ArticlePDF AvailableLiterature Review

Abstract

Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater patient autonomy, and improved understanding of the benefits and limitations of current treatment modalities. Expected final online publication date for the Annual Review of Clinical Psychology Volume 12 is March 28, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
CP12CH09-Zucker ARI 24 February 2016 11:49
Gender Dysphoria in Adults
Kenneth J. Zucker,1,Anne A. Lawrence,2
and Baudewijntje P.C. Kreukels3
1Gender Identity Clinic, Child, Youth, and Family Services, Centre for Addiction and Mental
Health and Department of Psychiatry, University of Toronto, Toronto, Ontario M5T 1R8,
Canada; email: ken.zucker@utoronto.ca
2Department of Psychology, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
3Department of Medical Psychology, VU University Medical Center and EMGO Institute for
Health and Care Research, Amsterdam 1081 HV, The Netherlands
Annu. Rev. Clin. Psychol. 2016. 12:217–47
First published online as a Review in Advance on
January 18, 2016
The Annual Review of Clinical Psychology is online at
clinpsy.annualreviews.org
This article’s doi:
10.1146/annurev-clinpsy-021815-093034
Copyright c
2016 by Annual Reviews.
All rights reserved
Corresponding author
Keywords
gender dysphoria, gender identity disorder, transsexualism, causal
mechanisms, treatment
Abstract
Gender dysphoria (GD), a term that denotes persistent discomfort with one’s
biologic sex or assigned gender, replaced the diagnosis of gender identity
disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013.
Subtypes of GD in adults, defined by sexual orientation and age of onset,
have been described; these display different developmental trajectories and
prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult
natal males and 1 in 30,000 adult natal females experience GD, but such
estimates vary widely. GD in adults is associated with an elevated prevalence
of comorbid psychopathology, especially mood disorders, anxiety disorders,
and suicidality. Causal mechanisms in GD are incompletely understood,
but genetic, neurodevelopmental, and psychosocial factors probably all con-
tribute. Treatment of GD in adults, although largely standardized, is likely
to evolve in response to the increasing diversity of persons seeking treat-
ment, demands for greater client autonomy, and improved understanding of
the benefits and limitations of current treatment modalities.
217
Click here to view this article's
online features:
• Download figures as PPT slides
• Navigate linked references
• Download citations
• Explore related articles
• Search keywords
ANNUAL
REVIEWS
Further
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Contents
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
TERMINOLOGYAND PHENOMENOLOGY.................................. 219
Developmental Trajectories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
EPIDEMIOLOGY................................................................ 221
Prevalence and Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
SexRatio....................................................................... 222
DIAGNOSIS..................................................................... 223
Placementin theNomenclature................................................. 223
SubstantiveChanges inthe DSM-5.............................................. 223
GenderDysphoria andthe ICD-11.............................................. 224
ASSESSMENT................................................................... 225
Psychological Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Biological Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
ASSOCIATED PSYCHOPATHOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Increased Prevalence of Associated Psychopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Studies that Find Little or No Increased Prevalence
of Associated Psychopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Self-Report Measures of Associated Psychological Symptoms . . . . . . . . . . . . . . . . . . . . . 229
Increased Prevalence of Suicidality and Self-Harm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Explanations of Associated Psychopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
CAUSALMECHANISMS ........................................................ 230
Biological Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
PsychosocialProcesses.......................................................... 234
THERAPEUTICS................................................................ 235
Diagnosing GD and Comorbid Conditions and the Role
ofMental HealthProfessionals............................................... 236
Counseling and Psychotherapy for Adults with Gender Dysphoria . . . . . . . . . . . . . . . . 237
Real-LifeExperience inthe PreferredGender Role.............................. 238
HormoneTherapy ............................................................. 239
SexReassignment Surgery...................................................... 239
SUMMARY....................................................................... 240
INTRODUCTION
Gender dysphoria (GD) is a technical term that is familiar to specialist clinicians and researchers,
but it is perhaps less familiar to clinicians who have little or no experience in this area. It is also
a diagnostic term: In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5; Am. Psychiatr. Assoc. 2013), GD replaced prior diagnostic labels, including transsexu-
alism and gender identity disorder.
In the past few years, GD has received an unprecedented amount of attention in all forms of
media, perhaps under the broader rubric of the terms “transgender” or “transgenderism.” In 2014,
an essay in Time suggested that a “tipping point” had been reached with regard to “transgender
visibility” (Gray 2014). In his State of the Union address on January 20, 2015, Barack Obama was
the first US President to use the term “transgender” in public:
218 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
As Americans, we respect human dignity. ...That’s why we defend free speech, and advocate for
political prisoners, and condemn the persecution of women, or religious minorities, or people who are
lesbian, gay, bisexual, or transgender. We do these things not only because they’re right, but because
they make us safer. (Steinmetz 2015)
On May 4, 2015, the New York Times launched a series of editorials, entitled “Transgender
Today,” and around the same time, the American public appeared captivated by the very public
gender change from male to female, at the age of 65, of Olympic athlete Bruce (aka Caitlyn)
Jenner, whose name yielded 79,500,000 “hits” on Google as of July 1, 2015 (Bissinger 2015).
TERMINOLOGY AND PHENOMENOLOGY
The term “gender dysphoria” was first introduced by Fisk (1974) to describe individuals who
experience sufficient discomfort with their biological sex to form the wish for sex reassignment.
In the DSM-5, GD is defined as “an individual’s affective/cognitive discontent with the assigned
gender [usually at birth and referred to as natal gender]” (Am. Psychiatr. Assoc. 2013, p. 451).
The specialist clinician will be well aware of the multitude of terms currently in use to de-
scribe individuals whose gender identity or gender role behavior does not match up with societal
expectations or stereotypes associated with the (biological) male-female binary: apart from GD,
there are many other terms, such as gender variant, gender nonconforming, gender queer, gen-
der fluid, bigender, gender neutral, agender, and nonbinary, along with “trans,” transsexual, and
transgender. And, cross-culturally, there are many terms used to label individuals whose behavior
and subjective identity fall under the rubric of a “third gender” (Herdt 1994).
Developmental Trajectories
Table 1 shows the DSM-5 diagnostic criteria for GD in both children and adolescents/adults.
It is important to include the criteria for children because the phenomenology of GD in adults,
particularly in natal males, has at least two distinct pathways. Some adults with GD will recall a
childhood pattern of sex-typed behavior that corresponds to the behavioral indicators of GD in
childhood. In the contemporary literature, this is known as early-onset GD (Nieder et al. 2011)
or an early-onset of cross-gender identification, which might be present in the absence of an
explicit desire to be of the other gender. For other adults with GD, there is no clear evidence of
childhood cross-gender identification; rather, the indicators of GD emerge at puberty, if not much
later, which is called late-onset GD. An important methodological and interpretive issue pertains
to what “counts” as early onset. On this point, the literature is quite variable: Some researchers
consider early onset to be any time prior to puberty, whereas other researchers consider early
onset to be during the toddler and preschool years, the developmental period in which both
gender identity and gender role behaviors are first expressed (Lawrence 2010, pp. 531–532).
If age of onset is used as the independent variable, one can ask if it correlates with any other
variables that might be of importance from a clinical perspective. One such variable is sexual
orientation. Nieder et al. (2011) found that early-onset female-to-male (FtM) clients were more
likely to be sexually attracted to females than were late-onset clients, and early-onset male-to-
female (MtF ) clients were more likely to be sexually attracted to males than were late-onset
clients, particularly when it was the clinician who classified the client’s sexual orientation.
If sexual orientation is used as the independent variable, one can also ask which, if any, variables
it is correlated with. In the best-studied sexual orientation typological scheme, adults with GD are
divided into two subtypes: in the case of males, the two subtypes are those who are sexually attracted
to males versus those who are sexually attracted to females, both males and females, or neither males
www.annualreviews.org Gender Dysphoria in Adults 219
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Table 1 Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for gender dysphoria in
children, adolescents, and adults
Criteria for gender dysphoria in children
A. A marked incongruence between one’s experienced/expressed gender and assigned gender, of at least six months’
duration, as manifested by at least six of the following (one of which must be Criterion A1):
1. A strong desire to be of the other gender or an insistence that one is the other gender (or some alternative gender different from
one’s assigned gender)
2. In boys (assigned gender), a strong preference for cross-dressing or simulating female attire; in girls (assigned gender), a strong
preference for wearing only typical masculine clothing and a strong resistance to the wearing of typical feminine clothing
3. A strong preference for cross-gender roles in make-believe play or fantasy play
4. A strong preference for the toys, games, or activities stereotypically used or engaged in by the other gender
5. A strong preference for playmates of the other gender
6. In boys (assigned gender), a strong rejection of typically masculine toys, games, and activities and a strong avoidance of
rough-and-tumble play; or in girls (assigned gender), a strong rejection of typically feminine toys, games, and activities
7. A strong dislike of one’s sexual anatomy
8. A strong desire for the primary and/or secondary sex characteristics that match one’s experienced gender
B. The condition is associated with clinically significant distress or impairment in social, school, or other important areas
of functioning.
Specify if: with a disorder of sex development
Criteria for gender dysphoria in adolescents and adults
A. A marked incongruence between one’s experienced/expressed gender and assigned gender, of at least six months’
duration, as manifested by at least two of the following:
1. A marked incongruence between one’s experienced/expressed gender and primary and/or secondary sex characteristics (or in
young adolescents, the anticipated secondary sex characteristics)
2. A strong desire to be rid of one’s primary and/or secondary sex characteristics because of a marked incongruence with one’s
experienced/expressed gender (or in young adolescents, a desire to prevent the development of the anticipated secondary sex
characteristics)
3. A strong desire for the primary and/or secondary sex characteristics of the other gender
4. A strong desire to be of the other gender (or some alternative gender different from one’s assigned gender)
5. A strong desire to be treated as the other gender (or some alternative gender different from one’s assigned gender)
6. A strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender different from
one’s assigned gender)
B. The condition is associated with clinically significant distress or impairment in social, occupational, or other
important areas of functioning.
Specify if: with a disorder of sex development
Specify if: posttransition, the individual has transitioned to full-time living in the desired gender (with or without legalization of
gender change) and has undergone (or is preparing to have) at least one cross-sex medical procedure or treatment
regimen—namely, regular cross-sex hormone treatment or gender reassignment surgery confirming the desired gender (e.g.,
penectomy, vaginoplasty in a natal male; mastectomy or phalloplasty in a natal female)
nor females (Blanchard 1989). In the case of females, the two subtypes are those who are sexually
attracted to females versus those who are sexually attracted to males, both males and females, or
neither males nor females. Gender-dysphoric males who are not exclusively sexually attracted to
males often have transvestic disorder (Blanchard 2010), in which there is sexual arousal associated
with cross-dressing or autogynephilia, defined in the DSM-5 as sexual arousal associated with a
man’s thought or image of himself as a woman (for details, see Blanchard 2005, Lawrence 2013).
Although this taxonomic scheme did not begin to receive empirical validation until the 1980s,
220 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
the importance of sexual orientation as a subtype goes back to some of the earliest writings by
clinicians who worked with transsexual clients. For example, Harry Benjamin, an endocrinologist
considered to be the father of transsexualism (Green 2009), described quite clearly male clients
who could be classified as either homosexual or nonhomosexual (in relation to birth sex) (Schaefer
& Wheeler 1995).
For natal females, the older literature suggested an almost complete predominance of the
early-onset form of GD, with a corresponding sexual orientation toward females. More recently,
however, a greater proportion of natal females with the late-onset form of GD have been described
in the literature, with a sexual attraction to natal males and who from a subjective point of view
identify as gay men (Bockting et al. 2009, Chivers & Bailey 2000).
In contemporary times, consideration of sexual orientation in relation to GD has been an
extremely contentious issue. Some clinicians and transgender activists object to the idea that GD
in males might be associated with autogynephilia because they worry that this might result in the
GD being taken less seriously and viewed simply as a paraphilic sexual condition (Dreger 2008,
Lawrence 2013).
There is a historical reason for this concern. When sex reassignment surgery (SRS), or what
is now called gender-confirming surgery, for adults with GD began to receive more credence as
a legitimate therapeutic option in the 1960s and 1970s (Meyerowitz 2002), clinicians were wary
about recommending this treatment for late-onset males. For example, a male client who had a
history of transvestic fetishism, was (or had been) married to a woman, had children, and had
lived for a long time in the male gender role was viewed as a more dubious candidate for SRS in
comparison with other male clients. And such male clients often present with the request for SRS at
a later age than do early-onset males (Blanchard 1994, Lawrence 2010, Nieder et al. 2011). Indeed,
Stoller (1968) considered such clients to be “secondary” rather than “primary” transsexuals. Other
clinicians in this era noted that such clients had a more episodic history with regard to GD and
the wish for sex reassignment, which was deemed to be a reason for caution in recommending
an irreversible medical treatment (Wise & Meyer 1980). And perhaps there was good reason to
be cautious, as there is evidence that instances of “regrets” after SRS are more common in this
subgroup (Blanchard et al. 1989).
The primary-secondary classificatory scheme has now been largely abandoned, and eligibility
for SRS takes into account different parameters, which are described more fully in the section
on therapeutics, but it is noted here that the debate has remained a very political, contentious
issue. In the seventh revision to the Standards of Care for the Health of Transsexual, Transgender,
and Gender-Nonconforming People (SOC-7) published by the World Professional Association for
Transgender Health (Coleman et al. 2011), terms such as sexual orientation, transvestic fetishism,
and autogynephilia are never mentioned. We would argue that this reflects a kind of intellectual
erasure in the discourse on phenomenology, which may inadvertently (or, perhaps, intentionally)
obscure the importance of these parameters with regard to theoretical issues, empirical research
on causal mechanisms, and therapeutic care.
EPIDEMIOLOGY
Prevalence and Incidence
In the late 1970s, the epidemiology of psychiatric disorders was examined with the use of the
Diagnostic Interview Schedule (DIS) (Robins et al. 1981), which was designed to assess DSM-III
diagnoses. Interestingly, Robins and colleagues (1981) noted that the module pertaining to trans-
sexualism was “omitted” because it “had not been cleared by NIMH for submission to [the] OMB
www.annualreviews.org Gender Dysphoria in Adults 221
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
[the US Office of Management and Budget]” (p. 388). Thus, in the 1980s, the US studies on DIS
prevalence did not contain any specific information on transsexualism. However, Hwu et al. (1989)
reported on the prevalence of transsexualism in Taiwan for 11,004 adults ranging in age from 18
to 64+years. Depending on geographic area, lifetime prevalence ranged from 0.3 to 2.0:1,000,
with a higher prevalence for females than for males (range, 0.7–4.2:1,000 versus 0–0.4:1,000).
One-year prevalence ranged from 0 to 1.0:1,000. Stef´
ansson et al. (1994) reported prevalence data
on 862 Icelanders at the age of 55 to 57 years, who were all born in 1931: Lifetime prevalence was
0.1%, and point prevalence (one month to one year) was 0.0%.
Estimates of prevalence have also relied on less rigorous methods, such as the number of adults
seeking clinical care at specialized gender identity clinics in a particular country or the number
of such clients approved for or already receiving cross-sex or gender-affirming hormonal treat-
ment. Zucker & Lawrence (2009) reviewed this quasi-epidemiological literature on prevalence and
identified 25 relevant studies. Population-based data from European countries provided the best
estimates of the prevalence of GD in Western societies. In Belgium, for example, the prevalence
of transsexualism, defined as having undergone sex reassignment, was 1:12,900 for adult males
and 1:33,800 for adult females; data from the Netherlands were similar: 1:11,900 adult males and
1:30,400 adult females.
Since the 2009 review, two new studies have been published. Dhejne et al. (2014) reported a
point prevalence in December 2010 of 1:7,750 adult males and 1:13,120 females in Sweden who
had applied for a legal name change, and Judge et al. (2014) reported a prevalence of 1:10,154
adult males and 1:27,668 adult females referred for hormonal treatment in Ireland. Arcelus et al.
(2015) provided a meta-analytic review of 21 studies (many of which were included in Zucker
& Lawrence 2009) and concluded that the prevalence of transsexualism in (predominantly) adult
males was 1:14,705 and 1:38,461 in (predominantly) adult females.
Because these studies have relied on clients seen by gender identity specialists or clinics, it has
been argued that the true prevalence of GD (transsexualism) could be underestimated because
not all affected individuals might seek out such care at specialized centers. Veale (2008) gauged
the prevalence of transsexualism in New Zealand on the basis of the number of individuals,
15 years of age and older, who requested, for example, an “X” on their passport instead of M (for
male) or F (for female) after they had been living as a member of the opposite sex and had made
a legal name change. On this basis, Veale reported a higher prevalence rate of 1:3,630 in males
and 1:22,714 in females.
In the past few years, some novel data have emerged that also suggest higher prevalence rates;
however, these studies have tended to use definitions of “caseness” that are looser than the defini-
tions used for clients seen in specialty clinics. Conron et al. (2012) examined a probability sample
of 28,176 adults (age range 18–64 years) who participated in a telephone health survey. They
found that 0.5% of the adults considered themselves to be transgender (e.g., “a person born into
a male body, but who feels female or lives as a woman”) (see also Kuyper & Wijsen 2014, Van
Caenegem et al. 2015). Although these new data should be interpreted with caution because of the
less restricted definition of caseness, they may well reflect a bona fide increase in the prevalence
of adults who self-identify somewhere along the transgender spectrum; some of these individuals
may eventually seek out gender change with biomedical treatments.
Sex Ratio
From the clinic-based studies, it is apparent that the prevalence of male-to-female transsexualism is
consistently higher than female-to-male transsexualism in adults. If these estimates reflect, even in
a crude way, sex differences in true prevalence, one can ask why GD is more common in biological
222 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
males than in biological females. One explanation pertains to sex differences in the prevalence of
subtypes of GD. As noted previously, the best-established evidence for a sex difference in subtypes
pertains to sexual orientation. This sex ×sexual orientation difference may well explain the higher
prevalence in biological males (of course, the interaction itself also requires an explanation).
