PRIMARY AND SECONDARY SEX DEVELOPMENT

-(AMBIGUOUS EXTERNAL GENITALIA) 

Dr. Alexander E. Omu. MB,BS; FMCOG; FWACS; FICS; FRCOG.

Professor and Chairman

Department of Obstetrics and Gynaecology, Faculty of Medicine,
Kuwait University, and Maternity Hospital, Kuwait.
 

September 18, 2016

1
 Objectives of the Presentation
1 Definition of Ambiguous External Genitalia
2. Biology of Sex development
3. Epidemiology of Disorders of sex development.
Congenital Adrenal Hyperplasia, Molecular Genetics of AIS, 5 reductase
deficiency, Abnormal SRY, Mixed and pure gonadal dysgenesis (Swyer
Syndrome)and ovo-testis
4. Concepts of management disorders of sex development
5. Normal and Abnormal Puberty
6. Definition of Puberty
7. Onset of Puberty and significance-Reproduction
8. Abnormal Puberty-Precocious, Delayed and Hypogonadotropic
Hypoganadism (HH)
9. Cultural, fertility and social implications of DSD (sports- XY female and XX
male
10. Conclusion
2
AMBIGUOUS EXTERNAL GENITALIA

External Genitalia that physically 
do not appear to be either male or 
female in form.

Discordance/Conflict

3
 GENDER IDENTITY 
* Genetic- XY or XX

* Gonadal- testis or ovary

* Internal genitalia

* External genitalia

* social and Sex of rearing (sex of rearing)

* Legal (Birth certificate or passport)

INTERSEX (DSD)
Discordance/Conflict
4
 Early Knowledge of XY Female 
in History
1. Talmud 400 BC

2 Joan of Arc, the French Heroine (1412)

3 Queen Elizabeth the First- The Virgin

Queen (1533-1603) “Video et Taceo”
Medical hypothesis 1985; 17:277-284.
ncidence
1 in 60,000 to 65,000 genetic male- Degroot/Jagiello and Atwell
1 in 2,000 to 20,000 Hauser/ Adams-Smith
1 in 20,400 by Bangsboll et al: analysis from national Danish 5
register of male births (hospitalised cases only).
Early Knowledge of Abnormaility of Sex Differentiation- AIS
1. 1817, when Steglehner described the case of an apparently normal woman who
had undescended testes.

2. Dieffenbach, an American geneticist, 1906, a hereditary pattern to AIS.

3 Petterson and Bonnier (1937), the affected persons are genetically male.

4. Morris (1953) first used the term "testicular feminization."

5. Morris and Mahesh (1963) subsequently described an incomplete form of the

condition.
6. Wilkins (1957) first demonstrated that the basic defect is tissue
unresponsiveness to androgens. Hence Androgen Insensitivity Syndrome.

7. Netter and colleagues (1958) reported this disorder in a famous photographic

model and Marshall and Harder (1958) reported affected twins who worked as
airline stewardesses.

8. In 1974 Migeon showed that the condition results from androgen receptor
resistance.
6
9. The androgen receptor gene was cloned and sequenced in 1988.
 Normal sexual differentiation

Gender identity: end result of genetic, hormonal and

morphologic sex as influenced by the environment

Genetic sex (chromosome

Gonadal sexual (testis, ovaries)

¯
Hormones affecting sex development of fetus


External genitalia Hormone production at Puberty CNS

Sex assignment and rearing

Gender identity 7
8
 

9
10
11
 

  

12
inding, while the COOH-terminal region is involved in NADPH-binding (2

Figure 4. Metabolism of Testosterone to 5-Dihydrotestosterone by

the enzyme 5-Reductase type 2 (SDR5A2).

