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DISORDERS OF SEXUAL

DEVELOPMENT
VOICHITA MOGOS MD, PhD
Clinic of Endocrinology
University of Medicine and Pharmacy
Gr.T.Popa Iasi Romania

BIPOTENTIAL GONAD
DAX1
Sex determination 7
week genes

SRY

OVARY

TESTIS
WNT4 +

Sex differentiation II-III m


month internal genitalia
homones
Sex Differentiation III-I Vm
month external genitalia
Brain Diff. VI-IX month
hormones
Childhood

Adolescence

Adolescence to
adulthood

Wolfian structures

AMH -

Mullerian structures

T, DHT
Wolfian structures

No T, DHT
MALE

FEMALE

BRAIN
Gender identity : phenotype + education persons self
representation as female or male
Gender role : prenatal and pubertal hormones: sex-typical behaviourpsychological chacteristics that are sexaully dymorphic
Sexual orientation : direction(s) of erotic interest: hetero, homo,
bisexual
Adapted after Lee PA et al Pediatrics 2006,118,e488-e500

Sexual determination and differentiation - testis

Mendoca BB, Domenice S., Arnhold IP, Costa EM.: 46 XY Disorders of sex
developement. Clinical Endocrinology (Oxf) 2009, 70, 173-187

Sexual determination and differentiation - testis

Mendoca BB, Domenice S., Arnhold IP, Costa EM.: 46 XY Disorders of


sex developement. Clinical Endocrinology (Oxf) 2009, 70, 173-187

Sexual determination and differentiation - ovary

Ocal G. Current concepts in disorders of sexual


development.J.Clin.Res.Ped.Endo.2011, 3,3 , 105-114

DISORDERS OF SEXUAL
DEVELOPMENT
Definition: DSDs are congenital condition in which development of
chromosomal, gonadal and anatomical sex is atypical
2005: Chicago consensus
2006: European Society for Pediatric Endocrinology and LWPES reviews the overal
mangement of intersex disorders and proposed changes in terminology
Purposes of new nomenclature:
- To eliminate controversial terms such as hermaphroditism, intersex, sex reversal
which are stigmatizing, unhelpful and perceived as pejorative by some affected
individual and families
Lee PA, Houk P.Pediatrics 2006, 118, e488-e500, Hughes IA. Best Practice &
Research in Endocrinol &Metabolism 2008, 22, 119-134, Cools M et al. Endocrine
Reviews 2006, 27, 568-584, ul G. J. Clin. Res.Ped.Endocrinol.2011, 3, 105-114

DISORDERS OF SEXUAL
DEVELOPMENT
Impact of new classification:
Chromosomal and patient orientation of care
Gives an universal language of communication
Increases chances for advocacy
New classification was due to:
Improved knowledges about sex determination and differentiation
More elaborated chromosonal analyses
Micro array comparative genomic hybridisation (CGH)
Analysis of fetal DNA within maternal blood and amniotic fluid

Hughes IA. Best Practice & Research in Endocrinol &Metabolism 2008, 22, 119-134,

DISORDERS OF SEXUAL DEVELOPMENT New


classification

Hughes IA et al. Arc.Dic.Child.2006,91,554-563


ESPE and LWPES

DISORDERS OF SEXUAL DEVELOPMENT


New classification- gonadal determination

Hughes IA et al. Best Practice &Research in


Endocrinology & Metabolism 2008, 22, 119-134

DISORDERS OF SEXUAL DEVELOPMENT


New classification sexul diferentiation

46 XY DSD

46 XX DSD

Hughes IA et al. Best Practice &Research in


Endocrinology & Metabolism 2008, 22, 119-134

DISORDERS OF SEXUAL DEVELOPMENT


New classification other

Hughes IA et al. Best Practice &Research in


Endocrinology & Metabolism 2008, 22, 119-134

DISORDERS OF SEXUAL DEVELOPMENTprevalence


Confirming the cause of DSD and planning the management is one of the most chalanging issue
for the team that assess such conditions

1/200 newborn mai arise concern about the development of treir


external genitalia1
1/4500 1/5000 - after careful analysis2
1/2000 sex chromosome DSD:
46 XX CAH: 1/14.000 (classic) with vigurous prevalence in some
ethnic groups3
Turners syndrome: 1/2000 1/50004
Klinefelter syndrome: 1/500 1/10004
1.Ahmed SF et al. Clinica Endocrinology 2011, 75, 12-26, 2.Thyen U et al. Horm.
Res.2006, 66, 195-203, 3. Ahmed SF et al. British. Med.Bull. 2013, 106, 67-89.
4.Erdogan S et al. J.Clin.Res.Pediatr.Endo. 2011, 3, 77-83