DIAGNOSIS
Placement in the Nomenclature
Transsexualism as a psychiatric diagnosis (for adolescents and adults) appeared for the first time
in the DSM in 1980 (the corresponding diagnosis for children was gender identity disorder of
childhood). In 1994, transsexualism and gender identity disorder of childhood were merged into
one diagnosis, gender identity disorder (GID), with distinct criteria sets for children and adoles-
cents/adults (Am. Psychiatr. Assoc. 1994). In the DSM-5 (Am. Psychiatr. Assoc. 2013), GID was
renamed GD, with a chapter of its own.
Substantive Changes in the DSM-5
Zucker et al. (2013) outlined the key changes to the diagnosis of GID between DSM-IV and
DSM-5. Before describing the changes relevant to adults, it should be noted that the subworkgroup
on Sexual and Gender Identity Disorders reflected on a more fundamental matter, namely, whether
to retain the diagnosis in the DSM-5 at all. Some transgendered activists and some clinicians
wanted the diagnosis to be removed in its entirety, arguing that GID was not a mental disorder,
and the arguments for removal drew on many of the same reasons that led homosexuality to be
removed in 1973 from the DSM-II (Am. Psychiatr. Assoc. 1968) (Bayer 1981): Transsexualism
or GID was nothing more than a normal variant of a cisgender identity, that its presence in the
DSM contributed to stigma, and that there was nothing inherently “wrong” with a gender identity
incongruent with one’s natal sex (Ault & Brzuzy 2009, Vance et al. 2010). Two members of the
DSM-5 subworkgroup wrote reviews that, in part, considered the question of whether to leave
the diagnosis in the DSM or take it out (Drescher 2010, Meyer-Bahlburg 2010; see also Zucker
& Duschinsky 2016).
The recommendation of the subworkgroup to retain the diagnosis was based on at least two
key considerations: access to care and a reconceptualization of the diagnosis. If there were no psy-
chiatric diagnosis, access to care, including insurance coverage for SRS, would be threatened. The
argument that GID is a nonpsychiatric medical condition [e.g., a neural, central nervous system
(CNS)-limited intersex condition] (Meyer-Bahlburg 2011) was considered, but it was deemed that
the evidence for this was far from clear and could not be justified.
To retain the diagnosis in the DSM-5, a reconceptualization was articulated in which “identity”
per se was not considered a sign of a mental disorder. Rather, it was the incongruence between
one’s felt gender and assigned sex/gender (usually at birth) leading to distress and/or impairment
that was the core feature of the diagnosis. As a result, the subworkgroup argued for a change in
name from GID to GD in order to better reflect this incongruence. Once a consensus within the
subworkgroup was reached with regard to retention, five substantive changes were proposed and
implemented:
1. The diagnostic criteria for adolescents and adults moved to a more detailed polythetic format
(Table 1), replacing the rather vague criteria that were used in the DSM-IV. The threshold
of two symptoms (out of six) was based, in part, on secondary data analyses, which indicated
that the presence of at least two indicators yielded a sensitivity rate of 94.2% and a specificity
rate of 99.3%.
www.annualreviews.org Gender Dysphoria in Adults 223
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
2. A lower-bound six-month duration criterion was introduced based on clinical consensus,
but, unfortunately, without formal empirical evidence. The inclusion of a duration criterion
was, however, deemed important for clinical reasons, namely, to caution against a hasty
diagnosis with the potential unintended consequence of inappropriate treatment for clients
in which the symptoms might well prove to be transitory.
3. Whether or not individuals with a physical intersex condition, now termed a disorder of sex
development (DSD), should be diagnosed with GD has had a back-and-forth history since
the DSM-III (Kraus 2015; Meyer-Bahlburg 1994, 2010, 2015). Since the publication of the
DSM-IV, considerable evidence has accumulated that some individuals with a DSD expe-
rience GD and may wish to change their assigned gender (Berenbaum & Meyer-Bahlburg
2015, Meyer-Bahlburg 2010, Pasterski et al. 2015, Richter-Appelt & Sandberg 2010). Al-
though the percentage of DSD clients who develop GD is DSD syndrome dependent, such
clients express a phenomenology that is both similar to and different from clients with GD
with no known DSD, and similarities and differences also exist in developmental trajectories.
Because the presence of a DSD suggests a specific causal mechanism that may not be present
in individuals without a DSD, it was included as a specifier in the DSM-5.
4. For adolescents and adults, the DSM-IV specifier for sexual attraction (to males, to females,
to both, to neither) was removed in the DSM-5. This was an issue that was debated intensely
by the subworkgroup. On the one hand, there is considerable evidence, particularly for na-
tal males, that sexual orientation in adults with GD is related to a whole host of variables,
including developmental phenomenology and trajectories, and is likely related to somewhat
distinct causal mechanisms. Indeed, sexual orientation (or sexual attraction) fits well with the
DSM-IV definition of a subtype (“mutually exclusive and jointly exhaustive phenomenolog-
ical subgroupings”), and there is considerable evidence for its validity as a subtype (Lawrence
2010). On the other hand, it can be argued that sexual orientation per se does not, in and of
itself, constitute a symptom of GD (“symptom expression”), which is a cornerstone of the
meaning of a specifier in DSM-5. As a result, the subworkgroup recommended that sexual
attraction be removed as a specifier but described in the text as an important component of
variations in developmental trajectories and with regard to research on causal mechanisms.
5. A posttransition specifier was added to the GD criteria for adolescents and adults. The addi-
tion of this specifier was deemed necessary because there are many individuals who, after a
gender transition (social and/or biomedical), no longer meet the criteria set for GD; however,
they continue to undergo chronic hormone treatment, further gender-confirming surgery,
or intermittent psychotherapy/counseling to facilitate the adaptation to life in the desired
gender and the social consequences of the transition. Although the concept of posttransition
was modeled on the concept “in [partial or full] remission” as used for mood disorders, “re-
mission” has implications in terms of symptom reduction that do not apply directly to GD.
Cross-sex hormone treatment of gonadectomized individuals could, of course, be coded as
treatment of hypogonadism, but this would not apply to individuals who have not undergone
gonadectomy but receive hormone treatments. In the DSM-5 text, it is noted that the course
specifier of “full remission” in its original meaning does apply to a small number of adults.
Gender Dysphoria and the ICD-11
The World Health Organization intends to publish the eleventh revision to its International Clas-
sification of Diseases and Related Health Problems (ICD-11) in 2018. Advisory groups have been
assembled for the Mental and Behavioural Disorders section (First et al. 2015). Two members
of the DSM-5 Work Group on Sexual and Identity Disorders, Cohen-Kettenis and Drescher,
224 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
served on a subgroup of three. A general proposal has been made to move the ICD-10 diagnoses
pertaining to GD, the sexual dysfunctions, and the paraphilic disorders out of the Mental and Be-
havioural Disorders section to a new section provisionally entitled Conditions Related to Sexual
Health (Drescher 2013, 2015; Drescher et al. 2012), with the DSM-5 “gender dysphoria” label
replaced with the label of “gender incongruence.” This proposal appears to be based in part on
the argument that such a section would be agnostic with regard to whether or not gender incon-
gruence is best conceptualized as a psychiatric or nonpsychiatric medical condition. Retention in
the ICD-11 in this new section would, in theory, allow national health care systems or private
insurance companies to continue to provide coverage and thereby not threaten access to care for
clients unable to pay for medical care out of pocket.
ASSESSMENT
Psychological Assessment
Psychological assessment of GD, particularly dimensional evaluation, can be used to complement
a detailed clinical history, including an appraisal of the symptoms that constitute the DSM-5 diag-
nosis. For example, the gender-related scales [masculinity-femininity, masculine gender, feminine
gender (Mf, GM, and GF, respectively)] of the Minnesota Multiphasic Personality Inventory-2
(MMPI-2) (Martin & Finn 2010) provide objective measures of clients’ gender-typical or atypical
attitudes and interests (G ´
omez-Gil et al. 2008). The Feminine Gender Identity Scale for Males
(Freund et al. 1977) and the Masculine Gender Identity Scale for Females (Blanchard & Freund
1983) were developed, in part, to provide dimensional assessment of some indicators of transsex-
ualism (both historic and concurrent) during the period when the diagnosis was either about to
appear in the DSM-III or shortly thereafter.
More recently, the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and
Adults (GIDYQ-AA) has been developed (Deogracias et al. 2007). The GIDYQ-AA consists of
27 items that pertain to gender identity and GD and are designed to capture multiple indicators
of gender identity and GD, including subjective (n=13 items), social (n=9 items), somatic (n=3
items), and sociolegal (n=2 items) parameters. The GIDYQ-AA has parallel male and female
versions. Each item is rated on a 5-point response scale ranging from 1 (never) to 5 (always) based
on a time frame of the past 12 months. A total score is calculated by summing scores on the
completed items and dividing by the number of marked responses.
The psychometric properties of the GIDYQ-AA were examined by Deogracias et al. (2007)
with a sample of 462 participants that included both university students and gender identity clients.
A principal factor analysis indicated a one-factor solution was the best fit, accounting for 61.3%
of the total variance. The measure successfully discriminated gender identity clients from both
heterosexual and nonheterosexual controls, with large effect sizes. Using a cut-point of 3.00,
selected on the basis of visual inspection of the frequency distributions of mean scores, Deogracias
et al. (2007) found the scale to have excellent sensitivity (90.4%) and specificity (99.7%). Similarly,
using clinical controls, Singh et al. (2010) found a specificity rate of 100% and sensitivity rates
of 93.3% and 87.3% for adolescents and adults with GID, respectively. These findings suggest
that the GIDYQ-AA can be used to identify ‘‘caseness” in clients referred to a specialized gender
identity clinic and that the questionnaire does not simply identify clinical problems in general. It
has also been used to identify potential “cases” in client groups for whom it has been surmised
contain an overrepresentation of individuals with GD, such as women with borderline personality
disorder (Singh et al. 2011). Other contemporary dimensional measures of GD include the Utrecht
Gender Dysphoria Scale (Schneider et al. 2015); however, one advantage of the GIDYQ-AA is
www.annualreviews.org Gender Dysphoria in Adults 225
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
that it uses a specific time frame and has parallel items for males and females, whereas the Utrecht
Gender Dysphoria Scale does not have identical items for the two sexes.
An important component of GD pertains to body image and body dissatisfaction. Although
signs of body image dissatisfaction, including anatomic dysphoria, can be detected in some pre-
pubertal children with GD, this becomes much more salient with the onset of puberty, which
accentuates the incongruence between one’s felt gender and somatic sex with the emergence of
secondary sex characteristics (Feusner et al. 2015).
Several measures have been used to assess this body image dissatisfaction, including the Body
Image Scale (Lindgren & Pauly 1975, van de Grift et al. 2015), the Body Uneasiness Test (Bandini
et al. 2013), and the Hamburg Body Drawing Scale (Becker et al. 2015). Becker and colleagues
found the expected elevation in body image dissatisfaction with regard to sex-specific body features,
but they also found some elevations in more general aspects of body image. Along similar lines,
Vocks et al. (2009) reported that gender-dysphoric adults showed impairment in body image
related to eating disorders (e.g., restrained eating behavior). Body image is an important variable
to assess because a reduction in dissatisfaction is an important metric in identifying improvement
in psychosocial well-being following a gender social transition and corresponding biomedical
treatments (Kraemer et al. 2008).
Biological Assessment
Physical examination and laboratory testing are generally viewed as having limited value for clients
with GD. For adults who have a co-occurring DSD, this has invariably been documented prior
to an assessment for GD. Almost all clients with GD have a normal sex chromosome karyo-
type (Auer et al. 2013a). Nonautosomal positive findings in males most commonly indicate the
presence of Klinefelter syndrome (47,XXY) or an XYY karyotype (Auer et al. 2013a, Buhrich &
McConaghy 1978). Only a few case reports in the literature have identified a sex chromosomal
abnormality in females with GD (Auer et al. 2013a, Khandelwal et al. 2010).
ASSOCIATED PSYCHOPATHOLOGY
Understanding the nature and prevalence of psychopathologic conditions that occur in association
with GD can potentially improve diagnostic precision, inform treatment planning, and provide
insights into the causes and consequences of GD. A review of existing research in this area,
however, reveals a wide range of inconsistent, confusing, and at times seemingly contradictory
results. Many studies have significant limitations. These include the use of small and potentially
unrepresentative samples and reliance on brief self-report measures rather than structured clinical
interviews. Some investigators have combined male-to-female (MtF ) and female-to-male (FtM)
persons for purposes of analysis, and subtypes based on sexual orientation or age of onset have
rarely been taken into consideration.
Increased Prevalence of Associated Psychopathology
Comorbid psychopathology is significantly more prevalent in adults with GD than in the general
population. Mood and anxiety disorders are especially likely to occur in association with GD.
Two large, recently published, methodologically strong studies illustrate these points; they also
provide a standard against which the results of other investigations can be compared. These two
reports are summarized in the first two rows of Supplemental Table 1 (follow the Supplemental
Material link in the online version of this article or at http://www.annualreviews.org).
226 Zucker ·Lawrence ·Kreukels
Supplemental Material
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Dhejne et al. (2011) reported the results of a longitudinal, population-based follow-up study
of all persons who underwent SRS in Sweden between 1973 and 2003, a cohort consisting of
191 MtF and 131 FtM transsexuals. Data were obtained from several Swedish national reg-
istries, which contain information about births, deaths, hospital discharges and diagnoses, criminal
records, etc. Each client was compared with 10 randomly selected, age-matched persons of both
their birth sex and their reassigned or final sex. Dhejne et al. (2011) found that 19% of MtF clients
and 17% of FtM clients had been hospitalized for psychiatric problems other than GD prior to
undergoing sex reassignment, compared to only 3–4% of both birth-sex and final-sex matched con-
trols. After SRS, clients with GD were 2.8 times more likely than controls to have been hospitalized
for a psychiatric problem other than GD, even after adjustment for prior psychiatric comorbidity;
they were 4.2 times more likely prior to this adjustment. After SRS, transsexual clients were 4.9
times more likely to have made a suicide attempt and 19.1 times more likely to have died from
suicide, again after adjusting for prior psychiatric comorbidity. The prevalence of these conditions
was similar in MtFs and FtMs. The multiple strengths of this study—longitudinal design, absence
of selection bias, well-chosen control groups, and unusually long follow-up times—suggest that
its findings are likely to be highly reliable.
Heylens et al. (2014a) described the prevalence of current and lifetime comorbid psychopathol-
ogy in 305 clients with GD (182 MtFs, 123 FtMs) seen from 2007 through 2010 in gender clinics
in Belgium, Germany, the Netherlands, and Norway that participated in the European Network
for the Investigation of Gender Incongruence. Data were collected using the Mini International
Neuropsychiatric Interview-Plus and the Structured Clinical Interview for DSM-IV Axis II Per-
sonality Disorders. Approximately 38% of clients had a current Axis I disorder and about 69%
had a lifetime Axis I disorder, with similar prevalence figures in MtFs and FtMs. The most com-
mon Axis I conditions were mood disorders (27% current, 60% lifetime) and anxiety disorders
(17% current, 28% lifetime). Although this study did not employ a formal control group, these
figures substantially exceed prevalence rates of comorbid psychopathology in the general popula-
tion in Western European countries. For example, Alonso & L´
epine (2007) used the Composite
International Diagnostic Interview and found that, in a representative sample of adults from six
European countries, only 26% reported a lifetime prevalence of any mental disorder. About 30%
of both MtFs and FtMs had either attempted suicide or reported recent suicidal ideation. About
15% of GD clients had one or more DSM-IV Axis II disorders, a prevalence similar to that of
the general population in the countries that participated in the European Network for the Inves-
tigation of Gender Incongruence. There were no significant differences in comorbid conditions
between early-onset and late-onset GD groups, except for a higher prevalence of Axis II disorders
in late-onset FtMs.
Eight other studies that used structured clinical interviews for data collection (Colizzi et al.
2015; G ´
omez-Gil et al. 2009; Guzm´
an-Parra et al. 2015; Haraldsen & Dahl 2000; Hepp et al.
2005; Madeddu et al. 2009; Mazaheri Meybodi et al. 2014a,b) reported generally similar results
(see Supplemental Table 1): Most found about a 30–40% prevalence of current comorbid psy-
chopathology and about a 50–80% prevalence of lifetime comorbid psychopathology in adults
with GD, including a 20–60% prevalence of personality disorders. Another large study by Land´
en
et al. (1998), which used data from Swedish national registries—the same method that Dhejne
et al. (2011) subsequently employed—reported similar results, as did three smaller studies by
Miach et al. (2000) and De Cuypere et al. (1995, 2006), all of which found a high prevalence
of associated psychopathology despite the use of unstructured clinical interviews. The studies by
Dhejne et al. (2011) and Heylens et al. (2014a) and these 12 other studies, summarized in the first
14 rows of Supplemental Table 1, probably provide the most reliable estimates of the prevalence
of associated psychopathology in adults with GD.
www.annualreviews.org Gender Dysphoria in Adults 227
Supplemental Material
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Four other studies have used self-report screening instruments to assess current depression,
anxiety, and psychological distress in large cohorts of US transgender adults, some of whom
probably would not have met full diagnostic criteria for GD (Bockting et al. 2013, Budge et al.
2013, Clements-Nolle et al. 2006, Nuttbrock et al. 2013). All of these studies found that current
depression and anxiety were significantly more prevalent in adults with GD than in the general
population: about a 45–60% prevalence of current depression and about a 35–40% prevalence of
current anxiety. The results of these studies are summarized in the final four rows of Supplemental
Table 1.
