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PubMed This is a summary of 10 peer-reviewed journal articles Updated
Endocrinology

Hormone Replacement Therapy and Long-Term Health

At a Glance

After a gonadectomy for Androgen Insensitivity Syndrome (AIS), life-long Hormone Replacement Therapy (HRT) is medically necessary. Whether using estrogen or testosterone, HRT is essential for preventing osteoporosis, protecting heart health, and maintaining emotional well-being.

Once the decision has been made to remove the gonads (gonadectomy), the body no longer has a natural source of hormones. In AIS, Hormone Replacement Therapy (HRT) is not just about physical appearance; it is a mandatory medical requirement for long-term health, particularly for the protection of your bones and heart [1][2].

Why HRT is Vital

Before surgery, the internal testes provide the body with testosterone, which the body converts into estrogen [3]. After surgery, this natural factory is gone. Without a replacement, the body enters a state similar to menopause, which can lead to:

  • Low Bone Density: Estrogen is essential for keeping bones strong. Without it, people with AIS are at a high risk for osteoporosis (brittle bones) and fractures [4][5].
  • Cardiovascular Health: Hormones help regulate cholesterol and blood pressure. Long-term HRT helps protect the heart as you age [1].
  • Emotional Well-being: Maintaining stable hormone levels is key to managing mood, energy, and overall quality of life [1][6].

Your HRT Options

Managing HRT requires a specialized endocrinologist. There is no single “right” hormone; the choice depends on how your body responds and your personal goals. Finding the right hormone dose—and choosing between estrogen or testosterone—often involves trial and error. It may take time for your mood and energy levels to feel “normal” after a gonadectomy [1].

Estrogen Monotherapy

This is the most common treatment for individuals with a female gender identity (typical in CAIS). Estrogen can be delivered via:

  • Transdermal (Patches or Gels): Often preferred because the hormone is absorbed through the skin, which is generally easier on the liver and provides more stable levels [7].
  • Oral (Pills): A common and convenient option, though levels may fluctuate more than with patches.

Testosterone Therapy

While it may seem surprising for someone with a female identity, testosterone is increasingly used as an alternative or addition to estrogen for some people with AIS [7].

  • How it works: Because the androgen receptor is entirely non-functional in Complete AIS (CAIS), the body cannot directly use testosterone for masculinization or standard libido pathways. Instead, the body naturally converts it into estrogen (via a process called aromatization) [3].
  • The Experience: Some patients report feeling better or preferring testosterone for libido and energy. However, because it still functions primarily by converting to estrogen, its superiority over estrogen monotherapy remains an area of ongoing research and personal preference [7][8].

Long-Term Health Checklist

Living well with AIS means staying proactive with your health. Because there are no universal “one-size-fits-all” guidelines yet, you and your doctor should develop a personalized monitoring timeline [9].

Health Area What to Monitor Suggested Frequency
Bone Health DEXA Scan (measures bone density) Baseline at age 16–18; then every 2–5 years [5].
Hormone Levels Blood tests (Estradiol, Testosterone, LH/FSH) Every 6–12 months once a stable dose is found [1].
Metabolic Health Blood pressure and Cholesterol (Lipid panel) Annually, especially as you enter adulthood [1].
Sexual Health Discussion of libido and comfort At every annual endocrine check-up [7].
Mental Health Screening for anxiety, depression, or body image concerns Ongoing, with specialized counseling as needed [1][6].

Remember, HRT is a lifelong journey. Your needs in your teens may be different from your needs in your 30s or 50s. Regular communication with an endocrinologist ensures that your treatment evolves with you [10][6].

