – Acne is driven by androgen action on skin glands. Without androgen effect, acne is mild or absent, even in teenage years.

14. Tall or slightly taller than average female height – Growth plates may close later, and early estrogen levels may differ, so many people with CAIS are somewhat taller than typical women in the same family. [7][19]

15. Emotional or psychological stress – Learning about chromosomes, infertility, and gonad removal can be very stressful. People may feel shock, confusion, or worry about gender and future relationships, and often benefit from psychological support. [2][4][24]

Diagnostic tests

Doctors use a combination of history, physical exam, hormone tests, imaging, and genetic tests to diagnose complete androgen resistance syndrome. [2][6][8]

Physical exam tests

1. General physical examination – The doctor looks at height, body build, and signs of puberty such as breast size, body hair, and skin. In CAIS, the pattern is usually female body shape, normal breasts, and sparse pubic hair. [2][7]

2. External genital examination – The doctor gently checks the genitals. In CAIS, the genitals look female, with no penis and no scrotum, but the vagina may be short. This visual exam gives the first strong clue to the diagnosis in babies and teens. [3][12]

3. Examination for inguinal masses or hernias – The groin area is checked for lumps that could be undescended testes. An inguinal hernia in a child raised as a girl should raise suspicion of CAIS or another 46,XY DSD. [3][8]

4. Breast and hair pattern assessment at puberty – The Tanner stage of breast development and pubic hair is recorded. Full breast development with little or no pubic hair is a classic pattern in CAIS. [2][7]

Manual tests

5. Gentle vaginal length assessment (using a gloved finger) – In older teens and adults, the doctor may carefully measure how deep the vagina is. A short blind-ending vagina without a cervix suggests CAIS or other conditions with Müllerian agenesis. [3]

6. Bimanual pelvic examination – In adults, a careful internal and external hand exam can check for the presence or absence of a uterus or large masses. In CAIS, no uterus is felt, but sometimes gonads can be felt in the pelvis.

7. Manual hernia examination in infants and children – For babies with groin swelling, the doctor gently palpates the hernia. Feeling a firm, oval structure suggests a testis in a child thought to be a girl, prompting further testing. [3][8]

Laboratory and pathological tests

8. Karyotype (chromosome test) – A blood test is used to look at the chromosomes. In CAIS, the result is 46,XY, even though the person looks female. This is one of the key tests to confirm a disorder of sex development. [1][2][6]

9. Serum testosterone level – Blood tests show normal or even high male-range testosterone levels for age, because the testes make testosterone normally. This does not match the female body appearance, which suggests androgen resistance. [2][7]

10. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels – Hormone levels may be high or in the upper normal range, because the brain senses that androgens are “not working” and tries to stimulate the testes more. [2][16]

11. Estradiol level – Estrogen levels are usually in the normal female range because some of the testosterone is turned into estrogen. This helps explain normal breast development. [2][7]

12. Anti-Müllerian hormone (AMH) level – AMH is made by Sertoli cells in the testes. In CAIS, AMH is usually high or normal, confirming the presence of functioning testicular tissue. [18][20]

13. Dihydrotestosterone (DHT) and testosterone/DHT ratio – These tests can help rule out other conditions like 5-alpha-reductase deficiency. In CAIS, DHT is usually normal and the ratio is not the main problem; instead, the receptor is faulty. [2]

14. Androgen receptor gene (AR) sequencing – A DNA test looks at the AR gene for mutations. Finding a damaging mutation strongly supports the diagnosis. In many, but not all, people with CAIS, a clear mutation is found. [1][2][17]

15. Pathology study of removed gonads (after gonadectomy) – If the testes are removed, the tissue is examined under a microscope. Findings may include under-developed seminiferous tubules, lack of sperm production, and sometimes early gonadal tumors or pre-cancer changes. [2][7][19]

Electrodiagnostic tests

16. Pelvic floor or nerve electrodiagnostic studies (rare and usually not needed) – These tests check the electrical activity of nerves and muscles in the pelvic area. They are not routine for CAIS but may be used if there is pain, nerve injury, or to rule out other causes of pelvic symptoms. In classic CAIS, these studies are usually normal.

