What can disorders of sex development (DSD) tell us about transsexualism?
The genetic information of humans is stored
in 46 chromosomes. Two of these chromosomes are called sex chromosomes – they
determine the sex of a person. While all other 22 chromosome pairs are
identical in males and females, men have the sex chromosomes X and Y and women two
of the sex chromosome X. In human biology, humans with a normal set of
chromosomes are consequently described as 46,XY or 46,XX. The concept seems
really quite simple – apart from the many exceptions that don’t fall into the
male = 46,XY and female = 46,XX dichotomy.
The field of so-called disorders of sex development (DSD), formerly called intersex disorders or
hermaphroditism, is too broad to be covered here. I just would like, as an
example, to focus on three different types of disorders of sex development:
androgen insensitivity syndrome (AIS), or more specifically on the two subtypes
of complete androgen insensitivity syndrome (CAIS) and partial androgen
insensitivity syndrome (PAIS), and thirdly on 5α-Reductase deficiency (5-ARD). Let’s
have a look at how these three disorders affect otherwise healthy males
(46,XY).
Androgen insensitivity syndrome
(AIS)
Androgen insensitivity syndrome (AIS) is typically caused by a mutation of a
gene responsible for the so-called androgen receptor. In most cases, the
mutated gene is on the X chromosome (although sometimes AIS is caused by
mutations in other genes, for example on chromosome 9). For males (46,XY) a
defective gene on the X chromosome is more problematic than for females
(46,XX), since the doubling of the chromosome (i.e. having another, non-mutated
copy) can reduce the impact of a mutated gene.
Complete androgen insensitivity syndrome (CAIS)
AIS affects the ability of cells to respond
to androgens (androgens are male sex hormones, such as testosterone). Even if
testosterone is being supplied by the body at the right time and in the right amount
for the development of a male body, the cells can process it only partly or not
all. In the case of complete androgen insensitivity syndrome (CAIS),
a baby (46,XY) will have female-looking genitalia and will therefore be assigned
the female gender role at birth. CAIS is often only detected in puberty due to
lack of menstruation.
Partial androgen insensitivity
syndrome (PAIS)
Partial androgen insensitivity syndrome (PAIS) is, as the name suggests, a
partial inability of cells to respond to androgens. Males (46,XY) affected by PAIS
can be born with male genitalia, ambiguous genitalia or female-looking
genitalia. Depending on the appearance of the genitals, babies are assigned and
raised as either males or females (babies with ambiguous genitalia are often
raised as girls). For individuals with female genitalia at birth, PAIS is often
detected only at puberty, when menstruation fails to begin.
5α-reductase-type-2 deficiency
(5-ARD)
5α-reductase-type-2 deficiency (5-ARD) is usually caused by a mutation of a
gene located on chromosome 2. This gene is responsible for an enzyme that
converts testosterone into dihydrotestosterone (DHT) in the prostate, testes,
hair follicles, and adrenal glands. DHT is a stronger androgen than
testosterone and is essential for formation of the male external genitalia.
Males (46,XY) affected by 5-ARD can be born with male genitalia, ambiguous
genitalia or female-looking genitalia. Again, depending on the appearance of
the genitals, babies are assigned and raised as either males or females (babies
with ambiguous genitalia are often raised as girls). At puberty, these
individuals will experience deepening of the voice, growth of facial hair and
enlargement of the clitoris (which explains the informal term for 5-ARD: “penis
at twelve”). Like CAIS and PAIS, puberty will often show first symptoms of 5-ARD,
leading to an eventual diagnosis.
Why is this relevant for
transsexualism? In humans affected by
CAIS, PAIS and 5-ARD, nature gives us three groups of people we can
observe to further our understanding of gender identity. Many 46,XY males with
female-looking genitalia at birth are raised as girls. In such cases, neither
parents nor the individuals themselves would have reason to suspect any disorder
of sex development. After all, the child is a girl, like all other girls. At
puberty, things change. When the first symptoms arise, the girl is taken to a
doctor, and eventually diagnosed with 46,XY with CAIS, PAIS or 5-ARD. What
happens then?
Even though they are genetic males, girls with
CAIS have a female gender identity. They feel female, they
look female, and society fully accepts them as females, without any
discrimination. They continue to live their lifes as normal women.
Individuals with 5-ARD
typically have a different outcome. A large part (up to 70 %) of 5-ARD patients
raised as girls will experience gender dysphoria and transition to a male
gender role at puberty. Children raised as males will typically retain their gender
identity.
With PAIS, the outcome is
different again. Individuals with PAIS are either raised male or female,
depending on the appearance of their genitalia (which gives a fair indication
of how severely the androgen processing is impeded). The majority of PAIS-patients
continue to live in their assigned gender role as either women or men, some (≈25
%) experience gender dysphoria at puberty or later in life and switch gender
roles.
And
now the sticking point:
This is exactly what we expect if the
hypothesis of sex hormones shaping the brains’s gender identity before and
around birth is true.
Without any experiments, without any deep
and complex analysis, we can observe how nature works. With CAIS, the failure
of the cells to respond to androgens leads to a female gender identity. With
PAIS, the results are mixed, with some individuals forming a female, others
forming a male gender identity. 5-ARD mainly affects the genitals, and does not
stop the brain being masculinised by androgens – hence the male gender identity
of the persons affected.