Studies that Find Little or No Increased Prevalence
of Associated Psychopathology
Some studies have identified no or little increased prevalence of associated psychopathology. These
reports are sometimes cited to support the idea that GD is “usually an isolated diagnosis” (Cole
et al. 1997, p. 13) or one that is “associated with a low level of psychopathology” (Fisher et al.
2013, p. 417). Few of these studies, however, employed structured clinical interviews. Hoshiai
et al. (2010) observed that investigations that use structured clinical interviews typically report
higher comorbidity rates than investigations that do not, and they suggested that the latter studies
could easily underestimate the prevalence of comorbid conditions:
Studies using the structured clinical interview revealed a relatively high comorbidity rate of Axis I
disorders (30–67%), while studies without a structured interview showed a lower comorbidity rate of
Axis I disorders (4–19%). The possibility that clinical diagnosis without a structured interview missed
psychiatric comorbidity among GID patients cannot be denied. (p. 517)
Some reports that found a relatively low prevalence of comorbid psychopathology also have
other methodological limitations that render their conclusions questionable.
Five studies that found little or no increased prevalence of associated psychopathology in adults
with GD are summarized in Supplemental Table 2 (follow the Supplemental Material link
in the online version of this article or at http://www.annualreviews.org). The report by Fisher
et al. (2013) is arguably the most detailed and methodologically sound; the prevalence figures it
found for current and lifetime associated psychopathology (approximately 15–20% current, and
approximately 30% lifetime) are lower than most of the studies listed in Supplemental Table 1
and are not greatly different from general population estimates in Western countries. Fisher et al.
found an especially low prevalence of personality disorders—lower than in the general population.
The report by Colizzi et al. (2014) described the same client cohort as the report by Colizzi
et al. (2015) in Supplemental Table 1 but found much lower prevalence figures for associated
psychopathology; the reasons for this difference are unclear, although it was noted that there were
“several patients with substantial functional impairment that did not receive a standard diagnosis
based on the DSM-IV-TR criteria due to an insufficient number/duration of symptoms” (p. 71).
The final three studies listed in Supplemental Table 2 are methodologically less strong
and may have underestimated the prevalence of comorbid psychopathology. The low prevalence
figures reported by Hoshiai et al. (2010) are especially puzzling, given the very high prevalence
of suicidal ideation, suicide attempts, and self-harm among their participants. Reports by Terada
et al. (2011, 2012), which examined subsets of the larger client cohort described by Hoshiai et al.
and which are not included in the table, found almost identical results: Comorbid psychiatric
diagnoses were uncommon, but approximately three-quarters of clients reported suicidal ideation
or suicide attempts.
228 Zucker ·Lawrence ·Kreukels
Supplemental Material
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Self-Report Measures of Associated Psychological Symptoms
Several investigators have used self-report measures, including the Symptom Checklist-90-Revised
(SCL-90-R), MMPI, and MMPI-2, to examine psychiatric symptoms in adults with GD. Reports
using the SCL-90-R have generally found that GD clients—at least prior to treatment—have sig-
nificantly higher mean scores than healthy control subjects (Auer et al. 2013b, Davey et al. 2014,
Haraldsen & Dahl 2000, Heylens et al. 2014b, Simon et al. 2011). Haraldsen & Dahl (2000) also
found, however, that the GD clients had significantly lower mean scores than clinical clients with
personality disorders. Differences between the mean SCL-90-R scores of GD clients and healthy
control subjects, although statistically significant, were typically small and in most cases clinically
unimportant. Unfortunately, investigators have not systematically examined differences in the per-
centages of clinically elevated SCL-90-R scores between GD clients and healthy control subjects.
Several studies have used the MMPI or MMPI-2 to assess psychopathology in adults with GD.
Most investigations conducted prior to 2000, however, involved small numbers of participants,
and their results have been inconsistent or contradictory (for reviews, see G ´
omez-Gil et al. 2008,
Miach et al. 2000). In one of the larger pre-2000 studies, which involved 93 MtFs and 44 FtMs,
Cole et al. (1997) found that mean MMPI clinical scale scores were in the normal range for both
MtF and FtM participants, but more than 20% of participants had Tscores 70 on at least one
clinical scale, excluding the Gender Identity Scale (Mf ). Miach et al. (2000) and G´
omez-Gil et al.
(2008) found similar results using the MMPI-2: Clients with GD had mean clinical scale scores
in the normal range, but 28% of MtFs and 27% of FtMs had Tscores 65 on one or more
clinical scales (excluding Mf ), especially those measuring depressive, psychopathic, paranoid, or
schizophrenic traits.
Increased Prevalence of Suicidality and Self-Harm
Supplemental Table 3 (follow the Supplemental Material link in the online version of this ar-
ticle or at http://www.annualreviews.org) summarizes the results of 13 studies that investigated
suicidality and self-harm in adults with GD. These studies suggest that about one in three adults
with GD has experienced suicidal ideation, attempted suicide, or engaged in suicidal or nonsui-
cidal self-harm. The results described by Dhejne et al. (2011)—a greatly increased likelihood of
attempted and completed suicide a decade or more after completion of SRS—are particularly dis-
concerting. Prevalence figures for suicide attempts, which usually reflect self-reports, vary widely
between studies—probably a result of varying standards for what constitutes an attempt. Dhejne
et al. (2011) found a 9.0% prevalence of documented suicide attempts in adults with GD over
a minimum 10-year follow-up period, compared to a 1.4% prevalence in age- and sex-matched
control subjects.
Explanations of Associated Psychopathology
Mental health professionals who agree that GD is a genuine mental disorder would probably
consider the increased prevalence of associated psychopathology in adults with GD unsurprising,
given that different types of mental disorders are significantly correlated with each other and that
having one mental disorder greatly increases the probability of having one or more other mental
disorders (Caspi et al. 2014, Newman et al. 1998). Mental health professionals who doubt that
GD is a genuine mental disorder generally invoke other explanations to account for the increased
prevalence of associated psychopathology; these include the psychological consequences of gender
incongruence and especially the effects of minority stress (Meyer 2003), a term that refers to the
www.annualreviews.org Gender Dysphoria in Adults 229
Supplemental Material
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
stressful consequences of the prejudice, discrimination, and victimization that persons with GD
often experience.
Meta-analytic reviews (Pascoe & Smart Richman 2009, Pieterse et al. 2012) demonstrate that
perceived prejudice and discrimination are associated with an increased prevalence of mental
health problems in minority groups, although effect sizes are small to medium: typical correlations
are about 0.20. Moreover, direction of effect cannot be conclusively determined (i.e., whether
prejudice and discrimination lead to a greater likelihood of developing mental health problems,
or whether mental health problems lead to a greater likelihood of experiencing—or perceiving—
prejudice and discrimination).
Several studies have investigated the relationship between psychosocial variables and associated
psychopathology or related symptoms (suicidality or self-harm) in persons with GD. Perceived
prejudice and discrimination have been found to be positively associated with general mental health
symptoms (Bockting et al. 2013), depression (Nuttbrock et al. 2013), suicidality (Clements-Nolle
et al. 2006), and self-harm (Claes et al. 2015). One study with implications for direction of effect
(Nuttbrock et al. 2013) found that gender-related abuse that had been experienced a year earlier
was associated with current depression in MtFs age 30 or younger—but not in MtFs older than
age 30. Bauer et al. (2015) found that greater social support was associated with less suicidality.
A number of studies have found that receiving treatment for GD, especially hormone treat-
ment, is associated with lower levels of psychopathology (Colizzi et al. 2014, 2015; Gorin-Lazard
et al. 2013; Heylens et al. 2014b; Murad et al. 2010; Newfield et al. 2006) and suicidality (Bauer
et al. 2015). Conversely, anxiety and depression are more prevalent early in the transition process
(Budge et al. 2013). Clients who have completed at least a year of hormone therapy and cross-living
and are applying for SRS demonstrate less psychopathology than clients undergoing evaluation
for hormone therapy (G ´
omez-Gil et al. 2008). In contrast to many of these findings, Dhejne et al.
(2011) reported that even after successful completion of SRS—and after adjustment for pretreat-
ment psychopathology—transsexuals exhibited much higher prevalence rates for psychopathology
and suicidality than age- and sex-matched control groups.
Investigators have also reported a few findings that are not easy to reconcile with the hy-
potheses that gender incongruence and minority stress are causally related to a higher prevalence
of psychopathology in adults with GD. For example, Bockting et al. (2013) found no signifi-
cant association between self-reported GD (as a symptom, not a formal diagnosis) and symptoms
of psychopathology in transgender adults. Moreover, Heylens et al. (2014a) and Terada et al.
(2012) found no significant relationship between age of onset of GD and prevalence of comorbid
psychopathology, which seems contrary to the expectation that an earlier onset of GD and a con-
sequent lengthier exposure to experiences of prejudice and discrimination ought to be associated
with more prevalent psychopathology. Interestingly, Terada et al. (2012) found that nonhomosex-
ual orientation in MtFs and analloeroticism (lack of attraction to either men or women) in FtMs
was positively associated with comorbid psychopathology.
CAUSAL MECHANISMS
Understanding the genesis of GD has relied on some general principles about “normative” or sex-
typical psychosexual development. A simple model is that the mechanisms involved in normative
sex-dimorphic psychosexual differentiation (including gender identity itself) are inverted in the
development of GD. Thus, a normative sex differentiation model, not only as used in human
studies but also in scores of animal studies (Wallen 2009), has guided much of the causal mechanism
research on the development of GD, whether such research is biological or psychosocial. It is,
230 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
however, important to note that within-sex models have also been utilized; such models involve
the identification of mechanisms that might explain a within-sex difference in a sex-dimorphic
trait. An example of this would be the fraternal birth order effect, namely, the finding that gay
men have more older brothers than do heterosexual men. Although there is an enormous sex
difference in sexual orientation, the hypothesized mechanism regarding the fraternal birth order
effect applies only to males (Blanchard 2004).
Biological Processes
In this section, we summarize research on biological mechanisms in two areas: genetics and the
role of prenatal sex hormones, including their effects on putative sex-dimorphic neural structures.
Genetics. Family and twin studies have examined whether genetic factors contribute to the de-
velopment of gender identity, GD, and related phenomena (Burri et al. 2011, G ´
omez-Gil et al.
2010, Heylens et al. 2012, Loehlin et al. 2005). Loehlin et al. (2005) examined the heritability of
gender diagnosticity, a scale that predicts whether an individual is masculine or feminine based on
gender-related interests: 25% to 47% of the total variance was explained by genetic factors. Re-
called gender nonconformity was studied in adult twins, with heritability estimates ranging from
0.50 to 0.57 in men and from 0.37 to 0.40 in women (Bailey et al. 2000). Burri et al. (2011) ex-
amined recalled childhood gender typicality, sexual orientation, and adult gender identity. Herit-
ability for the Adult Gender Identity Scale was only 0.11. A study in twins of which one was diag-
nosed with GID showed that 39.1% of the monozygotic twins were concordant for GID, whereas
none of the dizygotic twins were concordant (Heylens et al. 2012).
Genes that are involved in either sex steroid biosynthesis or action have been investigated
because it is known that sex steroids contribute to the sexual differentiation of the brain. Complete
loss of function of the androgen receptor in XY individuals with complete androgen insensitivity
syndrome almost invariably results in a female gender identity; therefore, it may be a candidate
gene that affects gender identity development. In MtFs, a longer CAG repeat length polymorphism
in the androgen receptor was found (Hare et al. 2009), but another study with a larger sample failed
to replicate this finding (Fern´
andez et al. 2014b). Estrogen receptor (ER) genes have also been
studied. The prevalence of a long CA repeat in ERβwas found to be higher in MtF transsexuals
than in control men (Henningsson et al. 2005). Because the CYP19 is important for aromatization
of androgens into estrogens, this gene may be another candidate, but none of the studies found
support for this gene’s involvement in the development of GD (Fern´
andez et al. 2014b, Hare et al.
2009, Henningsson et al. 2005, Ujike et al. 2009). In FtMs, there was a link to the CYP17 gene
(Bentz et al. 2008) and to polymorphism of the ERβgene (Fern´
andez et al. 2014a), but another
study did not find any associations with these polymorphisms (Ujike et al. 2009).
At present, no strong candidate gene has been found that can account for the development
of GD. Many human traits and diseases have a polygenic architecture, where the phenotype is
determined by variation in many genes. This is plausibly the case for GD, and future studies
should determine if the architecture is polygenic or if there are specific loci with larger effects. In
addition, gender identity is most likely a complex trait that results from a combination of multiple
genetic and environmental factors. In twin, adoption, or family studies, these factors can be dis-
sected. Furthermore, phenotypes should be carefully defined, and homogeneous groups should be
compared. In neuroimaging studies (see below), attention has now been drawn to the importance
of describing the phenotypes and taking into account sexual orientation and age of onset.
www.annualreviews.org Gender Dysphoria in Adults 231
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Prenatal sex hormones. Sexual differentiation of all somatic tissues has long been ascribed to
exposure of androgenic hormones in the fetus (Bocklandt & Vilain 2007), resulting in masculine
phenotypes in the presence of androgenic hormones and feminine phenotypes in the absence
of these hormones. These early effects of sex hormones on the brain are denoted as organizing
effects, as opposed to effects of circulating hormones later during life on the already organized
neural system (Phoenix et al. 1959). It is hypothesized that feelings of gender incongruence may
arise from atypical sexual differentiation of the brain under the influence of prenatal hormones
(Swaab & Garcia-Falgueras 2009). Time windows for prenatal development of genitals and the
brain are believed to differ; thus, exposure to atypical levels of prenatal hormones during a certain
gestational period may have an effect on the brain but not the body.
Sex-dimorphic neural structures. In the search for neurobiological underpinnings of GD, brain
structure and function have been studied to determine whether the brains of transgender indi-
viduals show atypical sexual differentiation. A series of Dutch studies fueled this line of research
by showing female-typical hypothalamic nuclei in MtF transsexuals (Garcia-Falgueras & Swaab
2008, Kruijver et al. 2000, Zhou et al. 1995). The aim of subsequent imaging studies was to deter-
mine whether the brains of people with GD would show more resemblance to their experienced
gender than their natal sex. Supplemental Table 4 (follow the Supplemental Material link
in the online version of this article or at http://www.annualreviews.org) summarizes imaging
studies in adults with GD before the start of cross-sex hormone treatment.
Gray matter is one of the main components of the CNS and largely consists of neuronal cell bod-
ies. Studies of nonhomosexual MtFs have shown that gray matter volumes were largely in line with
their natal sex (Luders et al. 2009, Savic & Arver 2011). For homosexual MtFs, some differences
have been observed: Like control women, homosexual MtFs showed larger gray matter volumes in
comparison with male controls and FtMs in several cortical regions (Simon et al. 2013). Another
measure of gray matter volume is cortical thickness (CTh). CTh is generally higher in women
than in men. Homosexual MtFs showed CTh similar to that of female controls but increased
CTh compared with male controls in the orbito-frontal, insular, and medial occipital regions of
the right hemisphere (Zubiaurre-Elorza et al. 2013). Using this measure, nonhomosexual MtFs
also showed higher CTh compared with control men (Luders et al. 2012).
The putamen, a nucleus that is part of the basal ganglia and mainly associated with motor
regulation, is the only subcortical structure that has shown differences, although the findings are
diverse: The right putamen of nonhomosexual MtFs was larger than that of control men and was
in the female range in one study (Luders et al. 2009), but relatively smaller than that of male and
female controls in another study (Savic & Arver 2011). In homosexual MtFs, the volume of the
putamen was comparable to that of male and female controls (Zubiaurre-Elorza et al. 2013).
White matter mainly contains myelinated nerve fibers. Diffusion tensor imaging (DTI) is a
technique that is used to visualize white matter microstructure. One DTI study found that homo-
sexual MtFs had a pattern that was significantly different from control men and control women
(Rametti et al. 2011b) and the values were in between male and female controls. A similar picture,
but with another DTI measure, was found in MtFs (in both homosexual and nonhomosexual sub-
groups): Mean diffusivity values were increased compared to control males (Kranz et al. 2014b).
Structural connectivity networks were also examined in the same participants (Hahn et al. 2014).
A decreased hemispheric connectivity ratio in subcortical/limbic regions was found in mainly
nonhomosexual MtFs compared to control men and women, which seemed to be related to an
increased interhemispheric lobar connectivity.
With regard to the sexual differentiation hypothesis, the following picture now emerges, taking
sexual orientation into account: Homosexual MtFs are dissimilar to their natal sex in gray matter
232 Zucker ·Lawrence ·Kreukels
Supplemental Material
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
volume (Simon et al. 2013), CTh (Zubiaurre-Elorza et al. 2013), and white matter microstruc-
ture (Rametti et al. 2011b). For nonhomosexual MtFs, the picture is less clear: Their gray matter
volumes were in line with their natal sex (Luders et al. 2009, Savic & Arver 2011), but they do
show differences in white matter microstructure compared to control men (Kranz et al. 2014b).
However, all groups in the Kranz et al. study were mixed with regard to sexual orientation, which
may have affected the results. Overall, evidence supports the sexual differentiation hypothesis in
homosexual MtFs, but not in nonhomosexual MtFs. Natal women with GD are more homoge-
neous with regard to sexual orientation (most are homosexual). FtMs (like control men) had larger
gray matter volumes than female controls and MtFs in several areas (Simon et al. 2013), and similar
CTh to control women (Zubiaurre-Elorza et al. 2013). Like male controls, they had a larger vol-
ume of the putamen than female controls (Zubiaurre-Elorza et al. 2013). White matter FA values
of FtMs were significantly greater than those of female controls but similar to those of male con-
trols in several fascicles (Rametti et al. 2011a). In one of the fascicles, the corticospinal tract, FtMs
had values in between male and female controls. Kranz et al. (2014b) found a significant decrease
in mean diffusivity values in FtMs compared with control females. Intrahemispheric connectivity
between the right subcortical/limbic and right frontal and temporal lobes was decreased in FtMs
compared with male and female controls and MtFs (Hahn et al. 2014). All structural studies in
adult FtMs thus far render support for atypical sexual differentiation of their brains.
