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Clinical Management of Gender Identity Disorder in Adolescents: A Protocol on Psychological and Paediatric Endocrinology Aspects

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Treatment outcome in transsexuals is expected to be more favourable when puberty is suppressed than when treatment is started after Tanner stage 4 or 5. In the Dutch protocol for the treatment of transsexual adolescents, candidates are considered eligible for the suppression of endogenous puberty when they fulfil the Diagnostic and Statistic Manual of Mental Disorders-IV-RT criteria for gender disorder, have suffered from lifelong extreme gender dysphoria, are psychologically stable and live in a supportive environment. Suppression of puberty should be considered as supporting the diagnostic procedure, but not as the ultimate treatment. If the patient, after extensive exploring of his/her sex reassignment (SR) wish, no longer pursues SR, pubertal suppression can be discontinued. Otherwise, cross-sex hormone treatment can be given at 16 years, if there are no contraindications. Treatment consists of a GnRH analogue (GnRHa) to suppress endogenous gonadal stimulation from B2-3 and G3-4, and prevents development of irreversible sex characteristics of the unwanted sex. From the age of 16 years, cross-sex steroid hormones are added to the GnRHa medication. Preliminary findings suggest that a decrease in height velocity and bone maturation occurs. Body proportions, as measured by sitting height and sitting-height/height ratio, remains in the normal range. Total bone density remains in the same range during the years of puberty suppression, whereas it significantly increases on cross-sex steroid hormone treatment. GnRHa treatment appears to be an important contribution to the clinical management of gender identity disorder in transsexual adolescents.
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Clinical management of gender identity disorder in adolescents:
a protocol on psychological and paediatric endocrinology
aspects
Henriette A Delemarre-van de Waal and Peggy T Cohen-Kettenis
Amsterdam Gender Clinic, Departments of Pediatrics and Medical Psychology, Institute for Clinical and Experimental Neuroscience, VU University Medical
Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
(Correspondence should be addressed to H A Delemarre-van de Waal; Email: h.delemarre@vumc.nl)
Abstract
Treatment outcome in transsexuals is expected to be more favourable when puberty is suppressed than
when treatment is started after Tanner stage 4 or 5. In the Dutch protocol for the treatment of
transsexual adolescents, candidates are considered eligible for the suppression of endogenous puberty
when they fulfil the Diagnostic and Statistic Manual of Mental Disorders-IV-RT criteria for gender
disorder, have suffered from lifelong extreme gender dysphoria, are psychologically stable and live in a
supportive environment. Suppression of puberty should be considered as supporting the diagnostic
procedure, but not as the ultimate treatment. If the patient, after extensive exploring of his/her sex
reassignment (SR) wish, no longer pursues SR, pubertal suppression can be discontinued. Otherwise,
cross-sex hormone treatment can be given at 16 years, if there are no contraindications. Treatment
consists of a GnRH analogue (GnRHa) to suppress endogenous gonadal stimulation from B2-3 and G3-
4, and prevents development of irreversible sex characteristics of the unwanted sex. From the age of 16
years, cross-sex steroid hormones are added to the GnRHa medication.
Preliminary findings suggest that a decrease in height velocity and bone maturation occurs. Body
proportions, as measured by sitting height and sitting-height/height ratio, remains in the normal
range. Total bone density remains in the same range during the years of puberty suppression, whereas
it significantly increases on cross-sex steroid hormone treatment. GnRHa treatment appears to be an
important contribution to the clinical management of gender identity disorder in transsexual
adolescents.
European Journal of Endocrinology 155 S131–S137
Introduction
Transsexuals are applying for sex reassignment (SR)
surgery at increasingly younger ages. Yet clinicians are
usually reluctant to start the SR procedure before
adulthood. They assume that adolescents are not able to
make a sensible decision about something as drastic as
SR. They fear that the risk of postoperative regrets will
be high and the treatment will have unfavourable
physical, psychological or social consequences. Post-
operative regret or any other unfavourable result of SR
naturally is of serious concern to clinicians. However,
the decision of what age to start SR should be a balanced
one. There are two main reasons to consider early
treatment as appropriate.
One reason for early treatment is that an eventual
delay or arrest in emotional, social or intellectual
development can be warded off more successfully
when the ultimate cause of this arrest has been taken
care of. Suffering from gender dysphoria without being
able to present socially in the desired social role, and/or
to stop the development of secondary sex characteristics
usually leads to problems in these areas. Adolescents
find it hard to live with a secret. Often have difficulties in
connecting socially and romantically with peers while
still in the undesired gender role, or the physical
developments create an anxiety that limits their
capacities to concentrate on other issues.