Here you have male-to-female transsexualism
explained:
Genetic males can have a female gender
identity, and the development of gender identity is not tied to the development
of the genitalia.
As shown by these examples of some
disorders of sex development, natural processes can cause gender identity to
develop out of alignment with sex chromosomes or the genitals. The resulting
gender identity is not a mental illness, not a paraphilia, not a
psychopathological problem and nothing to feel shame about. It results from the
same processes that form gender identity in every human – gender dysphoric or
not.
Postscript: Oh, and what kind of medical treatment do CAIS girls get? Removal
of the testicles (gonadectomy), estrogen hormone therapy, surgical correction
of the genitals, if necessary. Plus psychological help if required. All of that
without blaming and shaming, without judgement and gatekeeping, without long
waiting periods, paid for by health insurance, fully accepted by society, and
nobody bats an eye. This is wonderful, and exactly how it should be. When will
it be the same for transsexuals?
Post-postscript: And another point – I’m not aware of any religious groups
criticizing the “lifestyle” or “ideology” of CAIS women. Neither do they
command PAIS or 5-ARD individuals what gender role they have to live in. Why is that different for
transsexuals?
Congenital adrenal hyperplasia (CAH)
“When a Woman is not a Woman: Problems and perspectives of Congenital Adrenal Hyperplasia”
To provide evidence for the observations
above, a number of scientific studies are listed. Please have a browse.
I very much appreciate corrections,
amendments and additions.
All abstracts are taken verbatim from the
respective studies, only the highlighting is mine. To avoid distorting the
studies, the included abstracts are full-length, even if some parts are not
relevant to the observation detailed in the chapter. Please read the original
studies for more information; often the contents are even more interesting than
the carefully worded abstract. Some studies are listed twice to illustrate
separate points. I tried to provide mainly recently published and peer-reviewed
studies and avoided case studies with few participants.
I would like to express my gratitude to all
researchers and contributors to human biology and medicine – your work is
continuously making this world a much better place for all of us. Thank you so
much!
Gender experience and satisfaction with gender allocation
in adults with diverse intersex conditions (divergences of sex development,
DSD)
-
The aims of this mixed-methods
study were to: (1) describe the gender experience and level of satisfaction
with gender allocation of intersex persons and (2) explore the spectrum of
their gender identities. Of the 69 participants with a number of divergences of
sex development (DSD), gender allocation at birth was female in 83% and male in
17%. Seventy-five per cent were satisfied with
gender allocation. As adults, 81% lived in the female gender role, 12% in the
male role and 7% chose other roles. Nine per cent reported gender change or
reallocation. Twenty-four per cent reported an inclusive ‘mixed’ two-gender
identity, including both male and female elements, and 3% reported a neither
female nor male gender identity. Twenty-six per cent were highly uncertain
about belonging to a specific gender, 14% received increased transgender scores
on the gender identity questionnaire (GIQ). The dichotomous
categorisation of gender fails to capture the gender experiences of a
significant proportion of our participants. Uncertainty of belonging to the
female or male gender category as well as non-binary identifications highlight
the need for alternative gender categories. A reconsideration of the medical
approach towards intersexuality, which is currently based on a binary
categorisation, is discussed.
Author/-s: Katinka
Schweizer; Franziska Brunner; Christina Handford; Hertha Richter-Appelt
Publication: Psychology
& Sexuality, 2014
Web link: http://www.tandfonline.com/doi/abs/10.1080/19419899.2013.831216#.Uv-VP02YZhF
The effect of 5α-reductase-2 deficiency on human fertility
-
A most interesting and
intriguing male disorder of sexual differentiation is due to 5α-reductase-2
isoenzyme deficiency. These male infants are born with ambiguous external
genitalia due to a deficiency in their ability to catalyze the conversion of T
to dihydrotestosterone. Dihydrotestosterone is a potent androgen responsible
for differentiation of the urogenital sinus and genital tubercle into the
external genitalia, urethra, and prostate. Affected males are born with a
clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch
from incomplete closure of the urogenital sinus, and a rudimentary prostate. At puberty, the surge in mainly T production prompts
virilization, causing most boys to choose gender reassignment to male.
Fertility is a challenge for affected men for several reasons. Uncorrected
cryptorchidism is associated with low sperm production, and there is evidence
of defective transformation of spermatogonia into spermatocytes. The
underdeveloped prostate and consequent low semen volumes affect sperm
transport. In addition, semen may not liquefy due to a lack of
prostate-specific antigen. In the present review, we discuss the 5α-reductase-2
deficiency syndrome and its impact on human fertility.