Neural functioning. Functional connectivity is a method to evaluate interactions between re-
gions while performing a task (task-related functional connectivity) or while not performing a
particular task (resting-state connectivity). While viewing erotic and nonerotic interactions of
male-female couples, the functional connectivity of MtFs and FtMs (as a group) showed an in-
crease between the ventral tegmental area and the anterior cingulate cortex subregions compared
to controls (men and women together) (Ku et al. 2013). It was argued that because the ventral
tegmental area is associated with dimorphic genital representation and the anterior cingulate cor-
tex is central in conflict monitoring and social processing, the pattern could be a substrate of the
psychological distress of transgender individuals. These findings should thus not be viewed in
the realm of the sexual differentiation hypothesis, but rather are more suggestive of the brain’s
substrate for incongruence between body and identity.
Functional studies that focus on homosexual MtF adults do not exist, nor are there studies
that compare homosexual with nonhomosexual MtF adults. In nonhomosexual MtFs, a female-
like response in hypothalamic activation while smelling odorous steroids (Berglund et al. 2008)
and brain activity while viewing erotic videos (Gizewski et al. 2009) were detected, arguing for
sex-atypical reactions in these groups. Brain activation patterns during voice perception of a sexual-
orientation mixed group of MtFs differed from those of men and, partly, also of women (Junger
et al. 2014). Differences were shown in brain activation during a visuospatial task in MtFs with
unknown sexual orientation in comparison with controls of their natal sex (Sch¨
oning et al. 2010).
While processing positive affective images, FtMs under gonadal suppression with
gonadotropin-releasing hormone agonists (GnRHa) showed less activation in the right supe-
rior temporal lobe compared to control women (Soleman et al. 2016). The findings may well be
related to their GD instead of the GnRHa treatment because no associations with hormonal levels
were found.
Kranz et al. (2014a) studied the hemispheric asymmetry in the cerebral serotonin transporter
system in males, females, and MtF transsexuals because lateralization of emotional processing
has been shown. Serotonin is known to play an important role in emotional processing, and
hemispheric asymmetry of the serotonin system has been reported as well. MtFs differed from
www.annualreviews.org Gender Dysphoria in Adults 233
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
male controls in the midcingulate cortex (rightward asymmetry for male controls but not for MtFs
and female controls) and from female controls in the calcarine gyrus. It was concluded that MtFs
show asymmetries of the serotonin transporter system “that relate to both genetic sex, gender and
a special feature of gender dysphoria” (p. 180).
In sum, findings indicate structural as well as functional alterations in the brains of transgender
individuals, either as a consequence of atypical sexual differentiation or as a result of a mismatch
between their anatomical sex characteristics and their gender identity. Brain changes may also be
triggered by psychological distress. Future studies should carefully consider the phenotypes of
participants, ideally combining genetic profiles with neuroimaging measures.
Psychosocial Processes
Nascent markers of gender identity emerge very early in development (Martin et al. 2002). To
the extent that gender identity is a stable trait, psychosocial factors—to truly merit causal status—
should be able to account for the emergence of a cross-gender identity in the first few years of life,
when it is first expressed. Otherwise, psychosocial factors would be better conceptualized as having
a perpetuating role. If psychosocial factors can also account for instances of a cross-gender identity
that first manifest in adolescence or even later (the late-onset form of GD discussed previously),
they should also be operative prior to the time of onset.
Given these assumptions, it is obvious that the study of causal psychosocial factors in adults
with GD faces methodological barriers because it largely relies on retrospective methods, which
are subject to many interpretive problems. As an example, Cohen-Kettenis & Arrindell (1990) had
both MtF and FtM adult clients rate their parents on the Egna Minnen av Barndoms Uppfostran (My
Memories of Upbringing) questionnaire with regard to three dimensions of behavior: rejection,
emotional warmth, and overprotection (e.g., intrusiveness, strictness). Compared to a volunteer
sample of male community controls, the MtF clients did not differ significantly in their recollection
of maternal behavior; however, fathers were rated as significantly more rejecting, less warm, and
more overprotective. The FtM clients rated their mothers as significantly more rejecting, less
warm, and more overprotective than the female controls. They also rated their fathers as more
rejecting and less warm.
Regarding the MtF data, it could be argued that there was no support for the maternal over-
closeness hypothesis theorized to play a role in the development of GD (Stoller 1968); however,
ratings of the fathers could be interpreted as support for a distance hypothesis (Green 1987).
Regarding the FtM data, it could be argued that there was support for a maternal undercloseness
hypothesis that has been theorized (Stoller 1975), but there was no support for an overcloseness
hypothesis with the father, since the fathers were also rated as more rejecting and less warm.
Consider three challenges in interpreting these kinds of data. First is the direction-of-effect
conundrum. For example, perhaps fathers of MtF clients were more rejecting because they
themselves were alienated by the feminine-gendered behaviors of their son in childhood, so the
direction of effect was from son to father, not father to son (Freund & Blanchard 1983). Second,
the community controls were volunteers, so it is conceivable that this was a source of bias (e.g.,
perhaps they were more likely than a truly random sample to come from families that were more
harmonious). Third, the study lacked a clinical control group. A control group would have been de-
sirable to determine whether the adult clients with GD recalled patterns of parental behavior that
were unique or simply characteristic of clinical populations in general (Garber & Hollon 1991).
One conceptual issue is the extent to which gender identity is a stable, within-person trait,
almost impervious to external influences once it has become internalized. An ideal study would be
to sample a representative cohort of young children who have a clear-cut identity as a boy or as
234 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
a girl and to assess their gender identity again much later in development (e.g., in adolescence or
adulthood) in order to examine its stability. Although the data are limited, some evidence suggests
that gender identity is likely a very stable trait. In Green’s (1987) study of very feminine boys, a
control sample of boys, who were all behaviorally masculine in childhood and presumably had a
male gender identity, all had a male gender identity at follow-up in late adolescence. Steensma
et al. (2013b) used data from a longitudinal study of 879 Dutch children to assess the stability in
gender identity at two time points: any time between 4 and 12 years of age and then 24 years later
(mean ages, 7.5 years and 30.9 years, respectively). On the Child Behavior Checklist, 818 parents
indicated that their child did not express a wish to be of the other gender or to behave like the
other gender. At follow-up, 98.8% of these now grown-up children did not self-report a desire to
be of the other gender.
In clinical populations of children with GD, however, gender identity stability is less certain.
A number of studies have shown that the majority of these children do not persist in their desire
to be of the other gender when followed up in late adolescence or adulthood (Drummond et al.
2008, Green 1987, Singh 2012, Wallien & Cohen Kettenis 2008), particularly in samples in which
a social transition to living as the desired gender has not occurred prior to puberty (Steensma et al.
2013a).
If children with GD shift their gender identity in a direction that is more congruent with
their natal sex, and if there are some adults who initially identify as a sexual orientation minority
(Diamond & Butterworth 2008) but then shift their gender identity so that it is no longer congru-
ent with their natal sex, then it becomes important to understand the proximal factors that might
contribute to this change. One such factor may involve an iterative matching process between sur-
face expressions of gender role behavior and identity. Many children with GD show a diminution
of their cross-gender role behavior over time, which may lead to a shift in their underlying gender
identity or identification. Conversely, adults with a minority sexual identity and who have a his-
tory of marked gender-nonconforming behavior may eventually settle on a cross-gender identity
that is more comfortable for them, as noted by Diamond & Butterworth (2008). Taken together,
these data suggest that, for at least some individuals, gender identity may be a more dynamic, fluid
process than previously thought.
THERAPEUTICS
The treatment of adults with GD is now largely standardized in developed countries, reflecting the
influence of clinical guidelines promulgated by professional associations. The Standards of Care
for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7 (SOC-7;
Coleman et al. 2011) is the best known and most influential guideline; similar recommendations
have been published by the Royal College of Psychiatrists (Wylie et al. 2014), a task force of
the American Psychiatric Association (Byne et al. 2012), the Endocrine Society (Hembree et al.
2009), and other professional groups (for reviews, see Gooren & Asscheman 2014, Lawrence 2014,
Monstrey et al. 2014). These guidelines represent the views of experienced clinicians and scholars,
but many of their recommendations reflect a low quality of evidence (i.e., case-series reports and
expert opinion) (Byne et al. 2012).
The following subsections examine recent developments and controversies related to the treat-
ment of adults with GD. Two broad themes underlie these analyses. First, the contemporary
emphasis on reducing barriers to care and promoting client autonomy and self-determination is
not easily reconciled with some elements of current treatment guidelines. Second, the increasing
diversity of adults who qualify for a GD diagnosis has not been matched by an expanded range of
treatment options addressing this diversity.
www.annualreviews.org Gender Dysphoria in Adults 235
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Diagnosing GD and Comorbid Conditions and the Role
of Mental Health Professionals
The SOC-7 rescinded the longstanding requirement that the diagnosis of GD and any associated
psychopathology be made by mental health professionals (MHPs). Now, any “health professional
who is appropriately trained in behavioral health and competent in the assessment of gender
dysphoria” (Coleman et al. 2011, p. 181) may make these diagnoses and any contingent treatment
recommendations. This change, intended to reduce barriers to care, may unintentionally result in
underdiagnosis of comorbid psychopathology. As noted previously, even experienced MHPs tend
to underdiagnose comorbid psychopathology unless they employ structured clinical interviews.
MHPs have historically served as gatekeepers as well as diagnosticians for adults with GD,
because eligibility for hormone therapy and SRS has traditionally been contingent on assessments
that only MHPs were considered qualified to make. Some clinicians believe that such gatekeeping
functions are unnecessarily time consuming and potentially undermine individuals’ autonomy
and choice (Bouman & Richards 2013). The SOC-7 and other guidelines have deemphasized
the role of MHPs in recommending hormone therapy: Physicians are now allowed to prescribe
hormones without a MHP’s recommendation, particularly for clients using hormones without
medical supervision (Coleman et al. 2011, pp. 187, 191–192; Wylie et al. 2014, pp. 176–177). This
approach to prescribing is sometimes referred to as the informed consent model (Coleman et al.
2011, Deutsch 2012).
This liberalized approach reflects contemporary clinical realities, particularly the widespread
use of nonprescribed hormones by persons with GD. G ´
omez-Gil et al. (2009) reported that
approximately 60% of Spanish MtF applicants for sex reassignment had taken hormones without
medical supervision (see also Simonsen et al. 2015). Interestingly, some evidence indicates that
adults with GD who disregard traditional treatment guidelines and undergo hormone therapy
without the recommendation of a psychiatrist achieve psychosocial outcomes similar to those of
more compliant clients and achieve them more quickly (Pimenoff & Pf¨
afflin 2011).
It is not always clear what the informed consent model means. Deutsch (2012), who surveyed
12 clinics that claimed to prescribe hormones using this model, found that whereas “only four of
the 12 sites required any contact with a mental health provider” (p. 141), the average time clients
spent with MHPs during the intake process was 2.4 hours. Five clinics required a minimum
number of visits or imposed specified waiting periods before prescribing, suggesting a belief that
meaningful informed consent cannot be obtained quickly. It remains unclear whether informed
consent prescribing requires a formal diagnosis of GD or whether any transgender adult who is
able to give consent can receive hormones, regardless of diagnosis. It is similarly uncertain whether
informed consent requires that any comorbid psychopathology be satisfactorily controlled. A close
reading of the SOC-7 suggests that the latter is required—and that the informed consent model
is not very different from the standard model:
The difference between the Informed Consent Model and SOC,Version 7, is that the SOC puts greater
emphasis on the important role that mental health professionals can play in alleviating gender dyspho-
ria ...In the Informed Consent Model, the focus is on obtaining informed consent as the threshold
for the initiation of hormone therapy ...Less emphasis is placed on the provision of mental health
care ...unless significant mental health concerns are identified that would need to be addressed before
hormone prescription. (Coleman et al. 2011, p. 188)
It appears that what one might intuitively consider “informed consent prescribing”—offering
medically supervised hormone therapy without preconditions or delay to any transgender person
236 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
who requests it, is competent to consent (i.e., not psychotic or grossly mentally impaired), and
has received basic information about risks and benefits—is not yet widely available. Given the
prevalence of unsupervised hormone use, such a development is arguably overdue.
Counseling and Psychotherapy for Adults with Gender Dysphoria
In past decades, helping adults with GD find greater acceptance and comfort with their natal sex
and assigned gender was considered a legitimate goal of counseling and psychotherapy, especially
when undertaken at the client’s request. Current guidelines, however, describe such efforts as both
futile and unethical. According to the SOC-7:
Treatment aimed at trying to change a person’s gender identity and lived gender expression to become
more congruent with sex assigned at birth has been attempted in the past (Gelder & Marks 1969;
Greenson 1964), yet without success, particularly in the long-term (Cohen-Kettenis & Kuiper 1984;
Pauly 1965). Such treatment is no longer considered ethical. (Coleman et al. 2011, p. 186)
The citations allegedly demonstrating that such treatment efforts are “without success” date from
30 to 50 years ago, when adults with GD were much less prevalent and diverse than today. It is
recognized that GD can remit in some cases (Marks et al. 2000); perhaps psychotherapy could
facilitate such remission—or a reduction in GD symptoms, with greater congruence between
gender identity and expression and assigned sex—in some subset of the diverse group of adults
whose gender problems now qualify for a diagnosis of GD. Unfortunately, these possibilities have
not yet been investigated, and such investigations are strongly discouraged in the SOC-7. If a
client with GD decided that overt cross-gender expression carried too great a risk of unacceptable
consequences and requested a psychotherapist’s help in trying to make their gender identity
and gender expression more congruent with their assigned sex, would the therapist’s participation
always be unethical, as the SOC-7 seems to assert? If so, the SOC’s position would seem to conflict
with the client’s right to autonomy and self-determination. Perhaps the overarching treatment
goal of psychotherapy for GD—“long-term comfort in ...gender identity expression, with realistic
chances for success in ...relationships, education, and work” (Coleman et al. 2011, p. 184)—could
sometimes best be achieved by supporting clients in a decision to forego gender transition or
overt public cross-gender expression. This psychotherapeutic aim, which was explicitly set forth
in version 6 of the SOC [i.e., “acceptance of the need to maintain a job, provide for the emotional
needs of children, honor a spousal commitment, or not to distress a family member as currently
having a higher priority than the personal wish for constant cross-gender expression” (Meyer et al.
2001, pp. 19–20)], was expunged from the SOC-7.
These issues assume greater importance in light of recent evidence that sex reassignment is
associated with more serious psychological sequelae and more prevalent regret than had previously
been supposed. Two large population-based studies from Sweden (Dhejne et al. 2011, 2014)
are particularly relevant. The 2011 study, discussed previously, described the greatly elevated
prevalence of comorbid psychopathology, death by suicide, and suicide attempts in the cohort of
clients who underwent SRS between 1973 and 2013. The 2014 study examined the prevalence of
“regret applications” (applications for reversal of legal sex reassignment) in clients who underwent
SRS during the 1960–2010 period. Only 2.2% of these clients submitted regret applications, over
one-quarter of which came from the small cohort of clients who underwent SRS before 1972. But
regret applications were made a median of eight years after SRS, so some clients who underwent
SRS recently may yet submit such applications. Moreover, whereas only 10 clients who underwent
SRS between 1972 and 2000 submitted regret applications, 10 others who underwent SRS between
www.annualreviews.org Gender Dysphoria in Adults 237
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
1973 and 2003 died by suicide, and another 29 made documented suicide attempts (Dhejne et al.
2011). This suggests that regret applications underestimate the prevalence of genuine regret
or dissatisfaction after sex reassignment. Moreover, 3.3% of applications for SRS were denied,
sometimes due to comorbid psychopathology or failure to meet diagnostic criteria; had these
applicants undergone SRS under more liberal standards, they might have contributed to a still
greater prevalence of regret. Although a 2.2% prevalence of regret after SRS thus represents a
conservative estimate, it substantially exceeds figures previously reported by Pf¨
afflin (1992; 1.0–
1.5%) and Weitze & Osburg (1996; 0.4%). As Dhejne et al. (2014) noted, “This [difference] might
be explained by the extensive follow-up time in the present study and by the fact that virtually all
cases of regrets are captured in the Swedish registry system” (p. 1543).
A recent meta-analysis by Murad et al. (2010), examining outcomes of sex reassignment in
1,833 participants, confirmed both the benefits and limitations of this treatment. About 86% of
FtMs and 71% of MtFs reported improvement in GD symptoms after sex reassignment; about
84% of MtFs and 78% of FtMs reported improvement in quality of life. Thus, it appears that about
20% of clients do not experience significant benefit from sex reassignment. Many adults with GD
who now undergo sex reassignment would have been considered unsuitable or risky candidates in
years past (Dhejne et al. 2014). Smith et al. (2005) observed that factors predictive of less satisfac-
tory functioning after sex reassignment included nonhomosexual orientation relative to natal sex,
greater dissatisfaction with secondary sex characteristics, and more comorbid psychopathology,
yet adults with late-onset GD and nonhomosexual orientation, physical characteristics that are
highly incongruent with the desired sex, and significant comorbid psychopathology increasingly
request and undergo sex reassignment. Perhaps the SOC should reinstate its endorsement, at least
in certain cases, of psychotherapy that aims to increase comfort with assigned sex and gender role
and discourages sex reassignment.
