Defining Sex and Gender
Gender identity (Psychological sex)
Inner sense of owns maleness / femaleness.
◼
Sex of rearing
◼
Gender role
Sexual identity (Organic sex)
The biologic sexual differentiation
◼
Chromosomal sex
◼
Gonadal sex
◼
Internal genital sex
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External genital sex
◼
Hormonal sex
Human sexual differentiation
Chromosomal sex
Gonadal sex
External genital sex
Internal genital sex
SEX ASSIGNMENT
Gender identity
and role
Sex of rearing
Gonadal development
Gonadal development
SRY-gene (TDF)
Short arm of Y chromosome
Bipotential
Gonad
2 X chromosomes
Receptors
For H -Y antigen
OVARY
TESTES
Present
Absent
Internal genital organs development
Female
Male
Urogenital sinus
External genital organs develoment
Leydig
cells
Sertoli
cells
Testosterone
Mullerian inhibiting
factor
Wollfian duct
5a-reductase
Urogenital sinus
Regrsession of
Muuleian ducts
Male external genitalia
Male internal
Genital organs
DHT
Male development
Urogenital sinus
Female external genitalia
. Lower part of vagina
Mullerian ducts
Female internal genital
Organs
. Most of upper vagina
. Cervix and uterus
. Fallopian tubes
Neutral
Development
Absence of androgen exposure
Female development
Summary of Normal Sex
Differentiation
genetic sex is determined at fertilization.
testes develop in XY fetus, ovaries develop in XX
fetus.
XY fetus produces MIS and androgens and XX fetus
does not.
XY fetus develops Wolffian ducts and XX fetus
develops Mullerian ducts.
XY fetus masculinizes the female genitalia to make it
male and the XX fetus retains female genitalia.
INTERSEX
An individual in whom there is discordance between
chromosomal, gonadal, internal genital, and
phenotypic sex or the sex of rearing.
INTERSEXUALITY:
Discordance between any tow of the organic sex
criteria
TRANSSEXUALITY:
Discordance between oganic sex and psychological
sex components
CLASSIFICATION OF
INTERSEXUALITY
1. Virilization of genitically female foetus
Female pseudohemaphroditism
2. Incomplete musculinization of genitically male
foetus
Male pseudohermaphroditism (XY-FEMALE)
3. The presence of both ovarian and testicular tissue
in the same individual
True hermaphroditism
4. Chromosomal abnormality
Mixed gonadal dysgenesis ( 45,X0 / 46,XY)
How many children are born with
intersex conditions?
⚫
A conservative estimate is that 1 in 2000 children
born will be affected by an intersex condition.
⚫
98 % of affected babies are due to congenital
adrenal hyperplasia
FEMALE
PSEUDOHERMAPHRODITISM
EXCESS FETAL
ANDROGENS
Congenital adrenal
hyperplasia
21 -hydrxylase deficiency
11-hydroxylase
deficiency
3ß-hydroxysteroid
dehydrogenase deficiency
EXCESS MATERNAL
ANDROGENS
Maternal androgen
secreting tumours
(ovary, adrenal)
Maternal ingestion of
androgenic drugs
21-hydrxylase deficiency
congenital adrenal hyperplasia
Pituitary
ACTH
Adrenal cortex
Androgens
Cortisol
Cholesterol
Pregnenolone
Progesterone
17-OH progesterone
21-hydroxylase
Androgens
Cortisol
Congenital adrenal
hyperplasia
⚫
The commonest cause of genital
ambiguity at birth
⚫
21-Ohas deficiency is most
common form
⚫
Autosomal reccessive
⚫
Salt wasting form may be lethal in
neonates
⚫
SERUM 17OH-progesterone
(21OHase)
⚫
SERUM deoxycorticosterone,
11-deoxycotisol (11- OHase)
⚫
Treatment : cortisol replacement
and ? Surgery
Drugs with Androgenic side effects
ingested during pregnancy
- Testosterone
- Synthetic progestins
- Danocrine
- Diazoxide
- Minoxidil
- Phenetoin sodium
- Streptomycin
- Penicillamine
Male pseudohermaphroditism
(XY- FEMALE)
Failure to produce
testosterone
Pure XY gonadal
dysgenesis (swyer
’s
syndrome)