A second reason to start SR early is that the physical
treatment outcome following interventions in adult-
hood is far less satisfactory than when treatment is
started at an age at which secondary sex characteristics
have not yet been (fully) developed. Looking like a man
(woman) when living as a woman (man) creates
barriers that are not easy to overcome. This is obviously
an enormous and lifelong disadvantage. Indeed, Ross
This paper was presented at the 4th Ferring Pharmaceuticals
International Paediatric Endocrinology Symposium, Paris (2006).
Ferring Pharmaceuticals has supported the publication of these
proceedings.
European Journal of Endocrinology (2006) 155 S131–S137 ISSN 0804-4643
q2006 Society of the European Journal of Endocrinology DOI: 10.1530/eje.1.02231
Online version via www.eje-online.org
and Need (1) found that postoperative psychopathology
was primarily associated with factors that made it
difficult for postoperative transsexuals to pass success-
fully to their new gender or that continued to remind
them of their transsexualism. Furthermore, follow-up
studies show that unfavourable postoperative outcome
seems to be related to a late rather than an early start of
the SR procedure (for a review, see (2)). Age at the time
of assessment also emerged as a factor differentiating
two groups of male-to-female transsexuals (MFs), one
with and one without post-operative regrets (3).
The psychological problems of untreated adolescents
and the impact of an unfavourable physical appearance
significantly contributed to the decision of the Amsterdam
Gender Clinic for Adolescents and Children to prescribe
hormones before the age of 18 (legal adulthood). First,
patients were considered eligible for a staged hormone
treatment if they were (i) between 16 and 18 years, (ii)
suffering from life-long gender dysphoria that had
increased around puberty, (iii) functioning psychologi-
cally stable, and (iv) supported by their environment. For
females, the staged approach consisted of treatment with
progestagens to suppress menses for at least 3 months,
followed by androgen treatment. For males, antiandro-
gens were given first, followed by oestrogens. The first
retrospective and prospective studies among these
transsexual adolescents, who were found eligible for
treatment between 16 and 18 years, showed a significant
postsurgery decrease in gender dysphoria, and an
increase in body satisfaction. They were also functioning
psychologically in the normal range, and did socially quite
well (4, 5). They functioned psychologically better than
transsexuals, who were treated in adulthood, and
evaluated with partly the same instruments (6, 7). The
policy implied that younger adolescents (between 12 and
16 years), who were referred for SR, had no other option
than to wait for several years before they could be treated
medically.
Since the experience of a full biological puberty may
seriously interfere with healthy psychological functioning
and well being, we have changed our protocol after the
first follow-up studies on the 16–18-year olds (4, 5).
Adolescents are now allowed to start puberty suppressing
treatment with gonadotrophin-releasing hormone ana-
logues (GnRHa) if they were older than 12 years of age
and fulfil the same criteria as were used for the 16–18-
year olds. They should also have reached Tanner stage 2
or 3 in combination with pubertal levels of sex hormones.
The suppression of puberty using GnRHa is a reversible
phase of treatment. This treatment is a very helpful
diagnosticaid, as it allows the psychologist and the patient
to discuss problems that possibly underlie the cross-
gender identity or clarify potential gender confusion
under less time pressure. It can be considered as ‘buying
time’ to allow for an open exploration of the SR wish (8).
It is conceivable that lowering the age limit increases
the incidence of ‘false positives’. However, it most certainly
results in high percentages of individuals who more easily
pass into the opposite gender role than when treatment
commenced well after the development of secondary
characteristics. This implies an improvement in the
quality of life in these individuals, but may also result in
a lower incidence of transsexuals with postoperative
regrets or poor postoperative functioning. Clinically, it is
known that some patients who were treated in adulthood
regret SR because they have never been able to function
inconspicuously in the opposite gender role. This holds
especially for MFs, because beard growth and voice
breaking give so many of them a never disappearing
masculine appearance. But, since the number of ‘false
positives’ should be kept as small as possible, the
diagnostic procedure should be carried out with great
care. Until now, no patients who started treatment before
18 years have regretted their choice for SR.
The Amsterdam Gender Clinic has developed the
following protocol for the management of young
applicants for SR and is currently evaluating this
protocol in several studies.