Real-Life Experience in the Preferred Gender Role
It is now accepted that not all persons with GD will want or need all of the treatment elements
available to them. Accordingly, the SOC-7 endorses hormone therapy, real-life experience (RLE),
and SRS without psychotherapy; hormone therapy and RLE without SRS; and even RLE and SRS
without hormone therapy in certain cases. The ordinary eligibility requirements in the SOC-7,
however, do not allow SRS without a 12-month, full-time RLE, even when the client does not
desire a RLE. This exception to the principle of client autonomy and self-determination has never
been seriously challenged, despite a dearth of evidence supporting the value of RLE as an eligibility
criterion for SRS (Lawrence 2013, Levine 2009). Recognizing that SRS has significant risks, the
SOC-7 does not require adults with GD to undergo SRS if they can achieve satisfactory relief of
GD with hormone therapy and RLE alone. But RLE also carries significant psychosocial risks,
including loss of employment, impaired relationships with family and friends, and gender-based
discrimination and physical and mental abuse. Given these risks, the SOC arguably should not
require adults with GD to undertake a RLE if they can achieve satisfactory relief of GD with
hormone therapy and SRS alone.
This issue will probably soon become moot in light of language in the DSM-5 specifying
that adults with “a strong desire for the primary and secondary sex characteristics of the other
gender” can qualify for a diagnosis of GD on the basis of “a strong desire to be of the other
gender (or some alternative gender different from one’s assigned gender)” (Am. Psychiatr. Assoc.
2013, p. 452). Consequently, adults with GD who want to undergo SRS to achieve the primary
sex characteristics of the other gender but who identify with an “alternative gender” comprising
both male and female elements could theoretically satisfy the eligibility requirement of living for
238 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
12 months in a gender role that is congruent with one’s gender identity (Coleman et al. 2011) by
living part-time in their original gender role (e.g., in public) and part-time in the gender role of
the other sex (e.g., in private). When this option becomes more widely appreciated, the RLE will
be recognized as no longer meaningful and will cease to be an eligibility requirement for SRS.
Hormone Therapy
Recent investigations have largely confirmed the opinion that hormone therapy is an effective and
reasonably safe treatment in adults with GD. As noted previously, Murad et al. (2010) found that
cross-sex hormone treatment, usually accompanied by SRS, was associated with improvement in
GD, other psychological symptoms, and quality of life in about 80% of MtFs and FtMs. Cross-
sectional studies have also shown that hormone-treated MtFs and FtMs who have not undergone
SRS demonstrate significantly better quality of life (Gorin-Lazard et al. 2012), greater self-esteem,
better mood (Gorin-Lazard et al. 2013), and less psychological distress (Heylens et al. 2014b) than
persons who have not yet begun hormone treatment. But hormone therapy can be associated with
significant medical complications. Wierckx et al. (2012) found that, in 50 MtF clients who had
used feminizing hormones for a mean of 9.2 years, there were 3 (6%) thromboembolic events and
3 (6%) other cardiovascular complications, including 2 myocardial infarctions; moreover, about
one-quarter of MtF clients had significant osteoporosis. Wierckx et al. (2012) could not, however,
document any significant cardiovascular events or other serious complications in 50 FtM clients
who had used masculinizing hormones for a mean of approximately 10 years. In a subsequent
prospective study of 53 MtFs and 53 FtMs who received cross-sex hormone therapy for one year,
Wierckx et al. (2014) found no evidence of serious complications.
Hormone therapy for adult males with GD has traditionally included testosterone suppression
with spironolactone, cyproterone acetate (not available in the United States), or GnRH agonists.
Although both the SOC-7 (Coleman et al. 2011) and the Endocrine Society guidelines (Hembree
et al. 2009) mentioned the use of GnRH agonists in adult males with GD, the SOC-7 deempha-
sized GnRH agonists because of their expense and administration by injection or subcutaneous
implantation; it described cyproterone and spironolactone as more cost effective. In contrast, the
recent Royal College of Psychiatrists guidelines (Wylie et al. 2014) emphasized the problems
associated with spironolactone and cyproterone acetate and recommended GnRH agonists as an
“alternative and preferable” means of testosterone suppression in adult males with GD. GnRH
agonists may soon supersede traditional antiandrogens in this role.
Sex Reassignment Surgery
Few controlled studies have examined the psychosocial outcomes of SRS per se. Mate-Kole et al.
(1990) compared 20 MtFs who underwent vaginoplasty on an expedited basis with 20 wait-list
control clients; SRS clients were more socially active and displayed less anxiety, depression, and
obsessionality. Barrett (1998) examined psychological and social functioning in 40 FtMs who had
undergone phalloplasty an average of four years previously and 23 FtMs who had been approved
for, but were still awaiting, phalloplasty; there were no significant between-group differences in
SCL-90-R scores. Udeze et al. (2008) studied 40 MtFs who completed the SCL-90-R before and six
months after undergoing SRS, with each client acting as her own control; no significant differences
in pre- and post-SRS scores were found. In a study discussed previously, Heylens et al. (2014b)
compared SCL-90-R scores in 46 MtFs and 11 FtMs before treatment, after hormone therapy, and
after SRS. Before treatment, clients’ mean subscale scores were significantly higher than those
of general population controls. After hormone therapy, clients’ scores no longer differed from
those of controls, but no further improvement was observed after SRS. Contemporary outcome
www.annualreviews.org Gender Dysphoria in Adults 239
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
studies of SRS are therefore consistent with earlier ones: Although the great majority of adults
with GD report improved subjective satisfaction, objectively measured psychological symptoms
neither improve nor worsen after SRS.
SUMMARY
In this article, we have provided an overview of GD in adults, including terminology and phe-
nomenology, epidemiology, diagnosis and assessment, associated psychopathology, causal mech-
anisms, and therapeutics. As transgender adults have attained increasing recognition, modern
cultures have undergone a remarkable change with regard to acceptance and support of people
with GD, including legal recognition and better access to health care. As more transgender adults
“come out,” we hope that this article will provide the contemporary clinician with a greater un-
derstanding of the research and clinical issues that will inform best practice in working with this
underserved population.
DISCLOSURE
Dr. Zucker was the Chair of the DSM-5 Workgroup on Sexual and Gender Identity Disorders.
LITERATURE CITED
Alonso J, L´
epine JP. 2007. Overview of key data from the European Study of the Epidemiology of Mental
Disorders (ESEMeD). J. Clin. Psychiatry 68(Suppl. 2):3–9
Am. Psychiatr. Assoc. 1968. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am.
Psychiatr. Publ. 2nd ed.
Am. Psychiatr. Assoc. 1980. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am.
Psychiatr. Publ. 3rd ed.
Am. Psychiatr. Assoc. 1994. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am.
Psychiatr. Publ. 4th ed.
Am. Psychiatr. Assoc. 2013. Diagnostic and Statistical Manual of Mental Disorders. Arlington, VA: Am. Psychiatr.
Publ. 5th ed.
Arcelus J, Bouman WP, Van Den Noortgate W, Claes L, Witcomb G, Fernandez-Aranda F. 2015. Systematic
review and meta-analysis of prevalence studies in transsexualism. Eur. Psychiatry 30:807–15
Auer MK, Fuss J, Stalla GK, Athanasoulia P. 2013a. Twenty years of endocrinologic treatment in transsex-
ualism: analyzing the role of chromosomal analysis and hormonal profiling in the diagnostic work-up.
Fertil. Steril. 22:1103–10
Auer MK, H ¨
ohne N, Bazarra-Castro M ´
A, Pfister H, Fuss J, et al. 2013b. Psychopathological profiles in
transsexuals and the challenge of their special status among the sexes. PLOS ONE 8(10):e78469
Ault A, Brzuzy S. 2009. Removing gender identity disorder from the Diagnostic and Statistical Manual of Mental
Disorders: a call for action. Soc. Work 54:187–89
Bailey JM, Dunne MP, Martin NG. 2000. Genetic and environmental influences on sexual orientation and its
correlates in an Australian twin sample. J. Personal. Soc. Psychol. 78:524–36
Bandini E, Fisher AD, Castellini G, Lo Sauro C, Lelli L, et al. 2013. Gender identity disorder and eating
disorders: similarities and differences in terms of body uneasiness. J. Sex. Med. 10:1012–23
Barrett J. 1998. Psychological and social function before and after phalloplasty. Int. J. Transgend. 2:1
Bauer GR, Scheim AI, Pyne J, Travers R, Hammond R. 2015. Intervenable factors associated with suicide
risk in transgender persons: a respondent driven sampling study in Ontario, Canada. BMC Public Health
15:525
Bayer R. 1981. Homosexuality and American Psychiatry: The Politics of Diagnosis. New York: Basic Books
Becker I, Nieder TO, Cerwenka S, Briken P, Kreukels BPC, et al. 2015. Body image in young gender dysphoric
adults: a European multi-center study. Arch. Sex. Behav. doi: 10.1007/s10508-015-0527-z
240 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Bentz EK, Hefler LA, Kaufmann U, Huber JC, Kolbus A, et al. 2008. A polymorphism of the CYP17 gene
related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism.
Fertil. Steril. 90:56–59
Berenbaum SA, Meyer-Bahlburg HFL. 2015. Gender development and sexuality in disorders of sex develop-
ment. Horm. Metab. Res. 47:361–66
Berglund H, Lindstrom P, Dhejne-Helmy C, Savic I. 2008. Male-to-female transsexuals show sex-atypical
hypothalamus activation when smelling odorous steroids. Cereb. Cortex 18:1900–8
Bissinger B. 2015. Call me Caitlyn. Vanity Fair,July.http://www.vanityfair.com/hollywood/2015/06/
caitlyn-jenner-photos-interview-buzz-bissinger
Blanchard R. 1989. The classification and labeling of nonhomosexual gender dysphorias. Arch. Sex. Behav.
18:315–34
Blanchard R. 1994. A structural equation model for age at clinical presentation in nonhomosexual male gender
dysphorics. Arch. Sex. Behav. 23:311–20
Blanchard R. 2004. Quantitative and theoretical analyses of the relation between older brothers and homo-
sexuality in men. J. Theor. Biol. 230:173–87
Blanchard R. 2005. Early history of the concept of autogynephilia. Arch. Sex. Behav. 34:439–46
Blanchard R. 2010. The DSM diagnostic criteria for transvestic fetishism. Arch. Sex. Behav. 39:363–72
Blanchard R, Freund K. 1983. Measuring masculine gender identity in females. J. Consult. Clin. Psychol.
51:205–14
Blanchard R, Steiner BW, Clemmensen L, Dickey R. 1989. Prediction of regrets in postoperative transsexuals.
Can. J. Psychiatry 34:43–45
Bocklandt S, Vilain E. 2007. Sex differences in brain and behavior: hormones versus genes. Adv. Genet. 59:245–
66
Bockting W, Benner A, Coleman E. 2009. Gay and bisexual identity development among female-to-male
transsexuals in North America: emergence of a transgender sexuality. Arch. Sex. Behav. 38:688–701
Bockting WO, Miner MH, Swinburne Romine RE, Hamilton A, Coleman E. 2013. Stigma, mental health,
and resilience in an online sample of the US transgender population. Am. J. Public Health 103:943–51
Bouman WP, Richards C. 2013. Diagnostic and treatment issues for people with gender dysphoria in the
United Kingdom. Sex. Relatsh. Ther. 28:165–71
Budge SL, Adelson JL, Howard KA. 2013. Anxiety and depression in transgender individuals: the roles of
transition status, loss, social support, and coping. J. Consult. Clin. Psychol. 81:545–57
Buhrich N, McConaghy N. 1978. Two transsexuals with 47-XYY karyotype. Br.J.Psychiatry133:77–81
Burri A, Cherkas L, Spector T, Rahman Q. 2011. Genetic and environmental influences on female sexual
orientation, childhood gender typicality and adult gender identity. PLOS ONE 6:e21982
Byne W, Bradley SJ, Coleman E, Eyler AE, Green R, et al. 2012. Report of the American Psychiatric Associ-
ation Task Force on Treatment of Gender Identity Disorder. Arch. Sex. Behav. 41:759–96
Caspi A, Houts RM, Belsky DW, Goldman-Mellor SJ, Harrington H, et al. 2014. The p factor: one general
psychopathology factor in the structure of psychiatric disorders? Clin. Psychol. Sci. 2:119–37
Chivers ML, Bailey JM. 2000. Sexual orientation of female-to-male transsexuals: a comparison of homosexual
and nonhomosexual types. Arch. Sex. Behav. 29:259–78
Claes L, Bouman WP, Witcomb G, Thurston M, Fernandez-Aranda F, Arcelus J. 2015. Non-suicidal self-
injury in trans people: associations with psychological symptoms, victimization, interpersonal functioning,
and perceived social support. J. Sex. Med. 12:168–79
Clements-Nolle K, Marx R, Katz M. 2006. Attempted suicide among transgender persons: the influence of
gender-based discrimination and victimization. J. Homosex. 51(3):53–69
Cohen-Kettenis PT, Arrindell WA. 1990. Perceived parental rearing style, parental divorce and transsexualism:
a controlled study. Psychol. Med. 20:613–20
Cole CM, O’Boyle M, Emory LE, Meyer WJ. 1997. Comorbidity of gender dysphoria and other major
psychiatric diagnoses. Arch. Sex. Behav. 26:13–26
Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, et al. 2011. Standards of Care for the
Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7.Int. J. Transgend. 13:165–
232
www.annualreviews.org Gender Dysphoria in Adults 241
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Colizzi M, Costa R, Todarello O. 2014. Transsexual patients’ psychiatric comorbidity and positive effect of
cross-sex hormonal treatment on mental health: results from a longitudinal study. Psychoneuroendocrinology
39:65–73
Colizzi M, Costa R, Todarello O. 2015. Dissociative symptoms in individuals with gender dysphoria: Is the
elevated prevalence real? Psychiatry Res. 226:173–80
Conron KJ, Scott G, Stowell GS, Landers SJ. 2012. Transgender health in Massachusetts: results from a
household probability sample of adults. Am. J. Public Health 102:118–22
Davey A, Bouman WP, Arcelus J, Meyer C. 2014. Social support and psychological well-being in gender
dysphoria: a comparison of patients with matched controls. J. Sex. Med. 11:2976–85
De Cuypere G, Elaut E, Heylens G, Van Maele G, Selvaggi G, et al. 2006. Long-term follow-up: psychosocial
outcomes of Belgian transsexuals after sex reassignment surgery. Sexologies 15:126–33
De Cuypere G, Janes C, Rubens R. 1995. Psychosocial functioning of transsexuals in Belgium. Acta Psychiatr.
Scand. 91:180–84
Deogracias JJ, Johnson LL, Meyer-Bahlburg HFL, Kessler SJ, Schober JM, Zucker KJ. 2007. The gender
identity/gender dysphoria questionnaire for adolescents and adults. J. Sex. Res. 44:370–79
Deutsch MB. 2012. Use of the informed consent model in the provision of cross-sex hormone therapy: a
survey of the practices of selected clinics. Int. J. Transgend. 13:140–46
Dhejne C, Lichtenstein P, Boman M, Johansson AL, La˚ ngstr ¨
om N, Land´
en M. 2011. Long-term follow-
up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLOS ONE
6(2):e16885
Dhejne C, Oberg K, Arver S, Landen M. 2014. An analysis of all applications for sex reassignment surgery in
Sweden, 2016–2010: prevalence, incidence, and regrets. Arch. Sex. Behav. 43:1535–45
Diamond LM, Butterworth M. 2008. Questioning gender and sexual identity: dynamic links over time. Sex
Roles 59:365–76
Dreger AD. 2008. The controversy surrounding The Man Who Would Be Queen: a case history of the politics
of science, identity, and sex in the Internet age. Arch. Sex. Behav. 37:366–421
Drescher J. 2010. Queer diagnoses: parallels and contrasts in the history of homosexuality, gender variance,
and the Diagnostic and Statistical Manual.Arch. Sex. Behav. 39:427–60
Drescher J. 2013. Controversies in gender diagnoses. LGBT Health 1:10–14
Drescher J. 2015. Queer diagnoses revisited: the past and future of homosexuality and gender diagnoses in
DSM and ICD. Int. Rev. Psychiatry 27:386–95
Drescher J, Cohen-Kettenis P, Winter S. 2012. Minding the body: situating gender identity diagnoses in the
ICD-11. Int. Rev. Psychiatry 24:568–77
Drummond KD, Bradley SJ, Badali-Peterson M, Zucker KJ. 2008. A follow-up study of girls with gender
identity disorder. Dev. Psychol. 44:34–45
Fern´
andez R, Esteva I, G ´
omez-Gil E, Rumbo T, Almaraz MC, et al. 2014a. The (CA)n polymorphism of ERβ
gene is associated with FtM transsexualism. J. Sex. Med. 11:720–28
Fern´
andez R, Esteva I, G ´
omez-Gil E, Rumbo T, Almaraz MC, et al. 2014b. Association study of ERβ,AR,
and CYP19A1 genes and MtF transsexualism. J. Sex. Med. 11:2986–94
Feusner JD, Dervisic J, Kosidou K, Dhejne C, Bookheimer S, Savic I. 2015. Female-to-male transsexual
individuals demonstrate different own body identification. Arch. Sex. Behav. doi: 10.1007/s10508-015-
0596-z
First MB, Reed GM, Hyman SE, Saxena S. 2015. The development of the ICD-11 clinical descriptions and
diagnostic guidelines for mental and behavioural disorders. World Psychiatry 14:82–90
Fisher AD, Bandini E, Casale H, Ferruccio N, Meriggiola MC, et al. 2013. Sociodemographic and clinical
features of gender identity disorder: an Italian multicentric evaluation. J. Sex. Med. 10:408–19
Fisk N. 1974. Gender dysphoria syndrome (the how, what, and why of a disease). In Proceedings of the Second
Interdisciplinary Symposium on Gender Dysphoria Syndrome, ed. D Laub, P Gandy, pp. 7–14. Palo Alto, CA:
Stanford Univ. Press
Freund K, Blanchard R. 1983. Is the distant relationship of fathers and homosexual sons related to the sons’
erotic preference for male partners, of the sons’ atypical gender identity, or to both? J. Homosex. 9:7–25
Freund K, Langevin R, Satterberg J, Steiner B. 1977. Extension of the Gender Identity Scale for males. Arch.