13
14
 Normal Sex Differentiation
Intermediate Mesoderm

WT/SF1
XY/XXY Bipotential gonads XX/XO
SRY SOX9 Wnt4
DAX1- Antitestis
Testis
Ovary

Granulosa Theca
Sertoli cell Leydig cell Cell Cell No AMH
No T
5-R
AMH T DHT
Mullerian
Wolffian Follicles Duct
No mullerian
Duct Duct
Oestrogen
Male internal Male External 15
Female
Progesterone
No uterus genitalia Genitalia Internal Genitalia
 Structure Primordium
URINARY SYSTEM
Kidney Metanephros
Ureter and renal pelvis Ureteric bud from lower end
of mesonephric duct
GENITAL SYSTEM
Male
Testis: Spermatids (secondary, haploid Germ cells (from root of sac) Spermatocytes)

Urogenital ridge
Tunica albuginea Coelomic epithelium
Seminiferous tubles,
including Sertoli cells Sex cords (primary, medullary cords)
Rete testis tubules
Interstitial (Leydig) cells Mesenchyme
Efferent ductules Mesonephros, excretory ducts
Epididymis
Vas deferens Mesonephric duct
Seminal vesicle (Wolffian system)
External genitalia
penis
Dorsum Genital tubercle
Ventral part
enclosing urethra Urethral folds (fused)
Cavernous bodies
Penile urethra Urogenital groove
Scrotum Genital swellings (fused) 16
Female
Ovary
     Oocytes (primary, diploid) Germ cells
Urogenital ridge
     Epithelial  covering       Coelomic epithelium
     Follicles
Granulosa cells       Sex cords (secondary, cortical)
Theca cells
     Stroma       Mesenchyme
Fallopian tube
Uterus Paramesonephric (Mullerian)
? Upper vagina                     ducts*
? Vaginal epithelium
Vagina Sinovaginal  bulbs  (from  urogenital 
sinus)*

External genitalia
      Clitoris Genital tubercle
      Vestibule Urogenital groove
      Labia minora urethral folds
            (including cavernous bodies)
     Labia majora Genital swellings
17
     Hymen  Urogenital membrane
DISORDERS OF SEX DEVELOPMENT

What’s in a name?

That which we call a rose by any other name would smell as

sweet.

–Shakespeare,
18
Romeo and Juliet
 Conscensus Statement
Proposed revised nomenclature
Previous  Proposed

Intersex Disorder of Sex  Development (DSD)

Male pseudohemaphrodite under virilisation of an  46; XY DSD
X Y male under masculirisation of an XY male   

Female  pseudohemaphrodite  overvirilisation of an  46; XX DSD
XX female.

True Hemaphrodite Ovotesticular DSD

XX male or  female sex reversal 46, XY testicular DSD

XY Sex reversal  46, XY complete gonadal dysgenesis

Arch Dis Child 2006; 91 (7): 554-563

19
  Epidemiology of DSD (classification)  
Sex chromosome DSD 46, XY DSD 46, XX DSD
A.  45X (Turner Syndrome & variants A.  Disorder of gonadal testicular  A.  Disorders of gonadal  
      development   (Ovarian  development)
B. 47 XXY (Klinefelter  1.   Complete gonadal  1.   Ovotestis DSD
syndrome and variants dysgenesis (Sywer syndrom)
2.   Testicular DSD (e 
        (12.1%) 2.   Partial gonadal dygenesis g SRY+dup SOX
3.   Gonadal regression
3.   Gonadal 
4.   Ovotestis DSD
dysgenesis
C.   45, X/46,XY (mixed gonadal B. Disorder in androgen B.   Androgen excess 
synthesis or action
      dysgenesis ovotesticular DSD
1. Androgen Biosynthesis defect
1.   Fetal (e g 21 
(e g 17-hydroxy steriod
hydrogenase 
D. 46, XX/46,XY (Chimeric  dehydrogenase deficiency, 5x deficiency, II 
ovotesticular DSD) deficiency St mutations hydroxylase 
2. Defect in androgen action (CAIS, deficiency
          (12.1%)
PAIS)
3. LH receptor defect (Leydig cell 2.   Fetoplacental  
E.         XX Male  DSD hypoplasia aplasia) (aromatase 
, 4. Disorders of AMH and AMH receptor deficiency, POF)
(persistent mullerian duct
syndrome) 3. Maternal (Luteoma 
C. Other (e.g severe hypospadia Exogenous)
cloacal extrophy) 4.  Other e.g Cloacal extrophy vaginal 
artresia MURCS, other syndrome  
( 58.5%) (18.5%)