Imaging tests

17. Pelvic and abdominal ultrasound – This is often the first imaging test. It uses sound waves to look for a uterus and ovaries and to find the location of the testes. In CAIS, no uterus is seen, and testes may be found in the groin or abdomen. [3][8][12]

18. Magnetic resonance imaging (MRI) of pelvis and abdomen – MRI gives more detailed pictures and is useful when ultrasound is unclear. It helps map exactly where the gonads are and can show any suspicious areas that might suggest tumors. [8][19]

19. Laparoscopy (keyhole surgery to look inside the abdomen) – A camera is inserted through a small cut in the abdomen. This allows direct viewing of the gonads, vas deferens, and other structures. Biopsies or removal of the gonads can be done at the same time, if needed. [2][19]

20. Bone density scan (DXA) – A scan to measure bone strength is often done later in life, especially after removal of the testes and start of hormone replacement therapy, because bone health can be affected by changes in sex hormone levels. [2][10][19]

Non-Pharmacological Treatments (Therapies and Other Approaches)

Each of these is supportive; none “cures” androgen resistance, but together they protect physical and emotional health.

1. Multidisciplinary specialist clinic
   Care in a team that includes endocrinologists, gynecologists, surgeons, geneticists, psychologists, and specialized nurses is central in CAIS. The purpose is to coordinate decisions about gonadectomy, hormone therapy, bone health, fertility counseling, and mental health in one place. The mechanism is organizational: regular combined visits reduce conflicting messages and help you receive consistent, evidence-based care over many years. [Multidisciplinary DSD care]

2. Psychological counseling and emotional support
   CAIS can raise difficult questions about body, gender, fertility, and relationships. Ongoing counseling with professionals who know about DSD helps process shock, sadness, anger, or confusion in a safe way. The mechanism is talking therapy: techniques like cognitive-behavioral therapy (CBT) and supportive psychotherapy reduce anxiety and depression and improve self-acceptance and coping skills. [Psychological care in AIS]

3. Peer support and community groups
   Meeting others living with CAIS or other intersex/DSD conditions can greatly reduce feelings of isolation. The purpose is to normalize the experience and share practical tips. The mechanism is social: online or in-person groups let people exchange stories, advice about doctors, and coping strategies, which is linked with better mental health and treatment satisfaction. [Patient support networks]

4. Genetic counseling for the person and family
   Genetic counseling explains how the AR gene variant causes CAIS, what X-linked inheritance means, and the chance of CAIS or carrier status in relatives or future pregnancies. The mechanism is education and risk assessment: understanding inheritance supports informed family planning, carrier testing when desired, and reduces blame or guilt. [Genetic counseling guidance]

5. Gender-affirming and identity-supportive care
   People with CAIS are typically raised as girls and often have a strong female gender identity. The purpose of gender-affirming care is to respect self-identified gender, pronouns, and presentation. Clinicians should avoid pathologizing language and focus on the person’s lived experience. The mechanism is social affirmation: when people feel respected as women, mental health and trust in doctors improve. [AIS care principles]

6. Education about the body and condition
   Clear, age-appropriate explanations about chromosomes, hormones, and anatomy help people with CAIS understand why they do not have periods or cannot get pregnant. The purpose is to reduce fear and confusion. The mechanism is knowledge: well-timed information improves adherence to follow-up, helps with safe sexual decision-making, and supports informed consent to any procedures. [Educational recommendations]

7. Lifestyle support for bone health (exercise)
   Because lack of androgen action and gonadectomy can reduce bone mineral density, lifestyle care is essential. Weight-bearing exercise (walking, light jogging, dancing, stair-climbing, resistance training) helps stimulate bone formation and maintain strength. The mechanism is mechanical loading: bones adapt to load, so regular safe exercise reduces osteoporosis and fracture risk, especially when combined with estrogen therapy. [Bone health in CAIS]

8. Sunlight exposure and daily physical activity
   Regular safe sun exposure helps the skin make vitamin D, which works with calcium and estrogen to build bones. Light activity such as walking, cycling, or yoga also improves muscle strength, posture, and balance. The mechanism is metabolic and mechanical: vitamin D improves calcium absorption, while movement reduces falls and supports a healthy weight, which indirectly protects bones and cardiovascular health. [Vitamin D and activity]

9. Nutrition counseling with a dietitian
   A registered dietitian can design an eating plan rich in calcium, vitamin D, protein, and heart-healthy fats to support bones and long-term health. The mechanism is nutrient optimization: appropriate calories, proteins, and micronutrients help maintain muscle mass, reduce low bone density, support normal cholesterol and blood pressure, and improve energy and mood. [Nutrition in hypogonadal states]