Diagnostic procedure
The recommended procedure in the Standards of Care of
the Harry Benjamin International Gender Dysphoria
Association (HBIGDA; now called World Professional
Association of Transgender Health or WPATH) – a
professional organization in the field – is to come to the
SR decision in various steps (9). In the first phase, it is
investigated whether an applicant fulfils Diagnostic and
Statistic Manual of Mental Disorders-IV-RT criteria for
gender identity disorder (GID). The next phase has three
elements: a real-life experience (RLE) in the desired role,
hormonal interventions (in order to suppress puberty
and cross-sex hormone treatment) and finally, surgery
to correct the genitals.
In the first diagnostic phase, information must be
obtained from both the adolescent and the parents on
various aspects of general and psychosexual development
of the adolescent, the adolescent’s current functioning
and functioning of the family. Standardized psychological
assessmentis a part of the procedure. The patient is always
seen by two members of the gender team. If a child and
adolescent psychologist makes the diagnosis, the child is
also seen by a child and adolescent psychiatrist and vice
versa. In order to prevent unrealistically high expectations
with regard to their future lives, the adolescent has to be
clearly informed about the possibilities and limitations of
SR and other kinds of treatment. The way a patient
responds to the reality of SR can be diagnostically
informative. The decision to start medical intervention is
always taken by the whole team (for a more detailed
description of the diagnostic procedure, see (10)).
During the RLE phase, applicants have to live
permanently in the role of the desired sex, if they were
not already doing so. Before this is done, significant
persons in the adolescents’ life have to be informed about
S132 H A Delemarre-van de Waal and P T Cohen-Kettenis EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
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the impending changes. The underlying idea of these
requirements is that applicants should have had ample
opportunity to appreciate in vivo the familial, inter-
personal, educational, and legal consequences of the
gender role change. In adolescents, who are referred at
very young ages (around 12 years), the RLE usually
starts when they are on GnRHa treatment only. However,
at this stage the RLE is not a requirement. When, after
the age of 16 years, the cross-sex hormone treatment is
started, the RLE is required for obvious reasons.
Medical interventions
For adolescents, the guidelines of the Royal College
ofPsychiatrists(11),aswellastheHBIGDA(or
WPATH) Standards of Care, make a distinction
between two stages of endocrine intervention: fully
reversible interventions and partially reversible
interventions. A fully reversible treatment can be
achieved using GnRHa, while a partially reversible
treatment consists of cross-sex hormone treatment (in
addition to the GnRHa treatment, for adolescents (Fig. 1)).
Fully reversible interventions
When the development of secondary sex characteristics
has begun, adolescents with extreme forms of GID and
fulfilling the earlier mentioned additional criteria are
eligible for GnRHa treatment in order to suppress the
production of sex steroids. Psychological or psychiatric
involvement, for a minimum period of six months before
GnRHa treatment and continuing until surgery, is
another requirement for endocrine intervention of
adolescents. The objective of this involvement is that the
treatment is thoughtfully and recurrently considered over
time.
The GnRHa will discontinue progression of puberty by
blocking the activityof the GnRH receptor at the pituitary
level,which results in a decreaseof gonadotrophin release.
In turn, a decrease in the stimulation of gonads will lead to
low, prepubertal, levels of oestrogens in girls and
androgens in boys. GnRHa treatment will lead to
regression of the first stages of the already developed sex
characteristics. In girls, the present breast tissue will
become weak and may disappear completely. In boys,
testicular volume will regress to a lower volume.
This protocol can also be applied to adolescents in
later phases of pubertal development. In contrast to
patients in early puberty, the various physical changes
of pubertal development, such as a late stage of breast
development in girls and lowering of the voice and facial
hair in boys, will not regress completely, although any
further progression will be stopped.
Partially reversible interventions
Adolescents eligible for cross-sex hormone therapy are
16 years of age or older. As in many European
countries, in The Netherlands, 16-year olds are
considered legal adults for medical decision-making.
Although parental consent is not required, it is
preferred, as adolescents need the support of their
parents in this complex phase of their lives.
In addition to the GnRHa treatment, which makes
the patient hypogonadotrophic, an ‘opposite sex pub-
erty’ is induced by adding cross-sex hormones to the
treatment. To induce female sex characteristics in MFs,
oestrogens are prescribed in an increasing dose
according to the schedule as presented in Table 1.
Breast development and a female-appearing body shape
will be initiated. When the patient is on an adult dose,
this will be prescribed for the rest of their lives.
