UNIB30004 Sex: Science and the Community
Disorders of sex development and
transsexualism in children
Lecture adapted from one given by
Dr Jackie Hewitt, RCH, 2011
Baby X
Canadian couple decide to allow their children to
discover their gender for themselves.
•
•
•
No announcement about baby’s sex
Names, clothing, hairstyle gender-neutral
Questions about child’s gender not answered
Is this harmful to the child? Is it a form of abuse?
• Biology of disorders
• Congenital Adrenal Hyperplasia (CAH)
• 5-Reductase deficiency
• Androgen insensitivity (CAIS)
• Case studies and ethical issues
XX = FEMALE
XY = MALE
AMH
regressed
Mullerian Duct
Testosterone
stimulated
Wolffian Duct
MD
(oviduct
and uterus)
regressing
WD
T
prostate
5α-reductase
DHT
external genitalia
Congenital Adrenal Hyperplasia
Adrenal Steroids
• defective enzymes
• adrenals cannot
make cortisol
• hyperstimulation
of adrenals 
overflow of
precursors into
androgen pathway
Testosterone
• enzyme defect  fetal adrenal makes
androgens
• virilisation of XX female fetuses with range
of severity
clitoral enlargement
(masculinised female)
labial fusion and
penile development
(male like)
• internal ovaries, oviduct,
uterus, vagina (no AMH)
5α-Reductase
deficiency
XY = MALE
AMH
regressed
Mullerian Duct
Testosterone
stimulated
Wolffian Duct
• Production of DHT
impaired or absent
• XY males  feminised
external genitals
• testes internal
• T  WD differentiation
• MD degenerates
T
prostate
5α-reductase
DHT
Androgen
Insensitivity
Syndrome
• Defective androgen
receptor. Partial of
complete insensitivity
CAIS)
XY = MALE
AMH
regressed
Mullerian Duct
Testosterone
stimulated
Wolffian Duct
T
prostate
5α-reductase
• XY males  feminised
external genitals
• testes internal
• WD regresses
• MD degenerates
DHT
When is gender identity formed?
• Core gender identity (Stoller) is the fundamental
sense of belonging to one sex
• Develops between 18 mo and 3 yrs
• Gender labelling - from 18 mo infant is able to label
individuals as M or F on external appearance.
Gender not seen as fixed.
• Gender constancy - by 3yr gender is part of the selfconcept
• Gender stability - reached by age 4-5 yr
What factors influence gender identity?
• Some understanding from children with disorders of sex
development (DSD) and gender identity disorder (GID)
 gender identity dysphoria (DSM-V)
• Infant’s interactions with carers
• Prenatal exposure to testosterone
• Functional androgen receptor
• Postnatal exposure of a genetic female to testosterone (e.g
NSW-CAH, 17B-HSD)
• Genetic factors (twin studies of GID)
• Other unknown factors
What is sex?
Either of the two main categories (male and female) into which
humans and most other living things are divided on the basis of
their reproductive functions.
No encompassing scientific definition.
Chromosomal sex
Gonadal sex
Anatomical sex
Brain sex
XX
XY
Ovaries
Testes
Vagina and uterus
Penis and scrotum
Female
Male
Sex, gender identity, gender role and sexual orientation are
different.
What is sex?
Either of the two main categories (male and female) into which
humans and most other living things are divided on the basis of
their reproductive functions.
No encompassing scientific definition.
Chromosomal sex
Gonadal sex
Anatomical sex
Brain sex
XX
XY
XX/XY
Ovaries
Testes
Ovotestes
Vagina and uterus
Penis and scrotum
Ambiguous
Female
Male
Neither
Sex, gender identity, gender role and sexual orientation are
different.
DSD and GID
• Disorders of sex development (DSD) are congenital conditions
where there is atypical development of the chromosomal,
gonadal or anatomic sex.
• Currently a biological diagnosis.
• Disagreement between patients on preferred terminology –
intersex, differences of sex development, variations of sex
development.
• Gender identity disorder (GID) is where an individual has a
persistent and profound incongruence between their gender
identity and their anatomic sex.
• Currently a mental health diagnosis.
• Other terminology used – transsexualism, transgender, gender
identity dysphoria.
Child Z: born in India
• Phenotypic female infant with inguinal testes, absent uterus and
46,XY karyotype
• Diagnosed as CAIS, recommendation to raise as female
• Father (lecturer in Islamic law) rejects medical advice and raises
child as male on cultural grounds and to give best chance of
economic independence
• Father’s arguments: under local Muslim law, a son may
1. Inherit from his father (daughters get half share)
2. Join the priesthood
3. Be employed and be economically independent
4. An infertile woman cannot be offered in marriage
5. Unmarried women are unemployable and are therefore
dependent on parents for life
6. IVF not an option
Child Z: born in India
• At 17, patient returns as young man with
sparse beard and pubic hair.