10. Pelvic floor and sexual-health physiotherapy
    Some people with CAIS may have concerns about intercourse comfort, pelvic pain, or post-surgical changes after vaginoplasty. Pelvic floor physiotherapists teach relaxation, stretching, and muscle control exercises. The mechanism is neuromuscular: improving pelvic muscle coordination can reduce pain, improve comfort with penetration, and increase confidence during sexual activity. [Pelvic PT in DSD]

11. Vaginal dilator therapy (when needed)
    If the vagina is short or narrow, gentle use of graduated vaginal dilators under specialist guidance can help lengthen and widen the vaginal canal over time. The purpose is to allow comfortable intercourse without surgery when possible. The mechanism is slow tissue stretching: repeated, low-force pressure triggers tissue remodeling and increased elasticity. [Non-surgical vaginal lengthening]

12. Sexual-health and relationship counseling
    Trained sex therapists can help individuals and couples discuss intimacy, body image, and sexual function in a non-judgmental way. The mechanism is communication and skills training: learning to discuss preferences, boundaries, and worries reduces shame, improves pleasure, and supports long-term relationship satisfaction. [Sexual health in CAIS]

13. Fertility and family-building counseling
    Although people with CAIS cannot become pregnant, they can still build families through adoption, fostering, or, in some settings, use of partner’s gametes with gestational surrogacy. Counseling explains realistic options, timelines, costs, and ethical issues. The mechanism is planning: understanding paths to parenthood early can reduce grief and help set hopeful but realistic expectations. [Fertility counseling in AIS]

14. Structured surveillance for gonadal tumors (if testes retained)
    If gonadectomy is delayed or not done, careful regular surveillance is essential. This may include imaging and tumor markers. The purpose is early detection of pre-cancer or cancer in undescended testes. The mechanism is screening: finding suspicious changes early allows timely surgery before spread, balancing cancer risk against benefits of natural hormones. [Gonadal tumor risk]

15. Post-gonadectomy rehabilitation and follow-up
    After removal of testes, structured follow-up visits, wound care instructions, and gradual return to activity help smooth recovery. The mechanism is surgical aftercare: good rehabilitation reduces pain, infection, and scarring, and provides a natural point to start or adjust estrogen replacement. [Gonadectomy management]

16. School and workplace support
    Some people need time off for surgery, appointments, or mental health care. A doctor’s note and clear explanations (without sharing private details) can allow flexible schedules or exam timing. The mechanism is social support: reasonable adjustments reduce stress and help people keep up with studies or work while managing a chronic condition. [Chronic illness accommodations]

17. Body image and self-esteem therapy
    Many with CAIS feel different because of infertility, anatomy, or scars. Body-image-focused therapy uses techniques like mirror exposure, positive self-talk, and values-based goals to reduce shame. The mechanism is cognitive and emotional: changing how a person thinks about their body improves mood and willingness to attend medical care and engage in healthy relationships. [Body image in DSD]

18. Mind–body practices (mindfulness, relaxation, breathing)
    Simple tools like slow breathing, mindfulness apps, progressive muscle relaxation, or gentle yoga can reduce chronic stress before appointments or surgery. The mechanism is nervous-system regulation: calming the stress response can lower heart rate and blood pressure, improve sleep, and make it easier to cope with difficult conversations or exams. [Stress management]

19. Non-drug pain management strategies
    After surgery or during procedures, non-drug methods such as ice packs (when recommended), positioning, distraction, music, or guided imagery add to standard pain medicine. The mechanism is sensory and cognitive: shifting attention away from pain and reducing local inflammation can make pain feel less intense and limit the dose of pain medicines needed. [Peri-operative care]

20. Crisis and safety planning
    For those who struggle deeply with identity, stigma, or depression, a written crisis plan with warning signs, coping steps, and emergency contacts (family, friends, therapists, local helplines) is important. The mechanism is preparedness: having a clear plan reduces panic during emotional crises and guides the person to safe, supportive help instead of harmful choices. [Mental-health safety planning]

Drug Treatments (Mainly Hormone and Bone-Health Medicines)

Important: All medicines must be prescribed and monitored by qualified doctors. Doses below are examples from FDA-approved labeling for general indications, not specific instructions for CAIS. People should never start, stop, or change medicines without medical supervision. [FDA label database]

