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Abstract

The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person's genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person's desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons.
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1
Endocrine Treatment of Transsexual Persons
An Endocrine Society
Clinical Practice Guideline
June, 2009
Authors:
Wylie C. Hembree, Peggy Cohen-Kettenis, Henriette A. Delemarre,
Louis J. Gooren, Walter J. Meyer III, Norman P. Spack, Vin Tangpricha,
and Victor M. Montori
Affiliations:
Columbia University and New York Presbyterian Hospital (W.C.H.) New York, New York; Vrije University Medical
Center (P.C-K.) Amsterdam, The Netherlands; Vrije University Medical Center (H.A.D.) Amsterdam, The Nether-
lands; Androgen Consultant (L.J.G.) Bangkok, Thailand; University of Texas Medical Branch (W.J.M.) Galveston,
Texas; Harvard Medical School (N.P.S.) Boston, Massachusetts; Emory University School of Medicine (V.T.) At-
lanta, Georgia; and Mayo Clinic (V.M.M.) Rochester, Minnesota.
Co-sponsoring Associations:
European Society of Endocrinology (ESE), The World Professional Association for Transgender Health (WPATH),
Lawson Wilkins Pediatric Endocrine Society (LWPES)
This adolescent care-specific version of the original document (which included adult care guidelines)
focuses on information relating to endocrine treatment of transsexual adolescents and is intended for
use by families, youth and their medical providers. The adolescent-specific content is identical to the
original document.
In some instances the TransActive staff provides an opinion (clearly defined as such and highlighted in
purple) with regard to recommendations or conclusions stated in this Guideline.
Jenn Burleton
Executive Director
503-252-3000
www.TransActiveOnline.org
info@transactiveonline.org
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2
The Endocrine Society
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted
to research on hormones and the clinical practice of endocrinology. The Society works to foster a greater un-
derstanding of endocrinology amongst the general public and practitioners of complementary medical disci-
plines and to promote the interests of all endocrinologists at the national scientific research and health policy
levels of government.
Contact Information
Mailing Address:
8401 Connecticut Ave., Suite 900
Chevy Chase, MD 20815
Phone Numbers:
Main Phone: 1-888-363-6274 or 301-941-0200
Email Addresses:
Society Services - societyservices@endo-society.org
Hormone Foundation - hormone@endo-society.org
In August of 2006, TransActive founder Jenn Burleton realized that a gap
existed not only in services offered to trans and gender non-conforming
children, youth and their families, but more significantly, that children were
being left out of the struggle for transgender rights, respect and inclusion.
She realized that while online support groups are a valuable resource for
parents, the "real world" invisibility of trans/gender non-conforming children and youth has not really changed
much in the decades since she was herself, a transgender child.
TransActive has since grown into a diverse and motivated team, working together to provide these amazing
children and youth a present and future in which they can achieve their dreams and express their individuality.
Vision
Every child and youth has a right to freely express their gender identity as they experience it.
Families deserve access to accurate and supportive information regarding gender identity
development and expression.
Youth should be assisted in experiencing pubertal development that is congruent with their
gender identity, if they so desire.
Transgender and gender non-conforming identity in children and youth is no less authentic
than cisgender identity.
Contact Information:
Mailing Address:
1631 NE Broadway
Suite 355-T
Portland, OR 97008
Phone:
503-252-3000
Email:
info@transactiveonline.org
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3
Introduction
Men and women have experienced the confusion and pain resulting from simplistic, forced conformity to
sexual dimorphism throughout recorded history. Aspects of gender variance have been part of biological,
psychological, and sociological debates amongst humans in modern history. The twentieth century
marked the beginning of a social awakening for men and women whose bodies imprisoned them in the
wrong gender. Harry Benjamin and Magnus Hirshfeld, who met in 1907, pioneered the medical re-
sponses to those who sought relief and resolution of their torment, enabling the “transsexual,” a term
coined by Hirshfeld in 1923, to live a gender- appropriate life, occasionally facilitated by surgery.
Endocrine treatment of transsexual persons (note: In the current psychiatric classification system, the Di-
agnostic and Statistical Manual of Mental Disorders-IV-TR, the term gender identity disorder is used in-
stead of transsexualism [APA, 2001]), previously limited to ineffective elixirs, creams, and implants, be-
came reasonable with the availability of diethylstilbesterol in 1938 and following the isolation of testoster-
one in 1935. Personal stories of role models, treated with hormones and sex reassignment surgery, ap-
peared in the press during the second half of the twentieth century. The Harry Benjamin International
Gender Dysphoria Association (HBIGDA) was founded in September 1979; it is now known as the World
Professional Association of Transgender Health (WPATH). The Association’s “Standards of Care” was
first published by HBIGDA in 1979 and its sixth edition is currently being revised. These carefully pre-
pared documents have provided mental health and medical professionals with general guidelines for the
evaluation and treatment of transsexual persons.
Prior to 1975, few peer- reviewed articles were published concerning endocrine treatment of transsexual
persons. Since that time, more than 800 articles about various aspects of transsexual care have ap-
peared. It is the purpose of this guideline to make detailed recommendations and suggestions, based on
existing medical literature and clinical experience that will enable endocrinologists to provide safe and
effective endocrine treatment for individuals diagnosed with gender identity disorder (GID) or transsexual-
ism by mental health professionals. In the future, rigorous evaluation of the effectiveness and safety of
endocrine protocols is needed. What will be required is the careful assessment of 1) the effects of pro-
longed delay of puberty on bone, growth and development upon adolescents, 2) in adults, the effects on
outcome of both endogenous and cross-sex hormone levels during treatment, 3) the requirement for and
the effects of anti-androgens and progestins during treatment, and 4) long-term medical and psychologi-
cal risks of sex reassignment. These needs can be met only by a commitment of mental health and endo-
crine investigators to collaborate in long-term, large-scale studies across countries that employ the same
diagnostic and inclusion criteria, medications, assay methods, and response assessment tools.
Terminology and its use vary and continue to evolve. Table 1 (pg. 24) contains definitions of terms as
they are used throughout the Guideline.
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4
Abstract Objective: To formulate practice guidelines on the endocrine treat-
ment of transsexual patients.
Participants: An Endocrine Society appointed Task Force of experts, method-
ologist, and medical writer.
Evidence: This evidence-based guideline was developed using the Grading of
Recommendations, Assessment, Development, and Evaluation (GRADE) sys-
tem to describe both the strength of recommendations and the quality of evi-
dence, which was generally low or very low.
Consensus Process: One group meeting, several conference calls, and e-mail
communications enabled consensus. Committees and members of The Endo-
crine Society, European Society of Endocrinology, The World Professional As-
sociation for Transgender Health (WPATH), and Lawson Wilkins Pediatric En-
docrine Society reviewed and commented on preliminary drafts of these guide-
lines.
Conclusions: Transsexual persons seeking to develop the physical character-
istics of the appropriate gender require a safe and effective hormone regimen
that will 1) suppress endogenous hormone secretion determined by the per-
son’s genetic/biologic sex and 2) maintain sex hormone levels within the normal
range for the person’s gender. A mental health professional (MHP) must recom-
mend endocrine treatment and participate in the ongoing care throughout the
endocrine transition. The endocrinologist must confirm the diagnostic criteria the
MHP used to make this recommendation and collaborate with the MHP in mak-
ing the recommendation for surgical sex reassignment.
We recommend treating transsexual adolescents (Tanner stage 2) with sup-
pression of puberty with GnRH analogues until age 16 years old, only after
which time cross-sex hormones may be given. We suggest suppression of en-
dogenous sex hormones, maintaining physiologic levels of gender-appropriate
sex hormones and surveillance for known risks and complications in adult trans-
sexual persons.
TransActive disagrees
that cross-sex hormones
should be given only after
16 years of age. We rec-
ommend that cross-
gender hormones should
be available a maximum
of 2 years after the onset
of Tanner 2 pubertal sup-
pression assuming the
youth desires them and
there are no medical con-
traindications.
The Task Force also used consistent language and graphical descriptions of
both the strength of a recommendation and the quality of evidence.
In terms of the strength of the recommendation, strong recommendations use
the phrase “we recommend” and the number 1, and weak recommendations
use the phrase “we suggest” and the number 2.
