1) Androgen Insensitivity Syndrome is a genetic condition where people have male chromosomes and male gonads but experience partial or complete feminization due to a mutation in the Androgen Receptor gene. 2) There are three main types - complete androgen insensitivity (CAIS) where external genitalia are fully female, partial androgen insensitivity (PAIS) where genitalia range from fully female to ambiguous, and mild androgen insensitivity (MAIS) with impaired sperm development. 3) Treatment involves hormone replacement therapy, psychological support, and potentially surgery to address medical issues or gender identity. Orchidectomy is usually recommended to prevent cancer risks.

1. Androgen Insensitivity Syndrome
(Testicular Feminization)
Presented by:
Anish Dhakal
(Aryan)

2. Introduction
Genetic condition where affected people have male
chromosomes and male gonads with complete or
partial feminization of the external genitals
An inherited X-linked recessive disease with a
mutation in the Androgen Receptor (AR) gene
resulting in:
Functioning Y sex chromosome
Abnormality on X sex chromosome

3. Major Types:
I. CAIS (completely insensitive to AR gene)
External female genitalia
Lacking female internal organs (Sertoli cells markers AMH
and inhibin B present)
II. PAIS (partially sensitive-varying degrees)
External genitalia appearance on a spectrum (phenotypic
women with mild virilization to phenotypic men with
undervirilization and gynecomastia or infertility
III. MAIS (mildly sensitive, rare)
Impaired sperm development and/or impaired
masculinization

4. Aetiology
Peripheral receptors for testosterone
 absent or scanty
 they fail to respond to testosterone
(defective/mutated receptors)
In partial androgen insensitivity syndrome:
 Few receptors respond to testosterone
External genitalia are of female phenotype
Chromosome is XY

6. Clinical Features
 Gonads (testes) in the labia, or
inguinal canal or intra-abdominal
Maldeveloped testes
Diagnosis:
–Condition is not revealed until puberty
–Positive family history
–Childhood inguinal hernia discovers the
testes

7. Clinical Features
• Individual is typically feminine and tall
• External genitalia looks female
• Breast development is adequate
• Nipples are small with pale areola
• Pubic and axillary hairs are scanty or absent
• Primary amenorrhea and or infertility
• Vagina is short and blind

8. Clinical Features
In partial androgen insensitivity syndrome:
 Signs of virilisation in a girl with primary
amenorrhea
 Lack of virilisation in a boy

9. Testicular feminization—Bilateral inguinal gonads

10. Bilateral labial gonads (testes) and short blind vagina
in testicular feminization

11. A newborn genetic male
(46, XY) with complete
androgen insensitivity
syndrome and female
external genitalia 11
XY chromosome
pattern but
insensitivity to
androgens

12. Bilateral inguinal hernia

14. Investigations
• Chromosomal study: Karyotype is 46, XY.
• In infants and children, stimulation by hCG before
measurement of hormones needed.
• Serum testosterone is normal (or higher)
• Serum E2 level is high normal for males
• Serum LH level is normal or slightly elevated
• FSH is normal.
• USG:
–Ovaries, uterus, upper 2/3rd of vagina and tubes
are absent

15. Investigations
• Confirmation of diagnosis is by gonadal biopsy
• DNA sequencing for the AR gene is also possible
though low probability for detetction in PAIS
• Gonadal biopsy
– Seminiferous tubules are small, hyalinized.
– Spermatogenesis is absent.
– Leydig cells and Sertoli cells are normal.

16. Differential diagnosis:
Mullerian agenesis (for CAIS)
Partial gonadal dysgenesis
Defects in testosterone synthesis
17-beta-hydroxy steroid dehydrogenase type
3 deficiency (High level of androstenedione)
5-alpha reductase 2 deficiency (High ratio of
testosterone to DHT)

18. Management
• Medical care
• Surgical care

19. Medical care
• Hormone replacement therapy
• Psychological aspect

20. Hormonal Replacement Therapy
• Patient with complete androgen insensitivity
– oestrogen replacement
– progesterone not required because they have no
uterus
– has other benefits like osteoporosis prevention
• Patient with incomplete androgen insensitivity
– with male gender identity: testosterone and/or
dihydrotestosterone (DHT)
– With female gender identity: oestrogen

21. Current Guidelines for HRT:
In women with CAIS or PAIS, guidelines
suggest administration of oestrogen at the
time of expected puberty, if gonadectomy
was performed in childhood, or as soon as
gonadectomy is performed after puberty
However, testosterone therapy may also
have advantages in some patients with
proved CAIS with female identity

22. Psychological care
• Most important aspect of medical care
• Parents need genetic counseling to understand
the nature of the condition and the risk of
recurrence (25% for each subsequent pregnancy)
as well as to identify other potential carriers
• Whenever possible, obtain informed consent for
any procedures or therapy
• Any child, adolescent, or adult patient should
receive age-appropriate information about the
condition as well as psychological support
• Sex assignment

23. Sex Assignment
Usually assigned at birth with the expectation that
future gender identity will develop in alignment
with physical anatomy, initially assigned sex and
rearing.
Gender identity: Personal sense of one’s own
gender
Sex assignment of an intersex individual may also
contradict their future gender identity
Usually not attempted to change gender identity
after age 3 unless requested by the patient
(Possibility of gender dysphoria)

24. Surgical care
• Orchidectomy
– Standard care to prevent malignancy (3.4% at 25 years.
Up to 33% at 50 years of age)
– Malignant degeneration of testes
– Timing of surgery is debatable, individual
consideration is needed
– If early: avoid raising uncomfortable psychosexual
issues during adolescence or young adulthood
– If late (teenage years or early 20s ): Allows pubertal
development to occur spontaneously with the
production of estrogen

25. Current Recommendations for
Gonadectomy:
• Gonadectomy be delayed until after the pubertal
growth spurt and feminization in most subjects
with CAIS
• Gonadectomy might be recommended in female
sex identity patients at the time of diagnosis of
PAIS to prevent further virilization
• If male sex is assigned in PAIS, no gonadectomy
but surveillance is recommended
• GnRH agonists might prevent undesired virilization
in female identity patients if time is needed for
counseling and decision making

26. Additional Treatment for PAIS with
male gender identity:
• Surgical correction of cryptorchidism in boys
with PAIS soon after diagnosis to maintain
testicular function and minimize the risk of
malignancy
• In males with PAIS, hypospadias repair might
be undertaken at a younger age and
mastectomy is appropriate for disfiguring
persistent gynecomastia

27. • In female gender assigned patients with PAIS who
have some degree of masculinization of the
genitalia at birth, cosmetic reconstructive surgery.
Use of vaginal dilators to stretch its length if
sufficient length of vagina prevails
Vaginoplasty
–For those who desire marriage and
unsatisfactory response from dilator
therapy
• Counseling: Reproductive function not
possible

28. References:
• Shaw’s Textbook Of Gynaecology ,16th edition
• S. Peter, Pathogenesis and Clinical featires of
disorders of androgen action,
https://www.uptodate.com/contents/pathogen
esis-and-clinical-features-of-disorders-of-
androgen-action
• M. Alvin et al, Diagnposis and treatment of
disorders of androgen recpetors,
https://www.uptodate.com/contents/diagnosis-
and-treatment-of-disorders-of-the-androgen-
receptor
• DC DUTTA’ s textbook of gynecology, 7th edition