DISORDERS OF SEXUAL DEVELOPMENT- prevalence

Laino A et al. Endocrine Connections 2014, 3, 180-192

DISORDERS OF SEXUAL DEVELOPMENTgene/phenotype relatioship

SF1 loss of function: bilateral anorchia/vanishing testes

Cools M et al.World J.Pediatr.2009,5, 93-102

DISORDERS OF SEXUAL DEVELOPMENT


gene / phenotype / hormonal relatioship

Cools M et al.World J.Pediatr.2009,5, 93-102

DISORDERS OF SEXUAL DEVELOPMENT


gene / phenotype / hormonal / relationship

Cools M et al.World J.Pediatr.2009,5, 93-102

DISORDERS OF SEXUAL DEVELOPMENT


General concepts of care

All individuals should receive gender assignment


Gender assignment must be avoided before expert evaluation of the newborn
A complex multidisciplinary team is prerequisite for evaluation of DSDs
Patients and family concerns must be respected and addressed in strict
confidence
Open communication with patients and families is essential and participation
in decision-making is encouraged

Hughes IA et al. Arch.Dis.Child.2006,91,554-563


Lee PA et al. Consensus Statement of Management of
Intersex Disorders. Pediatrics 2006, 118, e488-e500

DISORDERS OF SEXUAL DEVELOPMENT


General concepts of care

Hiort O et al. Nature Reviews Endocrinology 2014, 10, 520-529

DISORDERS OF SEXUAL DEVELOPMENT


CRITERIA THAT SUGGEST DSD
In newborn

Overt genital ambiguity (cloacal


extrophy)
Apparent female genitalia with
enlarged clitoris, posterior labial
fusion, inguinal or labial mass
Apparent male with bilateral
undescended testes, isolated perineal
hypospadias with chordee, mild
hypospadias with andescended testes,
bifid scrotum
Family history of PAIS or CAIS
A discordance between genital
appearance and prenatal kariotype
Mendoca BB, et al Clinical Endocrinology (Oxf) 2009, 70, 173-187, Hughes IA et al.
Arch.Dis.Child.2006,91,554-563, Lee PA et al. Pediatrics 2006, 118, e488-e500, Ahmed SF et al.
Clinica Endocrinology 2011, 75, 12-26

DISORDERS OF SEXUAL DEVELOPMENT


CRITERIA THAT SUGGEST DSD
Any time during childhood, puberty
and even in adult

Girls with primary amenorrhea and no


uterus (46XX Mullerian agenesis,
46XX,CAIS), or with primary amenorrhea
Inguinal hernia in a girl
Genital surgery, need for steroid
replacement
Girls developing enlarged clitoris and
virilization at puberty (46XY, 17HSD)
Male with gynecomastia, infertility or
Previously nondiagnosed genital ambiguity
Male with uterus
Male with cyclic hematuria

Mendoca BB, et al Clinical Endocrinology (Oxf) 2009, 70, 173-187, Hughes IA et al. Arch. Dis. Child. 2006,
91, 554-563, Lee PA et al. Pediatrics 2006, 118, e488-e500, Ahmed SF et al. Clinica Endocrinology 2011,
75, 12-26

DISORDERS OF SEXUAL DEVELOPMENT


Plan of assessment
Family and prenatal history
Physical examination
Cytogenetic and molecular studies
Imaging studies
Hormone assessment
Required in some cases
Endoscopic and /or laparoscopic exploration
Gonadal biopsy
Mendoca BB, et al Clinical Endocrinology (Oxf) 2009, 70, 173-187, Hughes IA et al. Arch.
Dis. Child. 2006, 91, 554-563, Lee PA et al. Pediatrics 2006, 118, e488-e500, Ahmed SF
et al. Clinica Endocrinology 2011, 75, 12-26, Kim KS, Kim J. KJU 2012, 53, 11, 1-8

DISORDERS OF SEXUAL DEVELOPMENT


Family and prenatal history
Family history of consaquinity
Infant death (CAH)
Stillbirth, multiple misscariages
Systematic metabolic disorders
Maternal hirsutism, amenorrhea, infertility
Maternal virilization during previous pregnancy
Maternal medication (OC, steroids) or environmental disruptors
exposure
Maternal medication used in assisted reproduction techniques

Ahmed SF et al. Clinica Endocrinology 2011, 75, 12-26,


Kim KS, Kim J. KJU 2012, 53, 11, 1-8

DISORDERS OF SEXUAL DEVELOPMENT


Physical examination
Will take place in a worm room with child placed in supine frog like position. Clinical
evaluation is essential because most DSD may be recognized in the neonatal period
and precoccious diagnosis allows a better approach

Measure of stretch phallic length (<2cm.)