Cross-filled circles indicate the quality of the evidence, such that OOO de-
notes very low quality evidence; ⊕⊕OO low quality; ⊕⊕⊕O moderate quality;
and ⊕⊕⊕⊕ high quality.
The Task Force has confidence that patients who receive care according to the
strong recommendations will derive, on average, more good than harm. Weak
recommendations require more careful consideration of the patient’s circum-
stances, values, and preferences to determine the best course of action.
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Summary of Recommendations
1.0 DIAGNOSTIC PROCEDURE (see pg. 7)
1.1 We recommend that the diagnosis of gender identity disorder (GID) be
made by a mental health professional. For children and adolescents the
mental health professional should also have training in child and adoles-
cent developmental psychopathology. (1|⊕⊕OO)
1.2 Given the high rate of remission of GID after the onset of puberty, we rec-
ommend against a complete social role change and hormone treatment
in pre-pubertal children with GID. (1|OOO)
1.3 We recommend that physicians evaluate and ensure that applicants under-
stand the reversible and irreversible effects of hormone suppression
(e.g., GnRH analogue treatment) and cross-sex hormone treatment be-
fore they start hormone treatment. (1|OOO)
1.4 We recommend that all transsexual individuals be informed and counseled
regarding options for fertility prior to initiation of puberty suppression in
adolescents and prior to treatment with sex hormones of the desired sex
in both adolescents and adults. (1|⊕⊕⊕O) (see pg. 7)
2.0 TREATMENT OF ADOLESCENTS (see pg. 8)
2.1. We recommend that adolescents who fulfill eligibility and readiness criteria
for gender reassignment initially undergo treatment to suppress pubertal
development. (1|OOO) (see pg. 8)
2.2. We recommend that suppression of pubertal hormones start no earlier than
Tanner stages 2-3 and when girls and boys exhibit pubertal levels of es-
tradiol and testosterone, respectively. (1|⊕⊕⊕O) (see pg. 8)
2.3. We recommend GnRH analogues be used to achieve suppression of pu-
bertal hormones. (1⊕⊕OO) (see pg. 9)
2.4. We suggest that pubertal development of the desired, opposite sex be initi-
ated at about the age of 16 years, using a gradually increasing dose
schedule of cross-sex steroids. (2|ΟΟΟ) (see pg. 10)
2.5. We recommend referring hormone-treated adolescents for surgery when 1)
the real life experience has resulted in a satisfactory social role change,
2) the individual is satisfied about the hormonal effects, and 3) the indi-
vidual desires definitive surgical changes (1ΟΟΟ)
2.6 We suggest deferring surgery until the individual is at least 18 years old.
(2ΟΟΟ). (see pg. 11)
1.2
TransActive strongly
disagrees with both the
statement and recom-
mendation in 1.2
By referencing “complete
social role change” and
“hormone treatment in
pre-pubertal children” in
the same sentence, the
Task Force implies that
one necessarily follows
the other.
TransActive fully supports
social gender role change
for children and youth
who have exhibited an
expressed desire for such
and who fall within the
“persistent” and
“consistent” diagnostic
criteria.
2.4
As stated on page 3,
TransActive disagrees
that cross-sex hormones
should be given only after
16 years of age.
2.5
It is our experience that
all three of these criteria
are often achieved sev-
eral years prior to the
Task Force recom-
mended GRS age of 18
as stated in 2.6, which we
strongly disagree with.
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4.0 ADVERSE OUTCOME PREVENTION AND LONG-TERM CARE
4.1 We suggest regular clinical and laboratory monitoring every 3 months during
the first year and then once or twice yearly. (2|⊕⊕OO) (see pg. 12)
4.2 We suggest monitoring prolactin levels in male-to-female transsexual per-
sons treated with estrogens. (2|⊕⊕OO) (see pg. 12)
4.3 We suggest that transsexual persons treated with hormones be evaluated
for cardiovascular risk factors (2|⊕⊕OO) (see pg. 13)
4.4 We suggest that bone mineral density measurements be obtained if risk fac-
tors for osteoporosis exist, specifically in those who stop hormone ther-
apy after gonadectomy. (2|⊕⊕⊕O) (see pg. 13)
4.5 We suggest that male-to-female transsexual persons, who have no known
increased risk of breast cancer, follow breast screening guidelines rec-
ommended for biological women. (2|⊕⊕OO) (see pg. 14)
4.6 We suggest that male-to-female transsexual persons treated with estrogens
follow screening guidelines for prostatic disease and prostate cancer
recommended for biological men. (2|OOO) (see pg. 14)
4.7 We suggest that female-to-male transsexuals evaluate the risks and bene-
fits of including total hysterectomy and oophorectomy as part of sex re-
assignment surgery. (2|OOO) (see pg. 14)
5.0 SURGERY FOR SEX REASSIGNMENT (see pg. 15)
5.1 Genital sex reassignment surgery should be recommended by both the phy-
sician responsible for endocrine transition therapy and the mental health
professional. (1|OOO) (see pg. 16)
5.2 We recommend that genital sex reassignment surgery be recommended
only after completion of at least 1 year of consistent and compliant hor-
mone treatment.(1|OOO) (see pg. 16)
5.3 We recommend that the physician responsible for endocrine treatment
medically clear transsexual individuals for sex reassignment surgery and
collaborate with the surgeon regarding hormone use during and after
surgery. (1|OOO) (see pg. 16)
5.1
TransActive disagrees
with the recommendation
that another “gatekeeper”
be inserted into the Geni-
tal Reassignment Sur-
gery process. There is
currently an existing re-
quirement that a surgical
candidate obtain two let-
ters of referral prior to
surgery; one from a coun-
selor or therapist and a
second letter from a Ph.D
-level mental health prac-
titioner.
Further, surgery should
only be “recommended” if
and when the youth ex-
presses a consistent and
persistent desire for such.
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1.0 Diagnostic Procedure
Sex reassignment is a multidisciplinary treatment. It requires five processes:
diagnostic assessment
psychotherapy or counseling
real-life experience
hormone therapy
surgical therapy.
The focus of this Guideline is hormone therapy, although collaboration with ap-
propriate professionals responsible for each process maximizes a successful
outcome. It would be ideal if care could be given by a multidisciplinary team at
one treatment center, but this is not always possible. It is therefore important
that caregivers be aware of the contributions of the various disciplines.
1.4 Evidence
Because early adolescents may not feel qualified to make decisions about fertil-
ity and may not fully understand the potential effects of hormones, consent and
patient education should include parents, the referring mental health profes-
sional(s), and other members of their support group.
To our knowledge, there are no formally evaluated decision aids available to
assist in the discussion and decision regarding future fertility of adolescents or
adults beginning sex reassignment treatment. Prolonged pubertal suppression
using GnRH analogues is reversible and should not prevent resumption of pu-
bertal development upon cessation of treatment.
Although sperm production and development of the reproductive tract in early
adolescent biological males with GID are insufficient for cryopreservation of
sperm, they should be counseled that sperm production can be initiated follow-
ing prolonged gonadotropin suppression, prior to estrogen treatment. It should
be noted that the time required to obtain sufficient spermatogenesis to collect
sperm is unpredictable and will probably be associated with physical manifesta-
tions of testosterone production.
Girls should expect no adverse effects when treated with pubertal suppression.
They should be informed that no data are available regarding timing of sponta-
neous ovulation or response to ovulation induction following prolonged gonad-
otropin suppression. All referred subjects who satisfy eligibility and readiness
criteria for endocrine treatment, at age 16 or as adults, should be counseled re-
garding the effects of hormone treatment on fertility and available options that
may enhance the chances of future fertility, if desired (De Sutter 2007; De Sut-
ter 2001).
Reports of an increased incidence of polycystic ovaries in female-to-male (FTM) trans-
sexual persons, both prior to and as a result of androgen treatment, should be acknowl-
edged (Spinder 1989 Baba 2007). Pregnancy has been reported in FTM transsexual per-
sons who have had prolonged androgen treatment, but no genital surgery (Trebay 2008).
Counsel from a gynecologist prior to hormone treatment regarding potential fertility
preservation following ovariectomy will clarify available and future options (De Sutter
2003).
1.0
TransActive disagrees
with the statement that
sex reassignment
“requires five processes”.