In female-to-male transsexuals (FMs), androgens are
used in order to achieve virilization, including male body
features, such as a low voice, facial and body hair
growth, and a more masculine body shape. Androgen
treatment will also result in clitoral enlargement,
although the final size will never reach the size of a
normal male penis. If still present, mild breast develop-
ment will become more atrophic and may even
disappear.
Psychological Psychological counselling and medical intervention
assessment,
counselling
or psychological
treatment
Prepuberty Puberty
1st phase 2nd phase
---------------- ----------------------------------------------------------------------------
B 2 – 3 / G 3 – 4 16 yrs 18 yrs
GnRH analogue GnRH analogue + surgery +
cross sex steroids cross sex steroids continued
Figure 1 During the first phase, prepubertal children, who are referred for SR, will undergo a psychodiagnostic procedure to assess
the gender identity disorder. If the gender identity problem persists into puberty, a second diagnostic protocol is followed. For eligible
adolescents, the diagnostic phase can be extended (second phase) by suppressing puberty for several years. From the age of 16 years,
cross-sex hormones can be added, and at an adult age of 18 years, the final step can be taken by correction of the genitals.
Management of GID in adolescents S133EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
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Side effects of medical intervention with GnRH
analogues and cross-sex hormones
In both girls and boys, after a short activation of the
gonadal axes, GnRHa will bring the patients into a
hypogonadotrophic state. In girls, withdrawal of oestro-
gens may induce a withdrawal bleeding. Cycling is
disrupted. In early pubertal boys, the hypogonadotrophic
state will block the development of fertility. In older-
staged boys, fertility will regress. Therefore, in older boys,
cryopreservation of semen should be discussed prior to
the start of the treatment. As a result of the hypogonadal
state, MFs can have complaints of fatigue and a decrease
of body strength.
With respect to growth, the growth spurt will be
hampered and fusion of the growth plates delayed.
This phenomenon may give the opportunity to
manipulate growth. Since females are about 12 cm
shorter than males, we may intervene with growth-
stimulating treatment in order to adjust the female
height to an acceptable male height. In contrast, the
blocking of the pubertal growth spurt in males is not
a problem. During the treatment with oestrogens,
the epiphyses will close progressively resulting in
what would be a compromised final height for a non-
transsexual male, but a quite acceptable height
for MF.
During puberty, bone density shows a progressive
accretion of bone, which is related to the exposure to sex
hormones (12). Peak bone mass will be achieved at the
age of 25–30 years. The question arises whether
patients participating in this protocol may achieve a
normal development of bone density, or will end with a
decreased bone density, which is associated with a high
risk of osteoporosis.
During physiologic puberty, carbohydrate and fat
metabolisms change. Temporary insulin resistance
occurs and an increase in fat mass is seen in pubertal
girls. We do not know what the effects of GnRHa
treatment alone, or in combination with cross-sex
hormones, are on these metabolic aspects.
Surgery (irreversible interventions)
Surgery is not carried out prior to adulthood (18 years
of age). The Standards of Care emphasize that the
‘threshold of 18 should be seen as an eligibility criterion
and not an indication in itself for active intervention’. If
the RLE supported by the cross-sex hormones has not
resulted in a satisfactory social role change, if the
patient is not satisfied with, or is ambivalent about, the
hormonal effects or surgery, the applicant is not referred
for surgery.
In MFs, female-looking external genitals are created
by means of vaginoplasty, clitoroplasty and labiaplasty.
In cases of insufficient responsiveness of breast tissue to
oestrogen therapy administered for long enough, breast
enlargement may also be performed. After surgery,
intercourse is possible. Arousal and orgasm are also
reported postsurgically, though the percentages differ
between studies (13, 14).
In FMs, a mastectomy is often performed as the first
surgery to successfully pass into the desired role. When
skin needs to be removed, this will result in fairly visible
scar tissue. Considering the still continuing improve-
ments in the field of phalloplasty, some FMs do not want
to undergo genital surgery until they have a clear
reason for it. They may then choose to have a
neoscrotum with a testis prosthesis with or without a
metaidoioplasty (this technique transforms the hyper-
trophic clitoris into a microphallus) or a phalloplasty.