1. Oral estradiol tablets
   Oral estradiol is a synthetic form of estrogen used to replace the estrogen that would normally be produced by ovaries or, in CAIS, by converting circulating testosterone. The usual goal is a low dose at first, gradually increasing to produce and maintain breast development and protect bones. It belongs to the estrogen class. Doctors individualize dose and timing (often once daily) and monitor for side effects like nausea, breast tenderness, headache, and rare blood clots. [Estradiol tablet label]

2. Transdermal estradiol patch
   Estradiol skin patches release estrogen steadily through the skin and avoid first-pass liver metabolism. They are used once or twice weekly at a dose chosen by the specialist to mimic typical female estradiol levels and support bone health. This estrogen class medicine may cause skin irritation, breast tenderness, or rare clotting events. In CAIS after gonadectomy, patches are often preferred for long-term replacement because of stable hormone levels. [Transdermal system]

3. Estradiol gel or spray
   Estradiol gels and sprays are rubbed on the skin daily and absorbed into the bloodstream. The purpose is flexible dose adjustment and smooth hormone levels for puberty induction or maintenance. They are estrogens, and dosing is carefully titrated based on blood tests and clinical response. Side effects are similar to other estrogen forms and include breast tenderness, mild fluid retention, and rare clotting risks. [Estrogen replacement in DSD]

4. Intramuscular estradiol valerate or cypionate
   Injectable estradiol esters provide long-acting estrogen, given every few weeks. They are useful when oral or skin routes are not tolerated. As estrogen class drugs, they slowly release hormone, allowing development and maintenance of secondary sexual characteristics and bone mass. Doctors choose dose and interval individually. Possible side effects include injection-site pain, mood changes, breast tenderness, and rare thrombosis. [Depo-estradiol label]

5. Ethinyl estradiol (low-dose)
   Ethinyl estradiol is a potent synthetic estrogen used in many oral contraceptives and sometimes as part of CAIS hormone therapy regimens, especially historically. Very low doses may be given daily to induce puberty over 2–3 years. The mechanism is estrogen receptor activation in bones and other tissues. Side effects include nausea, headache, breast soreness, and increased risk of clots at higher doses, so specialists now often prefer natural estradiol. [Ethinyl estradiol products]

6. Conjugated estrogen tablets
   Conjugated estrogens are mixtures of estrogen compounds used to treat menopausal symptoms and prevent bone loss. In some adults with CAIS, they may be used instead of estradiol based on preference and response. Dose is once daily at the lowest effective level, adjusted by a physician. Side effects include uterine bleeding in women with uterus (not applicable in CAIS), breast tenderness, fluid retention, and clotting risk. [Conjugated estrogen label]

7. Vaginal estradiol tablets or cream
   For people with CAIS who have a vagina and experience dryness, discomfort, or superficial pain during intercourse, local vaginal estrogen can improve tissue thickness and lubrication. It is used at very low doses inserted into the vagina. The mechanism is local estrogen effect, with minimal systemic absorption. Side effects are usually mild, such as local irritation, and systemic clot risk is much lower than with full-dose oral estrogen. [Vaginal estradiol/Vagifem]

8. Calcium–vitamin D combination medicines
   Although often considered supplements, many are prescribed as medicines. Typical adult doses are about 1000–1200 mg elemental calcium and 600–800 IU vitamin D daily, adjusted for diet and lab results. The purpose is to provide the building blocks for bone mineralization alongside estrogen therapy. Side effects can include constipation or, rarely, kidney stones if taken in very high doses. [Bone health guidance]

9. Bisphosphonates (e.g., alendronate)
   Bisphosphonates are anti-resorptive drugs that slow bone breakdown by osteoclasts. In CAIS with significant osteoporosis despite optimized estrogen and lifestyle, a doctor may prescribe weekly oral alendronate or related drugs. The mechanism is inhibition of bone resorption, raising bone density and reducing fracture risk. Side effects include stomach upset, rare jaw problems, and bone pain; strict dosing instructions (empty stomach, upright) reduce risks. [Osteoporosis therapy]

10. Denosumab
    Denosumab is a monoclonal antibody given as an injection every 6 months to treat severe osteoporosis. It blocks a protein (RANKL) that stimulates bone-resorbing cells, so bones lose less mineral. In CAIS with very low bone mineral density and high fracture risk, specialists may consider it when other options fail. Side effects include low calcium, infections, and rare jaw problems; careful monitoring is essential. [Denosumab in osteoporosis]