20
21
 Abnormal sexual differentiation

Masculinized Females (XX DSD)

Definition:
Females by genetic sex (XX)
Possesses ovaries
Internal genitalia female
but external genitalia variably masculinized
Causes:
Congenital adrenal hyperplasia
Maternal androgen effect on fetus
drug ingestion, tumor secretion

***A third salting losing-hypertension, acidosis and death

Needs urgent diagnosis and electrolyte replacement 22
therapy
 Normal and abnormal sex differentiation

Female XX DSD: CAH, Types of Enzymes Block and their Consequences

Inherited defect in steroid biosynthesis of cortisol; ACTH
"Compensated" cortisol block and of precrusors (androgen,
corticoids).

¯20, 22 desmolase
Pregnenolone 17 - Hydroxy pregnenolone Dehydroeo
ia
¯ 3  - ol-dehydrogenase 4 , 5- isomerase ndrosteron
e
Progesterone 17 - Hydroxy progesterone Androsten Testosterone
e
¯ 21 - hydroxylase dione
11- Deoxycorticosterone 11 - Deoxy cortisol Estrone Estradiol

¯ 11- hydroxylase
Corticosterone cortisol

23
All CAH are due to autosomal recessive mutations.

21-hydroxylase deficiency accounts for 90-95% of cases.

Classical is severe 21-hydroxylase deficiency with salt-wasting (hyponatraemia, hypokalaemia, alkalosis,
hypotension), ambiguous genitalia in genetically female infants.
Simple virilizing is more mild 21-OH deficiency causing virilization in childhood, including accelerated
linear growth and skeletal maturation, early pubic hair and early phallic enlargement or clitoromegaly.
Non-classical is mildest 21-OH deficiency, causing hyperandrogenism/infertility in adult females, and
unlikely to be detected in adult males.

11β-hydroxylase deficiency accounts for 5-8% of cases.

Early-onset hypertension, mild to moderate - presumed due to excess DOC, though does not correlate well
with DOC levels.
Rarely, infants may also present with salt-wasting - this seems to be due to mineralocorticoid resistance in
infancy, DOC failing to substitute for aldosterone.
Moderate virilzation occurs, typically with some virilization of external genitalia in females, and early
puberty.

17α-hydroxylase deficiency
Mineralocorticoid excess - hypertension, hypokalaemic alkalosis
Sex steroid deficiency (normal female infants but no puberty; male infants range from female to
underdeveloped male, again no puberty)
Cortisol deficiency (but 50-100 times normal levels of corticosterone prevent adrenal crisis).
3β-HSD2 deficiency
Mineralocorticoid deficiency
Glucocorticoid deficiency
Excess DHEA (a weak androgen which can cause mild virilization in females, but may be inadequate for
normal male development, i.e. ambiguous genitalia possible in both sexes).
CAH, Genetic Aspects
Genetic defect:

autosomal recessive
Parents unaffected heterozgous carriers
1 in 4 unaffected carriers
2 in 4 unaffected carriers
1 in 4 unaffected noncarriers

Uniform clinical picture (location and severity of block)

within families

Affected, treated patient:

1 : 100 - 200 chance ® producing affected infant
25
 GENETICS of XY Female
Molecular Basis of XY Female

XY. 5 alpha reductase 
AIS. 46XY DSD gene-2. With single 
-mutation androgen receptor gene,
comprising 8 exons on X base substitution of  
chromosome between Xq13 and Thymidine (TGG) for 
Xp11. Receptor has six functional Cytosine on exon 5 
domains; with DNA binding causing a tryptophan 
domain. Lack , deficiency or Replacement of 
disturbance leads to 4 clinical arginine amino-acid.
conditions: Complete IAS, Partial
IAS, Reifenstein syndrome and
Mutation on exon 2 
male infertility. X-linked and exon 3 have been 
inheritance reported.