Quality of corpora cavernosa
Inspection of labia, labio-scrotal folds or scrotum
Presence and/or location of gonads (NB: only XY gonads will descend)
External masculinization score
Urethral opening
Vaginal opening
Anogenital distance as a marker of androgen action
General health status, Hypoglicaemia, dehydration (CAH)
Malformations: SOX9 (campomelic dysplasia, GATA 4, FOG 2)
Mendoca BB, et al Clinical Endocrinology (Oxf) 2009, 70, 173-187, Hughes IA et al. Arch. Dis. Child.
2006, 91, 554-563, Lee PA et al. Pediatrics 2006, 118, e488-e500, Ahmed SF et al. Clinica
Endocrinology 2011, 75, 12-26, Kim KS, Kim J. KJU 2012, 53, 11, 1-8, Thankamony A et al.
Environ,Health. Perspectives 2014, 122, 207-211

DISORDERS OF SEXUAL DEVELOPMENT


Physical examination

Hughes IA et al. Arc.Dic.Child.2006,91,554-563


Lee PA et al. Pediatrics 2006, 118, e488-e500

DISORDERS OF SEXUAL DEVELOPMENT


First line investigations: genetics
Kariotyping with X and Y specific
probe detection (even prenatal
kariotype is available
Molecular analyses
Micro array comparative genomic
hybridization
Quantitative fluorescent PCR
Fetal DNA in maternal blood and
amniotic fluid
Specific molecular studies for
mutations or gene dosage imbalance
(SRY, AR, SF1, WT1, SOX9, Cyp 21,
DAX1, 5HRD 2)
molecular analyses are limited by
cost, accessibility and quality control
and only

Gao X et al. J.Assist,


Reprod.Genet.2013,30,431-435
Mendoca BB, et al Clinical Endocrinology (Oxf) 2009,
70, 173-187, Hughes IA et al. Arch. Dis. Child.
2006, 91, 554-563, Lee PA et al. Pediatrics 2006,
118, e488-e500. Ahmed SF et al. Clinica
Endocrinology 2011, 75, 12-26. ul G. J. Clin.
Res.Ped.Endocrinol.2011, 3, 105-114. Ono M,
HarleyVR.Nat. Rev. Endocrinol. 2013, 9, 79-21

DISORDERS OF SEXUAL DEVELOPMENT


IMAGING STUDIES ULTRSOUND
Imaging plays an important role in demonstrating the anatomy and
associated anomalies, important for gender assignment and surgery
planning. Ultrasound diagnosis is examiner dependent

Ultrasound pelvis and kydney malformations observer dependent


sensitivity: 89.5%, specificity up to 100%
presence of mllerian structures at al ages
locate the gonads in intraabdominal, inguinal, labioscrotal position
streak gonads and ovaries are less visible

Chayhan GB et al. RadioGraphics 2008, 28, 1891-1904, Mendoca BB, et al.: 46 XY Disorders of sex
developement. Clinical Endocrinology (Oxf) 2009, 70, 173-187. Moshiri M et al. RadioGraphics
2012, 32, 1599-1618 , Al Jurayan N. Ann.Saudi Med. 2013, 33, 363-367

Moshiri M et al. RadioGraphics 2012, 32, 1599-1618

Moshiri M et al. RadioGraphics 2012,


32, 1599-1618

Turo R.et al. Can.Urol.Assoc.J. 2014, 8,


650-653

MRI

DISORDERS OF SEXUAL DEVELOPMENT


IMAGING STUDIES MRI
Specificity 100%
provides detailed information for:
internal pelvic structures
uterus and tubes
gonads, spermatic cords
hydronephrosis
Chayhan GB et al. RadioGraphics 2008, 28, 1891-1904, Mendoca BB, et al.: 46 XY Disorders of sex
developement. Clinical Endocrinology (Oxf) 2009, 70, 173-187. Moshiri M et al. RadioGraphics
2012, 32, 1599-1618 , Al Jurayan N. Ann.Saudi Med. 2013, 33, 363-367