11. Teriparatide (parathyroid hormone analog)
    Teriparatide is an anabolic (bone-building) medicine used in very severe osteoporosis. It is given as a daily injection for a limited time (often up to 2 years) to stimulate new bone formation. It may be considered in adults with CAIS and multiple fractures after other treatments. Side effects include nausea, leg cramps, and rare concerns about bone tumors in animal studies, so doctors weigh risks carefully. [Anabolic bone therapies]

12. SSRIs (e.g., sertraline) for anxiety or depression
    Some people with CAIS experience significant anxiety or depression. Selective serotonin reuptake inhibitors (SSRIs) such as sertraline can help balance brain chemicals linked to mood. Doses are started low and increased slowly under psychiatric care. Side effects can include nausea, sleep changes, or sexual side effects. SSRIs do not treat CAIS itself, but they can greatly improve quality of life when mental-health conditions are present. [Mental health in AIS]

13. Short-term NSAIDs (e.g., ibuprofen) for post-surgical pain
    After gonadectomy or other surgery, non-steroidal anti-inflammatory drugs (NSAIDs) help reduce pain and inflammation. They are taken for a few days with food. The mechanism is blocking enzymes (COX) that produce prostaglandins involved in pain and swelling. Side effects include stomach upset, kidney strain, and rare bleeding; they should not be used long-term without medical advice. [Peri-operative pain control]

14. Paracetamol (acetaminophen)
    Paracetamol is a gentle pain reliever and fever reducer often used after surgery or for mild aches. It works on pain pathways in the brain. Dose and maximum daily amount must be strictly respected to avoid liver damage. It does not affect inflammation, but combining it with non-drug methods can provide good comfort in CAIS care. [Analgesia guidance]

15. Topical anesthetic gels (e.g., lidocaine)
    Before genital exams or dilator use, some people benefit from a local anesthetic gel to reduce surface discomfort. These gels numb nerve endings in the skin and mucosa when applied for a short time. Side effects are usually mild, such as temporary stinging or rare allergic reactions. They do not treat CAIS, but they can make necessary exams more tolerable. [Procedural comfort]

16. Combined estrogen–SERM products (e.g., conjugated estrogens with bazedoxifene)
    In general menopause care, some products combine estrogens with a selective estrogen receptor modulator (SERM) to protect the uterus while reducing hot flashes and bone loss. In CAIS (no uterus), these combinations are usually not needed, but a specialist may consider them in rare complex cases. Side effects include similar estrogen risks, plus possible leg cramps or clot risk. [Combination estrogen therapy]

17. Progestins (usually not required in CAIS)
    Because people with CAIS lack a uterus, progestins are normally unnecessary for endometrial protection. However, in unusual anatomical variations, a progestin might be added. These hormones oppose some estrogen effects in the uterus. Side effects include mood changes, bloating, and bleeding changes. For most CAIS patients, specialists avoid routine progestin use. [HRT in DSD]

18. Vaccines (HPV, influenza, etc.)
    Routine vaccinations are important for everyone, including people with CAIS, to prevent infections that could complicate surgery or general health. HPV vaccination reduces risk of cervical and other HPV-related cancers for those with a cervix or engaging in relevant sexual activities; flu and other vaccines reduce serious infections. Dosing schedules follow national guidelines. Side effects are usually mild local reactions or fever. [Vaccination guidance]

19. Vitamin K2 preparations (sometimes used with bone therapy)
    In some settings, vitamin K2 is prescribed to support bone mineralization along with calcium, vitamin D, and estrogen, but evidence is still emerging. It may help direct calcium to bone and away from arteries. Dose and need are individualized. Side effects are uncommon but can include interactions with blood thinners, so medical supervision is essential. [Adjunct bone supplements]

20. Sleep-support medicines (short term, if needed)
    If anxiety around diagnosis, surgery, or body image severely disrupts sleep, a doctor may briefly prescribe sleep aids or certain antihistamines. The purpose is short-term symptom relief while psychological therapy starts to work. Because these drugs can cause dependence or next-day drowsiness, they are used at the lowest effective dose for the shortest possible time under close supervision. [Insomnia management]

Dietary Molecular Supplements

Supplements can interact with medicines. Always discuss them with your medical team before starting.

1. Calcium – Usually 1000–1200 mg elemental calcium per day (from food plus supplements) supports bone mineralization in people with low sex hormone action. It provides the basic building block for bones. The mechanism is simple: enough calcium in the blood allows bone cells to deposit mineral into the bone matrix when stimulated by estrogen and vitamin D. Too much may cause constipation or kidney stones.