Sex. Behav. 6:507–19
242 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Garber J, Hollon SD. 1991. What can specificity designs say about causality in psychopathology research?
Psychol. Bull. 110:129–36
Garcia-Falgueras A, Swaab DF. 2008. A sex difference in the hypothalamic uncinate nucleus: relationship to
gender identity. Brain 131:3132–46
Gizewski ER, Krause E, Schlamann M, Happich F, Ladd ME, et al. 2009. Specific cerebral activation due to
visual erotic stimuli in male-to-female transsexuals compared with male and female controls: an fMRI
study. J. Sex. Med. 6:440–48
G´
omez-Gil E, Esteva I, Almaraz MC, Pasaro E, Segovia S, Guillamon A. 2010. Familiality of gender identity
disorder in non-twin siblings. Arch. Sex. Behav. 39:546–52
G´
omez-Gil E, Trilla A, Salamero M, God´
as T, Vald´
es M. 2009. Sociodemographic, clinical, and psychiatric
characteristics of transsexuals from Spain. Arch. Sex. Behav. 38:378–92
G´
omez-Gil E, Vidal-Hagemeijer A, Salamero M. 2008. MMPI-2 characteristics of transsexuals requesting sex
reassignment: comparison of patients in prehormonal and presurgical phases. J. Personal. Assess. 90:368–74
Gooren L, Asscheman H. 2014. Sex reassignment: endocrinological interventions in adults with gender dys-
phoria. In Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge,ed.BPC
Kreukels, TD Steensma, ALC de Vries, pp. 277–97. New York: Springer
Gorin-Lazard A, Baumstarck K, Boyer L, Maquigneau A, Gebleux S, et al. 2012. Is hormonal therapy associated
with better quality of life in transsexuals? A cross-sectional study. J. Sex. Med. 9:531–41
Gorin-Lazard A, Baumstarck K, Boyer L, Maquigneau A, Penochet JC, et al. 2013. Hormonal therapy is
associated with better self-esteem, mood, and quality of life in transsexuals. J. Nerv. Ment. Dis. 201:996–
1000
Gray E. 2014. The transgender tipping point. Time,June9.http://time.com/135480/transgender-tipping-
point/
Green R. 1987. The “Sissy Boy Syndrome” and the Development of Homosexuality. New Haven, CT: Yale Univ.
Press
Green R. 2009. The three kings: Harry Benjamin, John Money, Robert Stoller. Arch. Sex. Behav. 38:610–13
Guzm´
an-Parra J, S´
anchez- ´
Alvarez N, de Diego-Otero Y, P´
erez-Costillas L, Esteva de Antonio I, et al. 2015.
Sociodemographic characteristics and psychological adjustment among transsexuals in Spain. Arch. Sex.
Behav. doi: 10.1007/s10508-015-0557-6
Hahn A, Kranz GS, K ¨
ublb ¨
ock M, Kaufmann U, Ganger S, et al. 2014. Structural connectivity networks of
transgender people. Cereb. Cortex 25:3527–34
Haraldsen IR, Dahl AA. 2000. Symptom profiles of gender dysphoric patients of transsexual type compared
to patients with personality disorders and healthy adults. Acta Psychiatr. Scand. 102:276–81
Hare L, Bernard P, S´
anchez FJ, Baird PN, Vilain E, et al. 2009. Androgen receptor repeat length polymorphism
associated with male-to-female transsexualism. Biol. Psychiatry 65:93–96
Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ 3rd, et al. 2009.
Endocrine treatment of transsexual persons: an Endocrine Society Clinical Practice Guideline. J. Clin.
Endocrinol. Metab. 94:3132–54
Henningsson S, Westberg L, Nilsson S, Lundstr¨
om B, Ekselius L, et al. 2005. Sex steroid-related genes and
male-to-female transsexualism. Psychoneuroendocrinology 30:657–64
Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A. 2005. Psychiatric comorbidity in gender identity
disorder. J. Psychosom. Res. 58:259–61
Herdt G, ed. 1994. Third Sex, Third Gender: Beyond Sexual Dimorphism in Culture and History. New York: Zone
Books
Heylens G, De Cuypere G, Zucker KJ, Schelfaut C, Elaut E, et al. 2012. Gender identity disorder in twins: a
review of the case report literature. J. Sex. Med. 9:751–57
Heylens G, Elaut E, Kreukels BP, Paap MC, Cerwenka S, et al. 2014a. Psychiatric characteristics in transsexual
individuals: multicentre study in four European countries. Br.J.Psychiatry204:151–56
Heylens G, Verroken C, De Cock S, T’Sjoen G, De Cuypere G. 2014b. Effects of different steps in gender
reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder.
J. Sex. Med. 11:119–26
Hoshiai M, Matsumoto Y, Sato T, Ohnishi M, Okabe N, et al. 2010. Psychiatric comorbidity among patients
with gender identity disorder. Psychiatry Clin. Neurosci. 64:514–19
www.annualreviews.org Gender Dysphoria in Adults 243
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Hwu H-G, Yeh E-K, Chang L-Y. 1989. Prevalence of psychiatric disorders in Taiwan defined by the Chinese
Diagnostic Interview Schedule. Acta Psychiatr. Scand. 79:136–47
Judge C, O’Donovan C, Callaghan G, Gaoatswe G, O’Shea D. 2014. Gender dysphoria—prevalence and
co-morbidities in an Irish adult population. Front. Endocrinol. 5:87
Junger J, Habel U, Brohr S, Neulen J, Neuschaefer-Rube C, et al. 2014. More than just two sexes: the neural
correlates of voice gender perception in gender dysphoria. PLOS ONE 9:e111672
Khandelwal A, Agarwal A, Jiloha RC. 2010. A 47,XXY female with gender identity disorder. Arch. Sex. Behav.
39:1021–23
Kraemer B, Delsignore A, Schnyder U, Hepp U. 2008. Body image and transsexualism. Psychopathology 41:96–
100
Kranz GS, Hahn A, Baldinger P, Haeusler D, Philippe C, et al. 2014a. Cerebral serotonin transporter asym-
metry in females, males and male-to-female transsexuals measured by PET in vivo. Brain Struct. Funct.
219:171–83
Kranz GS, Hahn A, Kaufmann U, K ¨
ublb ¨
ock M, Hummer A, et al. 2014b. White matter microstructure in
transsexuals and controls investigated by diffusion tensor imaging. J. Neurosci. 34:15466–75
Kraus C. 2015. Classifying intersex in DSM-5: critical reflections on gender dysphoria. Arch. Sex. Behav.
44:1147–63
Kruijver FP, Zhou JN, Pool CW, Hofman MA, Gooren LJ, et al. 2000. Male-to-female transsexuals have
female neuron numbers in a limbic nucleus. J. Clin. Endocrinol. Metab. 85:2034–41
Ku H-L, Lin C-S, Chao H-T, Tu P-C, Li C-T, et al. 2013. Brain signature characterizing the body-brain-mind
axis of transsexuals. PLOS ONE 8:e70808
Kuyper L, Wijsen C. 2014. Gender identities and gender dysphoria in the Netherlands. Arch. Sex. Behav.
43:377–85
Land´
en M, Wa˚ linder J, Lundstr¨
om B. 1998. Clinical characteristics of a total cohort of female and male
applicants for sex reassignment: a descriptive study. Acta Psychiatr. Scand. 97:189–94
Lawrence AA. 2010. Sexual orientation versus age of onset as bases for typologies (subtypes) of gender identity
disorder in adolescents and adults. Arch. Sex. Behav. 39:514–45
Lawrence AA. 2013. Men Trapped in Men’s Bodies: Narratives of Autogynephilic Transsexualism. New York:
Springer
Lawrence AA. 2014. Treatment of gender dysphoria. In Gabbard’s Treatments of Psychiatric Disorders,ed.GO
Gabbard, pp. 695–719. Arlington, VA: Am. Psychiatr. Publ. 5th ed.
Levine SB. 2009. Real-life test experience: recommendations for revisions to the Standards of Care of the
World Professional Association for Transgender Health. Int. J. Transgend. 11:186–93
Lindgren TW, Pauly IB. 1975. A body image scale for transsexuals. Arch. Sex. Behav. 4:639–56
Loehlin JC, Jonsson EG, Gustavsson JP, Stallings MC, Gillespie NA, et al. 2005. Psychological masculinity-
femininity via the gender diagnosticity approach: heritability and consistency across ages and populations.
J. Personal. 73:1295–319
Luders E, Sanchez FJ, Gaser C, Toga AW, Narr KL, et al. 2009. Regional gray matter variation in male-to-
female transsexualism. NeuroImage 46:904–7
Luders E, Sanchez FJ, Tosun D, Shattuck DW, Gaser C, et al. 2012. Increased cortical thickness in male-to-
female transsexualism. J. Behav. Brain Sci. 2:357–62
Madeddu F, Prunas A, Hartmann D. 2009. Prevalence of Axis II disorders in a sample of clients undertaking
psychiatric evaluation for sex reassignment surgery. Psychiatr. Q. 80:261–67
Marks I, Green R, Mataix-Cols D. 2000. Adult gender identity disorder can remit. Compr. Psychiatry 41:273–75
Martin CL, Ruble DN, Szkrybalo J. 2002. Cognitive theories of early gender development. Psychol. Bull.
128:903–33
Martin H, Finn SE. 2010. Masculinity and Femininity in the MMPI-2 and MMPI-A. Minneapolis: Univ. Minn.
Press
Mate-Kole C, Freschi M, Robin A. 1990. A controlled study of psychological and social change after surgical
gender reassignment in selected male transsexuals. Br. J. Psychiatry 157:261–64
Mazaheri Meybodi A, Hajebi A, Ghanbari Jolfaei A. 2014a. Psychiatric Axis I comorbidities among patients
with gender dysphoria. Psychiatry J. 2014:971814
244 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Mazaheri Meybodi A, Hajebi A, Ghanbari Jolfaei A. 2014b. The frequency of personality disorders in patients
with gender identity disorder. Med. J. Islam. Repub. Iran 28:90
Meyer IH. 2003. Prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: conceptual
issues and research evidence. Psychol. Bull. 129:674–97
Meyer W, Bockting WO, Cohen-Kettenis P, Coleman E, DeCeglie H, et al. 2001. The Standards of Care for
Gender Identity Disorders, Sixth Version. D¨
usseldorf, Ger.: Symposion
Meyer-Bahlburg HFL. 1994. Intersexuality and the diagnosis of gender identity disorder. Arch. Sex. Behav.
23:21–40
Meyer-Bahlburg HFL. 2010. From mental disorder to iatrogenic hypogonadism: dilemmas in conceptualizing
gender identity variants as psychiatric conditions. Arch. Sex. Behav. 39:461–76
Meyer-Bahlburg HFL. 2011. Transsexualism (“gender identity disorder”): a CNS-limited form of intersexu-
ality? Adv. Exp. Med. Biol. 707:75–79
Meyer-Bahlburg HFL. 2015. Commentary on Kraus’ (2015) “Classifying Intersex in DSM-5: Critical Reflec-
tions on Gender Dysphoria.” Arch. Sex. Behav. 44:1737–40
Meyerowitz J. 2002. How Sex Changed: A History of Transsexuality in the United States. Cambridge, MA: Harvard
Univ. Press
Miach PP, Berah EF, Butcher JN, Rouse S. 2000. Utility of the MMPI-2 in assessing gender dysphoric
patients. J. Personal. Assess. 75:268–79
Monstrey SJ, Buncamper M, Bouman M-B, Hoebeke P. 2014. Surgical interventions for gender dysphoria.
In Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge, ed. BPC Kreukels,
TD Steensma, ALC de Vries, pp. 299–318. New York: Springer
Murad MH, Elamin MB, Garcia MZ, Mullan RJ, Murad A, et al. 2010. Hormonal therapy and sex reassign-
ment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin. Endocrinol.
72:214–31
Newfield E, Hart S, Dibble S, Kohler L. 2006. Female-to-male transgender quality of life. Qual. Life Res.
15:1447–57
Newman DL, Moffitt TE, Caspi A, Silva PA. 1998. Comorbid mental disorders: implications for treatment
and sample selection. J. Abnorm. Psychol. 107:305–11
Nieder TO, Herff M, Cerwenka S, Preuss WF, Cohen-Kettenis PT, et al. 2011. Age of onset and sexual
orientation in transsexual males and females. J. Sex. Med. 8:783–91
Nuttbrock L, Bockting W, Rosenblum A, Hwahng S, Mason M, et al. 2013. Gender abuse, depressive symp-
toms, and HIV and other sexually transmitted infections among male-to-female transgender persons: a
three-year prospective study. Am. J. Public Health 103:300–7
Pascoe EA, Smart Richman L. 2009. Perceived discrimination and health: a meta-analytic review. Psychol. Bull.
135:531–54
Pasterski V, Zucker KJ, Hindmarsh PC, Hughes IA, Acerini C, et al. 2015. Increased cross-gender identifi-
cation independent of gender role behavior in girls with congenital adrenal hyperplasia: results from a
standardized assessment of 4- to 11-year-old children. Arch. Sex. Behav. 43:1363–75
Pf¨
afflin F. 1992. Regrets after sex reassignment surgery. J. Psychol. Hum. Sex. 5:69–85
Phoenix CH, Goy RW, Gerall AA, Young WC. 1959. Organizing action of prenatally administered testos-
terone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65:369–
82
Pieterse AL, Todd NR, Neville HA, Carter RT. 2012. Perceived racism and mental health among Black
American adults: a meta-analytic review. J. Couns. Psychol. 59:1–9
Pimenoff V, Pf¨
afflin F. 2011. Transsexualism: treatment outcome of compliant and noncompliant patients.
Int. J. Transgend. 13:37–44
Rametti G, Carrillo B, Gomez-Gil E, Junque C, Segovia S, et al. 2011a. White matter microstructure in female
to male transsexuals before cross-sex hormonal treatment: a diffusion tensor imaging study. J. Psychiatr.
Res. 45:199–204
Rametti G, Carrillo B, Gomez-Gil E, Junque C, Zubiarre-Elorza L, et al. 2011b. The microstructure of white
matter in male to female transsexuals before cross-sex hormonal treatment: a DTI study. J. Psychiatr. Res.
45:949–54
www.annualreviews.org Gender Dysphoria in Adults 245
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Richter-Appelt H, Sandberg DE. 2010. Should disorders of sex development be an exclusion criterion for
gender identity disorder in DSM 5? Int. J. Transgend. 12:94–99
Robins LN, Helzer JE, Croughan J, Ratcliff KS. 1981. National Institute of Mental Health Diagnostic Inter-
view Schedule: its history, characteristics, and validity. Arch. Gen. Psychiatry 38:381–89
Santarnecchi E, Vatti G, Dettore D, Rossi A. 2012. Intrinsic cerebral connectivity analysis in an untreated
female-to-male transsexual subject: a first attempt using resting-state fMRI. Neuroendocrinology 96:188–93
Savic I, Arver S. 2011. Sex dimorphism of the brain in male-to-female transsexuals. Cereb. Cortex 21:2525–33
Schaefer LC, Wheeler CC. 1995. Harry Benjamin’s first ten cases (1938–1953): a clinical historical note. Arch.
Sex. Behav. 24:73–93
Schneider C, Cerwenka S, Nieder TO, Briken P, Cohen-Kettenis PT, et al. 2015. Measuring gender dysphoria:
a multicenter examination and comparison of the Utrecht Gender Dysphoria Scale and the Gender
Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. Arch. Sex. Behav. In press
Sch ¨
oning S, Engelien A, Bauer C, Kugel H, Kersting A, et al. 2010. Neuroimaging differences in spatial
cognition between men and male-to-female transsexuals before and during hormone therapy. J. Sex.
Med. 7:1858–67
Simon L, Kozak LR, Simon V, Czobor P, Unoka Z, et al. 2013. Regional grey matter structure differences
between transsexuals and healthy controls—a voxel based morphometry study. PLOS ONE 8:e83947
Simon L, Zsolt U, Fogd D, Czobor P. 2011. Dysfunctional core beliefs, perceived parenting behavior and
psychopathology in gender identity disorder: a comparison of male-to-female, female-to-male transsexual
and nontranssexual control subjects. J. Behav. Ther. Exp. Psychiatry 42:38–45
Simonsen R, Hald GM, Giraldi A, Kristensen E. 2015. Sociodemographic study of Danish individuals diag-
nosed with transsexualism. Sex. Med. 3:109–17
Singh D. 2012. A follow-up study of boys with gender identity disorder. PhD Thesis, Univ. Toronto
Singh D, Deogracias JJ, Johnson LL, Bradley SJ, Kibblewhite SJ, et al. 2010. The gender identity/gender
dysphoria questionnaire for adolescents and adults: further validity evidence. J. Sex. Res. 47:49–58
Singh D, McMain S, Zucker KJ. 2011. Gender identity and sexual orientation in women with borderline
personality disorder. J. Sex. Med. 8:447–54
Smith YLS, van Goozen SHM, Kuiper AJ, Cohen-Kettenis PT. 2005. Sex reassignment: outcomes and pre-
dictors of treatment for adolescent and adult transsexuals. Psychol. Med. 35:89–99
Soleman RS, Staphorsius AS, Cohen-Kettenis PT, Lambalk CB, Veltman DJ, et al. 2016. Oestrogens are not
related to emotional processing: a study of regional brain activity in female-to-male transsexuals under
gonadal suppression. Cereb. Cortex 26:510–16
Steensma TD, McGuire JK, Kreukels BPC, Beekman AJ, Cohen-Kettenis PT. 2013a. Factors associated with
desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J. Am. Acad.