DISORDERS OF SEXUAL DEVELOPMENT


IMAGING: RETROGRADE GENITOGRAM

Type of urethra
Presence of vagina and cervix
Urogenital synus
Fistulas
Complex anomalies

Chayhan GB et al. RadioGraphics 2008, 28, 1891-1904,


Moshiri M et al. RadioGraphics 2012, 32, 1599-1618

RETROGRADE GENITOGRAM
Lee HG et al. Ann.Pediatr.Endo.Metab. 2014, 19, 100-103

DISORDERS OF SEXUAL DEVELOPMENT


HORMONE MEASUREMENTS
Basal hormone measurements
Serum, plasma steroids, serum electrolytes for CAH suspicion to avoid lifethreatening salt-wasting condition first 1-2 day
Urinalysis and spot urine or urine collection before starting glucocorticoid
therapy which may start in the first 1-2 days
Refined analyses: liquid chromatography in tandem with mass spectrometry
for POR deficiency
In the first 100 days Testosterone and DTH may vary largely
Mendoca BB, et al Clinical Endocrinology (Oxf) 2009, 70, 173-187
Hughes IA et al. Arch.Dis.Child.2006,91,554-563,
Ahmed SF et al. Clinica Endocrinology 2011, 75, 12-26,
ul G. J. Clin. Res.Ped.Endocrinol.2011, 3, 105-114

DISORDERS OF SEXUAL DEVELOPMENT HORMONE MEASUREMENTS


Cario
type

Hormone

Values

Significance

46 XX

ACTH,
17OHP,
DHEA, A, T

Increased

21 OH CAH, 11 OH CAH,

46 XY

DHEA, A, T,
DHT
T, DHT
T/DHT

Decreased

Disorders of testosterone synthesis 17OH, 17-20 liase,


17HSD
CAIS, PAIS
5 reductase type 2 deficiency

46XX
46XY

FSH, LH

Normal
Increased

CAH,
Any CGD, MGD, PGD, CAIS, PAIS

46XX

AMH

Normal for XY

Inhibin

Undetectable
Detectable

46XX testicular or ovotesticular DSD. It detects


testicular tissue and correlates with mass of testicular
tissue
CGD, PGD
Function of Seroli cells

46XY

Normal
/incresed
Incresed at hCG
test

46XX All hormones normal


Armatase deficiency, prenatal exposure to maternal
androgens, endocrine dysruptors, other DSD
46
XY
Mendoca
BB, et al Clinical Endocrinology (Oxf) 2009,
70, 173-187, Hughes IA et al. Arch. Dis. Child. 2006,

91, 554-563, Ahmed SF et al. Clinica Endocrinology 2011, 75, 12-26. ul G. J. Clin. Res. Ped.
Endocrinol. 2011, 3, 105-114, Simard J et al. Endocrinologist 2003, 13, 195-200

DISORDERS OF SEXUAL DEVELOPMENT HORMONE MEASUREMENTS TESTS

TEST

Protocol

Significance

ACTH
stimulation
test

25g.iv.before 2 years
250 g iv after 2 years

17 OHP over 10,000 ng/mL classic CAH 21 OH


17OHP increased and 11DOC increased 11 OH CAH

hCG
Stimulation
test

100 IU/Kg.bw
5000 IU/1.72 m2 bs (short)
1000-1500IU/ 3days (short)
Measure steroids at 72 and
96 h
1500 IU for 2days/week for
2weeks, measure steroids
day 26

Sometimes only post test values are necessary and


important
Failure to respond, Increased FSH, LH :CGD, anorhia
T, DHT increased, Normal T/DHS ratio : CAIS, PAIS
High T/DHT ratio = 5 reductase type 2 deficiency
10-15 fold increase in A/T ratio: 17 HSD deficiency

FSH
stimulation
test

Infant: rhFSH 25 IU x 3 days


Adult:rhFSH 150 IU x 3
days

Ultrasound evaluation: cyst appear on ovotestis


Increased E2/T ratio
Increased inhibin B
Identifies ovarian structures before laparoscopy

Kim KS, Kim J. Disorders of sex Development. KJU 2012, 53, 11, 1-8. Ahmed SF et al. Clinica Endocrinology
2011, 75, 12-26, French S et al. Int.J.Pediatr. Endocrinol. 2009, id. 597964, Kolon TF, Miller OF.
J.Urol.2001,166,1451-1454