Under the current
WPATH Standards of
Care, it is recommended
that trans-identified youth
receive a diagnostic as-
sessment, counseling
and be living in their tar-
get gender role as pre-
requisites for hormone
therapy. We do not agree
that desire for “surgical
therapy” should be, in all
cases, an expected or
required diagnostic even-
tuality.
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8
2.0 Treatment of Adolescents
Over the past decade, clinicians have progressively acknowledged the suffering
of young transsexual adolescents that is caused by their pubertal development.
Indeed, an adolescent with GID often considers the pubertal physical changes
to be unbearable.
As early medical intervention may prevent this psychological harm, various clin-
ics have decided to start treating young adolescents with GID with puberty-
suppressing medication (a GnRH analogue). As compared to starting sex reas-
signment long after the first phases of puberty, another benefit of pubertal sup-
pression is relief of gender dysphoria and a better psychological and physical
outcome.
The physical changes of pubertal development are the result of maturation of
the hypothalamo-pituitary-gonadal axis and development of the secondary sex
characteristics. Gonadotropin secretion increases with a day-night rhythm with
higher levels of LH during the night. The night time LH increase in boys is asso-
ciated with a parallel testosterone increase. Girls do not show a day-night
rhythm, although in early puberty, the highest estrogen levels are observed dur-
ing the morning as a result of a delayed response by the ovaries (Boyar 1976).
In girls the first physical sign of the beginning of puberty is the start of budding
of the breasts followed by an increase in breast and fat tissue. Breast develop-
ment is also associated with the pubertal growth spurt, with menarche occurring
approximately two years later. In boys the first physical change is testicular
growth. A testicular volume equal to or above 4 ml is seen as the first pubertal
increase. From a testicular volume of 10 ml, daytime testosterone levels in-
crease, leading to virilization (Wennink 1989).
2.1-2.2 Evidence
Pubertal suppression aids in the diagnostic and therapeutic phase, in a manner
similar to the real life experience. (Delemarre-Van de Waal 2006, Cohen-
Kettenis 2008). Management of gender dysphoria usually improves. In addition,
the hormonal changes are fully reversible, enabling full pubertal development in
the biologic gender if appropriate. Therefore, we advise starting suppression of
puberty before irreversible development of sex characteristics.
The experience of full biologic puberty, an undesirable condition, may seriously
interfere with healthy psychological functioning and well-being. Suffering from
gender dysphoria without being able to present socially in the desired social role
or to stop the development of secondary sex characteristics may result in an
arrest in emotional, social, or intellectual development.
Another reason to start sex reassignment early is that the physical outcome fol-
lowing intervention in adulthood is far less satisfactory. Looking like a man
(woman) when living as a woman (man) creates difficult barriers which have
enormous life-long disadvantages.
Pubertal suppression maintains end-organ sensitivity to sex steroids observed
during early puberty, enabling satisfactory cross-sex body changes with low
doses and avoiding irreversible characteristics that occur by mid-puberty.
2.1-2.2
TransActive strongly sup-
ports these clinical rec-
ommendations as they
reflect our experience in
working directly with pre
& post adolescent trans
youth.
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9
The protocol of suppression of pubertal development can also be applied to
adolescents in later pubertal stages. In contrast to effects in early pubertal ado-
lescents, physical sex characteristics, such as breast development in girls and
lowering of the voice and outgrowth of the jaw and brow in boys will not regress
completely.
Unlike the developmental problems observed with delayed puberty, this protocol
requires a mental health professional skilled in child- and adolescent- psychol-
ogy to evaluate the response of the adolescent with GID after pubertal suppres-
sion. Adolescents with GID should experience the first changes of their biologic,
spontaneous puberty because their emotional reaction to these first physical
changes has diagnostic value. The early treatment in puberty risks limited
growth of the penis and scrotum that may make the surgical development of a
vagina from scrotal tissue more difficult.
2.1-2.2.Values and Preferences
This recommendation places a high value on the increasing likelihood of a satis-
factory physical change when secondary sexual characteristics have become
manifest and irreversible while offering the adolescent the experience of the de-
sired gender, and places a lower value in avoiding potential harm from early
hormone therapy.
2.1-2.2 Remarks
Tanner stages of breast and male genital development are given in Table 6.
Blood levels of sex steroids during Tanner stages of pubertal development are
given in Table 7. Careful documentation of hallmarks of pubertal development
will ensure precise timing of initiation of pubertal suppression later initiation of
cross-sex hormone treatment later. Irreversible and, for transsexual adoles-
cents, undesirable sex characteristics are in female puberty large breasts and
short stature and in male puberty Adam’s apple, low voice, male bone configu-
ration such as large jaws, big feet and hands, tall stature and male hair pattern
on the face and extremities.
2.3. Evidence
Suppression of pubertal development and gonadal function is accomplished
most effectively by gonadotropin suppression with GnRH analogues and an-
tagonists. Analogues suppress gonadotropins after a short period of stimulation,
whereas antagonists immediately suppress pituitary secretion (Tuvemo 2006,
Roth 2002). Since no long-acting antagonists are available for use as pharma-
cotherapy, long-acting analogues are the currently preferred treatment option.
During treatment with the GnRH analogues, slight development of sex
characteristics will regress and, in a later phase of pubertal development, will be
halted. In girls, breast development will become atrophic and menses will stop;
in boys, virilization will stop and testicular volume will decrease (Delemarre
2006). An advantage of using GnRH analogues is the reversibility of the inter-
vention. If, after extensive exploring of his/her reassignment wish, the patient no
longer desires sex reassignment pubertal suppression can be discontinued.
Spontaneous pubertal development will resume immediately (Manasco1988).
In children with central precocious puberty, bone density is relatively high for
age. Suppressing puberty in these children using GnRH analogues will result in
a further increase in BMD and stabilization of BMD standard deviation scores
The statement that
“Adolescents with GID
should experience the
first changes of their bio-
logic, spontaneous pu-
berty” fails to take into
account the life experi-
ences of children who
transitioned to their true
gender role at a very
young age. The majority
of their socialization has
been in the gender role
they identify with, rather
than with their biologic
sex. To use “distress” as
a diagnostic tool on such
children is both unneces-
sary and cruel.
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10
(Neely 1995). Initial data in transsexual subjects demonstrate no change of
bone density during GnRH analogue therapy. (Delemarre 2006).
GnRH analogues are expensive and not always reimbursed by insur-
ance companies. For financial reasons, treatment with progestins can be an al-
ternative. They suppress gonadotropin secretion and exert a mild peripheral anti
-androgen effect in boys. Depo-medoxyprogesterone will suppress ovulation
and progesterone production for long periods of time, although residual estro-
gen levels vary. In high doses, progestins are relatively effective in suppression
of menstrual cycling in girls/women and androgen levels in boys/men. However,
at these doses, side effects such as suppression of adrenal function and sup-
pression of bone growth may occur (Raudrant 2003). Anti-estrogens in girls and
anti-androgens in boys can be used in order to delay the progression of puberty
(Mieszczak 2007, Jain 2004). Their efficacy, however, is far less than that of the
GnRH analogues.
2.3 Values and Preferences
For patients who can afford the therapy, our recommendation of GnRH ana-
logues places a higher value on the superior efficacy, safety and reversibility of
the pubertal hormone suppression achieved as compared with the alternatives
and a relatively lower value on limiting the cost of therapy. Of the available alter-
natives, depot progestin preparations may be partially effective, but not as safe;
its lower cost makes it an acceptable treatment for patients who cannot afford
GnRH.
2.3 Remarks
Measurements of gonadotropin and sex steroid levels give precise information
about suppression of the gonadal axis. If the gonadal axis is not completely sup-
pressed, the interval of GnRH analogue injections should be shortened. During
treatment, adolescents should be monitored for negative effects of delaying pu-
berty, including a halted growth spurt as well as impaired bone accretion. The
clinical protocol to be used is shown in Table 8. Glucose and lipid metabolism,
complete blood counts and liver and renal function should be monitored during
suppression and cross-sex hormone substitution. For the evaluation of growth
anthropometric measurements are well informative. To assess bone density,
dual energy X-ray absorptiometry (DEXA) scans can be performed.
2.4. Evidence
In many countries, 16-year-olds are legal adults with regard to medical decision
making. This is probably because, at this age, most adolescents are able to
make complex cognitive decisions. Although parental consent may not be re-
quired, obtaining it is preferred since the support of parents should improve the
outcome during this complex phase of the adolescent’s life (Delemarre-Van de
Waal 2006).