Other genital procedures include the removal of the
uterus and ovaries. Whether FMs can have sexual
intercourse using their neopenis depends on the
technique and quality of the phalloplasty. Although
some patients, who had a metaidoioplasty, report that
they are able to have intercourse, the hypertrophic
clitoris usually is too small for coitus. In most cases, the
capacity of sexual arousal and orgasm remains intact.
When the gonads of the patient are surgically
removed, the patient can discontinue the GnRHa
treatment, but will continue the cross-sex hormone
treatment.
Legal consequences
In many countries that derive their law from Napoleon’s
Civil Code of 1804, the birth certificate is the source for
all other personal documents. Therefore, it is essential to
change the sex in this document to endow a person with
the full rights of his/her new gender. Since the ruling of
the European Court of Human Rights (ECHR), in 2002,
in the case of Goodwin vs The United Kingdom, all
46-member states of the ECHR do now fully accept a
legal sex change. In the Netherlands, a change of birth
certificate is only possible after the patient has been
gonadectomized.
Table 1 Treatment schedules to initiate pubertal development.
Induction of female puberty with 17-beta oestradiol, increasing the
dose every 6 months:
5mg/kg per day
10 mg/kg per day
15 mg/kg per day
20 mg/kg per day
Adult doseZ2 mg per day
Induction of male puberty with testosterone esters increasing the
dose every 6 months:
25 mg/m
2
per 2 weeks i.m.
50 mg/m
2
per 2 weeks i.m.
75 mg/m
2
per 2 weeks i.m.
100 mg/m
2
per 2 weeks i.m.
Adult dose 250 mg per 3–4 weeks
S134 H A Delemarre-van de Waal and P T Cohen-Kettenis EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
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Follow-up protocol
In order to investigate the efficacy and safety of GnRHa
treatment in adolescents with gender dysphoria, a
follow-up protocol has been designed.
During the protocol the following aspects are
investigated:
The patients are seen every 3 months by their
psychologist or psychiatrist.
Laboratory measurements include levels of gonado-
trophins and sex hormones, metabolic parameters such
as fasting glucose, insulin, cholesterol, high-density
lipoprotein and low-density lipoprotein levels. In
addition, safety parameters, such as renal and liver
functions, are estimated.
Growth Anthropometric measurements are performed
including height, weight, sitting height, hip and waist
circumferences and Tanner pubertal stages. Yearly, a
skeletal age is estimated using an X-ray of the left hand.
Bone density Just prior to start of the treatment with
either GnRHa or the addition of cross-sex hormones a
bone density measurement using dual-energy X-ray
absorptiometry is performed. The locations of measure-
ment are the non-dominant hip and the lumbar spine as
well as the whole body.
First experiences with the protocol
At present, 54 patients are being treated according to
this protocol, 30 of whom are FMs. The GnRHa
triptorelin (TRP) is administered in a dose of 3.75 mg
every 4 weeks intramuscularly or subcutaneously. At
the introduction of the treatment, an extra dose is given
at 2 weeks.
Preliminary results of the first 21 patients (11 FMs,
10 MFs), treated for 2 years or longer, are as follows:
With respect to the gonadal axis TRP treatment
resulted in an adequate suppression of the pituitary
gonadal axis, with low gonadotrophin levels and
suppressed prepubertal values for oestradiol in FMs
and testosterone in MFs. There was no progression of
the pubertal stage. In boys, testicular volume decreased.
In girls, when treatment was started in the late pubertal
stages B4 and B5, frequent hot flushes occurred, which
decreased in frequency with time. When cross-sex
hormones were added, FMs started to virilize with
lowering of the voice, clitoral enlargement and growth
of facial and body hair. In MFs, oestrogen treatment
induced breast development.
With respect to growth Height SDS in patients with
still-growth potential (bone age in girls !13 years and
in boys !15 years) showed a significant decrease,
while sitting-height:height ratio did not change.
Figure 2 shows the growth curve in an MF patient. In
general, during TRP, slowing down of height velocity is
observed. Oestrogens did not elicit a clear growth spurt,
while substitution with androgen did (Fig. 3).
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Figure 2 Growth curve (depicted on a male and female curve
respectively) of MF during treatment with GnRH analogue (GnRHa)
and combination treatment of GnRHa with cross-sex hormones
from the age of 16 years. Patient was in stage G2 at the start of the
treatment. Since testicular volume decreased to below 4 ml,
pubertal stage regressed to G1.