DISORDERS OF SEXUAL DEVELOPMENT

Laparotomy and laparoscopy


Final diagnosis in some DSD
are based only on histological
findings in the biopsied gonad
Gonadal biopsy is manditory in
all XY gonadal dysgenesies
especially for those bearing
GBY gonadoblastoma
susceptibility locus on Y
chromosome to detect CIS or
more advanced neoplasia

Algorithms for diagnosis of DSDs


Algorithms do exist but with such complex
conditions every case must an individual
appropriate approach

Ambigous genitalia / pubertal problems

46 XY DSD

KARIOTYPE
GONADS

Absent

Uterus
Agonadism

Ovotestis

Uterus

Ovotesticular
DSD

Dysgenetic
testes
Uterus

Partial
gonadal
dysgenesis

Streak gonad

Uterus +

Complete
gonadal
dysgenesis

Testis/testis

Uterus Androgen
biosynthesis def.
LH receptor def.
CAIS/PAIS
5Red.def.

ul G. J. Clin. Res.Ped.Endo.2011, 3, 105-114

Ambigous genitalia / pubertal problems

46 XX DSD

KARIOTYPE
GONADS

Testis/testis

Uterus 46 XX
testicular
DSD

Streak/streak

Uterus

Complete
gonadal
dysgenesis

ovotestis

Uterus

Ovotesticular
DSD

Ovary / ovary

Uterus +

17 OH
progesterone
high

17 OH
progesterone
normal

CAH

Non CAH

ul G. J. Clin. Res.Ped.Endo.2011, 3, 105-114

DISORDERS OF SEXUAL DEVELOPMENT

RISK FOR TUMORS


Risk for gonadal tumors development depends of:
Expression of GBY Gonadoblastoma susceptibility locus on Y chromosome
Expression of TSPY testis specific protein Y encoded
Risk is higher in 46 XY DSD with undervirilization
Even in 46 XY streak gonad some surviving germ cells may produce tumors
Tumors may be:
Non invasive: CIS and gonadoblastoma (prophylactic gonadectomy 38.5%)
Invasive: disgerminoma or seminoma (prophylactic gonadectomy:38.5%)
Late gonadectomy: CIS 100%

Hughes IA et al. Arch.Dis.Child.2006,91,554-563. Mendoca BB, et al..


Clinical Endocrinology (Oxf) 2009, 70, 173-187. Cools M et al.
Endocrine Reviews 2006, 27, 568-584. Cools M et al. World J Pediatr.
2009,5, 93-102

Cools M et al. Endocrine Reviews 2006, 27, 568-584.

DISORDERS OF SEXUAL DEVELOPMENT

GENDER ASSIGNMENT
Factors influencing gender assignment
Diagnosis
Genital appearance
Gonadal function, internal genitalia
Surgical option and abilities. Risk for malignancy
Potential for fertility
Presumed prenatal brain virilization, genital appearance is a
poor predictor of brain virilization
Need for lifelong replacement therapy
Wish of the family, family acceptance, ethnic traditions
Related to cultural practice
Mendoca BB, et al.. Clinical Endocrinology (Oxf) 2009, 70, 173-187. Hughes IA et al.
Arch.Dis.Child.2006,91,554-563. Schonbucher V et al. J.Sex.Med. 2012, 9, 3154-3171

DISORDERS OF SEXUAL DEVELOPMENT


TRADITIONAL GENDER ASSIGNMENT
FEMALE

MALE

46XX DSD with fetal androgen excess


46XY CAIS
46XY CGD

PAIS, 5 reductase def.


46 XY PGD, 46 XY MGD
Ovotesticular DSD
Cloacal extrophy

Sex reassignment

PAIS, PGD, 17HSD: 25 % are dissatisfied

46 XX CAH: 90% raised females


Female to male reassignment in severelly
virilized individuals with delayed diagnosis
5 reductase: 50 % of individuals raised
female change sex at puberty or after

weather raised male or female


MGD 45X/46XY: 65 % assigned female
but depending on prenatal brain virilization
and pubertal virilization some require sex
reassignment
ovotesticular DSD: decision making after
gonadal biopsy and assuming that genitalia
are or can be made consistent with the
chosen sex

Hughes IA et al. Arch.Dis.Child.2006,91,554-563, Mendoca BB et alClinical Endocrinology (Oxf)