MGD  Gonadal mosaicism Pure Gonadal Dysgenesis
45 X/46.XY. Mutation of WT1 at Ch 11p13, 
Y-SRY,SOX9 at Ch.17q24-25, AMH at  Swyer Syndrome. XY.Deletion of SRY 
19q13.3  X-linked inheritance or Gene mutation. Presence of 
Reccessive or dominant uterus, no ovary or Testis 26
 Abnormal Sexual Differentiation

Abnormal Gonadogenesis: True Hermaphrodites

(OVO-Testis DSD)
Definition:
Genetic sex: 50% female XX, few male XY, many
mosaics
Gonadal sex: both ovarian and testicular tissue,
unilateral or combined (ovotestis)
Internal genitalia: Correspond to adjacent gonad
External genitalia : mostly ambiguous predominantly
masculinized with hypospadias

Clinically:
Most raised as males only to develop gynecomastia and
27
menstruate at puberty
 XX MALE-CASE PRESENTATION

Primary Infertility for 15 years, married at 32 years, Divorced for 1 year.
 
Normal pubertal development-12 years –night and morning emissions.

Examination: Healthy looking male with moustache, sideburns, male voice
1.70 m tall and weighed 74 kg. BP 125/70 mmHg. Systems-no abnormalities.

External genitalia- Normal circumcised penis> 6.0 cm and testes low in the 
scrotum, small but firm consistency (5 out of 10), no varicocele, normal prostate
Investigations
FSH 28.2 IU/L (1.6-11), LH 12 (1.7-8.6), Testosterone 15.6 nmol/L (5.0-35)

Karyotype –XX SRY. DSD

Testicular biopsy- Hyalinised seminiferous tubules, with thick basement membrane 
with sertoli cell only.Interstitium showed increased number of Leydig cells

Mechanism: SRY Translocation

Omu et al. 2008 (Unpublished)
28
 DIFFERENTIAL DIAGNOSIS AND TREATMENT
• Sex Assignment
• Guidelines:
•  (1)    Do not assign a new born DSD to the sex for which it cannot by 
surgery be made coitally adequate, regardless of genetic, gonadal or 
hormonal sex, which can be controlled pharmacologically.
•  (2) Do not impose a sex reassignment on older children and adult 
with DSD
• Investigations in the neonate
• Chromosome studies
• Urinary and plasma hormone assays, 
           Radiography and/or ultrasonography.
• Exploratory laparotomy or laparoscopy with facilities for frozen section 
of biopsied gonads.
• In children with severe adrenal hyperplasia, evidence of salt loss may  
make treatment mandatory before hormonal confirmation of the 
diagnosis.

29
 TREATMENT

Aim: FUNCTIONALITY OR FERTILITY POTENTIAL?

Surgical
Gonadectomy : Pre or post Puberty
Clitoroplasty
Vaginoplasty,
McIndoe-Reed : sigmoid colon, skin,amnion, rectum,
peritoneum and myo cutaneous flaps.

Non-surgical procedures William and Frank

Medical
Androgens or Oestrogens
Psychological support
Psychotherapy- and anguish: help patients and parents
30
deal with anxiety
 FACTORS AFFECTING DECISION ON MANAGEMENT

1. Risk of Germ Cell Malignancy According to Diagnosis

Risk Group Disorder Malignancy Recommended

Risk %
High GD   (+Y)  Intraabdominal  15 – 35 Gonadectomy
PAIS (nonscrotal) 50 Gonadectomy
Fraser 60 Gonadectomy
Denys-Drash  (+Y) 40 Gonadectomy
Intermediate Turner  (+Y) 12 Gonadectomy
17-hydroxysteroid 28 Watchful  Waiting
GD (+Y) Scrotal Unknown Biopsy & ? Irradiation
PAIS Scrotal  gonadal  2 Biopsy 