Common questions in this guide

Why do I need hormone replacement therapy after an AIS gonadectomy?
After the surgical removal of the internal testes, your body no longer has a natural source to produce hormones. Hormone replacement therapy is medically necessary to prevent menopause-like symptoms and to protect your long-term bone density and cardiovascular health.
What are the HRT options for Complete AIS?
The most common option is estrogen monotherapy, which can be taken via patches, gels, or pills. Some individuals choose testosterone therapy, which the body naturally converts into estrogen to help support energy levels and overall health.
How does testosterone therapy work for people with CAIS?
Because the androgen receptors do not function in Complete AIS, the body cannot use testosterone for masculinization. Instead, the body naturally converts the testosterone into estrogen through a process called aromatization, which then supports your bone and heart health.
How often should my bone density be checked with AIS?
It is recommended to get a baseline DEXA scan between the ages of 16 and 18 to measure your bone density. Afterward, doctors typically recommend repeating the scan every 2 to 5 years to monitor for osteoporosis.
Why am I still experiencing fatigue or low mood on HRT?
It can take time to find the right hormone dose and delivery method that works best for your body. Finding the optimal balance between estrogen and testosterone often involves trial and error while working closely with a specialized endocrinologist.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which HRT delivery method (patch, gel, or pill) do you recommend for me or my child, and why?
  2. 2.If we experience low libido or fatigue on estrogen, at what point should we consider trying testosterone therapy?
  3. 3.How often will we need to check hormone levels in the blood to ensure the dosage is correct?
  4. 4.What is the specific plan for monitoring bone health—how frequently will DEXA scans be performed?
  5. 5.Does my AIS subtype change the cardiovascular risks I should be monitoring as I get older?

Questions For You

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References

References (10)
  1. 1

    Complete androgen insensitivity syndrome in twins with discordant phenotypes: a case report and review of the literature.

    Liao K, Wang Y, Yi X

    Journal of medical case reports 2025; (19(1)):113 doi:10.1186/s13256-025-05139-9.

    PMID: 40083004
  2. 2

    Complete androgen insensitivity syndrome: a case report and literature review.

    Guo M, Huang JC, Li CF, Liu YY

    The Journal of international medical research 2023; (51(2)):3000605231154413 doi:10.1177/03000605231154413.

    PMID: 36851849
  3. 3

    Complete androgen insensitivity syndrome in a 15-year-old female with primary amenorrhea and undescended testes: a rare case report.

    Zerin F, Bhadra TK, Sadia R, Shahriar Z

    Radiology case reports 2026; (21(1)):329-332 doi:10.1016/j.radcr.2025.09.075.

    PMID: 41209089
  4. 4

    Physical and Reported Subjective Health Status in 222 Individuals with XY Disorder of Sex Development.

    Gong XL, Raile K, Slowikowska-Hilczer J, et al.

    Journal of the Endocrine Society 2021; (5(8)):bvab103 doi:10.1210/jendso/bvab103.

    PMID: 34258493
  5. 5

    Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome.

    Misakian A, McLoughlin M, Pyle LC, et al.

    Frontiers in endocrinology 2021; (12()):727131 doi:10.3389/fendo.2021.727131.

    PMID: 34526969
  6. 6

    Complete Androgen Insensitivity Syndrome in Three Generations of Indian Pedigree.

    Kar B, Sivamani S, Kundavi S, Varma TR

    Journal of obstetrics and gynaecology of India 2016; (66(Suppl 1)):358-62 doi:10.1007/s13224-015-0736-3.

    PMID: 27651630
  7. 7

    Oestrogen versus androgen in hormone-replacement therapy for complete androgen insensitivity syndrome: a multicentre, randomised, double-dummy, double-blind crossover trial.

    Birnbaum W, Marshall L, Werner R, et al.

    The lancet. Diabetes & endocrinology 2018; (6(10)):771-780 doi:10.1016/S2213-8587(18)30197-9.

    PMID: 30075954
  8. 8

    Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene.

    Marino L, Messina A, S Acierno J, et al.

    Endocrinology, diabetes & metabolism case reports 2021; (2021()).

    PMID: 34152287
  9. 9

    Screening for gonadal malignancy in androgen insensitivity syndrome: A systematic review.

    Mazhari N, Freedman A, Marshall C, Kokorowski P

    Journal of pediatric urology 2026; (22(1)):105624 doi:10.1016/j.jpurol.2025.09.030.

    PMID: 41102125
  10. 10

    Complete Androgen Insensitivity Syndrome in a Young Girl with Primary Amenorrhea and Suspected Delayed Puberty: A Case-Based Review of Clinical Management, Surgical Follow-Up, and Oncological Risk.

    Fraccascia B, Sodero G, Pane LC, et al.

    Diseases (Basel, Switzerland) 2024; (12(10)) doi:10.3390/diseases12100235.

    PMID: 39452478

This page provides educational information about HRT options for Androgen Insensitivity Syndrome. Always consult with your specialized endocrinologist to determine the safest hormone therapy and monitoring schedule for your personal health needs.

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