2009, 70, 173-187 , Schonbucher V et al. J.Sex.Med. 2012, 9, 3154-3179

DISORDERS OF SEXUAL DEVELOPMENT


SURGICAL MANAGEMENT
A surgeon with expertise is needed
Feminizing surgery only in severe Prade III-IV in common with urogenital
synus repair
Emphasizing on functional outcome rather than cosmetic appearance: to
maintain clitoral sensitivity and ability to reach orgasm
Procedure of choice: total genital mobilization and clitoroplasty
Early separation of vagina from urethra will improve better estrogen
activation and avoid complications
Surgery must be done in the first year of life to avoid family distress and
improve attachment
Vaginal dilatations must be avoid before puberty. Vaginoplasty: at puberty
Streak gonads will be removed at diagnosis
Testes in DSD raised female should be removed at puberty or after
Hughes IA et al. Arch.Dis.Child.2006,91,554-563, Schonbucher V et al. J.Sex.Med. 2012, 9,
3154-3179, Recommendations of the American Academy of Pediatrics

DISORDERS OF SEXUAL DEVELOPMENT


SURGICAL MANAGEMENT
DSD with hypospadias
Chordee repair and hypospadias repair
Urethral reconstruction
Judicious use of androgen supplimentation
Phaloplasty in adulthood with prostesis
Patient should not be given unrealistic expectations about penile
reconstruction
Streak gonads in MGD and testes in patients with androgen synthesis
defects should be removed at diagnosis
Scrotal testes in patients with 46 XY DSD have risk of malignancy and biopsy
must assess premalignant states CIS at puberty
Patients with bilateral ovotestis may be potentially fertile from their ovarian
tissue. Ovarian and testicular tissues must be separated if possible in early
life (dificult)
Hughes IA et al. Arch.Dis.Child.2006,91,554-563,

DISORDERS OF SEXUAL DEVELOPMENT


STEROID REPLACEMENT THERAPY
Hipogonadism in the common state
Hormonal induction of puberty should attempt to replicate normal pubertal
development , to mimic pubertal growth spurt and allow psychological
maturation
Males: testosterone depot
25-50 mg / month initially and maintenance dose in adults: 200-250 mg every 2
weeks
200 250 mg twice a week in PAIS

Females: estrogen replacement in progressive doses

Glucorticoid replacement therapy in CAH


Hughes IA et al. Arch.Dis.Child.2006, 91, 554-563, Mendoca BB et alClinical Endocrinology
(Oxf) 2009, 70, 173-187

DISORDERS OF SEXUAL DEVELOPMENT


FERTILITY
Impaired in 46 XY DSD
Undescended testis
Penoscrotal hypospadias
Complications after surgery
Low semen volume and high viscozity perclude natural occuring
fertility
Intrauterine insemination
FIV

Mendoca BB et alClinical Endocrinology (Oxf) 2009, 70, 173-187

DISORDERS OF SEXUAL DEVELOPMENT


PSYCHOLOGICAL MANAGEMENT
Mental health staff with expertise in DSD
Once the chils is sufficiently developed for psychological
assessment of gender identity reassignment should be
discussed
Atypical gender role which is common in DSD should not be
taken as an indicator for gender reassignment
Quality of life in DSD

Falling in love
Dating ability to develop relationship
Avoid frequent genital examination
Local photographs under anestesia

Hughes IA et al. Arch.Dis.Child.2006, 91, 554-563, Mendoca BB et alClinical Endocrinology


(Oxf) 2009, 70, 173-187, Lee PA et al. Pediatrics 2006, 118, e488-e500

DISORDERS OF SEXUAL DEVELOPMENT


CULTURAL AND SOCIAL FACTORS

DSD may carry stigma


Social and hormonal factors may influence gender role
Fertility is perclude for phenotypical females in some societies
Risk to develop fatalism and quilt feelings in relation with
genital malformations

Hughes IA et al. Arch.Dis.Child.2006, 91, 554-563,

Conclusions
DSD are relatively rare disorders but represent a are challanging
issues for the team which is involved with their management
DSD may result as disorders of sexual determination of gonad
or/and sexual differentiation of internal and external genitalia
The diagnosis of DSD relies on kariotyping , refined genetic studies,
imagery of pelvis and kidney, hormonal assessment (basal and
dynamic tests). Algorithms for assessment do exist but with such
complex issues as DSD individualized investigations are necessary.
Hormonal investigations must identify first life-threatening conditions
such disorders of steroid synthesis in both adrenals and gonads
Gender assignment must be done in every individual according
diagnosis, genital appearance, gonadal function, internal genitalia,
surgical option and abilities, risk for malignancy,potential for
fertility,presumed prenatal brain virilization and familial acceptance