Low CAIS 3 Biopsy

Ovotesticular DSD 3 Testicular tissue
Turner (-Y) None -
5 RD2 Unresolved -
Leydig cell Hypoplasia Unresolved -

GD – Gonadal dysgenesis 31
Paediatrics 2006 : 118; 8488-500
 2. Prader’s Classification in the Management of XY Female

    

Grading scheme for clinical classification of AIS. Grades are I through 7 in order of increasing severity (more 
defective masculinization). Grade 1: normal masculinization in utero; grade 2:with mild defect in masculinization 
(eg, isolated hypospadias); grade 3: severe defect in masculinization—small penis, perineoscrotal hypospadias, 
bifid scrotum or cryptorchidism; grade 4: severe genital ambiguity— clitoral-like phallus, labioscrotal folds, single 
perineal orifice; grade 5: female phenotype with posterior labial fusion and clitoromegaly; grade 6/7: female 
phenotype (grade 6 if pubic hair present in adulthood, grade 7 if no pubic hair in adulthood) 33
 Endocrine Rev 1995; 1 6(3):282; Diamond et al Clin N Am 2004; 13: 623-640. 
3. Type of XY DSD. e,.g Swyer Syndrome

THE 

PREGNANT

MAN

34
 NORMAL PUBERTY
Denifition:   Puberty is a process leading to physical and sexual maturation that involves 
the development of secondary sexual characteristics as well as growth, changes in body 
composition and psychosocial maturation

Onset: Normal puberty begins between eight and 14 years of age in girls and between 
nine and 14 years of age in boys. Pubic hair distribution is used to stage puberty, along 
with breast size and contour in girls and testicular volume in boys. 

Abnormal Puberty: Sequence of normal pubertal milestones is disrupted. 

•Constitutional sexual precocity is likely to be pathologic in very young children
•Contrasexual development 
*    Delayed puberty may be constitutional, but pathologic causes should be considered. 

The etiology of a pubertal disorder can often be determined with the use of a focused 

-medical history, 
-directed physical examination and 
-appropriate diagnostic tests.

Treatment for disorders of puberty is determined by the underlying cause.
 POSTULATED DUAL MECHANISM OF RESTRAINT OF PUBERTY
                     INVOLVING SEX STEROID - DEPENDENT  
                          AND INDEPENDENT PROCESSES 

Highly   sensitive   negative
         feedback system
   (sex - steroid dependent)
+
Intrinsic CNS inhibitory mechanism
       (independent of sex steroids)
¯
        Inhibition

                 MBH*
Hypothalamus         Gn RH neurons
         (pulse generator)  

¯
( Suppression of  pulse   frequency  &  amplitude )
Pituitary Gonadotropes
* (MBH - Medical basal 
¯    Hypothalamus)
FSH  & LH
Stimulatory and inhibitory effectors of GnRH pulsatile secretion.

Studies in human subjects with hypogonadotropic hypogonadism (HH) have disclosed a 
number of genes that are necessary for normal reproductive function.
1.Kiss1 gene, that produces Kisspeptin, and its receptor, G Protein Coupled Receptor 54 
(GPR54) or Kiss1r have emerged as key players in the regulation of reproduction. 

     Neurons that express Kiss1 are distributed within hypothalamus predominantly in the 
infundibular nucleus and scattered in the medial preoptic area. 
      
     Expression of Kiss1r transcript has been reported in human placenta, pituitary, spinal 
cord, and pancreas, as well as in other tissues (such as various brain regions, stomach 
and intestines.
2.   Kisspeptin and GPR54 are expressed in hypothalamic GnRH neurons, suggesting 
that both GnRHR and GPR54 may act as paracrine and/or autocrine regulators of GnRH 
neuronal function.