For the induction of puberty, we use a similar dose scheme of induction of pu-
berty in these hypogonadal transsexual adolescents as in other hypogonadal
individuals (Table 9). We do not advise the use of sex steroid creams or
patches since there is little experience for induction of puberty. The transsexual
adolescent is hypogonadal and may be sensitive to high doses of cross-sex
steroids, causing adverse effects of striae and abnormal breast shape in girls
and cystic acne in boys.
While TransActive
agrees that the support
of parents regarding
cross-gender hormone
therapy is the preferred
treatment model, we
don’t believe that ab-
sence of parental con-
sent should, in all
cases, be grounds for
denial of treatment.
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11
In FTM (female-to-male) transsexual adolescents, suppression of puberty may
halt the growth spurt. To achieve maximum height, slow introduction of andro-
gens will mimic a “pubertal” growth spurt. If the patient is relatively short, one
may treat the patient with oxandrolone, a growth-stimulating anabolic steroid
also applied in women with Turner syndrome (Nilsson 1996).
In MTF (male-to-female) transsexual adolescents, extreme tall stature is often a
genetic probability. The estrogen dose may be increased in a faster schedule,
estrogens may be started before the age of 16, or estrogens can be prescribed
in growth-inhibiting doses (Delemarre-Van de Waal 2006).
We suggest that treatment with GnRH analogues be continued during treatment
with cross-sex steroids in order to maintain full suppression of pituitary gonad-
otropin levels and, thereby, gonadal steroids. When puberty is initiated with a
gradually increasing schedule of sex steroid doses, the initial levels will not be
high enough to suppress endogenous sex steroid secretion (Table 7). Endoge-
nous production of sex steroid hormone of the undesired sex can interfere with
the effectiveness of the treatment. GnRH analogue treatment is advised until
gonadectomy.
2.4 Values and Preferences
Identifying an age at which pubertal development is initiated will be by necessity
arbitrary but the goal is to start this process at a time when the individual will be
able to make informed mature decisions and engage in the therapy, while at the
same time developing with his or her peers. Growth targets reflect personal
preferences, often shaped by societal expectations. Individual preferences
should be the key determinant, rather than the professional deciding a priori that
MTF transsexuals should be shorter than FTM transsexuals.
2.4 Remarks
Protocols for induction of puberty can be found in Table 9.
We recommend monitoring clinical pubertal development as well as laboratory
parameters (Table 10). Sex steroids of the desired sex will initiate pubertal de-
velopment, which can be (partially) monitored using Tanner stages. In addition,
the sex steroids will affect growth and bone development as well as insulin sen-
sitivity and lipid metabolism as in normal puberty (Ball 2006, Reinehr 2005).
2.6 We suggest deferring for surgery until at least 18 years old.
Surgery is an irreversible intervention. The WPATH SOC (Standards of Care)
(Meyer 2001) emphasize that the “threshold of 18 should be seen as an eligibil-
ity criterion and not an indication in itself for active intervention.” If the real life
experience supported by sex hormones of the desired sex has not resulted in a
satisfactory social role change, if the patient is not satisfied with or is ambivalent
about the hormonal effects, or if the patient is ambivalent about surgery, then
the applicant should not be referred for surgery.(Monstrey 2001, Monstrey
2007)
We support these rec-
ommendations. It is
also TransActive’s po-
sition that the recom-
mendations to the left
contradict (rightfully so)
the earlier recommen-
dation to withhold
cross-gender hormone
treatment until age 16,
by which time much of
the damage mentioned
at left would have been
done and irreversible.
TransActive agrees
with the recommenda-
tions at left and further
believes that individual
preferences rather than
an arbitrary age should
be the determining fac-
tor as to when cross-
gender hormone treat-
ment is initiated.
While surgery at any
age certainly should
not proceed if the indi-
vidual is ambivalent
about the process, we
believe that having a
third-party subjectively
evaluate whether or
not a “satisfactory so-
cial role change” has
occurred opens the
door to stereotypical
gender-role/
appearance expecta-
tions.
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12
4.0 Adverse Outcome Prevention and Long-term Care
Cross-sex hormone therapy confers the same risks associated with sex hor-
mone replacement therapy in biological males and females. The risk of cross-
sex hormone therapy arises from and is worsened by inadvertent or intentional
use of supraphysiologic doses of sex hormones or inadequate doses of sex hor-
mones to maintain normal physiology (Gooren 2008b, Gooren 2008a).
4.1 Evidence
Pretreatment screening and appropriate regular medical monitoring is recom-
mended for both FTM and MTF transsexual persons during the endocrine tran-
sition and periodically thereafter (Meyer 2006, Meyer 1981). Monitoring of
weight and blood pressure, directed physical exams, routine health questions
focused on risk factors, medications, complete blood counts, renal and liver
function, lipid and glucose metabolism should be carried out.
Female-to-male transsexual persons
A standard monitoring plan for individuals on testosterone therapy is found in
Table 15. Key issues include maintaining testosterone levels in the physiologic
normal male range and avoidance of adverse events resulting from chronic tes-
tosterone therapy, particularly erythrocytosis, liver dysfunction, hypertension,
excessive weight gain, salt retention, lipid changes, excessive or cystic acne
and adverse psychological changes (Bhasin 2006) Since oral 17-alkylated tes-
tosterone is not recommended, serious hepatic toxicity is not anticipated using
parenteral or transdermal testosterone (Bird 1979, Westaby 1977). Still, periodic
monitoring is recommended given that up to 15% of FTM persons treated with
testosterone have transient elevations in liver enzymes (Van Kesteren 1997).
Male-to-female transsexual persons
A standard monitoring plan for individuals on estrogens, gonadotropin suppres-
sion or anti-androgens is found in Table 16. Key issues include avoiding supra-
physiologic doses or blood levels of estrogen, which may lead to increased risk
for thromboembolic disease, liver dysfunction, and development of hyperten-
sion.
4.2 Evidence
Estrogen therapy can increase the growth of pituitary lactrotroph cells. There
have been several reports of prolactinomas occurring after long-term estrogen
therapy (Gooren 1988, Kovacs 1994, Serri 1996). Up to 20% of transsexual
women treated with estrogens may have elevations in prolactin levels associ-
ated with enlargement of the pituitary gland (Asscheman 1988). In most cases,
the serum prolactin levels will return to the normal range with a reduction or dis-
continuation of the estrogen therapy (Gooren 1985).
The onset and time course of hyperprolactinemia during estrogen treatment are
not known. Prolactin levels should be obtained at baseline and then at least an-
nually during the transition period and biannually thereafter. The major present-
ing symptoms of micro-prolactinomas (gynecomastia, and hypogonadism) are
not apparent in MTF transsexual persons.
Because transsexual persons are diagnosed and followed throughout sex reas-
signment by a mental health professional, it is likely that some will receive psy-
chotropic medications that can increase prolactin levels.
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13
4.3 Evidence
Female-to-male transsexual persons
Testosterone administration to FTM transsexual persons will result in a more
atherogenic lipid profile with lowered HDL cholesterol and higher triglyceride
values (Giltay 1999, Elbers 2003, Berra 2006). Studies of the effect of testoster-
one on insulin sensitivity have mixed results (Elbers 2003, Polderman 1994).
Numerous studies have demonstrated effects of cross-sex hormone treatment
on the cardiovascular system. (Giltay 1998, Giltay1999, Giltay 2003, Giltay
2004) Long-term studies from the Netherlands found no increased risk for car-
diovascular mortality (Van Kesteren 1997). Likewise, a meta-analysis of 19 ran-
domized trials in men examining testosterone replacement showed no in-
creased incidence of cardiovascular events (Calof 2005) (Haddad 2007). A sys-
tematic review of the literature found no conclusive evidence to suggest that
normal physiologic replacement doses of testosterone do or do not increase
cardiovascular events in FTM transsexual persons (Elamin [In Preparation].
Male-to-female transsexual persons
A prospective study of MTF subjects found favorable changes in lipid parame-
ters with increased HDL and decreased LDL concentrations (Elbers 2003).