2. Vitamin D3 (cholecalciferol) – Common maintenance doses range from 600–1000 IU daily, adjusted by blood levels. Vitamin D increases calcium absorption from the gut and supports bone mineralization. In CAIS, it works together with estrogen replacement and exercise to reduce osteoporosis risk. High doses without monitoring can cause high calcium, so lab checks are needed.

3. Vitamin K2 (menaquinone) – Often taken at 45–180 µg/day in some bone-health protocols, vitamin K2 helps activate proteins that bind calcium into bone and may reduce vascular calcification. In CAIS, it is sometimes used as a supportive measure alongside standard therapy, although evidence is still limited. People on blood thinners must only use it under strict medical guidance.

4. Magnesium – Typical supplemental doses are 200–400 mg/day, depending on diet and kidney function. Magnesium is a cofactor in many bone and muscle enzymes and can help reduce muscle cramps. In CAIS, adequate magnesium supports overall neuromuscular health and may indirectly help bone quality. Too much can cause diarrhea or, in kidney disease, serious imbalances.

5. Omega-3 fatty acids (EPA/DHA) – Doses around 250–1000 mg/day of combined EPA and DHA from fish oil or algae oil may support heart health and reduce inflammation. In CAIS, omega-3s are not specific treatment but help maintain cardiovascular health, which is important for anyone on long-term hormone therapy. Side effects include fishy aftertaste or mild stomach upset.

6. Protein supplements (whey or plant-based) – When diet alone does not provide enough protein, 10–20 g protein shakes can support muscle mass. Strong muscles protect bones by supporting balance and reducing fall risk. The mechanism is anabolic: amino acids provide the materials for muscle repair and growth after exercise. People with kidney disease must discuss protein amounts with their doctor.

7. B-complex vitamins – B vitamins support energy metabolism and nervous-system function. In CAIS, they do not fix hormone resistance but may help with fatigue, especially when diet is poor. Typical doses match daily recommended amounts. Very high doses of some B vitamins can cause nerve issues or other problems, so “more” is not always better.

8. Vitamin C – Usually 75–500 mg/day is enough. Vitamin C helps build collagen, an important part of bone and connective tissue, and supports immune function. It can support wound healing after surgery. Excessive doses may cause stomach upset or kidney stones in some people.

9. Probiotics – Probiotic capsules or yogurts provide beneficial gut bacteria that may slightly improve nutrient absorption and immune regulation. In CAIS, they can support general digestive and immune health, but they are not specific therapy. Doses vary by product; people with severe immune problems should check with a doctor first.

10. Soy isoflavones (phytoestrogens) – These plant-based compounds have mild estrogen-like effects. Some people use them to support menopausal symptoms, but evidence is mixed. In CAIS, they may have very modest effects compared with medical estrogen therapy and should never replace prescribed hormones. Typical doses are standardized capsules once or twice daily. They can interact with certain hormone-sensitive conditions, so medical advice is important.

Drugs for Immunity / Regenerative Support and Stem-Cell Context

Currently, there are no approved stem-cell or regenerative drugs that cure CAIS or fix the androgen receptor. Research in gene therapy and stem-cell approaches is ongoing, but it remains experimental and not available as routine treatment. [Research updates]

Instead, doctors focus on:

1. Vaccinations – Following national vaccine schedules strengthens immune defenses and reduces infection risk around surgeries and in daily life.

2. Vitamin D (as above) – Supports both bone and immune function; deficiency correction is standard in many chronic conditions.

3. Bone-anabolic drugs like teriparatide – Not regenerative for CAIS itself, but they stimulate new bone formation in severe osteoporosis, helping the skeleton “repair” some damage.

4. Healthy-lifestyle-supported immune function – Sleep, exercise, and stress reduction remain the safest “immune boosters.”

Because these approaches are already covered above, physicians rarely add special “immune-booster drugs” beyond standard good health care in CAIS. Any experimental stem-cell or gene-therapy trial must be done only in approved research centers with strict ethical oversight.

Surgical Treatments

1. Gonadectomy (removal of undescended testes)
   Undescended testes carry an increased risk of tumors over time. Gonadectomy removes this tissue, usually through minimally invasive surgery in the abdomen or groin. Many experts now recommend delayed gonadectomy after spontaneous puberty, so natural hormones can support puberty and bone mass before removal. The purpose is to balance cancer prevention and natural hormone benefits.