3.   Hypothalamic kiss-1 system transmits metabolic information to gonadotropic axis.

4    GnRH neurons activation by kisspeptin is essential for the onset of puberty and there 
are data from mice that the activation of kisspeptin neurons are driven by circulating 
estradiol.
Stimulatory and inhibitory effectors of GnRH pulsatile secretion.

Studies in human subjects with hypogonadotropic hypogonadism (HH) have disclosed a 
number of genes that are necessary for normal reproductive function.
1.Kiss1 gene, that produces Kisspeptin, and its receptor, G Protein Coupled Receptor 54 
(GPR54) or Kiss1r have emerged as key players in the regulation of reproduction. 

     Neurons that express Kiss1 are distributed within hypothalamus predominantly in the 
infundibular nucleus and scattered in the medial preoptic area. 
      
     Expression of Kiss1r transcript has been reported in human placenta, pituitary, spinal 
cord, and pancreas, as well as in other tissues (such as various brain regions, stomach 
and intestines.
2.   Kisspeptin and GPR54 are expressed in hypothalamic GnRH neurons, suggesting 
that both GnRHR and GPR54 may act as paracrine and/or autocrine regulators of GnRH 
neuronal function.

3.   Hypothalamic kiss-1 system transmits metabolic information to gonadotropic axis.

4    GnRH neurons activation by kisspeptin is essential for the onset of puberty and there 
are data from mice that the activation of kisspeptin neurons are driven by circulating 
estradiol.
 Neuroendocrinology

Kisspeptin: a critical regulator of puberty and reproductive function.

Kisspeptin has emerged as a critical player in the initiation of puberty and reproductive 
function. 
*In humans. Inactivating mutations of the kisspeptin receptor result in 
hypogonadotrophic hypogonadism 
*Kisspeptin receptor activating mutations cause precocious puberty. 

 *Kisspeptin signalling presents a novel target for therapeutic manipulation of the HPG 
axis.
 MEAN  AGE  AT  ADVENT  OF  MATURATIONAL  EVENTS  IN FEMALES

  Pubic hair
 Breast budding
   Axillary hair
      Menarche
            Menstrual    regularity
                            Menstrual pain
11 12 13 14
Age in years
TANNER’S Breast developmental stages

41
 ABNORMAL  PUBERTY

* Sexual  precocity / Precocious puberty
* Delayed puberty
* Excessive menstrual bleeding (Anovulatory)
* Primary Amenorrhoea
* Cryptomenorrhoea
* Dysmenorrhoea
* Premarital sexual indulgence, multiple partners
   and risk of STD.
 Abnormal Puberty
4.  Sexual precocity/precocious puberty
The patients present with indices of early sexual development and it is 
considered precocious puberty if it  appears before the age 8 years in girls.
- early breast budding 
- rapid linear growth with increase velocity growth 
- appearance of pubic and axiallary hair 
- body odor
- Menarche
- These children have full fertility  potential
Causes
 (a)  Central or true/ complete isosexual precocity 
         *Fertility potential
Causes :Intracranial lesion-meningitis, encephalitis   a  cerebral tumour and 
Alblight's syndrome (cystic changes in bones (polyostotic fibrous dysplasia), 
cafe aulait changes on the skin and precocious puberty.
(b) Pseudo precocious puberty
No fertility potential.
Causes:  pelvic tumour like feminising tumour Rx operative removal and MPA 
(medroxy progesterone acetate injections.
 Abnormal Puberty
4.  Sexual precocity/precocious puberty
The patients present with indices of early sexual development and it is 
considered precocious puberty if it  appears before the age 8 years in girls.
- early breast budding 
- rapid linear growth with increase velocity growth 
- appearance of pubic and axiallary hair 
- body odor
- Menarche
- These children have full fertility  potential
Causes
 (a)  Central or true/ complete isosexual precocity 
         *Fertility potential
Causes :Intracranial lesion-meningitis, encephalitis   a  cerebral tumour and 
Alblight's syndrome (cystic changes in bones (polyostotic fibrous dysplasia), 
cafe aulait changes on the skin and precocious puberty.
(b) Pseudo precocious puberty
No fertility potential.
Causes:  pelvic tumour like feminising tumour Rx operative removal and MPA 
(medroxy progesterone acetate injections.
DIFFERENTIAL DIAGNOSIS
Constitutional Delay. Puberty can be delayed in otherwise healthy children. They 
demonstrate prepubertal levels of FSH, LH and estradiol or testosterone. Since the 
GnRH stimulation test shows a prepubertal response. Spontaneous puberty occurs, 
allowing the child to become a normal adult, treatment is controversial. Some authorities 
recommend continued observation as the only therapy, while others recommend 
induction of puberty with sex steroids.