Child Adolesc. Psychiatry 52:582–90
Steensma TD, van der Ende J, Verhulst FC, Cohen-Kettenis PT. 2013b. Gender variance in childhood and
sexual orientation in adulthood: a prospective study. J. Sex. Med. 10:2723–33
Stef´
ansson JG, L´
ındal E, Bj ¨
ornsson JK, Gu ˆ
omundsd ´
ottir ´
A. 1994. Period prevalence rates of specific mental
disorders in an Icelandic cohort. Soc. Psychiatry Psychiatr. Epidemiol. 29:119–25
Steinmetz K. 2015. Why it’s a big deal that Obama said “transgender.” Time, Jan 21. http://time.com/
3676881/state-of-the-union-2015-barack-obama-transgender/
Stoller RJ. 1968. Sex and Gender,Vol.1:On the Development of Masculinity and Femininity.NewYork:Science
House
Stoller RJ. 1975. Sex and Gender,Vol.2:The Transsexual Experiment. New York: Jason Aronson
Swaab DF, Garcia-Falgueras A. 2009. Sexual differentiation of the human brain in relation to gender identity
and sexual orientation. Funct. Neurol. 24:17–28
Terada S, Matsumoto Y, Sato T, Okabe N, Kishimoto Y, Uchitomi Y. 2011. Suicidal ideation among patients
with gender identity disorder. Psychiatry Res. 190:159–62
Terada S, Matsumoto Y, Sato T, Okabe N, Kishimoto Y, Uchitomi Y. 2012. Factors predicting psychiatric
co-morbidity in gender-dysphoric adults. Psychiatry Res. 200:469–74
Udeze B, Abdelmawla N, Khoosal D, Terry T. 2008. Psychological functions in male-to-female transsexual
people before and after surgery. Sex. Relatsh. Ther. 23:141–45
246 Zucker ·Lawrence ·Kreukels
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12CH09-Zucker ARI 24 February 2016 11:49
Ujike H, Otani K, Nakatsuka M, Ishii K, Sasaki A, et al. 2009. Association study of gender identity disorder
and sex hormone-related genes. Prog. Neuropsychopharmacol. Biol. Psychiatry 33:1241–44
Van Caenegem E, Wierckx K, Elaut E, Buysse A, Dewaele A, et al. 2015. Prevalence of gender nonconformity
in Flanders, Belgium. Arch. Sex. Behav. 44:1281–87
van de Grift T, Cohen-Kettenis PT, Steensma TD, De Cuypere G, Richter-Appelt H, et al. 2015. Body
satisfaction and physical appearance in gender dysphoria. Arch. Sex. Behav. doi: 10.1007/s10508-015-
0614-1
Vance SR, Cohen-Kettenis PT, Drescher J, Meyer-Bahlburg HFL, Pf¨
afflin F, Zucker KJ. 2010. Opinions
about the DSM gender identity disorder diagnosis: results from an international survey administered to
organizations concerned with the welfare of transgender people. Int. J. Transgend. 12:1–14
Veale JF. 2008. Prevalence of transsexualism among New Zealand passport holders. Aust. N. Z. J. Psychiatry
42:887–89
Vocks S, Stahn C, Loenser K, Legenbauer T. 2009. Eating and body image disturbances in male-to-female
and female-to-male transsexuals. Arch. Sex. Behav. 38:364–77
Wallen K. 2009. The organizational hypothesis: reflections on the 50th anniversary of the publication of
Phoenix, Goy, Gerall, and Young 1959. Horm. Behav. 55:561–65
Wallien MSC, Cohen-Kettenis PT. 2008. Psychosexual outcome of gender dysphoric children. J. Am. Acad.
Child Adolesc. Psychiatry 47:1413–23
Weitze C, Osburg S. 1996. Transsexualism in Germany: empirical data on epidemiology and application of
the German Transsexuals’ Act during its first ten years. Arch. Sex. Behav. 25:409–25
Wierckx K, Mueller S, Weyers S, Van Caenegem E, Roef G, et al. 2012. Long-term evaluation of cross-sex
hormone treatment in transsexual persons. J. Sex. Med. 9:2641–51
Wierckx K, Van Caenegem E, Schreiner T, Haraldsen I, Fisher A, et al. 2014. Cross-sex hormone therapy
in trans persons is safe and effective at short-time follow-up: results from the European Network for the
Investigation of Gender Incongruence. J. Sex. Med. 11:1999–2011
Wise TN, Meyer JK. 1980. The border area between transvestism and gender dysphoria: transvestitic appli-
cants for sex reassignment. Arch. Sex. Behav. 9:327–42
Wylie K, Barrett J, Besser M, Bouman WP, Bridgman M, et al. 2014. Good practice guidelines for the
assessment and treatment of adults with gender dysphoria. Sex. Relatsh. Ther. 29:154–214
Zhou JN, Hofman MA, Gooren LJ, Swaab DF. 1995. A sex difference in the human brain and its relation to
transsexuality. Nature 378:68–70
Zubiaurre-Elorza L, Junque C, Gomez-Gil E, Segovia S, Carrillo B, et al. 2013. Cortical thickness in untreated
transsexuals. Cereb. Cortex 23:2855–62
Zucker KJ, Cohen-Kettenis PT, Drescher J, Meyer-Bahlburg HFL, Pf¨
afflin F, Womack WM. 2013. Memo
outlining evidence for change for gender identity disorder in the DSM-5. Arch. Sex. Behav. 42:901–14
Zucker KJ, Duschinsky R. 2016. Dilemmas encountered by the Sexual and Gender Identity Disorders Work
Group for DSM-5: an interview with Kenneth J. Zucker. Psychol. Sex. 7:23–33
Zucker KJ, Lawrence AA. 2009. Epidemiology of gender identity disorder. Int. J. Transgend. 11:8–18
RELATED RESOURCES
Lin CS, Ku HL, Chao HT, Tu PC, Li CT, Cheng CM, et al. 2014. Neural network of body
representation differs between transsexuals and cissexuals. PLOS ONE 9:e85914
Lobato MI, Koff WJ, Manenti C, da Fonseca Seger D, Salvador J, et al. 2006. Follow-up of sex
reassignment surgery in transsexuals: a Brazilian cohort. Arch. Sex. Behav. 35:711–15
Mathy RM. 2003. Transgender identity and suicidality in a nonclinical sample: sexual orientation,
psychiatric history, and compulsive behaviors. J. Psychol. Hum. Sex. 14:47–65
Nawata H, Ogomori K, Tanaka M, Nishimura R, Urashima H, et al. 2010. Regional cerebral blood
flow changes in female to male gender identity disorder. Psychiatry Clin. Neurosci. 64:157–61
Verschoor AM, Poortinga J. 1988. Psychosocial differences between Dutch male and female
transsexuals. Arch. Sex. Behav. 17:173–78
www.annualreviews.org Gender Dysphoria in Adults 247
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12-FrontMatter ARI 2 March 2016 14:46
Annual Review of
Clinical Psychology
Volume 12, 2016
Contents
The Efficacy of Exposure Therapy for Anxiety-Related Disorders and
Its Underlying Mechanisms: The Case of OCD and PTSD
Edna B. Foa and Carmen P. McLean pppppppppppppppppppppppppppppppppppppppppppppppppppppppp1
History of the Concept of Addiction
Peter E. Nathan, Mandy Conrad, and Anne Helene Skinstad ppppppppppppppppppppppppppppp29
Conducting Clinical Research Using Crowdsourced Convenience
Samples
Jesse Chandler and Danielle Shapiro pppppppppppppppppppppppppppppppppppppppppppppppppppppppp53
Computerized Adaptive Diagnosis and Testing of Mental Health
Disorders
Robert D. Gibbons, David J. Weiss, Ellen Frank, and David Kupfer ppppppppppppppppppppp83
Diagnostic Issues and Controversies in DSM-5: Return of the False
Positives Problem
Jerome C. Wakefield pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp105
The Importance of Considering Clinical Utility in the Construction of
a Diagnostic Manual
Stephanie N. Mullins-Sweatt, Gregory J. Lengel, and Hilary L. DeShong pppppppppppp133
Internet-Delivered Psychological Treatments
Gerhard Andersson ppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp157
Developmental Demands of Cognitive Behavioral Therapy for
Depression in Children and Adolescents: Cognitive, Social,
and Emotional Processes
Judy Garber, Sarah A. Frankel, and Catherine G. Herrington ppppppppppppppppppppppppp181
Gender Dysphoria in Adults
Kenneth J. Zucker, Anne A. Lawrence, and Baudewijntje P.C. Kreukels ppppppppppppppp217
Mental Imagery in Depression: Phenomenology, Potential
Mechanisms, and Treatment Implications
Emily A. Holmes, Simon E. Blackwell, Stephanie Burnett Heyes, Fritz Renner,
and Filip Raes pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp249
vii
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
CP12-FrontMatter ARI 2 March 2016 14:46
Resolving Ambiguity in Emotional Disorders: The Nature and Role of
Interpretation Biases
Colette R. Hirsch, Frances Meeten, Charlotte Krah´e, and Clare Reeder ppppppppppppppppp281
Suicide, Suicide Attempts, and Suicidal Ideation
E. David Klonsky, Alexis M. May, and Boaz Y. Saffer pppppppppppppppppppppppppppppppppp307
The Neurobiology of Intervention and Prevention in Early Adversity
Philip A. Fisher, Kate G. Beauchamp, Leslie E. Roos, Laura K. Noll,
Jessica Flannery, and Brianna C. Delker pppppppppppppppppppppppppppppppppppppppppppppp331
Interactive and Mediational Etiologic Models of Eating Disorder
Onset: Evidence from Prospective Studies
Eric Stice pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp359
Paraphilias in the DSM-5
Anthony R. Beech, Michael H. Miner, and David Thornton pppppppppppppppppppppppppppp383
The Role of Craving in Substance Use Disorders: Theoretical and
Methodological Issues
Michael A. Sayette pppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppp407
Clashing Diagnostic Approaches: DSM-ICD Versus RDoC
Scott O. Lilienfeld and Michael T. Treadway ppppppppppppppppppppppppppppppppppppppppppppp435
Mental Health in Lesbian, Gay, Bisexual, and Transgender (LGBT)
Youth
Stephen T. Russell and Jessica N. Fish ppppppppppppppppppppppppppppppppppppppppppppppppppppp465
Risk Assessment in Criminal Sentencing
John Monahan and Jennifer L. Skeem pppppppppppppppppppppppppppppppppppppppppppppppppppp489
The Relevance of the Affordable Care Act for Improving Mental
Health Care
David Mechanic and Mark Olfson pppppppppppppppppppppppppppppppppppppppppppppppppppppppp515
Indexes
Cumulative Index of Contributing Authors, Volumes 3–12 pppppppppppppppppppppppppppp543
Cumulative Index of Article Titles, Volumes 3–12 ppppppppppppppppppppppppppppppppppppppp548
Errata
An online log of corrections to Annual Review of Clinical Psychology articles may be
found at http://www.annualreviews.org/errata/clinpsy
viii Contents
Annu. Rev. Clin. Psychol. 2016.12:217-247. Downloaded from www.annualreviews.org
Access provided by University of Toronto Library on 03/30/16. For personal use only.
... Although there are many studies investigating the etiology of GD, we still do not know what the etiology of GD is. However, the available information about the etiology of GD indicates that the role of biological mechanisms [4][5][6], such as genetic factors [7][8][9][10] and prenatal androgen exposure [11][12][13], is more pertinent than the role of environmental factors [14], such as parental relationships [5,14]. ...
... Although there are many studies investigating the etiology of GD, we still do not know what the etiology of GD is. However, the available information about the etiology of GD indicates that the role of biological mechanisms [4][5][6], such as genetic factors [7][8][9][10] and prenatal androgen exposure [11][12][13], is more pertinent than the role of environmental factors [14], such as parental relationships [5,14]. ...
... These results pave the path for candidate gene association [7,8,16,17], and epigenetic [18,19] and brain-structure studies [6] in the field. Most genetic studies that analyze the genetic component of gender formation, based on the known effects of sex hormones on the sexual differentiation of the brain [11][12][13][14]20], focus on the receptors of these hormones or on genes that have an effect on their synthesis pathways [8]. These studies examine the implications of genetic polymorphisms related to the androgen receptor, estrogen receptor-alpha and beta (ER-α, ER-β), and aromatase in GD individuals (CYP17A1 and CYP19A) [16,[21][22][23][24], as well as their haplotypes and the interaction effects between their polymorphisms [17,25]. ...
Article
Full-text available
The role of genetics in the etiology of gender dysphoria (GD) is an important yet understudied area. Yet whether genetic analysis should be carried out during the gender affirmation process at all is a matter of debate. This study aims to evaluate the cytogenetic and molecular genetic findings of individuals with GD. We retrospectively reviewed the medical records of individuals with GD who were followed up in a tertiary clinic. After the exclusion criteria were applied, the study sample consisted of 918 individuals with GD; 691 of whom had female-to-male (FtM) and 227 male-to-female (MtF) GD. The cytogenetic analysis revealed that 223 out of 227 (98.2%) individuals with MtF GD had the 46,XY karyotype, while 683 out of 691 (98.8%) individuals with FtM GD had the 46,XX karyotype. In the Y chromosome microdeletion analysis, azospermic factor c (AZFc) deletion was detected in only two individuals with MtF GD. Our findings suggest that there are few chromosomal abnormalities in individuals with GD. Thus, this research calls into question both the role of chromosomal abnormalities in GD etiology and why the application of chromosomal analysis is in Turkey a routine part of the baseline evaluation of GD.
... We should note here that not all GI individuals experience GD (Olson-Kennedy et al., 2016). As to the prevalence of cooccurring mental health conditions, research has shown that it is significantly higher in GD/GI adults than in the general population (e.g., Dhejne et al., 2016;Zucker et al., 2016). Research has also shown that GD/GI children and adults are at increased risk of self-harm and suicidality (e.g., Aitken et al., 2016;Cerel et al., 2021;de Graaf et al., 2020). ...
... As such, we decided to include them in the current meta-analysis as separate studies. Of the studies that reported evidence about the prevalence of ASD traits, we excluded two studies (i.e., VanderLaan, Postema, et al., 2015;Zucker et al., found that 5.5% of transgender adults diagnosed with GD or GID scored ≥ 32 on the Autism-Spectrum Quotient (AQ-50; Baron-Cohen et al., 2001), suggesting clinically significant levels of ASD traits, Kristensen and Broome (2015) reported that 39% of gender-variant adults should be referred for an ASD diagnostic assessment as they scored > 6 on the AQ-10 (Allison et al., 2012). ...
Article
Full-text available
The suggested overlap between autism spectrum disorder (ASD) and gender dysphoria/incongruence (GD/GI) has been much disputed. This review showed a relationship between ASD traits and GD feelings in the general population and a high prevalence of GD/GI in ASD. Our meta-analyses revealed that the pooled estimate of the prevalence of ASD diagnoses in GD/GI people was 11% (p < .001) and the overall effect size of the difference in ASD traits between GD/GI and control people was significant (g = 0.67, p < .001). Heterogeneity was high in both meta-analyses. We demonstrated that the chances that there is not a link between ASD and GD/GI are negligible, yet the size of it needs further investigation.
... These diagnoses entail marked, prolonged unease or distress related to a perceived "mismatch" between one's gender identity and their birth-categorized sex based on genital appearance. It is evidenced by a strong desire for a gender presentation that better accords with their felt gender and is associated with clinically significant distress or impairment in daily life (Zucker, Lawrence, and Kreukels 2016). ...
... For instance, it would be relevant to take into account what limited data there is about the well-being impact of such interventions on individuals in similar circumstances who have already undergone them. While a majority of individuals who undergo so-called sex reassignment surgery note marked improvements in well-being, some studies suggest that about 20 per cent do not experience significant benefit (Murad et al. 2010) and some 2 per cent come to regret it (Dhejne et al. 2014)-although some have argued these estimates are likely conservative (Zucker, Lawrence, and Kreukels 2016). In the case of an individual with gender dysphoria and autistic traits, does the presence of the latter increase or decrease those chances of regret? ...
Article
Full-text available
Transgender healthcare faces a dilemma. On the one hand, access to certain medical interventions, including hormone treatments or surgeries, where desired, may be beneficial or even vital for some gender dysphoric trans people. But on the other hand, access to medical interventions typically requires a diagnosis, which, in turn, seems to imply the existence of a pathological state—something that many transgender people reject as a false and stigmatizing characterization of their experience or identity. In this paper we argue that developments from the human enhancement debate can help clarify or resolve some of the conceptual and ethical entanglements arising from the apparent conflict between seeking medicine while not necessarily suffering from a pathology or disorder. Specifically, we focus on the welfarist account of human enhancement and argue it can provide a useful conceptual framework for thinking about some of the more contentious disagreements about access to transgender healthcare services.
... Además, esta visión que patologiza el día a día y propone el diagnóstico de «incongruencia de género» va en contravía con las transiciones que son propias de la niñez y la adolescencia, momentos propicios para una búsqueda identitaria. Asimismo, esta categoría no solo discrimina la búsqueda de identidades de género alternativas, sino que también viene acompañada de afectaciones graves a la salud mental: estigma-discriminación, insatisfacción corporal, altos niveles de ansiedad o depresión, abuso de sustancias y un mayor riesgo de autolesión o suicidio [10][11][12][13][14] . En esto persiste el sesgo normativo para la sexualidad, ya que se vuelve evidente que una diferencia sexual natural es, en realidad, una lectura del cuerpo tamizada por significados y valores culturalmente situados que contribuyen a generar una distribución sexo-política de los cuerpos 15 . ...
Article
En el 2013, la Asociación Psiquiátrica Americana (APA) publicó la quinta versión del Manual Diagnóstico y Estadístico (DSM-5) con algunas innovaciones en relación con los comportamientos e identidades sexuales. Entre las más notorias, se observaron la separación de las disfunciones sexuales de los trastornos parafílicos y la presentación de una categoría polémica: la disforia de género. Los colectivos militantes consideran que sobre la “incongruencia” o “disforia de género” se han impuesto juicios que corresponden más con argumentos jurídicos que intentan regular el comportamiento sexual en la vida privada de los ciudadanos. Esta perspectiva desconoce la diversidad en la sexualidad humana desde la perspectiva cultural. Por otra parte, la visión de trastorno corresponde con una visión normativista de la enfermedad, que vincula la identidad con un distanciamiento de lo que es socialmente deseable. En 2018, la Organización Mundial de la Salud (OMS), después de varios de aplazamientos, lanzó la undécima versión de la Clasificación Internacional de Enfermedades, CIE-11. En consonancia, con la homóloga APA, la OMS introdujo modificaciones en la clasificación de los comportamientos e identidades sexuales.