2. Inguinal hernia repair with gonad assessment
   Many CAIS cases are first found when a “hernia” in the groin is investigated in a child raised as a girl; the hernia sac contains testes. Surgeons repair the hernia and may biopsy or reposition the gonads. The purpose is to prevent bowel complications and examine the testes safely.

3. Vaginoplasty (vaginal lengthening surgery)
   If the vagina is too short for comfortable intercourse and dilation fails or is not acceptable, surgeons can create or lengthen a vagina using local tissues or grafts. The purpose is to allow pain-free sexual activity if desired. It does not change chromosomes or fertility. Timing and technique are carefully discussed with the patient once they are mature enough to decide.

4. Laparoscopic exploration and removal of abnormal tissue
   Laparoscopy uses small cuts and a camera to look inside the abdomen. It can confirm anatomy, remove remnants, or take biopsies. In CAIS, it may be used when imaging is unclear or tumor risk is suspected. The purpose is accurate diagnosis and safe removal of risky tissue with minimal scarring and faster recovery.

5. Reconstructive or scar-revision procedures
   Rarely, people may have pain, tightness, or cosmetic concerns from earlier operations. Reconstructive surgery can adjust scars, revise vaginal openings, or correct other issues. The purpose is to improve comfort, function, and body image. Decisions are highly individualized and always made with full, informed consent.

Ways to Prevent or Reduce Complications

Remember: CAIS itself (the gene change) cannot be prevented, but many complications can be reduced.

1. Attend regular follow-up in a specialist clinic for lifelong monitoring.

2. If testes are retained, follow agreed cancer-screening and imaging schedules.

3. Take estrogen replacement exactly as prescribed after gonadectomy to protect bones and overall health.

4. Maintain a bone-healthy lifestyle: exercise, calcium- and vitamin-D-rich diet, no smoking.

5. Limit heavy alcohol intake, which damages bone and liver.

6. Seek early psychological support when feeling overwhelmed, instead of waiting until symptoms are severe.

7. Get routine vaccines and health checks to prevent infections and manage blood pressure, lipids, and weight.

8. Avoid unsupervised hormones, “natural” estrogen pills, or internet hormone products; these can be unsafe or fake.

9. Discuss surgery timing carefully with the team to balance cancer risk, bone health, and psychological impact.

10. Keep clear written records of diagnosis, karyotype, and past treatments to share with new doctors when needed.

When to See Doctors

You should be under regular specialist follow-up (for example, once or twice a year) throughout life. In addition, it is important to seek medical help as soon as possible if:

• You are a teen and have no periods by about age 15–16 and have not yet been evaluated.

• You know you have CAIS and notice new groin or abdominal lumps, persistent pain, or changes near old surgical scars.

• You have sudden severe bone pain, height loss, or fractures after minor injuries.

• You are taking estrogen and develop chest pain, severe headache, sudden vision changes, severe leg pain or swelling, or shortness of breath (possible clot). This is an emergency.

• Mood becomes very low, hopeless, or anxious for many days, or you lose interest in usual activities. Talk to a trusted adult and a health professional.

Diet: Things to Eat and to Avoid

There is no “special CAIS diet,” but a bone- and heart-healthy diet is recommended.

Helpful to eat more of

1. Calcium-rich foods – such as milk, yogurt, cheese, or calcium-fortified plant milks, to support bones together with estrogen and vitamin D.

2. Vitamin-D-rich foods – like oily fish (if eaten), eggs, or fortified products, to help your body absorb calcium.

3. High-quality proteins – beans, lentils, fish, lean meat, eggs, tofu, and nuts to maintain muscle and bone strength.

4. Fruits and vegetables – a variety of colorful produce provides vitamins, minerals, and antioxidants that support general health and recovery after surgery.

5. Whole grains and healthy fats – whole-grain rice, oats, and breads plus olive oil, nuts, and seeds help heart health and steady energy.

Better to limit or avoid

6. Very salty foods – such as instant noodles with lots of seasoning or salty snacks, because extra salt can increase calcium loss in urine and raise blood pressure.

7. Sugary drinks and snacks – large amounts of sugar can lead to weight gain and worsen bone and heart health over time.

8. Excess caffeine – too much coffee, strong tea, or energy drinks may slightly increase calcium loss and disturb sleep.

9. Heavy alcohol use – alcohol damages bones, liver, and mental health; in growing teens and young adults, this effect is especially strong.