However, these favorable lipid changes were attenuated by increased weight,
blood pressure, and markers of insulin resistance. The largest cohort of MTF
subjects (with a mean age of 41) followed for a mean of 10 years showed no
increase in cardiovascular mortality despite a 32% rate of tobacco use (van Ke-
steren 1997). Thus, there is limited evidence to determine whether estrogen is
protective or detrimental in MTF transsexual persons (Elamin [In preparation]).
With aging there is usually an increase of body weight and therefore, as with
non-transsexual individuals, glucose and lipid metabolism and blood pressure
should be monitored regularly.
4.4 Evidence
Female-to-male transsexual persons
Adequate dosing of testosterone is important to maintain bone mass in FTM
transsexual persons (van Kesteren 1998, Turner 2004). In this study, serum LH
levels were inversely related to bone mineral density, suggesting that low levels
of sex hormones were associated with bone loss. Thus, LH levels may serve as
an indicator of the adequacy of sex steroid administration to preserve bone
mass. The protective effect of testosterone may be mediated by peripheral con-
version to estradiol both systemically and locally in the bone.
Male-to-female transsexual persons
Studies in aging genetic males suggest that serum estradiol more positively cor-
relates with BMD than testosterone (Amin 2000, Genari 2008a, Genari 2008b)
and is more important for peak bone mass (Khosla 1998). Estrogen preserves
BMD in MTF transsexuals who continue on estrogen and anti-androgen thera-
pies (van Kesteren 1998, Ruetsche 2005, Mueller 2005).
Fracture data in transsexual men and women are not available. Gonadec-
tomized transsexual persons may not continue consistent cross-sex steroid
treatment after hormonal and surgical sex reassignment, thereby becoming at
risk for bone loss.
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14
4.5-4.6 Evidence
Breast cancer is a concern in transsexual women. A few cases of breast cancer
in MTF transsexual persons have been reported in the literature (Pritchard
1988, Ganly 1995, Symmers 1968). In the Dutch cohort of 1800 transsexual
women followed for a mean of 15 years (range 1 to 30 years), only one case of
breast cancer was found. The Women’s Health Initiative study reported that
women taking conjugated equine estrogen without progesterone for 7 years did
not have an increased risk of breast cancer as compared with women taking
placebo (Anderson 2004). Women with primary hypogonadism (XO) treated
with estrogen replacement exhibited a significantly decreased incidence of
breast cancer as compared with national standardized incidence ratios
(Schoemaker 2008, Bosze 2006). These studies suggest that estrogen therapy
does not increase the risk of breast cancer in the short term (<20-30 years).
Long-term studies are required to determine the actual risk and the role of
screening mammograms. Regular exams and gynecologic advice should deter-
mine monitoring for breast cancer.
Prostate cancer is very rare, especially with androgen deprivation therapy, be-
fore the age of 40 (Smith 2006) Childhood or pubertal castration results in re-
gression of the prostate and adult castration reverses benign prostate hypertro-
phy (BPH) (Wilson 1999). Although van Kesteren (1996) reported that estrogen
therapy does not induce hypertrophy or pre-malignant changes in the prostate
of MTF transsexual persons (van Kesteren 1996), cases of. BPH have been
reported in MTF transsexual persons treated with estrogens for 20-25 years
(Casella, 2005,) (Brown, 1997). Three cases of prostate carcinoma have been
reported in MTF transsexual persons (van Haarst 1998, Dorff 2007, Thurston
1994). However, these individuals initiated cross-hormone therapy after age 50,
and whether these cancers were present before the initiation of therapy is un-
known. The limited evidence suggests that prostate cancer risk may be in-
creased in the older individual initiating on cross-hormone therapy.
4.7 Evidence
Although aromatization of testosterone to estradiol in FTM transsexual persons
has been suggested as a risk factor for endometrial cancer (Futterweit 1998),
no cases have been reported. When FTM transsexual persons undergo hyster-
ectomy, the uterus is small and there is endometrial atrophy. (O’Hanlan 2007,
Miller 1986). The androgen receptor has been reported to increase in the ova-
ries after long-term administration of testosterone, which may be an indication of
increased risk of ovarian cancer (Chadha 1994). Cases of ovarian cancer have
been reported (Hage 2000, Dizon 2006). The relative safety of laparoscopic to-
tal hysterectomy argues for preventing the risks of reproductive tract cancers
and other diseases through surgery (Mueller 2008).
4.7 Values
Given the discomfort that FTM transsexual persons experience accessing gyne-
cologic care, our recommendation for total hysterectomy and oophorectomy
places a high value upon eliminating
the risks of female reproductive tract dis-
ease and cancer and a lower value on avoiding the risks of these surgical pro-
cedures (related to the surgery and to the potential undesirable health conse-
quences of oophorectomy) and their associated costs.
Many transgender/
transsexual adoles-
cents can be particu-
larly sensitive about
exposing their bodies
to others. It is impor-
tant to make every ef-
fort to establish a trust-
based relationship with
these youth.
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15
5.0 Surgery for Sex Reassignment
The surgical techniques have improved markedly during the past 10 years. Cos-
metic genital surgery with preservation of neurological sensation is now the
standard. The satisfaction rate with surgical reassignment of sex is now very
high (Murad [In preparation]). In addition, the mental health of the individual
seems to be improved by participating in a treatment program that defines a
pathway of gender identity treatment that includes hormones and surgery (Cole
1997). The person must be both eligible and ready for such a procedure. (Table
17.).
Sex reassignment surgeries available to the MTF transsexual persons consist of
gonadectomy, pinectomy, and creation of a vagina.(Selvaggi 2005, Turgnet
2007). The skin of the penis is often inverted to form the wall of the vagina. The
scrotum becomes the labia majora. Cosmetic surgery is used to fashion the
clitoris and its hood, preserving the neurovascular bundle at the tip of the penis
as the neurosensory supply to the clitoris. Most recently plastic surgeons have
developed techniques to fashion labia minora. Endocrinologists should remind
the patient to use their tampon dilators to maintain the depth and width of the
vagina throughout the post- operative period until the neovagina is being used
frequently in intercourse.
Ancillary surgeries for more cosmetic appearance are not within the scope of
this guideline. When possible, less surgery is desirable. For instance, voice les-
sons by a speech pathologist is preferred to laryngeal shaving and other surgi-
cal methods to raise the tone of the voice (McNeill 2006).
Breast size in genetic females exhibits a very broad spectrum. For the patient to
make the best-informed decision, breast augmentation surgery should be de-
layed until at least 2 years of estrogen therapy have been completed since the
breasts continue to grow during that time with estrogen stimulation (Meyer
1981).
Another major effort is the removal of facial and masculine- appearing body hair
using either electrolysis or laser treatments. Other feminizing surgery, such as
surgery to feminize the face and the external genitalia, is now becoming more
popular. (Becking 2006, Goddard2007, Giraldo 2004).
Sex reassignment surgeries available to the FTM transsexual persons have
been less satisfactory. The cosmetic appearance of a neopenis is now very
good but the surgery is multistage and very expensive (Hage 1993, Monstrey
2003). Neopenile erection can be achieved only if some mechanical devise is
imbedded in the penis, e.g., a rod or some inflatable apparatus (Chen 2007).
Many choose a metadoioplasty that exteriorizes or brings forward the clitoris
and allows for voiding while standing. The scrotum is created from the labia ma-
jora with a good cosmetic effect and artificial testicular-size structures can be
implanted and appear as testes. Ovariectomy, vaginectomy, and complete hys-
terectomy are needed after a few years of androgen therapy since androgens
can be responsible for ovarian tumors (Dizon 2006). These procedures are now
done vaginally and with the aid of a laparoscope.
The ancillary surgery for the female to male that is extremely important is the
mastectomy. Breast size only partially regresses with androgen therapy. Mas-
tectomy should be considered at the same time or soon after androgen therapy
is begun.
Physicians should not
assume that their trans
-female patients are
heterosexual and
therefore committed to
penetrative, vaginal
intercourse. The impor-
tance of post-operative
dilation should be con-
veyed to the individual
without expectation of
a particular sexual ori-
entation.
With effective hormo-
nal intervention begin-
ning at Tanner 2-3,
trans-female adoles-
cents should develop a
vocal tone within a typi-
cal female range.
One of the key advan-
tages of pubertal sup-
pression and cross-
gender hormone ther-
apy is the elimination
of the need for and ex-
pense of these reactive
procedures.