... Dlatego obecnie bardziej adekwatne wydaje się operowanie pojęciem "transpłciowość" i określeniem "inna płeć", a nie "płeć przeciwna" w celu podkreślenia specyficznych aspektów doświadczania własnej płci w ramach różnorodnych tożsamości płciowych innych niż tożsamość transseksualna [3,12]. ...
Article
Full-text available
Gender incongruence according to the ICD-11, compiled by the World Health Organization in 2019, is a sense of inconsistency between experienced and assigned gender that does not have to be associated with discomfort or suffering. However, the aspect of suffering is emphasized in the understanding of the diagnostic unit of gender dysphoria according to the DSM-5 of the American Psychiatric Association. People with gender incongruence are exposed to misunderstanding, persecution and stigmatization, often related to experienced minority stress. The aim of this study was to analyze the available literature in terms of the relationship between gender dysphoria and some mental disorders and minority stress, and to draw attention to the suffering of these people in the context of social confrontation with the phenomenon of gender transposition. The unfavorable image of a person with gender dysphoria created by some media, persecution and, as a result, bans on gender reassignment in some countries mean that a steady increase in mental disorders in these patients can be expected. The main psychiatric problems in people with gender dysphoria, accompanied by minority stress for most of their lives so far, concern the coexistence of depressive and anxiety disorders, self-destructive behaviors and the tendency to addiction. An important aspect of the functioning of people with gender dysphoria are also difficulties in taking up and maintaining employment, fear of losing income due to attempting to live in accordance with the perceived gender. The authors of the presented review wanted to emphasize the importance of minority stress in the lives of these people and the need for social education and a change in the approach to the concept of "employee, " excluding the record gender from it, which-according to the authors-could help people with gender incompatibility in their working life by reducing minority stress.
... His homosexual activities started around early adolescence, and he started experiencing gender dysphoria parallel to these encounters. Gender is a fluid construct and psychosocial factors influence expression of gender identity (2). His relationship with boys when his gender identity was being formed might have played a role in his gender dysphoria. ...
... Also, some are identified due to a history of psychopathological comorbidity, such as substance abuse, depression, anxiety or suicide attempts. 3,10,15,18,19 Early treatment and social and family support may reduce these situations. In our case series, none of the individuals have been diagnosed with any psychiatric disorders. ...
Article
Introduction Although there is an increasing experience in the management of transgender individuals, this has not been thoroughly explored in children. The need to establish a comprehensive and transdisciplinary management is of critical importance. In order to solve this issue, we want to report the results of a cohort of individuals with gender dysphoria (GD) seen by our transdisciplinary group from a social and clinical and health access perspective. Methods A 10-year retrospective case series of all patients that had been seen by our transdisciplinary team was reviewed. The main demographic characteristics were described, as well as impact variables in terms of diagnosis and treatment of these individuals. A social description of each individual was described. Frequency, distribution, and central tendency measures were evaluated for data presentation. IBM SPSS Statistics for Windows, version 24.0 (IBM Corp, Armonk, NY) software was used. Results Four cases of GD were included. Three had male to female dysphoria and one female to male. The median reported age of GD awareness was 6 years old (between 4 and 8 years old), and the median time between GD awareness and the 1st medical evaluation was 7 years for all individuals. The median age at gender role expression was 12 years old (between 10 and 14 years old). All patients had already assumed their experienced gender role before the 1st evaluation by our group. The median age at the 1st evaluation by our group was 13 years old (between 10 and 16 years old); three of the patients were evaluated after initiation of puberty. In the present study, individuals with GD demonstrated having health care access barriers for their transition process. Referral times are high, and individuals with GD are cared after pubertal development, which is related to suboptimal outcomes. The spectrum of GD is broad, and management must be individualized according to expectations. Conclusion Individuals with GD face multiple access barriers that limit their possibility of being seen by a transdisciplinary team. This reflects in longer waiting times that negatively impact medical management. Gender dysphoria is a wide spectrum, and individuals should be evaluated individually by a transdisciplinary team.
... Therefore, at present, the gender confirmation or affirmation or sex reassignment therapies (SRT), seem to be the only authentic option in relieving GD (Meyerowitz 2009). Table 2 presents diagnostic criteria for GD in adults and children (Zucker et al. 2016). ...
Article
Gender dysphoria (GD), a conflict between one's self-perceived gender identity and the biological sex has been a wholly enigma and a source of contention between experts of various disciplines since long. This is a narrative review of the medical literature utilizing PubMed, Scopus, and Web of science databases, on the social status of GD patients, their therapeutic options, as well as the medical and ethical debate on GD that are of especial interest to the Muslim readers. Gender dysphoric patients or transgender people have a long history of social discrimination, marginalization, abuse, and neglect all around the world. Currently, large scale social developments supporting of transgender rights are rapidly underway in the west. Clinical evidence-based guidelines have also been published and are available for the management of GD, albeit with some medical and ethical concerns. On the other hand, the transgender community is continued to suffer profoundly in the developing and majority of Muslim nations, due to generalized unawareness, neglect, cultural and religious boundaries on this issue. Currently, Muslim youth or young adults are showing passionate interest in GD and are actively seeking information to comprehend its complexities, but they face more dilemma on this matter than the people in the West. This article addresses and discusses key transgender issues and controversies and provides a logical explanation that demonstrates that GD is real medical condition needing attention and that its treatment guidelines are justified. We hope this article will stimulate a new and broader perspective in minds of young Muslims and will urge them to take pragmatic steps in alleviating the travails of long-suffering and neglected transgender community.
Article
Objective: We estimated the prevalence of diagnosed eating disorders, overall and by select demographics, among commercially insured individuals identified as transgender in a national claims database. Methods: From the 2018 IBM® MarketScan® Commercial Database, there were 10,415 people identifiable as transgender based on International Classification of Disease (ICD-10) codes and procedure codes, specific to gender-affirming care, from inpatient and outpatient claims. Eating disorders were identified from ICD-10 codes and included anorexia nervosa, bulimia nervosa, binge eating disorder, eating disorder not otherwise specified, avoidant restrictive feeding and intake disorder, and other specified feeding and eating disorders. We estimated the prevalence of specific eating disorders diagnoses by selecting patient characteristics. Results: Of individuals receiving some form of gender-affirming care, 2.43% (95% confidence interval: 2.14%-2.74%) were diagnosed with an eating disorder: 0.84% anorexia nervosa, 0.36% bulimia nervosa, 0.36% binge eating disorder, 0.15% avoidant restrictive feeding and intake disorder, 0.41% other specified feeding and eating disorders, and 1.37% with an unspecified eating disorder. Among transgender-identifiable patients aged 12-15 years, 5.60% had an eating disorder diagnosis, whereas 0.52% had an eating disorder diagnosis in patients aged 45-64 years. Discussion: In patients identifiable as transgender, with receipt of gender-affirming care, the prevalence of diagnosed eating disorders was low compared to extant self-reported data for eating disorder diagnosis in transgender individuals. Among this population, eating disorders were highest in adolescents and young adults. Clinically verified prevalence estimates for eating disorder diagnosis in transgender people with a history of gender-affirming care warrant further investigation. Public significance: The present study aims to provide clinically validated, contemporary prevalence estimates for diagnosed eating disorders among a medically affirmed population of transgender adults and children in the United States. We report low prevalence of having any eating disorder relative to prevalence estimates reported in prior literature without clinical validation. These findings may be explained by access to affirming care and medical care generally.
Article
Trans women (TW) have a high prevalence of poor mental health. Gender-affirming treatments could reduce distress regarding their gender incongruity. However, psychiatric comorbidities might complicate the management or even confirmation of being transgender. We reported three TW with complex mental illnesses, including anxiety disorder with cultural explanation, neurodevelopmental disorders with cross-dressing, and severe personality disorder accompanied by major depression. All cases received both psychiatric and gender-affirming treatments, which demonstrated promising outcomes. Along with gender dysphoria (GD), psychiatric comorbidities also altered these TW’s identity and manifestations. Recognition of such conditions would be beneficial in providing care for all TW, both with and without GD.
Article
Full-text available
The present study reports on the construction of a dimensional measure of gender identity (gender dysphoria) for adolescents and adults. The 27-item gender identity/gender dysphoria questionnaire for adolescents and adults (GID YQ-AA) was administered to 389 university); students (heterosexual and nonheterosexual) and 73 clinic-referred patients with gender identity disorder. Principal axis factor analysis indicated that a one-factor solution, accounting for 61.3% of the total variance, best fits the data. Factor loadings were all >= 30 (median,.82; range,.34-96). A mean total score (Cronbach's alpha,.97) was computed, which showed strong evidence for discriminant validity in that the gender identity patients had significantly more gender dysphoria than both the heterosexual and nonheterosexual university students. Using a cut-point of 3.00, we found the sensitivity was 90.4% for the gender identity patients and specificity was 99.7% for the controls. The utility of the GIDYQ-AA is discussed.
Article
Full-text available
This study examined two instruments measuring gender dysphoria within the multicenter study of the European Network for the Investigation of Gender Incongruence (ENIGI). The Utrecht Gender Dysphoria Scale (UGDS) and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) were examined for their definitions of gender dysphoria and their psychometric properties, and evaluated for their congruence in assessing the construct. The sample of 318 participants consisted of 178 male-to-females (MtF) and 140 female-to-males (FtM) who were recruited from the four ENIGI gender clinics. Both instruments were significantly correlated in the group of MtFs. For the FtM group, there was a trend in the same direction but smaller. Gender dysphoria was found to be defined differently in the two instruments, which led to slightly different findings regarding the subgroups. The UGDS detected a difference between the subgroups of early and late onset of gender identity disorder in the group of MtFs, whereas the GIDYQ-AA did not. For the FtM group, no significant effect of age of onset was found. Therefore, both instruments seem to capture not only similar but also different aspects of gender dysphoria. The UGDS focusses on bodily aspects, gender identity, and gender role, while the GIDYQ-AA addresses subjective, somatic, social, and sociolegal aspects. For future research, consistency in theory and definition of gender dysphoria is needed and should be in line with the DSM-5 diagnosis of gender dysphoria in adolescents and adults.
Article
Objective: Investigating psychopathological profiles of transsexuals raises a very basic methodological question: are control groups, which represent the biological or the phenotypic sex, most suited for an optimal evaluation of psychopathology of transsexuals? Method: Male-to-female (MtF) (n = 52) and female-to-male transsexuals (FtM) (n = 32), receiving cross-sex hormone treatment, were compared with age matched healthy subjects of the same genetic sex (n = 178) and with the same phenotypic sex (n = 178) by means of the Symptom Check List-90-Revisited instrument (SCL-90-R). We performed analyses of covariance (ANCOVA) to test for group and sex effects. Furthermore, we used a profile analysis to determine if psychopathological symptom profiles of transsexuals more closely resemble genotypic sex or phenotypic sex controls. Results: Transsexual patients reported more symptoms of psychopathological distress than did healthy control subjects in all subscales of the SCL-90-R (all p < 0.001), regardless of whether they were compared with phenotype or genotype matched controls. Depressive symptoms were more pronounced in MtF than in FtM (SCL-90-R score 0.85 vs. 0.45, p = 0.001). We could demonstrate that FtM primarily reflect the psychopathological profile of biological males rather than that of biological females (r = 0.945), while MtF showed a slightly higher profile similarity with biological females than with biological males (r = 0.698 vs. r = 0.685). Conclusion: Our findings suggest that phenotypic sex matched controls are potentially more appropriate for comparison with the psychopathology of transsexual patients than are genetic sex matched controls.
Article
Transsexualism is a rare condition. Although its etiology is unknown, it has been speculated that sex steroids may play an important role during early brain development. There may be a genetic component based on reports of an association between male to female (MtF) transsexualism and a CA repeat polymorphism in the estrogen receptor beta gene. CYP17 A2 T>C is a functional single nucleotide polymorphism (SNP) of the common cytochome P-450 that is associated with elevated serum and plasma levels of estradiol (E2), progesterone, and testosterone. The authors hypothesized that CYP17 A2 T>C is associated with transsexualism and that mutant alleles would be overrepresented among individuals with this condition. This case-control study assesses the association between transsexualism and allele and genotype frequencies of CYP17 A2 T>C SNP in a series of Caucasian transsexuals compared with controls. The participants were 102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls. The mean age at presentation of FtM transsexuals was 33.2 and that of MtF transsexuals was 41.8 years. CYP17 A2 T>C SNP allele frequencies were statistically significantly different between FtM transsexuals and female controls (CYP17 T: 56% and CYP17 C: 44% versus CYP17 T: [69%] and CYP17 C: [31%], respectively). Genotype distributions were also different between FtM transsexuals and female controls. In contrast, no statistically significantly differences between MtF transsexuals and male controls were found in the CYP17 A2 T>C allele and genotype distributions. The allele distribution of CYP17 A2 T>C was gender-specific among male and female controls in that a higher mutant C allele frequency occurred in the male controls (CYP17 C: males; [40%] versus females [31%]), respectively; P ≤ .001. Allele distribution in the MtF transsexuals was equivalent to male controls. In contrast, FtM transsexuals did not follow the gender-specific allele distribution of female controls but instead had an allele distribution equivalent to MtF transsexuals and male controls. The overrepresentation of CYP17 A2 T>C SNP among FtM transsexuals but not MtFs supports this polymorphism as a candidate gene of FtM transsexualism. The loss of a female-specific CYP17 A2 T>C allele distribution pattern may predispose women to become transsexuals.
Chapter
For individuals with pronounced gender dysphoria, surgery is the ultimate and the most radical step in the process of gender reassignment and follows a period of real-life experience and hormone treatment. In this chapter, a complete overview is first provided of all surgical procedures, both in male-to-female and female-to-male transsexuals: These include aesthetic operations, breast surgery, and genital surgical interventions. For the male-to-female individual, a more in-depth description is provided of facial feminizing surgery (FFS), of breast augmentation, as well as of the different techniques for vaginal reconstruction. Emphasis is placed on functional outcomes, on the reduction of complications, and on aesthetic improvements. In the female-to-male transsexual, the subcutaneous mastectomy (SCM) or male chest contouring and the different surgical options for phalloplasty or penile reconstruction are described in more detail. The advantages and disadvantages of the different techniques are addressed. It is concluded that in order to obtain optimal results in transgender surgery, a close cooperation between the different professionals involved is an absolute requirement.
Article
People with emotional disorders, such as social anxiety disorder (SAD), generalized anxiety disorder (GAD), and depression, demonstrate a consistent tendency, or bias, to generate negative interpretations of ambiguous material. This is different from people without emotional disorders who tend, in general, to make positive interpretations of ambiguity. If central components of an emotional disorder have high levels of inherent ambiguity (e.g., concern about the negative perceptions of others in SAD, or worry in GAD), then interpretive bias may have a causal maintaining role, and this has been demonstrated in studies using cognitive bias modification techniques. This research has also shown that interpretation biases combine with other cognitive processes, such as imagery and memory, which could exacerbate distress. Psychological interventions will benefit from effectively targeting negative interpretations, and future experimental research can inform ways to improve facilitation of more benign inferential processing to maximize amelioration of key components of emotional disorders.
Chapter
Transgender people may wish to transition to the other sex, usually to the fullest extent possible. Part of that transition is enabled by the administration of cross-sex hormones and part by surgical adaptation. The treatment of male-to-female transgender people consists of blocking androgen action and allowing estrogens to feminize the body. For virilization of female-to-male transgender people, androgens usually suffice. In adulthood, certain features of the sex hormone-induced body shape cannot be undone (such as the larger size of bones in males, the hip configuration in females). After about 2–3 years, the maximally attainable effects of cross-sex hormones have been reached. With competent endocrinological advice, cross-sex hormone treatment is usually uneventful. The estrogen ethinyl estradiol is to be avoided in view of the risks of venous thrombosis and cardiovascular disease. Androgen administration does not lead to an increase in cardiovascular disease. Hormone-dependent cancers have been observed in transgender people but not to an alarming degree. The relative rarity of transsexualism and the scattering of endocrine treatment over many centers is an impediment to build a solid body of knowledge with regard to efficacy and safety of cross-sex hormone treatment.
Article
There are no quantitative assessments of the benefits of phalloplasty in a female transsexual population. The study addresses this question, comparing transsexuals accepted for such surgery with transsexuals after such surgery has been performed. A population of 23 transsexuals accepted for phalloplasty was compared to a population of 40 who had undergone such surgery between six and one hundred and sixty months previously. The General Health Questionnaire (GHQ), Symptom Checklist 90 (SCL-90), Bem Sex Role Inventory and Social Role Performance Schedule (SRPS) were employed. Additionally, a questionnaire assessing satisfaction with cosmetic appearance, sexual function, relationship and urinary function was used, along with a semi-structured interview quantifying alcohol, cigarette and drug usage, and current sexual practice. There were significant differences between the populations. The post operative group showed higher depression ratings on the depression subscale of the GHQ. The masculine pre-operative Bem scores were neutral post-operatively as feminine sub-scores increased. There was improved satisfaction with genital appearance post-operatively, but satisfaction with relationships fell, although to a non-significant extent. Most other changes were in the expected direction but did not achieve significance. Transsexuals accepted for phalloplasty have very good psychological health. Tendency to further improvement is the case after phalloplasty. Depression is commoner, however, and quality of relationships declines somewhat, perhaps in consequence. Surgeons might advise partners as well as patients of realistic expectations from such surgery.