Author/-s: Hey-Joo
Kang; Julianne Imperato-McGinley; Yuan-Shan Zhu; Zev Rosenwaks
Publication: Fertility
and Sterility, 2014
Web link: http://www.fertstert.org/article/S0015-0282(13)03388-8/abstract
Clinical and Laboratorial Features That May Differentiate
46,XY DSD due to Partial Androgen Insensitivity and 5α-Reductase Type 2
Deficiency
-
Abstract: The aim of this study was to search for clinical and laboratorial
data in 46,XY patients with ambiguous genitalia (AG) and normal testosterone
(T) synthesis that could help to distinguish partial androgen insensitivity syndrome
(PAIS) from 5α-reductase type 2 deficiency (5α-RD2) and from cases without
molecular defects in the AR and SRD5A2 genes. Fifty-eight patients (51
families) were included. Age at first evaluation, weight and height at birth,
consanguinity, familial recurrence, severity of AG, penile length, LH, FSH, T,
dihydrotestosterone (DHT), Δ4-androstenedione (Δ4), and T/DHT and T/Δ4 ratios
were evaluated. The AR and SRD5A2 genes were sequenced in all cases. There were
9 cases (7 families) of 5α-RD2, 10 cases (5 families) of PAIS, and 39 patients
had normal molecular analysis of SRD5A2 and AR genes. Age at first evaluation,
birth weight and height, and T/DHT ratio were lower in the undetermined group,
while penile length was higher in this group. Consanguinity was more frequent
and severity of AG was higher in 5α-RD2 patients. Familial recurrence was more
frequent in PAIS patients. Birth weight and height, consanguinity, familial
recurrence, severity of AG, penile length, and T/DHT ratio may help the
investigation of 46,XY patients with AG and normal T synthesis.
-
Discussion (excerpt): […] The differential diagnosis of
PAIS and 5α-reductase type 2 deficiency should be established as soon as
possible because individuals with PAIS are usually recommended to be raised as
females, whereas those with 5α-reductase type 2 deficiency as males, when the
diagnosis is made early in childhood.
A correct and early diagnosis is very important
because as a result of pre- and/or postnatal brain exposure to androgens,
almost 70 % of individuals with 5α-reductase type 2 deficiency and 46,XY
karyotype raised as girls develop a male gender identity and change the gender
behavior in adolescence or early adulthood. The degree of external genital
masculinization at birth does not seem to be related to gender role changes.
[…]
Author/-s: Nélio
Neves Veiga-Junior; Pedro Augusto Rodrigues Medaets; Reginaldo José Petroli; Flávia
Leme Calais; Maricilda Palandi de Mello; Carla Cristina Telles de Sousa Castro;
Guilherme Guaragna-Filho; Letícia Espósito Sewaybricker; Antonia Paula
Marques-de-Faria; Andréa Trevas Maciel-Guerra; Gil Guerra-Junior
Publication: International
Journal of Endocrinology, 2012
Web link: http://www.hindawi.com/journals/ije/2012/964876/
DSD due to 5α-reductase 2 deficiency – from diagnosis to
long term outcome
-
Most of the patients with 5α-RD 2 deficiency are reared in the
female social sex due to their severely undervirilized external genitalia but ≈60 %
who have not been submitted to orchiectomy in childhood undergo male social sex
change at puberty. In our cohort of 30 cases
from 18 families, all subjects were registered in the female social sex except
for two children-one who had an affected uncle and the other who was diagnosed
before being registered. The majority of the patients were satisfied with the
long-term results of their treatment and surprisingly, penile length was not
associated with satisfactory or unsatisfactory sexual activity. Steroid 5α-RD2 deficiency should be included in the
differential diagnosis of all newborns with 46,XY DSD with normal testosterone
production before gender assignment or any surgical intervention because these
patients should be considered males at birth.
Author/-s: E.
M. Costa; S. Domenice; M. H. Sircili; M. Inacio; B. B. Mendonca
Publication: Seminars
in reproductive medicine, 2012
Web link: http://www.ncbi.nlm.nih.gov/pubmed/23044880
Gender dysphoria associated with disorders of sex
development
-
Disorders of sex development
(DSDs) are estimated to be prevalent in 0.1-2% of the global population,
although these figures are unlikely to adequately represent non-white patients
as they are largely based on studies performed in Europe and the USA. Possible
causes of DSDs include disruptions to gene expression and regulation-processes
that are considered essential for the development of testes and ovaries in the
embryo. Gender dysphoria generally affects between 8.5-20% of individuals with
DSDs, depending on the type of DSD. Patients with simple virilizing congenital
adrenal hyperplasia (CAH), as well as those with CAH and severe virilization,
are less likely to have psychosexual disorders than patients with other types
of DSD. Early surgery seems to be a safe option for most of these patients.
Male sex assignment is an appropriate alternative in patients with Prader IV or
V DSDs. Patients with 5α-reductase 2 (5α-RD2) and
17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiencies exhibit the highest
rates of gender dysphoria (incidence of up to 63%). Disorders such as
ovotesticular DSD and mixed gonadal dysgenesis are relatively rare and it can
be difficult to conclusively evaluate patients with these conditions. For all
DSDs, it is important that investigators and authors conform to the same
nomenclature and definitions to ensure that data can be reliably analysed.
Author/-s: P.
S. Furtado; F. Moraes, R. Lago; L. O. Barros; M. B. Toralles; U. Barroso Jr.
Publication: Nature
reviews. Urology., 2012
Web link: http://www.ncbi.nlm.nih.gov/pubmed/23045263
Gender Identity and Sex-of-rearing in Children with
Disorders of Sexual Differentiation
-
Aim: To compare declared sexual identity to sex-of-rearing in
individuals with disorders of sexual differentiation.