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16
5.1.-5.3 Evidence
When a transsexual individual decides to have sex reassignment surgery, both
the endocrinologist and the mental health professional must certify that he/she
satisfies the eligibility and readiness criteria of the Standard of Care (Meyer
2001) (Table 17).
There is some concern that estrogen therapy causes an increased risk for ve-
nous thrombosis post surgery (Elamin [In preparation]. For this reason, the sur-
geon and the endocrinologist should collaborate in making a decision about the
use of hormones during the month before surgery.
Although one study suggests that preoperative factors such as compliance are
less important than the physical postoperative results (Lawrence 2003), other
studies and clinical experience dictate that individuals who do not follow medical
instructions and work with their physicians toward a common goal do not do
achieve treatment goals (Liberopoulos 2008) and experience higher rates of
postoperative infections and other complications (Forbes 2008, Davis 2008). It
is also important that the person requesting surgery feel comfortable with the
anatomical changes that have occurred during hormone therapy. Dissatisfaction
with social and physical outcomes during the hormone transition may be a con-
traindication to surgery (Monstrey 2007).
Transsexual individuals should be monitored by an endocrinologist after sur-
gery. Those who undergo gonadectomy will require hormone replacement ther-
apy or surveillance or both to prevent adverse effects of chronic hormone defi-
ciency.
The WPATH SOC
state that a candidate
for gender reassign-
ment surgery must
have two letters of cer-
tification: one(1) from a
licensed therapist/
counselor and one (1)
from a psychiatrist. The
already existing third
gatekeeper is, obvi-
ously, the surgeon who
will perform the proce-
dure(s).
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17
R
EFERENCES
American Psychiatric Association (APA) 2001 Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision (DSM-IV-TR). Washington, DC: APA
Amin S, Zhang Y, Sawin CT, Evans SR, Hannan MT, Kiel DP, et al 2000 Association of hypogonadism and es-
tradiol levels with bone mineral density in elderly men from the Framingham Heart Study. Ann Intern Med
133:951-963.
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R,
Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A,
Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N,
Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C,
Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R,
Wassertheil-Smoller S; Women's Health Initiative Steering Committee 2004 Effects of conjugated
equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized
controlled trial. JAMA 291:1701-12
Asscheman H, Gooren LJ, Assies J, Smits JP, de Slegte R 1988 Prolactin levels and pituitary enlargement in
hormone-treated male-to-female transsexuals. Clin Endocrinol (Oxf) 28:583-8
Baba T, Endo T, Honnma H, Kitajima Y, Hayashi, Ikeda H, Masumori N, Kamiya H, Moriwaka O, Saito T 2007
Association between polycystic ovary syndrome and female-to-male transsexuality. Hum Reprod 22:1011-
1016
Balen A 2001 Polycystic ovary syndrome and cancer. Hum Reprod Update 7(6):522-5
Ball GD, Huang TT, Gower BA, Cruz ML, Shabibi GQ, Weigensberg MJ, Goran MI 2006 Longitudinal changes
in insulin sensitivity, insulin secretion, and beta-cell function during puberty. J Pediatr 148:16-22
Becking AG, Tuinzing DB, Hage JJ, Gooren LJ 2007 Transgender feminization of the facial skeleton. Clin Plast
Surg 34:557-564
Berra M, Armillotta F, D'Emidio L, et al 2006 Testosterone decreases adiponectin levels in female to male trans-
sexuals. Asian J Androl 8:725-729
Bhasin S, Cunningham GR, Hayes F, Matsumoto AM, Synder PJ, Swerdloff RS, Montori VM 2006 Testoster-
one therapy in adult men with androgen deficiency syndromes. J Clin Endocrinol Metab 91:1995-2010
Bird D, Vowles K, Anthony PP 1979 Spontaneous rupture of a liver cell adenoma after long term methyltestoster-
one: report of a case successfully treated by emergency right hepatic lobectomy. Br J Surg 66:212-213
Blanchard R 1997 Birth order and sibling sex ratio in homosexual\versus heterosexual males and females. Annu
Rev Sex Res 8:27-67
Blanchard R 2001 Fraternal birth order and the maternal immune hypothesis of male homosexuality. Horm Behav
40:105-14
Bocklandt S, Vilain E 2007 Sex differences in brain and behavior: hormones versus genes. Adv Genet 59:245-66
Bosze P, Toth A, Torok M 2006 Hormone replacement and the risk of breast cancer in Turner’s syndrome. N Engl
J Med 355:2599-2600
Boyar RM, Wu RHK, Roffwarg H, Kapen S, Weitzman E, Hellman L, Finkelstein JW 1976 Human puberty:
twenty-four hour estradiol patterns in pubertal girls. J Clin Endocrinol Metab 43:1418-1421
Brown JA, Wilson TM 1997 Benign prostatic hyperplasia requiring transurethral resection of the prostate in a 60-
year-old male-to-female transsexual. Brit J Urol 80:956-957
Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S 2005 Adverse events associated
with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-
controlled trials. J Gerontol A Biol Sci Med Sci 60:1451-7
Casella R, Bubendorf L, Schaefer DJ, Bachmann A, Gasser TC, Sulser T 2005 Does the prostate really need
androgens to grow? Transurethral resection of the prostate in a male-to-female transsexual 25 years after
sex-changing surgery. Urol Int 75:288-290
Chadha S, Pache TD, Huikeshoven JM, Brinkmann AO, van der Kwast TH 1994 Androgen receptor expression
in human ovarian and uterine tissue of long-term androgen-treated transsexual women. Hum Pathol
25:1198-1204
Chen HC, Gedebou TM, Yazar S, Tang YB 2007 Prefabrication of the free fibula osteocutaneous flap to create a
functional human penis using a controlled fistula method. J Reconstr Microsurg 23:151-154
Magdeleyns EJ, Tans G, Gooren LJ, Rosing J. 2007 Prolactinoma and estrogens: pregnancy, contraception and
hormonal replacement therapy. Ann Endocrinol (Paris) 68:106-112
Cohen-Kettenis PT 2001 Gender identity disorder in DSM? J Am Acad Child Adolesc Psychiatry 40:391
Cohen –Kettenis PT, Delemarre-Van de Waal HA, Gooren LJG 2008 The Treatment of Adolescent Transsexu-
als: Changing Insights. J Sex Med 5: 1892-1897
Cohen-Kettenis PT, Gooren LJ 1999 Transsexualism: a review of etiology, diagnosis and treatment. J Psycho-
som Res 46:315-333.
Distributed by: TransActive Education & Advocacy—www.TransActiveOnline.org
18
Cohen-Kettenis PT, Owen A, Kaijser VG, Bradley SJ, Zucker KJ 2003 Demographic characteristics, social com-
petence, and behavior problems in children with gender identity disorder: a cross-national, cross-clinic com-
parative analysis. J Abnorm Child Psychol 31:41-53
Cohen-Kettenis PT, van Goozen SH 1997 Sex reassignment of adolescent transsexuals: a follow-up study. J Am
Acad Child Adolesc 36:263-271
Cohen-Kettenis PT, van Goozen SH 1998 Pubertal delay as an aid in diagnosis and treatment of a transsexual
adolescent. Eur Child Adolesc Psychiatry 7:246-248
Cole CM, O’Boyle M, Emory L E, Meyer WJ 3rd 1997 Comorbidity of gender dysphoria and other major psychiat-
ric diagnoses. Arch Sex Behav 26:13-26
Coolidge FL, Thede L, Young SE 2002 The heritability of gender identity disorder in a child and adolescent twin
sample. Behav Genet 32:251-257
Davis PJ, Spady D, de Gara C, Forgie SE 2008 Practices and Attitudes of Surgeons Toward Prevention of Surgi-
cal Site Infections: A Provincial Survey in Alberta Canada. Infect Control Hosp Epidemiol [Epub Publication]
De Sutter P 2001 Gender reassignment and assisted reproduction: present and future reproductive options for
transsexual people. Hum Reprod 16:612-614
De Sutter P 2003 Donor inseminations in partners of female to male transsexuals: should the question be asked?