Management of GID in adolescents S135EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
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With respect to bone density During GnRHa treat-
ment, bone density remained in the same range. There
were no significant changes in bone densities at three
locations: lumbar spine, non-dominant hip and total
body, during TRP treatment. However, when calculated
as a Z-score, there appears to be a significant decrease
during this period. During cross-sex hormone treat-
ment, bone density increased significantly in both MFs
and FMs, which is associated with an increase in the
bone density Z-score. Figure 4 shows the data of bone
density in an MF patient during 2 years of TRP
treatment, followed by 2 years of combination therapy
with cross-sex hormones.
With respect to body composition During the first
year of TRP treatment, the percentage of fat mass
increased significantly, but remained at the same level
thereafter. Lean body mass showed a contrary effect, i.e.
a significant decrease during the first year of treatment
followed by stabilization at the same level.
Carbohydrate and lipid metabolism did not show any
change during treatment either with TRP alone or in
combination with cross-sex hormones.
In general, patients repeatedly reported that they are
satisfied with the suppression of their pubertal develop-
ment. This is confirmed in the reports of their parents.
Discussion
The present protocol, developed to ameliorate treatment
outcome in adolescent patients with an early onset of
GID, appears to be a suitable way to treat such patients.
It seems possible to select patients who will profit from
early interventions, starting at 12 years with GnRHa
andfollowedat16yearsbycross-sexhormone
treatment, provided that the diagnostic procedure is
carried out with great care and by an experienced team.
Careful diagnosis should focus on the assessment of
the GID as well as potential risk factors (e.g. severe
co-morbidity). If any risk factors are present, these
should be addressed first, before any medical interven-
tion takes place. Since the diagnostic procedure is
lengthy, there is ample time for patient, the family and
the psychologist or psychiatrist to make the final
decision. Making a balanced decision on SR is far
more difficult for adolescents, who are denied medical
treatment (GnRHa included), because much of their
energy will be absorbed by obtaining treatment rather
than exploring in an open way whether SR actually is
the treatment of choice for their gender problem. By
starting with GnRHa their motivation for such
exploration enhances and no irreversible changes
have taken place if, as a result of the psychotherapeutic
interventions, they would decide that SR is not what
they need. However, until now, none of the patients who
were selected for pubertal suppression has decided to
stop taking GnRHa. On the contrary, they are usually
very satisfied with the fact that the secondary sex
characteristics of their biological sex did not develop
further.
Side effects of pubertal suppression result from the
physiological developments occurring during this
period. The normal pubertal growth spurt will not
continue, resulting in a delay of growth. In girls, we
should therefore try to overcome the 12 cm difference
that exists between non-patient boys and girls. In the
period of suppression, growth-stimulating medication
can be offered in order to increase the height velocity.
Androgens, which will be introduced in increasing
doses from the age of 16 years, may elicit a ‘puberty
growth spurt’ when skeletal maturation is retarded.
Boys, who are taller than girls, will also experience
growth retardation during GnRHa treatment. Since
oestrogen treatment has a growth-inhibiting effect
0.7
0.75
0.8
0.85
Bone mineral density (g/cm2)
0.9
0.95
1
LS FN TB
0
12 months
24 months
Figure 3 Bone mineral density of the lumbar spine (LS), femoral
neck (FS) and total body (TB) in nine transsexual adolescents
during a period of 24 months of treatment with a GnRH analogue
(GnRHa), measured just prior to the start of the GnRHa treatment (0)
and after 12 and 24 months. There were no significant differences.
Figure 4 Bone mineral density in a FM individual at the lumbar spine
(LS), femoral neck (FN) and total body (TB). The left most bar
indicates bone density at the start of treatment with the GnRH
analogue (GnRHa). The following two bars to the right indicate bone
density at 12 and 24 months on the GnRHa. Oestrogen therapy to
induce female puberty starts at 24 months. The two bars on the right
side show bone densities in combination treatment of the GnRHa
and oestrogens.
S136 H A Delemarre-van de Waal and P T Cohen-Kettenis EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
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shortly after the start of treatment (15), oestrogen
medication to initiate female puberty may not be
associated with a pubertal growth spurt and therefore
may result in a more appropriate ‘female’ final height.
Since puberty is an important phase for the increase
of bone density, which lasts until peak bone mass,
suppression of puberty may interfere with a normal
bone mass increase. The first clinical data suggest that
bone mineral density remains at the same level during
treatment, which indicates a decrease in Z-score when
compared with reference values. However, when, at the
age of 16 years, suppression of puberty is combined
with cross-sex hormone treatment, a catch-up for bone
accretion is observed, resulting in a decrease and
normalization of the bone mineral density Z-score.