10. Smoking or nicotine products – tobacco is harmful to bones and blood vessels and increases risk of blood clots with estrogen. Nicotine products should be avoided completely.

Frequently Asked Questions (FAQs)

1. Is complete androgen resistance syndrome the same as CAIS?
   Yes. “Complete androgen resistance syndrome” and “Complete Androgen Insensitivity Syndrome (CAIS)” describe the same condition: a 46,XY individual whose body cannot respond to androgens at all and therefore develops a typical female external body pattern.

2. Is CAIS a disease or a difference?
   CAIS is best understood as a genetic difference of sex development (DSD). It does create health issues that need medical care (bone health, tumor risk, infertility), but it is not an infection or something you “catch.” Many people prefer language like “variation” or “difference” instead of “disorder.”

3. Can someone with CAIS get pregnant?
   No. People with CAIS do not have a uterus or ovaries, so they cannot carry a pregnancy. Their testes do not make eggs; they make sperm, but sperm cannot be used without very complex, experimental methods that are not available. Many choose adoption, fostering, or other paths to parenthood instead.

4. Does CAIS shorten life expectancy?
   When well managed, with appropriate gonadectomy decisions, hormone replacement, and bone and heart care, life expectancy is thought to be close to normal. The biggest risks arise from untreated gonadal tumors, severe osteoporosis, or unrecognized mental-health difficulties, so regular follow-up is important.

5. Why remove the testes if they are making natural hormones?
   Undescended testes carry a higher risk of cancer over time. Delaying removal until after puberty allows natural hormones to support breast and bone development, but long-term, many teams recommend removal to reduce cancer risk. The timing is decided together with the person and family, not rushed.

6. Will hormone replacement make me “less myself”?
   In CAIS, estrogen replacement after gonadectomy is replacing hormones the body would otherwise lose. It helps maintain mood, bones, and sexual health. When properly dosed, many people feel more stable and energetic, not less themselves. Problems usually mean the dose or formulation needs adjustment—not that hormones are “wrong.”

7. Are there medicines that can “fix” the androgen receptor?
   At present, no drug can repair the faulty androgen receptor in CAIS. Research is exploring gene therapy and molecular treatments, but these are still experimental and not available as standard care. Current treatments focus on estrogen replacement and supportive care rather than restoring androgen responsiveness.

8. Will I need hormones for life?
   After gonadectomy, yes—lifelong estrogen replacement is usually needed to protect bones, maintain sexual characteristics, and support general health. The dose or type may change with age, but stopping estrogen completely can lead to rapid bone loss and other problems.

9. Is it safe to use estrogen for so long?
   Estrogen has risks and benefits. In CAIS, it is replacing missing sex hormones rather than being added on top of normal function. Using the lowest effective dose, avoiding smoking, managing weight, and regular monitoring can keep risks relatively low. Your team will review personal and family history to choose the best plan.

10. Can I choose not to have gonadectomy?
    In some centers, adults with CAIS may choose to keep their testes with careful tumor monitoring, especially when cancer risk appears lower in certain gene variants. This decision requires very close follow-up and detailed counseling about risks and benefits; recommendations can differ between countries and teams.

11. Does CAIS affect my brain or intelligence?
    CAIS does not directly reduce intelligence. People with CAIS can have normal school performance and careers. Emotional stress or stigma may affect concentration, but with proper support, most lead full academic and professional lives.

12. Is CAIS common?
    CAIS is rare, estimated at about 1 in 20,000–60,000 births, so many doctors see very few cases. That is why being followed in a specialized center is so important.

13. How is CAIS diagnosed?
    Diagnosis usually includes a detailed exam, chromosome test (karyotype showing 46,XY), hormone blood tests (male-range testosterone with high LH), imaging (to look for uterus and location of gonads), and often genetic testing of the AR gene. Together, these results confirm CAIS.

14. Can family members be carriers?
    Yes. Because CAIS is X-linked, mothers and some female relatives may be carriers of the AR gene change, and siblings can also be affected or carriers depending on inheritance. Genetic counseling and, if desired, testing can clarify risks.

15. Where can I find reliable information and support?
    Good sources include [GeneReviews], [MedlinePlus], [Orphanet summaries], and reputable hospital or endocrine society websites on androgen insensitivity syndrome, plus established patient support groups. These resources explain CAIS in clear language and connect you to others living with the condition.

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.