-
Methods: All 84 patients > or =5 years old in a pediatric psychosexual
development clinic were assessed for sex-of-rearing and sexual identity.
Diagnoses included 1) male-typical prenatal androgen effects but an absent or
severely inadequate penis - 45 patients with cloacal exstrophy or aphallia; 2)
inadequate prenatal androgens and a Y-chromosome - 28 patients with partial
androgen insensitivity (pAIS), mixed gonadal dysgenesis (MGD), hermaphroditism,
or craniofacial anomalies with genital ambiguity; 3) inappropriate prenatal
androgen effects and a 46,XX karyotype - 11 patients with congenital adrenal
hyperplasia (CAH).
-
Results: Of 73 patients with disordered sexual differentiation and a
Y-chromosome, 60 were reared female; 26 of the 60 (43%) declared female
identity while 32 (53%) declared male identity including 18 (55%) with cloacal
exstrophy, six (55%) with MGD, four (40%) with pAIS, one (50%) with aphallia,
one (100%) with hermaphroditism, and two (67%) with craniofacial anomalies; two
(3%) declined to discuss identity. Nine of 11 patients with CAH and a 46,XX
karyotype were reared female and two reared male; six (55%) declared female
identity and five (45%) declared male identity. Of 84 total patients, 69 were
reared female, but only 32 lived as female, while 29 lived as male; four
patients refused to discuss sex-of-living; parents of four patients rejected
their declarations of male identity. All 15 patients reared male lived as male
including two genetic females.
-
Conclusion: Active prenatal androgen effects
appeared to dramatically increase the likelihood of recognition of male sexual
identity independent of sex-of-rearing. Genetic males with male-typical
prenatal androgen effects should be reared male.
Author/-s: W.
G. Reiner
Publication: Journal
of Pediatric Endocrinology and Metabolism, 2011
Web link: http://www.degruyter.com/view/j/jpem.2005.18.6/jpem.2005.18.6.549/jpem.2005.18.6.549.xml
Practical approach to steroid 5alpha-reductase type 2
deficiency
-
The aim of this article is to
review the literature on steroid 5alpha-reductase type 2 deficiency (5α-RD2) to
provide clinicians with information to guide their management of patients with
this disorder. The 5alpha-reductase type 2 is encoded by the 5alpha-reductase
type 2 gene (SRD5A2) on chromosome 2 and is predominantly expressed in external
genital tissues and the prostate. Mutations of the SRD5A2 gene leads to an
uncommon autosomal recessive disorder affecting sexual differentiation in
individuals with 46,XY karyotype; their phenotype can range from almost normal
female structures to a distinct male phenotype with ambiguous genitalia at
birth. These phenotypes result from impaired conversion of testosterone to
dihydrotestosterone due to mutations in the SRD5A2 gene. Patients exhibit virilization at puberty without breast
development, which is often accompanied by gender identity change from female
to male. More than 40 mutations have been reported in all five exons of
the SRD5A2 gene. Phenotype-genotype correlations for 5α-RD2 have not been well
established. The newborn phenotypes of male pseudohermaphrodites with 5α-RD2,
partial androgen insensitivity syndrome (PAIS), or 17β-hydroxysteroid
dehydrogenase type 3 (17β-HSD3) enzyme deficiency may be indistinguishable. We
conclude that steroid 5α-RD2 should be included in the differential diagnosis
of newborns with 46,XY DSD. It is important that
the diagnosis be made in infancy by biochemical and molecular studies before
gender assignment or any surgical intervention because these patients should be
considered males at birth.
Author/-s: Chong
Kun Cheon
Publication: European
Journal of Pediatrics, 2011
Web link: http://www.ncbi.nlm.nih.gov/pubmed/20349245
46,XY DSD with Female or Ambiguous External Genitalia at
Birth due to Androgen Insensitivity Syndrome, 5α-Reductase-2 Deficiency, or
17β-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life
Outcomes
-
Abstract: Disorders of sex development refer to a collection of congenital
conditions in which atypical development of chromosomal, gonadal, or anatomic
sex occurs. Studies of 46,XY DSD have focused largely on gender identity,
gender role, and sexual orientation. Few studies have focused on other domains,
such as physical and mental health, that may contribute to a person’s quality
of life. The current review focuses on information published since 1955
pertaining to psychological well-being, cognition, general health, fertility,
and sexual function in people affected by androgen insensitivity syndromes, 5-α
reductase-2 deficiency, or 17β-hydroxysteroid dehydrogenase-3 deficiency—reared
male or female. The complete form of androgen insensitivity syndrome has been
the focus of the largest number of investigations in domains other than gender.
Despite this, all of the conditions included in the current review are
under-studied. Realms identified for further study include psychological
well-being, cognitive abilities, general health, fertility, and sexual
function. Such investigations would not only improve the quality of life for
those affected by DSD but may also provide information for improving physical
and mental health in the general population.