Reprod Biomed Online 6:382-383
De Sutter P 2007 Reproduction and fertility issues for transpeople. In: Ettner R, Monstrey S, Eyler AE, eds. Princi-
ples of Transgender Medicine and Surgery. New York: The Haworth Press; 209-221
Delemarre-Van de Waal HA, Cohen-Kettenis PT 2006 Clinical management of gender identity disorder in adoles-
cents: a protocol on psychological and paediatric endocrinology aspects. Eur J Endocrinol 155(Suppl
1):S131-S137
Dessens AB, Slijper FM, Drop SL 2005 Gender dysphoria and gender change in chromosomal females with con-
genital adrenal hyperplasia. Arch Sex Behav 34:389-97
Di Ceglie D, Freedman D, McPherson S, Richardson P 2002 Children and adolescents referred to a specialist
gender identity development service: clinical features and demographic characteristics. Int J Transgender-
ism 6(1). Available at: http://www.symposion.com/ijt/ijtvo06no01_01.htm
Dickersin K, Munro MG, Clark M, Langenberg P, Scherer R, Frick K, Zhu Q, Hallock L, Nichols J, Yalcinkaya
TM; Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding (STOP-DUB) Re-
search Group 2007 Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding: a
randomized controlled trial. Obstet Gynecol 110:1279-1289
Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A 2005 Endocrine treatment of male-to-
female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 113:586-
592
Dizon DS, Tejada-Berges T, Koelliker S, Steinhoff M, Granai CO 2006 Ovarian cancer associated with testos-
terone supplementation in a female-to-male transsexual patient. Gynecol Obstet Invest 62:226-228
Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA 1999 Pharmacokinetics, efficacy, and
safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections
of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 84(10):3469-78.
Dorff TB, Shazer RL, Nepomuceno EM, Tucker SJ 2007 Successful treatment of metastatic androgen-
independent prostate carcinoma in a transsexual patient. Clin Genitourin Cancer 5:344-346
Drummond KD, Bradley SJ, Peterson-Badali M, Zucker KJ 2008 A follow-up study of girls with gender identity
disorder. Dev Psychol 44:34-45
Elbers JM, Giltay EJ, Teerlink T, et al 2003 Effects of sex steroids on components of the insulin resistance syn-
drome in transsexual subjects. Clin Endocrinol (Oxf) 58:562-571
Forbes SS, Stephen WJ, Harper WL, Loeb M, Smith R, Christoffersen EP, McLean RF 2008 Implementation of
evidence-based practices for surgical site infection prophylaxis: results of a pre- and postintervention study.
J Am Coll Surg 207: 336-341.
Finkelstein JS, Neer RM, Biller BM, Crawford JD, Klibanski A 1992 Osteopenia in men with a history of delayed
puberty. N Engl J Med 326:600-4
Futterweit W 1998 Endocrine therapy of transsexualism and potential complications of long-term treatment. Arch
Sex Behav 27:209-26
Gadducci A, Gargini A, Palla E, Fanucchi A, Genazzani AR 2005 Polycystic ovary syndrome and gynecological
cancers: is there a link? Gynecol Endocrinol 20:200-8
Ganly I, Taylor EW 1995 Breast cancer in a trans-sexual man receiving hormone replacement therapy. Br J Surg
82:341
Genari L, Khosla S, Bilezikian JP 2008a Estrogen effects on bone in the male skeleton. IN: Principles of Bone
Biology (Bilezikian JP, Martin TJ, Raisz LG, eds.) 3
rd
Edition, Elsevier/Academic Press, San Diego, 1801-
1818.
Genari L, Khosla S, Bilezikian JP 2008b Estrogen and fracture risk in men. J Bone Min Res 23: 1548-1818.
Distributed by: TransActive Education & Advocacy—www.TransActiveOnline.org
19
Giltay EJ, Gooren LJ 2000 Effects of sex steroid deprivation/administration on hair growth and skin sebum pro-
duction in transsexual males and females. J Clin Endocrinol Metab 85:2913-21
Giltay EJ, Hoogeveen E, Elbers J, Gooren L, Asscheman H, Stehouwer C 1998 Effects of sex steroids on
plasma total homocysteine levels: a study in transsexual males and females. J Clin Endocrinol Metab
83:550-553
Giltay EJ, Lambert J, Gooren LJ, Elbers JM, Steyn M, Stehouwer CD 1999 Sex steroids, insulin, and arterial
stiffness in women and men. Hypertension 34: 590-597
Giltay EJ, Toorians AW, Sarabdjitsingh AR, de Vries NA, Gooren LJ 2004 Established risk factors for coronary
heart disease are unrelated to androgen-induced baldness in female-to-male transsexuals. J Endocrinol
180:107-12
Giltay EJ, Verhoef P, Gooren L, Geleijnse J, Schouten E, Stehouwer C 2003 Oral and transdermal estrogens
both lower plasma total homocysteine in male-to-female transsexuals. Atherosclerosis 168:139-146
Giraldo F, Esteva I, Bergero T, Cano G, Gonzalez C, Salinas P, Rivada E, Lara JS, Soriguer F; Andalusia
Gender Team 2004 Corona glans clitoroplasty and urethropreputial vestibuloplasty in male-to-female
transsexuals: the vulval aesthetic refinement by the Andalusia Gender Team. Plast Reconstr Surg
114:1543-1550
Goddard JC, Vickery RM, Terry TR 2007 Development of feminizing genitoplasty for gender dysphoria. J Sex
Med 4:981-989
Gooren L 1990 The endocrinology of transsexualism: a review and commentary. Psychoneuroendocrinology 15:3-
14
Gooren L 2005 Hormone treatment of the adult transsexual patient. Horm Res 64(Suppl 2):31-36
Gooren L 2006 The biology of human psychosexual differentiation. Horm Behav 50:589-601
Gooren L 2007 Treatment of transsexualism. Published electronically on the UpToDate website.
Gooren LJ, Assies J, Asscheman H, de Slegte R, van Kessel H 1988 Estrogen-induced prolactinoma in a man.
J Clin Endocrinol Metab 66:444-446
Gooren LJ, Giltay EJ 2008a Review of studies of androgen treatment of female-to-male transsexuals: effects and
risks of administration of androgens to females. J Sex Med 5:765-776
Gooren LJ, Giltay EJ, Bunck MC 2008b Long-term treatment of transsexuals with cross-sex hormones: extensive
personal experience. J Clin Endocrinol Metab 93:19-25
Gooren LJ, Harmsen-Louman W, van Kessel H 1985 Follow-up of prolactin levels in long-term oestrogen-treated
male-to-female transsexuals with regard to prolactinoma induction. Clin Endocrinol (Oxf) 22:201-7
Green R 1998 Sexual functioning in post-operative transsexuals: male-to-female and female-to-male. Int J Impot
Res 10(Suppl 1):S22-24
Hage JJ, de Graaf FH, Bouman FG, Bloem JJ 1993 Sculpturing the glans in phalloplasty. Plast Reconstr Surg
92:157-161
Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E 2000 Ovarian cancer in female-to-male transsexuals:
report of two cases. Gynecol Oncol 76:413-415
Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A 2005 Psychatric comorbidity in gender identity disorder.
J Psychsom Res 58:254-261
Hines M 2004 Brain Gender. New York: Oxford University Press
Jain J, Dutton C, Nicosia A, Wajszczuk C, Bode FR, Mishell DR 2004 Pharmacokinetics, ovulation suppression
and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera. Contraception
70:11-18
Kersting A, Reuteman M, Gast U, Ohrmann P, Suslow T, Michael N, Arolt V 2003 Dissociative disorders and
traumatic childhood experiences in transsexuals. J Nerv Ment Dis 191:182-189
Khosla S, Melton LJ III, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL 1998 Relationship of serum sex steroid
levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable
estrogen. J Clin Endocrinol Metab 83:2266-2274
Knafo A, Iervolono AC, Plomin R 2005 Masculine girls and feminine boys: Genetic and environmental contribu-
tions to atypical gender development in early childhood. J Pers Soc Psychol 88: 400-412
Kovacs K, Stefaneanu L, Ezzat S, Smyth HS 1994 Prolactin-producing pituitary adenoma in a male-to-female
transsexual patient with protracted estrogen administration. A morphologic study. Arch Pathol Lab Med
118:562-565
Krauss DJ, Taub HA, Lantinga LJ, et al 1991 Risks of blood volume changes in hypogonadal men treated with
testosterone enanthate for erectile impotence. J Urol 146:1566-70.