This medical intervention, therefore, does not seem to
harm bone development in the short term, but long-
term data on peak bone mass should be assessed before
a final conclusion can be drawn.
With respect to metabolic parameters, the only
significant changes are an increase in fat mass
accompanied by a decrease of lean body mass. These
changes occurred only during the first year of suppres-
sion of puberty. Thereafter, body composition remained
at the same level. During treatment with cross-sex
hormones, the percentages return to the pretreatment
values. The ultimate effect of this manipulation on
pubertal development should be investigated in a long-
term follow-up.
During puberty, developmental processes also take
place in the brain. In the adult brain, a number of sex
differences have been reported. For example, the
amount of grey matter is higher in adult females than
males in the gyrus cingulatus, the median frontal area
and the lobus paracentralis in particular (16). It is not
clear yet how pubertal suppression will influence brain
development. From our experience with adolescents,
who have been taking GnRHa and are now adults,
no gross effects on their functioning are detectable.
However, a study on brain development of adolescent
transsexuals, who have used GnRHa, will be carried out
to detect eventual subtle functional and structural
effects.
Acknowledgements
The authors are very grateful to Ferring Pharma-
ceuticals for the financial support of studies on the
treatment of adolescents with gender identity disorders.
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Received 12 May 2006
Accepted 20 June 2006
Management of GID in adolescents S137EUROPEAN JOURNAL OF ENDOCRINOLOGY (2006) 155
www.eje-online.org
... Adolescents have the opportunity to explore their gender identity in greater tranquility, without having to worry about the development of secondary sexual attributes [22]. Therapy with hypothalamic blockers can be considered a diagnostic tool since it allows a greater understanding of the degree and persistence of adolescent distress [23] and improves the accuracy of the diagnosis itself [20]. ...
... Furthermore, in adolescents who are already biologically mature but are undecided about cross-sex hormone therapy, hypothalamic blockers can inhibit those physiological functions that are perceived as unpleasant, such as menstruation in girls and erections in boys, in the intervening period, until the actual decision [11]. Regarding the efficacy of the drugs, the suppression of the activation of the hypothalamic-pituitary-gonadal axis has been demonstrated, with a reduction in testicular volume, in the levels of gonadotropins and prepubertal steroid sex hormones [23]. ...
... Hypothalamic blockers are generally well tolerated, with the exception of possible hot flashes [23], fatigue, migraine, mood changes, injection pain, and abscesses [5]. Some cases of arterial hypertension following the administration of Triptorelin were observed in three male transsexual adolescents in a sample of 138 subjects [5,44]; and in two treated patients, with complications in one out of two patients related to increased intracranial pressure, which resulted in a temporary interruption of treatment [45]. ...
Chapter
Full-text available
Gender identity does not always develop in line with biological sex. Gender dysphoria at young age implies a strong incongruence between gender identity and the assigned sex; the rejection of one\'s sexual attributes and the desire to belong to the opposite sex; and a significant clinical suffering or impaired individual functioning in life spheres. The purpose of this chapter is a narrative review of the literature available on puberty suppression therapy through GnRH analogues. Biological puberty provides intense suffering to the adolescent with gender dysphoria who does not recognize himself in his own body. These drugs suppress the production of endogenous gametes and sex hormones. Although the effects of therapy are reversible, and biological development resumes spontaneously once the medication is stopped, the administration of GnRH analogues at a young age has fueled a scientific debate on the matter of the ethics of pharmacological intervention with minors. In conclusion, the studies considered show that GnRH analogues do not have long-term harmful effects on the body; prevent the negative psychosocial consequences associated with gender dysphoria in adolescence (suicidal ideation and attempts, self-medication, prostitution, self-harm); improve the psychological functioning of young transsexuals; and are diagnostic tools that allow adolescents to buy time to explore their gender identities.
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Transgenderism and Intersexuality in Childhood and Adolescence: Making Choices presents an overview of the research, clinical insights, and ethical dilemmas relevant to clinicians who treat intersex youth and their families. Exploring gender development from a cross-cultural perspective, esteemed scholar Peggy T. Cohen-Kettenis and experienced practitioner Friedemann Pfäfflin focus on assessment, diagnosis, and treatment issues. To bridge research and practical application, they include numerous case studies, definitions of relevant terminology, and salient chapter summaries.
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