-
Summary and Conclusions
(excerpt): […] Possibly,
greater emphasis has been placed on studying CAIS apart from gender because
female rearing in this particular DSD is undisputed. In contrast, male or
female rearing occurs in people affected by PAIS, 5α-RD-2, and 17β-HSD-3
deficiencies. […] In conditions in which
GI/R does not always develop in concordance with sex of rearing—such as PAIS,
5α-RD-2 deficiency, and 17β-HSD-3 deficiency—a better understanding of factors
that influence QoL may help to explain the developmental trajectory of GI/R in
people for whom GI/R development does not match their initial gender assignment.
[…]
Author/-s: Amy
B. Wisniewski; Tom Mazur
Publication: International
Journal of Pediatric Endocrinology, 2009
Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777017/
Gender identity of children and young adults with
5alpha-reductase deficiency
-
Male pseudohermaphroditism
(46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last
few decades. There is scant literature on this entity in India. We compiled
data on five patients with this disorder. Four of
our five patients were reared as females. Our assessment of these children
reveals that they had male gender identity from childhood. Three of the four
reared as females chose to change gender role at adolescence, while the fourth
is still prepubertal. We conclude that all these patients had male gender
identity from early childhood. The parents took note of this only after
the appearance of male secondary sexual characteristics at puberty, thereby
giving an impression of change in gender identity and gender role.
Author/-s: E.
P. Praveen; A. K. Desai; M. L. Khurana; J. Philip; M. Eunice; R. Khadgawat; B. Kulshreshtha;
K. Kucheria; D. K. Gupta; A. Seith; A. C. Ammini
Publication: Journal
of pediatric endocrinology & metabolism: JPEM, 2008
Web link: http://www.ncbi.nlm.nih.gov/pubmed/18422030
Consensus statement on management of intersex disorders
-
Gender assignment in
newborn infants (excerpt): […] More than 90 % of 46,XX CAH patients and all 46,XY
CAIS assigned females in infancy identify as females. Evidence supports the
current recommendation to raise markedly virilised 46,XX infants with CAH as
female. Approximately 60 % of 5α‐reductase (5αRD2) deficient patients
assigned female in infancy and virilising at puberty (and all assigned male)
live as males. In 5αRD2 and possibly 17β‐hydroxysteroid dehydrogenase (17βHSD3)
deficiencies, where the diagnosis is made in infancy, the combination of a male
gender identity in the majority and the potential for fertility (documented in
5αRD2, but unknown in 17βHSD3) should be discussed when providing evidence for
gender assignment. Among patients with PAIS, androgen biosynthetic defects, and
incomplete gonadal dysgenesis, there is dissatisfaction with the sex of rearing
in about 25 % of individuals, whether raised male or female. […]
Author/-s: I.
A. Hughes; C. Houk; S. F. Ahmed; P. A. Lee; et al.
Publication: Archives
of Disease in Childhood, 2006
Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082839/
Consensus Statement on Management of Intersex Disorders
-
Gender Assignment in
Newborns (excerpt): […] More than 90 % of patients with 46,XX CAH and all
patients with 46,XY CAIS assigned female in infancy identify as females.
Evidence supports the current recommendation to raise markedly virilized 46,XX
infants with CAH as female. Approximately 60 % of 5-α-reductase
(5αRD2)-deficient patients assigned female in infancy and virilizing at puberty
(and all assigned male) live as males. In 5αRD2 and possibly 17β-hydroxysteroid
dehydrogenase deficiencies, for which the diagnosis is made in infancy, the
combination of a male gender identity in the majority and the potential for
fertility (documented in 5αRD2 but unknown in 17β-hydroxysteroid dehydrogenase
deficiencies) should be discussed when providing evidence for gender
assignment. Among patients with partial androgen insensitivity syndrome (PAIS),
androgen biosynthetic defects, and incomplete gonadal dysgenesis, there is
dissatisfaction with the sex of rearing in ≈25 % of individuals whether
raised male or female. […]
Author/-s: Peter
A. Lee; Christopher P. Houk; S. Faisal Ahmed; Ieuan A. Hughes
Publication: Pediatrics,
2006
Web link: http://pediatrics.aappublications.org/content/118/2/e488.long
Gender change in 46,XY persons with 5alpha-reductase-2
deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency
-
Individuals
with 5alpha-reductase-2 deficiency (5alpha-RD-2) and 17beta-hydroxysteroid
dehydrogenase-3 deficiency (17beta-HSD-3) are often raised as girls. Over the
past number of years, this policy has been challenged because many individuals
with these conditions develop a male gender identity and make a gender role
change after puberty. The findings also raised doubts regarding the
hypothesis that children are psychosexually neutral at birth and emphasized the
potential role of prenatal brain exposure to androgens in gender development.
If prenatal exposure to androgens is a major contributor to gender identity
development, one would expect that all, or nearly all, affected individuals,
even when raised as girls, would develop a male gender identity and make a
gender role switch later in life. However, an estimation of the prevalence of
gender role changes, based on the current literature, shows that gender role
changes occur frequently, but not invariably. Gender
role changes were reported in 56–63 % of cases with 5alpha-RD-2 and 39–64 %
of cases with 17beta-HSD-3 who were raised as girls. The changes were
usually made in adolescence and early adulthood. In these two syndromes, the
degree of external genital masculinization at birth does not seem to be related
to gender role changes in a systematic way.