Elite athletes involved in extensive training,  an eating disorder and those who are 
malnourished.

Hypopituitarism. This condition is caused by a variety of diseases that affect the 
hypothalamic-pituitary axis. Present with growth failure, secondary hypothyroidism, 
adrenal insufficiency and diabetes insipidus, as well as delayed puberty. 

Kallmann's syndrome is associated with anosmia or hyposmia, and hypogonadotropic 
hypogonadism. Treatment includes initiation of hormone replacement therapy.

Chromosomal Abnormalities.
Turner's syndrome (about one case in 3,000 live female births). In these cases, patients 
may present with only growth failure and pubertal delay, or with the more pathognomonic 
features of this disorder: inner canthal folds with ptosis, a short webbed neck and a 
“shield chest” with widely spaced nipples.
 Other syndromes (e.g., Noonan's syndrome) also be associated with delayed puberty.
 2. Hypergonadotropic 
Hypogonadism.
• Males
• a. Syndrome of seminiferous tubular dysgenesis and its variants (Klinefelter
•                               syndrome). 
• b. Other forms of primary testicular failure 
• Chemotherapy 
• Radiation therapy
• LH resistance
• Sertoli  only syndrome
• Testicular biosynthetic defects
• Anorchia and cryptocrchidism
• Females
• a.  Syndrome of gonodal disgenesis (Turner's syndrome) and its variants
• b. 46, XX  and 46XY gonadal dysgenesis
• c. Other forms of primary ovarian failure 
• 1.     Premature menopause 
• II.    radiation therapy
• II.    Chemotherapy
• IV.   Autoimmune Oophoritis
• v.     Resistant ovary 
• VI.   Polycystic ovary disease
• VII.  Pseudo-Turner’s syndrome
• VII.  Galactosemia 
4. Significant Issues during Management
 1. TACKLING SHAME— psychoeducation,
     Shame can best be dealt with when we talk about it. 

2. Meeting others who share similar challenges.

Support groups

3.  HELPING PARENTS THINK ABOUT ELECTIVE SURGERY 
      Discuss choices available evidence. There’s no urgent
need for surgery.

4. TIMING OF HORMONAL THERAPY

     Elective sex hormone treatments can wait until the
     patient is approaching  puberty
5. Tanner stages of breast development

6.  TELLING THE TRUTH
    Not withholding critical information like karyotype, diagnosis.

7. Parents should be offered professional counseling. 

48
4. Significant Issues during Management
 1. TACKLING SHAME— psychoeducation,
     Shame can best be dealt with when we talk about it. 

2. Meeting others who share similar challenges.

Support groups

3.  HELPING PARENTS THINK ABOUT ELECTIVE SURGERY 
      Discuss choices available evidence. There’s no urgent
need for surgery.