• Genitalia now ambiguous – penis has
grown
• Diagnosis: deficiency of
17α-hydroxylase  reduced ability to
make testosterone
• extra stimulation of testes at puberty 
testosterone production for partial
virilisation
Gender “assignment”
• A decision made by doctors and parents about sex of rearing;
decision about genital surgery follows
• Based on a prediction of what the gender identity will be
• Uncertainty acknowledged, but influence of carers and
environment was thought to be more powerful than influence of
hormones
RCH data: perspective on diagnosis
Bhullar & Hewitt et al. J Ped Adol Gyn 2011.
• 199 patients aged 0-10 yrs seen at RCHM 1999-2008
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•
•
•
•
46,XY 54%
46,XX 32%
Mixed chromosome DSD (45,X/ 46,XY) 14%
Definitive diagnosis reached for 87.5% of 46,XX DSD
No definitive diagnosis in 71% of 46,XY DSD
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•
•
•
Sex of rearing
46,XY – 92% male, 8% female
46,XX – 98% female, 2% male
Mixed chromosomes – 68% male, 32% female
Accuracy of gender assignment
• 95% accurate in females with CAH
• Exceptions often present late or are exposed to androgen for
long periods during childhood
• Other conditions: most affirm a gender that conforms to their
original assigned sex
• Partial androgen insensitivity syndrome – 25% of adults
unhappy about gender regardless of sex of rearing (but only a
few want surgery to change genitalia)
• in 5α-reductase deficiency and 17β-HSD deficiency – usually
identify as girls when young but have ambiguous genitalia.
Greater likelihood of male gender identity after puberty onset.
Accuracy of gender assignment
• Does early gonadectomy change gender shift?
• How great is the risk if feminizing genital surgery (which involves
removal of erectile tissues) is undertaken?
• Are these surgical procedures ethical if one cannot be certain
about the child’s future gender identity?
• Is it ethical to raise a child with ambiguous genitalia, especially
against the wishes of the parents?
Ethical principles for decision making in DSD
Gillam, Hewitt & Warne. Horm Res 2010.
1. Minimizing physical risk to the child
2. Minimizing psychosocial risk to the child
3. Preserving potential for fertility
4. Preserving or promoting capacity to have satisfying sexual relations
5. Leaving options open for the future
6. Respecting the parents’ wishes and beliefs
Do any of these principles have greater importance in decision-making?
Queensland and court involvement in medical
decision making
• Four cases of DSD
• Doctors recommended removal of dysgenetic gonads because
of a known risk of cancer and because they might cause
unwanted masculine development in a girl
• All cases were referred to the Family Court of Australia for a
judge to authorize removal of gonads
• Created legal precedent redefining ‘special medical procedure’
• The doctors and the hospital were concerned about
- Making infertility a certainty, instead of a probability
- The risk of being sued if a patient’s affirmed gender identity
proved to be different from the assigned sex
Why was this a problem?
• Taking the cases to court created a legal precedent that is binding
on all doctors throughout Australia
• Each court case costs approximately $20,000 (in some states this
cost will need to be borne by the family)
• The court supported the doctors in every case
Alternative approaches:
• A multi-disciplinary specialist team could have provided a
consensus recommendation on the best course of treatment (this
is what occurs internationally)
• An ethics committee could have analysed the issues and provided
valuable advice to the clinicians, without costing any money or
creating legal precedent
• If legal involvement was required, a children’s tribunal for special
medical procedures would provide consistency and expertise, at
less individual cost
In a hospital in New South Wales
• Doctors decide not to recommend genital surgery for any infants
• Decisions about surgery are left until the patients are old enough
to decide for themselves
• But when are they considered competent to make this decision?
• Who can give valid consent? The parents? The patient? Or only
the court?
Gender dysphoria
• The sense of discomfort or disease with one’s biological sex and
assigned gender role
• May be profound and persistent – high risk of self harm, suicide
Gender dysphoria in DSD
• Distress intensified by having had medical treatment
• Some intrinsic gender instability possible (in PAIS gender
dysphoria not related to sex of rearing)
• Teenager with DSD and gender dysphoria may not talk about it
– but behaviour will reveal distress when hormone replacement
is given, as physical changes generate revulsion - (e.g. patient
with PAIS raised female may request surgical mastectomy and
testosterone treatment in adult life, even after living in female
role for a long period of time, including marriage to a male)
• Parents may deny because of guilt and anxiety (“just a stage”)
Screening for GD in DSD
• Acknowledge the possibility and allow patient to express their
emotions
• Say “some people feel ....”
• Observe reactions and behaviour, especially when hormonal
therapy is being offered
• Refer to an experienced mental health professional when GD is
suspected
• Better still, always involve mental health professional as team
member
Management of GD in DSD
• Psychotherapy. Most patients with GD do not want surgery
(different from GID)
• Surgical options are poor if genital tissues have been removed;
satisfactory reconstruction is very difficult, if not impossible.