Author/-s: Peggy
T. Cohen-Kettenis
Publication: Archives
of sexual behaviour, 2005
Web link: http://www.ncbi.nlm.nih.gov/pubmed/16010463
Gender dysphoria and gender change in androgen
insensitivity or micropenis
-
This review article answers
three questions relevant to the medical management and care of individuals born
with complete androgen insensitivity syndrome (CAIS), partial androgen
insensitivity syndrome (PAIS), or a micropenis: (1) Do any of these individuals
reassign themselves from their initial gender assignment? (2) Do more reassign
than the ones who do not? (3) Is there evidence of gender dysphoria in those
who do not self-initiate reassignment? Reviewed were all articles on CAIS,
PAIS, and micropenis cited in K. J. Zucker (1999) plus articles published
through 2004. There were no documented cases of
gender change in individuals with CAIS (N= 156 females) or micropenis (N= 89:
79 males, 10 females). Nine (9.1%) out of 99 individuals with PAIS changed
gender. Thus, self-initiated gender reassignment was rare. Gender
dysphoria also appears to be a rare occurrence. The best predictor of adult
gender identity in CAIS, PAIS, and micropenis is initial gender assignment.
Author/-s: Tom
Mazur
Publication: Archives
of sexual behavior, 2005
Web link: http://www.ncbi.nlm.nih.gov/pubmed/16010464
Gender identity and sex-of-rearing in children with
disorders of sexual differentiation
-
Aim: To compare declared sexual identity to sex-of-rearing in
individuals with disorders of sexual differentiation.
-
Methods: All 84 patients > or =5 years old in a pediatric psychosexual
development clinic were assessed for sex-of-rearing and sexual identity.
Diagnoses included 1) male-typical prenatal androgen effects but an absent or
severely inadequate penis - 45 patients with cloacal exstrophy or aphallia; 2)
inadequate prenatal androgens and a Y-chromosome - 28 patients with partial
androgen insensitivity (pAIS), mixed gonadal dysgenesis (MGD), hermaphroditism,
or craniofacial anomalies with genital ambiguity; 3) inappropriate prenatal
androgen effects and a 46,XX karyotype - 11 patients with congenital adrenal
hyperplasia (CAH).
-
Results: Of 73 patients with disordered sexual
differentiation and a Y-chromosome, 60 were reared female; 26 of the 60 (43%)
declared female identity while 32 (53%) declared male identity including 18
(55%) with cloacal exstrophy, six (55%) with MGD, four (40%) with pAIS, one
(50%) with aphallia, one (100%) with hermaphroditism, and two (67%) with
craniofacial anomalies; two (3%) declined to discuss identity. Nine of
11 patients with CAH and a 46,XX karyotype were reared female and two reared
male; six (55%) declared female identity and five (45%) declared male identity.
Of 84 total patients, 69 were reared female, but only 32 lived as female, while
29 lived as male; four patients refused to discuss sex-of-living; parents of
four patients rejected their declarations of male identity. All 15 patients
reared male lived as male including two genetic females.
-
Conclusion: Active prenatal androgen effects
appeared to dramatically increase the likelihood of recognition of male sexual
identity independent of sex-of-rearing. Genetic males with male-typical
prenatal androgen effects should be reared male.
Author/-s: W.
G. Reiner
Publication: Journal
of pediatric endocrinology & metabolism: JPEM, 2005
Web link: http://www.ncbi.nlm.nih.gov/pubmed/16042322
Concordance of phenotypic expression and gender identity
in a large kindred with a mutation in the androgen receptor
-
A 14-year-old female
presented to the Pediatric Endocrine Clinic, Universidade Federal o Parana
Curitiba, Brazil, for obesity. A few years later, despite normal breast
development, the patient had failed to menstruate and lacked pubic and axillary
hair. Laboratory analyses revealed high levels of testosterone. Karyotype
analysis was XY. Direct sequencing of her genomic DNA showed a G to T
transition at nucleotide 2089 at exon 2 in the androgen receptor gene,
resulting in a substitution of Phe for Cys at position 576. This mutation disrupts
the first Zn finger critical to DNA binding and transcriptional activity and
results in complete androgen-insensitivity syndrome (CAIS). This individual was
part of 700-member multigenerational kindred of German origin living in small
villages in Southern Brazil. Family members who gave informed consent were
screened using a polymerase chain reaction-based method. Nineteen CAIS-affected
individuals and carriers were identified. All presented with infertility and
lack of or sparse pubic hair. The prevalence of common AIS within the kindred
greatly exceeds that of the general population and is due in part to their
isolated familial and community structures. All
individuals are genuinely feminine in their appearance, sex behavior, gender
identity, and integration within their communities. We conclude that CAIS leads
to complete feminization of XY individuals and results in individuals who are
psychologically and socially established and integrated as women within the
familial and cultural contexts of their communities.
Author/-s: H.