Anatomical testicular
failure (testicular
regression syndrome)
Leydig-cell agenesis
Enzymatic testicular
failur
Failure to utelize
testosterone
5-alpha-reductase
deficiency
Androgen receptor
deficiency
* Complete androgen
Insensitivity (TFS)
* Incomplete androgen
Insensitivity
Swyer
’s syndrome
46, XY
No SRY OR its receptors
STREAK GONADS
- NO MIF (Uterus +)
- NO SEX STEROIDS
Female
Internal
Genitalia
Female
external
Genitalia
Testicular regression syndrome
(congenital anorchia)
46-XY/SRY
Testis MIF
(self destruction)
± testosterone
± DHT
± Male
Internal
genitalia
Female or
ambiguous
External
genitalia
Leydig-cell agenesis
46-XY/SRY
TESTIS MIF
( partial/ complete absence
Of leydig-cells)
No or testosterone
No or DHT
± Male
Internal
Genitalia
Female or
ambiguous
external
Genitalia
Testicular enzymatic
failure
46-XY/SRY
Testis MIF
(defects in testosterone
Synthesis)
testosterone precursors
DHT
Male
Internal
Genitalia
Ambiguous
External
Genitalia
Autosomal recessive enzyme
deficiency :
-20-22 desmolase
-3-ß-ol-dehydrogenase
-17-
-hydroxylase
-17,20-desmolase
-17-ß –hydroxysteroid
oxyreductase
5-alpha-reductase
deficiency
46-XY/SRY
Testis MIF
Testosterone
5-
-rductase
Male Internal
Genitalia
Female or
Ambiguous
external Genitalia
DHT
Testicular feminization
syndrome
46-XY/SRY
TESTIS MIF
Testosterone
5-
-reductase
DHT
Absent androgen
receptors
Male
Internal
Genitalia
Female
External
Genitalia
Incomplete form Ambigious genitalia
Diagnosis of XY Female
Testosterone concentration
Normal
Male level
DHT
Normal
Low
Testicular
Feminization
Syndrome
5
-reductase
Deficiency
Low
Concentration of
Testosterone precurcers
Low
High
Absent testes or
Absent leydig-cell
Testicular
enzyme
Failure
Surgical exploration
MIXED GONADAL DYSGENESIS
⚫
Combined features of Turner
’s
syndrome and male
pseudohermaphroditism
⚫
Short stature
⚫
Streak gonad on one side with
a testis on the other
⚫
Unicornuate uterus & fallopian
tube- side of streak gonad
⚫
Karyotype 46XY / 45X0
⚫
Considrable variation in the
sexual phenotype
TRUE HERMAPHRODITISM
•
Gonads :
- ovary one side and testis on the other or
- bilateral ovotestis
• Karyotype :
46,XX most common(57%); XY(13%) and XX/XY(30%)
• Internal genitalia :
Both mullerian and wolffian derivates
• Phenotype is variable
• Gonadal biopsy is required for confirming diagnosis
DYSEMBROGENESIS
genital ambiguity with associated
anomalies
⚫
Can occur in both genitic males and genitic females
⚫
Most common genital malformation :
- Penoscrotal transposition
- Agenesis of phallus in a genitic male
⚫
Coexistence of other caudal or urologic abnormalities
should strongly suggest dysembryogenisis
CLINICAL PRESENTATION
OF INTERSEXUALITY
⚫
AT BIRTH
Ambiguous genitalia
⚫
DURING CHILDHOOD
Heterosexual features
⚫
AT ADOLESSCENCE
Delayed or Heterosexual Puberty
AMBIGUOUS GENITALIA AT BIRTH
The external genital
organs look unusual,
making it impossible
to identify the sex of
the newborn from its
outward appearance.
Any one of the following :
⚫
A small, hypospadiac
phallus and unilaterally
undescended gonad.
⚫
An enlarged phallus with
bilaterally impalpable
gonads.
⚫
An enlarged phallus and
a vagina in the same
infant.
MANAGEMENT OF NEWBORN WITH
AMBIGUOUS GENITALIA
GENERAL GIUDELINES
⚫
Medical and social emergency
⚫
Avoid immediate declaration of sex
⚫
Proper counselling of the parents
⚫
Team management; obstetrician,
neonatologist, pediatric endocrinolgist,
genetist and paediatric surgeon.
MANAGEMENT OF NEWBORN WITH
AMBIGUOUS GENITALIA
DIAGNOSIS
⚫
History : pregnancy; family
⚫
Detailed examination : abdomen; pelvis; external
genitalia; urethral and anal openings.