• Frustration leads to anger and depression (requiring help)
• Some patients prefer to live as the other gender, even though
they have had genital tissues removed, i.e feeling respected in
the affirmed social gender is a positive outcome.
Gender identity disorder
• A DSM-IV diagnosis, ie classified as a mental disorder
(Gender identity dysphoria in DSM-V)
• Untreatable by any form of psychotherapy
• Many experts consider GID a ‘variation of sexual formation’ in
which brain sex and anatomical sex don’t match
• Cause unknown
• By definition, DSD has been excluded
• A small genetic contribution (twin studies)
Progression of GID of childhood
• Very young children may display interest in what it would be like
to be the other sex
• An effeminate child in a strongly macho, homophobic culture
may be wrongly labelled
Differential diagnosis in an adolescent or adult
• Transsexual/ transgender – wishes to be identified as the other
sex, usually wants surgery
• Transvestite
• ‘
‘Genderqueer‘
’ (both sexes, neither sex, fluid)
• ‘‘
Voluntary eunuch‘
’ – wishes to be sexually neutral, to have sex
organs removed but wants no hormone replacement
• Other
Endocrine treatment of GID - aims
• Early intervention to block unwanted pubertal development
- relieves gender dysphoria, allows person to get on with life
- makes some surgery e.g mastectomies for FTM, unnecessary
- prevents voice change and beard growth for MTF patients
- allows person to grow up looking consistent with identified
gender
- hopefully prevents development of unhealthy life style on
the ‘
‘fringe‘
’ of society
- links young person to professional help
History of hormone treatment of GID in children
• GID clinic in the Netherlands found better outcomes for those
treated with hormones earlier - commenced paediatric hormone
treatment in 1980s.
• Guidelines for hormone treatment of children published in
Journal of Clinical Endocrinology and Metabolism 2009,
endorsed by ES, LWPES, ESPE, APEG.
• Child and adolescent clinics providing hormone treatment in US
(NY, Boston, LA, San Francisco, Cleveland, Chicago, Seattle),
Scandinavia (Sweden), Europe (Spain, Germany – Frankfurt
and Hamburg, Netherlands – Amsterdam and Utrecht), UK
(London: research) and Canada (Toronto and Vancouver), NZ.
History of hormone treatment of GID in children
• Re: Alex, Warne and Paul 2003
• Experience 2003-2011 reported Hewitt et al. MJA 2012
• Correspondence: argument for earlier treatment and more
services Hyde MJA 2012, and Gillick competence of older
children >16 years Handelsman et al. MJA 2012.
• Legal requirement for those <18 unclear re: Gillick
• Calls for specialised tribunal
Endocrine management of an adolescent with GID
• Diagnosis of GID confirmed by two experienced psychiatrists
• Endocrinologist’s role: exclude DSD or any other endocrine
disorder, examine for pubertal development
• Participate in clinical ethics committee review
• Prepare reports for court and give evidence
Endocrine treatment
• Administer court-authorized GnRH analogue when Tanner stage
2-3 has been reached (suppress puberty)
• At around age 16, start cross-sex hormone treatment (may need
separate authorization from court)
• Can stop GnRH analogue when adult doses of testosterone or
oestrogen are being given
• Monitor development and liaise with psychiatrist, other key
people e.g school teachers and counsellor
• Refer on to an adult service at age 18
Difficulties encountered
• Significant number of patients have associated psychological or
developmental problems, e.g Asperger’s syndrome
• Family may be stressed
• Young people push the boundaries
• Court costs substantial for families able to pay
• Complex patient + court process = time consuming
• Administrative issues such as name and sex on the medical
record
• Hormone treatment needs to be individualised
Risk of ‘regret’ and litigation
• Extremely rare in patients showing full picture of severe gender
dysphoria after onset of puberty
• Risk reduced if follow international guidelines, involve ethics
committee, have multidisciplinary team, only treat after full
assessment by psychiatrists and have long term mental health
follow up
GID at RCHM
Hewitt et al. MJA 2012.
• 41 patients reviewed by psychiatry
• 51% peri/post pubertal and reviewed by endocrinology - 2/3
biological males
• Behavioural co-morbidity in 25%
• Asperger’s syndrome in 15%
• Family history homosexuality or gender dysphoria in 1/3
Most patients plan hormone treatment
Hewitt et al. MJA 2012
Frequency of referrals is rising
Referrals to GID service 2003 - 2011
Hewitt et al. MJA 2012
Summary
• Biological basis of DSDs – genes and hormones
– CAH; CAIS/PAIS; androgen synthesis defects
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Gender identity vs gonadal / anatomical sex
Ethics and practicalities of Gender “assignment”
Legal issues
Gender dysphoria / Gender Identity disorder