T. Hooper; B. C. Figueiredo; C. C. Pavan-Senn; L. de Lacerda; R. Sandrini; J.
K. Mengarelli; K. Japp; L. P. Karaviti
Publication: Clinical genetics,
2004
Web link: http://onlinelibrary.wiley.com/doi/10.1111/j.0009-9163.2004.00197.x/abstract
Discordant Sexual Identity in Some Genetic Males with
Cloacal Exstrophy Assigned to Female Sex at Birth
-
Background: Cloacal exstrophy is a rare, complex defect of the entire pelvis
and its contents that occurs during embryogenesis and is associated with severe
phallic inadequacy or phallic absence in genetic males. For about 25 years,
neonatal assignment to female sex has been advocated for affected males to
overcome the issue of phallic inadequacy, but data on outcome remain sparse.
-
Methods: We assessed all 16 genetic males in our cloacal-exstrophy clinic at
the ages of 5 to 16 years. Fourteen underwent neonatal assignment to female sex
socially, legally, and surgically; the parents of the remaining two refused to
do so. Detailed questionnaires extensively evaluated the development of sexual
role and identity, as defined by the subjects' persistent declarations of their
sex.
-
Results: Eight of the 14 subjects assigned to
female sex declared themselves male during the course of this study, whereas
the 2 raised as males remained male. Subjects could be grouped according to
their stated sexual identity. Five subjects were living as females; three were
living with unclear sexual identity, although two of the three had declared
themselves male; and eight were living as males, six of whom had reassigned
themselves to male sex. All 16 subjects had moderate-to-marked interests and
attitudes that were considered typical of males. Follow-up ranged from
34 to 98 months.
-
Conclusions: Routine neonatal assignment of
genetic males to female sex because of severe phallic inadequacy can result in
unpredictable sexual identification. Clinical interventions in such
children should be reexamined in the light of these findings.
Author/-s: William
G. Reiner; John P. Gearhart
Publication: New
England Journal of Medicine, 2004
Web link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421517/
Psychological Outcomes and Gender-Related Development in
Complete Androgen Insensitivity Syndrome
-
We evaluated psychological
outcomes and gender development in 22 women with complete androgen
insensitivity syndrome (CAIS). Participants were recruited through a medical
database (n = 10) or through a patient support group (n = 12). Controls
included 14 males and 33 females, of whom 22 were matched to women with CAIS
for age, race, and sex-of-rearing. Outcome measures included quality of life
(self-esteem and psychological general well-being), gender-related
psychological characteristics (gender identity, sexual orientation, and gender
role behavior in childhood and adulthood), marital status, personality traits
that show sex differences, and hand preferences. Women
recruited through the database versus the support group did not differ
systematically, and there were no statistically significant differences between
the 22 women with CAIS and the matched controls for any psychological outcome.
These findings argue against the need for two X chromosomes or ovaries to
determine feminine-typical psychological development in humans and reinforce
the important role of the androgen receptor in influencing masculine-typical
psychological development. They also suggest that psychological outcomes in
women with CAIS are similar to those in other women. However, additional
attention to more detailed aspects of psychological well-being in CAIS is
needed.
Author/-s: Melissa
Hines; S. Faisal Ahmed; Ieuan A. Hughes
Publication: Archives
of Sexual Behavior, 2003
Web link: http://link.springer.com/article/10.1023%2FA%3A1022492106974
Androgens and male physiology the syndrome of
5alpha-reductase-2 deficiency
-
Dihydrotestosterone (DHT), a
potent androgen, is converted from testosterone by 5alpha-reductase isozymes.
There are two 5alpha-reductase isozymes, type 1 and type 2 in humans and
animals. These two isozymes have differential biochemical and molecular features.
Mutations in type 2 isozyme cause male pseudohermaphroditism, and many
mutations have been reported from various ethnic groups. The affected 46XY
individuals have high normal to elevated plasma testosterone levels with
decreased DHT levels and elevated testosterone/DHT ratios. They have ambiguous external genitalia at birth so that
they are believed to be girls and are often raised as such. However,
Wolffian differentiation occurs normally and they have epididymides, vas
deferens and seminal vesicles. Virilization
occurs at puberty frequently with a gender role change. The prostate in
adulthood is small and rudimentary, and facial and body hair is absent or
decreased. Balding has not been reported. Spermatogenesis is normal if the
testes are descended. The clinical, biochemical and molecular genetic analyses
of 5alpha-reductase-2 deficiency highlight the significance of DHT in male
sexual differentiation and male pathophysiology.
Author/-s: J.
Imperato-McGinley; Y. S. Zhu
Publication: Molecular
and cellular endocrinology, 2002
Web link: http://www.ncbi.nlm.nih.gov/pubmed/12573814
Long-term perspectives for 46,XY patients affected by
complete androgen insensitivity syndrome or congenital micropenis
-
Controversy concerning optimal
treatment for individuals affected by syndromes of abnormal sex differentiation
can best be resolved with knowledge about long-term medical, surgical, and
psychosexual outcomes of patients. Follow-up information has recently been
gathered on older cohorts of the following patient groups: (1) those affected
by complete androgen insensitivity syndrome (CAIS) raised female and (2) those
affected by congenital micropenis raised male or female. As a group, women with CAIS were satisfied with their
female gender and sexual function. However, a need for better patient
education was identified for this specific population. Most patients with
congenital micropenis, whether raised male or female, were satisfied with their
gender. Regardless of sex of rearing, dissatisfaction with the appearance and
function of the genitalia as judged by both physicians and subjects was
evident. For patients with congenital micropenis, male sex of rearing was
concluded to be optimal because genital reconstructive surgery is not required
with this choice.