Federman’s rule: a palpable gonad below the
inguinal ligament is testes until proven otherwise
MANAGEMENT OF NEWBORN WITH
AMBIGUOUS GENITALIA
Investigations
• Rule out cong. Adrenal hyperplasia: Serum electrolytes; 17-OHP
level and urinary levels of 17-ketosteroids
• Karyotype ( buccal smear; blood)
• Pelvic US and sometimes MRI or Genitogram
• Skin biopsy; fibroblast culture to measure 5alpha-reductase
activity or dihydrotestosterone binding
• Laparoscopy
• Gonadal biopsy (laparotomy)
A PROTOCOL FOR INVESTIGATION
OF A NEWBORN WITH AMBIGUOUS
GENITALIA
Karyotype all
Palpable gonad
YES
NO
CAH Sreen
Positive
- US / MRI
-? Genitogram
Negative
. Biochemical profile
. US / MRI /? genitogram
. ? Gonadal biopsy
Genitogram
TA US
Sex assignment
General guidelines
• Sex assignment should be decided after
detailed assessment, investigations and
accurate diagnosis
• Complete gender assignment by age 18
months
Sex assignment
• Male gender assignment :
- stretched phallus > 2 cm
- erectile tissue
- lack of severe hypospadias
• Female gender assignment :
- inadequate phallus
- cervix and uterus present
In difficult cases; sex assignment should be
to the sex which can be surgically made to be
adequate for coitus
SURGICAL CONSIDERATIONS
⚫
Phallic / clitoral reduction if the
assigned sex is female, before 3 years
of age
⚫
Removal of intra-abdominal gonads /
streaks in newborns carrying Y
chromosome
⚫
Vaginal construction / repair is better
performed around puberty
Concluding remarks on
Management of newborn with genital
ambiguity
The causes of ambiguous genitalia are many and
complex, so it is important to approach the treatment
of children with this disorder in a systematic fashion.
Evaluation should be done expeditiously, and
parents should be kept informed during the
evaluation to help them understand the embryologic
anomaly that led to their child's genital ambiguity.
Endocrine supplementation should be instituted
when necessary, and a pediatric surgeon should be
actively involved in assigning the child's sex of
rearing as well as performing any necessary
reconstructive surgery.
INTERSEXUALITY PRESENTING AT
ADOLESCENCE
Primary amenorrhea
- Complete androgen
insesitivity (TFS)
- Congenital anorchia
( early testicular
regression syndrome)
- Complete leydig-cell
agenesis
- Some forms of enzymatic
testicular failure
Ambiguous genitalia
- Neglected congenital
adrenal hyperplasia
- Mixed gonadal dysgenesis
- Partial androgen resistance
- Congenital anorchia ( Late )
- Testicular enzymatic failure
- Leydig cell agenesis
( incomplete)
- True hermaphrotidism
MANAGEMENT OF INTERSEXUALITY
PRESENTING AT ADOLESCENCE
⚫
Cortisol replacement therapy and ? Corrective
surgery in CAH
⚫
Corrective surgery in drug induced cliteromegally
⚫
In almost all other instances (XY- FEMALE),
whatever the diagnosis is to
Maintain the gender
role as female
⚫
In some cases of enzymatic testicular defects or
5
-reductase deficiency :
Some May seek to change the gender role
INTERSEXUALITY PRESENTING
AT ADOLESCENCE
Surgical aspects of manegement
⚫
Clitoral reduction
⚫
Removal of gonads in the presence of Y
chromosome
⚫
Vaginal repair and construction
VAGINAL CREATION
Vaginal dilatation
McIndoe Vaginoplasty
Colovaginoplasty
Transsexualism
⚫
Transsexualism occurs when a person strongly
believes that he or she belong to the opposite
sex.
⚫
This is typically a lifelong feeling and results in
varied degrees of physical/external changes
⚫
These patients should be referred to the
psychiatrist
Concluding remarks
Management of adolescent with
intersex
⚫
By following an approach that is based on a few embryological;
physiological and anatomical principles-and with a minimum of
tests- the clinician can arrive at a prompt and accurate diagnosis
in patients with intersexuality
⚫
If such a patient is managed correctly, she or he may live a
happy, well adjusted life and may even be fertile
⚫
If the patient is managed incorrectly, she or he may be doomed to
live as a sexual freak in loneliness and frustration
⚫
Gynecologists, endocrinologists, plastic surgeons, urologists
and psychiatrists should be actively involved in the management
of these patients