4. TIMING OF HORMONAL THERAPY

     Elective sex hormone treatments can wait until the
     patient is approaching  puberty
5. Tanner stages of breast development

6.  TELLING THE TRUTH
    Not withholding critical information like karyotype, diagnosis.

7. Parents should be offered professional counseling. 

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 Perception  by DSD women on finding out the diagnosis of DSD
1.  Confusion and Anger at Secrecy and Paternalism 
2.  Shame, identity crisis and low self esteem
3.   Stigma (why me?) and denial of fertility rites 
4.   Feeling of freakishness and isolation. 
5.   Inability to function in a relationship 
6.   Concerns with infertility 
7.   Burden of keeping a secret- no confidante?
8.  Retreat from medical care- e.g HRT- Osteoporosis.
9.  How to resolve personal questions of masculinity and femininity. 

Important points that need to be understood by someone with AIS during

Counselling.
1. There is more to sex and gender than chromosomal determination; gender identity 
    (appearance in society) is not synonymous with sexual  identity (biologic knowledge) 
2. One who has AIS is not a freak; the condition is not something to be ashamed 
3.  Being a woman or man is a mental and physical process 
4.  Typical family life with marriage and adopted children is possible 
5.  Freedom of choice is crucial in the management of one’s condition 
6. One is not alone; support groups and the medical community can help 
 
Sutton, A. (1998). “’Lesley’: The struggle of a teenager with an intersex disorder to find
an identity—Its impact on the ‘I’ of the beholder.” In D. DiCeglie & D. Freeman
50
(Eds.) A stranger in my own body: Atypical gender identity development and
Travails of DSD women in sports

Caster Semenya winning the 800 metre 
Santhi Soundarajan of India, left, is awarded a silver medal
 in the Women's 800-m event during the 15th Asian Games Doha 2006 in Qatar
at the  Berlin Games, August 2009.
1. In 2006 an Indian 800 metres runner, Santhi Soundarajan, was stripped of her 
    silver medal at the Asian Games after “failing” a sex test. She was later found to
    have AIS and was reported to have made a suicide attempt, which She denied later
A recent study, 
i  24 (62%) of those who had CAIS considered suicide and 9 (23%) had attempted it. 
ii  Among those who had PAIS, 11(61%) had considered suicide and 3 (17%) had 
attempted it. 
iii  The three who had attempted suicide did so before switching their sex of rearing. 
iv  Frequently, these considerations and attempts were associated with learning of their 
51
diagnosis or a problem with a specific amorous relationship. 
Frequently Asked questions about management of 46 XY DSD?

1. How should gender assignment be psychosocially managed in newborns, children
      adolescents and adults?

2.  Is surgery in infancy necessary?

3. How should the psychosocial aspects of genital surgery and sex-hormone treatment 
be managed?
4.   Is Gender Identity  Synonymous with sexual Identity?

5. How should disclosure of sensitive personal information be handled?

6. Does Testosterone enhance performance in Sports in women with DSD? If so, does 
removal of the source of Testosterone infringe on the right of the individual?

7.  What about individual Talent in Sports?

8. How can the need for clinical collaboration of multiple disciplines be accommodated?

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 Support Groups for Disorders of Sex differentiation
•Androgen Insensitivity Syndrome Support Group (AISSG)
http://www.medhelp.org/www/ais
Intersex Society of North America
http://www.isna.org
Klinefelter Syndrome and Associates
http://www.genetic.org
Magic Foundation for Children’s growth
http://www.magic.foundation.org
The Turner Syndrome Society of the United States
http://www.turner-syndrome-us.org

And many groups in UK.

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 CONCLUSIONS
1. Early diagnosis, full investigation of ambiguous external genitalia
and delay or absence of secondary sex characteristics before the
individual reaches age of participation in international sports.

2. Understanding of the molecular and cellular basis of XY female will

help in early diagnosis before assignation of appropriate sex of
rearing and principles of management

3. The realisation of cultural differences in the management is important.

4. Psychological care should be an integral part of management. The

patient should be part of the decision making.

5. Management of XY female should be team work, comprising the

Obstetrician, Paediatrician, Geneticist , Surgeon and Psychologist.54
  
THANK YOU

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