Author/-s: A.
B. Wisniewski; C. J. Migeon
Publication: Seminars
in reproductive medicine, 2002
Web link: http://www.ncbi.nlm.nih.gov/pubmed/12428209
The Postnatal Gonadotropin and Sex Steroid Surge – Insights
from the Androgen Insensitivity Syndrome
Author/-s: Charmian
A. Quigley
Publication: The
Journal of Clinical Endocrinology & Metabolism, 2002
Web link: http://press.endocrine.org/doi/full/10.1210/jcem.87.1.8265
Complete Androgen Insensitivity Syndrome: Long-Term
Medical, Surgical, and Psychosexual Outcome
-
Controversy concerning the most
appropriate treatment guidelines for intersex children currently exists. This
is due to a lack of long-term information regarding medical, surgical, and
psychosexual outcome in affected adults. We have assessed by questionnaire and
medical examination the physical and psychosexual status of 14 women with
documented complete androgen insensitivity syndrome (CAIS). We have also
determined participant knowledge of CAIS as well as opinion of medical and
surgical treatment. As a whole, secondary sexual development of these women was
satisfactory, as judged by both participants and physicians. In general, most women were satisfied with their
psychosexual development and sexual function. Factors reported to
contribute to dissatisfaction were sexual abuse in one case and marked obesity
in another. All of the women who participated
were satisfied with having been raised as females, and none desired a gender
reassignment. Although not perfect, the medical, surgical, and
psychosexual outcomes for women with CAIS were satisfactory; however, specific
ways for improving long-term treatment of this population were identified.
Author/-s: Amy
B. Wisniewski, Claude J. Migeon, Heino F. L. Meyer-Bahlburg, John P. Gearhart,
Gary D. Berkovitz, Terry R. Brown and John Money
Publication: The
Journal of Clinical Endocrinology & Metabolism, 2000
Web link: http://press.endocrine.org/doi/abs/10.1210/jcem.85.8.6742
Long-Term Psychological Evaluation of Intersex Children
-
Treatment of psychological
problems of 59 children with a physical intersex condition is described. The
group consisted of 18 female pseudohermaphrodites with congenital adrenal
hyperplasia (CAH), 20 male pseudohermaphrodites and 2 true hermaphrodites born
with ambiguous external genitalia assigned the female sex (ambiguous girls), 14
male pseudohermaphrodites born with completely female external genitalia and
assigned the female sex (completely female group), and 5 male
pseudohermaphrodites born with ambiguous external genitalia and assigned the
male sex. Despite the sex assignment, genital
organ correction soon after birth, psychological counseling of parents and
intensive psychotherapy of the children, general psychopathology developed
equally in all 4 groups (39% of total group). Although 87% of the girls with a
physical intersex condition developed in line with the assigned sex, 13%
developed a gender identity disorder though only 1 girl (2%) failed to accept
the assigned sex. Gender identity disorder and deviant gender role were in
evidence only in girls with CAH and girls of the ambiguous group. Biological
and social factors seem responsible for the development of gender identity
disorder, such as pre- and postnatal hormonal influences on the brain enabling
deviant gender role behavior to develop, and an inability on the part of
parents to accept the sex assignment. A reconsideration of the sex
assignment in male pseudohermaphrodites and true hermaphrodites born with
ambiguous external genitalia is discussed.
Author/-s: Froukje
M. E. Slijper; Stenvert L. S. Drop
Publication: Archives
of Sexual Behavior, 1998
Web link: http://link.springer.com/article/10.1023%2FA%3A1018670129611
Androgens and the evolution of male-gender identity among
male pseudohermaphrodites with 5alpha-reductase deficiency
-
To determine the contribution
of androgens to the formation of male-gender identity, we studied male
pseudohermaphrodites who had decreased dihydrotestosterone production due to 5
alpha-reductase deficiency. These subjects were born with female-appearing
external genitalia and were raised as girls. They have plasma testosterone
levels in the high normal range, show an excellent response to testosterone and
are unique models for evaluating the effect of testosterone, as compared with a
female upbringing, in determining gender identity. Eighteen of 38 affected subjects were unambiguously
raised as girls, yet during or after puberty, 17 of 18 changed to a male-gender
identity and 16 of 18 to a male-gender role. Thus, exposure of the brain to
normal levels of testosterone in utero, neonatally and at puberty appears to
contribute substantially to the formation of male-gender identity. These subjects
demonstrate that in the absence of sociocultural factors that could interrupt
the natural sequence of events, the effect of testosterone predominates,
over-riding the effect of rearing as girls.
Author/-s: J.
Imperato-McGinley; R. E. Peterson; T. Gautier; E. Sturla
Publication: The
New England journal of medicine, 1979
Web link: http://www.ncbi.nlm.nih.gov/pubmed/431680
|
|