Kuiper AJ, Cohen-Kettenis PT 1998 Gender role reversal among postoperative transsexuals. Int J Transgender-
sim 2. Available at: http://www.symposion.com/ijt/ijtc0502.htm
Landen M, Walinder J, Hambert G, Lundstrom B 1998 Factors predictive of regret in sex reassignment. Acta
Psychaitr Scand 97:284-289
Distributed by: TransActive Education & Advocacy—www.TransActiveOnline.org
20
Lawrence AA 2003 Factors associated with satisfaction or regret following male-to-female sex reassignment sur-
gery. Arch Sex Behav 32:299-315
Levy A, Crown A, Reid R 2003 Endocrine intervention for transsexuals. Clin Endocrinol (Oxf) 59:409-418
Levy J, Burshell A, Marbach M, Afilato L, Glick SM 1980 Interaction of spironolactone with oestradiol receptors
in cytosol. J Endocrinol 84:371-379
Liberopoulos EN, Florentin M, Mikhailidis DP, Elisaf MS. 2008 Compliance with lipid-lowering therapy and its
impact on cardiovascular morbidity and mortality. Expert Opin Drug Saf 7: 717-725.
Lindemalm G, Korlin D, Uddenberg N 1987 Prognostic factors vs. outcome in male-to-female transsexualism: a
follow-up study of 13 cases. Acta Psychiatr Scand 75:268-274
Lips P, Asscheman H, Uitewaal P, Netelenbos JC, Gooren L 1989 The effect of cross-gender hormonal treat-
ment on bone metabolism in male-to-female transsexuals. J Bone Miner Res 4:657-662
Lubbert H, Leo-Rosenberg I, Hammerstein J 1992 Effects of ethinyl estradiol on semen quality and various hor-
monal parameters in a eugondal male. Fertil Steril 58:603-608
Luders E, Narr KL, Thompson PM, Rex DE, Woods RP, Deluca H, Jancke L, Toga AW 2006 Gender effects on
cortical thickness and the influence of scaling. Hum Brain Mapp 27:314-324
Manasco PK, Pescovitz OH, Feuillan PP, Hench KD, Barnes KM, Jones J, Hill SC, Loriaux DL, Cutler GB
1988 Resumption of puberty after long term luteinizing hormone-releasing hormone agonist treatment of
central precocious puberty. J Clin Endocrinol Metab 67:368-72
McNeill EJ 2006 Management of the transgender voice. J Laryngol Otol 120:521-523
Meyer WJ 3rd, Bockting W, Cohen-Kettenis P, Coleman E, DiCeglie D, Devor H, Gooren L, Hage JJ, Kirk S,
Kuiper B, Laub D, Lawrence A, Menard Y, Monstrey S, Patton J, Schaefer L, Webb A, Wheeler CC
2001 Harry Benjamin International Gender Dysphoria Association’s The Standards of Care for Gender
Identity Disorders, 6th version. Int J Transgenderism 5:1-22. Available at: http://www.symposion.com/ijt/
soc_2001/index.htm
Meyer WJ 3rd, Webb A, Stuart CA, Finkelstein JW, Lawrence B, Walker PA 1986 Physical and hormonal
evaluation of transsexual patients: a longitudinal study. Arch Sex Behav 15:121-138
Meyer-Bahlburg HF 2005 Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal
exstrophy of the bladder, or penile ablation. Arch Sex Behav 34:423-38
Meyer-Bahlburg HF, Dolezal C, Baker SW, Carlson AD, Obeid JS, New MI 2004 Prenatal androgenization af-
fects gender-related behavior but not gender identity in 5-12-year-old girls with congenital adrenal hyper-
plasia. Arch Sex Behav 33:97-104
Meyer-Bahlburg HF, Dolezal C, Baker SW, Ehrhardt AA, New MI. 2006 Gender development in women with
congenital adrenal hyperplasia as a function of disorder severity. Arch Sex Behav 35:667-684
Mieszczak J, Eugster EA 2007 Treatment of precocious puberty in McCune-Albright syndrome. Pediatr Endocrinol
Rev 4(Suppl 4):419-422
Miller N, Bedard YC, Cooter NB, Shaul DL 1986 Histological changes in the genital tract in transsexual women
following androgen therapy. Histopathology 10:661-669
Mittan D, Lee S, Miller E, Perez RC, Basler JW, Bruder JW 2002 Bone loss following hypogonadism in men with
prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab 87:3656-61
Monstrey S, De Cuypere G, Ettner R 2007 Surgery: General Principles. In: Ettner SR,Monstrey S, Eyler AE,
eds. Principles of Transgender Medicine and Surgery. New York: The Haworth Press; 89-104
Monstrey S, Hoebeke P, Dhont M, De Cuypere G, Rubens R, Moerman M, Hamdi M, Van Landuyt K, Blon-
deel P 2001 Surgical therapy in transsexual patients: a multi-disciplinary approach. Acta Chir Belg 101:200
-209
Moore E, Wisniewski A, Dobs A 2003 Endocrine treatment of transsexual people: a review of treatment regimens,
outcomes, and adverse effects. J Clin Endocrinol Metab 88:3467-3473
Mueller A, Dittrich R, Binder H, Kuehnel W, Maltaris T, Hoffmann I, Beckmann MW 2005 High dose estrogen
treatment increases bone mineral density in male-to-female transsexuals receiving gonadotropin-releasing
hormone agonist in the absence of testosterone. Eur J Endocrinol 153:107-13
Mueller A, Gooren L 2008 Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones.
Eur J Endocrinol 159:197-202
Neely EK, Bachrach LK, Hintz RL, Habiby RL, Siemenda CW, Feezle L, Pescovitz OH 1995 Bone mineral den-
sity during treatment of central precocious puberty. J Pediatr 127:819-22
Nillson KO, Albertsson-Wikland K, Alm J, Aronson S, Gustafsson J, Hagenäs L, Häger A, Ivarsson SA, Karl-
berg J, Kriström B, Marcus C, Moell C, Ritzen M, Tuvemo T, Wattsgård C, Westgren U, Westphal O,
Aman J 1996 Improved final height in girls with Turner’s syndrome treated with growth hormone and oxan-
drolone. J Clin Endocrinol Metab 81:635-40
O’Hanlan KA, Dibble SL, Young-Spint M 2007 Total laparoscopic hysterectomy for female-to-male transsexuals.
Obstet Gynecol 110:1096-1101
Distributed by: TransActive Education & Advocacy—www.TransActiveOnline.org
21
Olsson SE, Moller A 2006 Regret after sex reassignment surgery in a male-to-female transsexual: a long-term
follow-up. Arch Sex Behav 35:501-506
Pfäfflin F, Junge A 1992 Geschlechtsumwandlung: Abhandlungen zur Transsexualität (Sex Change: Treatises on
Transsexualism). Stuttgart: Schattauer
Polderman KH, Gooren LJ, Asscheman H, Bakker A, Heine RJ 1994 Induction of insulin resistance by andro-
gens and estrogens. J Clin Endocrinol Metab 79:265-271
Prasad P, Powell MC 2008 Prospective observational study of thermablate endometrial ablation system as an out-
patient procedure. J Minim Invasive Gynecol 15:476-479
Pringsheim T, Gooren L 2004 Migraine prevalence in male to female transsexuals on hormone therapy. Neurol-
ogy 63:593-4
Pritchard TJ, Pankowsky DA, Crowe JP, Abdul-Karim FW 1988 Breast cancer in a male-to-female transsexual.
A case report. JAMA 259:2278-2280
Raudrant D, Rabe T 2003 Progestogens with antiandrogenic properties. Drugs 63:463-492
Reinehr T, Kiess W, Andler W 2005 Insulin sensitivity indices of glucose and free faty acid metabolism in obese
children and adolescents in relation to serum lipids. Metabolism 54:397-402
Reiner WG 2005 Gender identity and sex-of-rearing in children with disorders of sexual differentiation. J Pediatr
Endocrinol Metab 18:549-53
Riman T, Nilsson S, Persson IR 2004 Review of epidemiological evidence for reproductive and hormonal factors
in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand 83:783-95
Rishpon-Meyerstein N, Kilbridge T, Simone J, Fried W 1968 The effect of testosterone on erythropoietin levels
in anemic patients. Blood 31:453-60
Ross MW, Need JA 1989 Effects of adequacy of gender reassignment surgery on psychological adjustment: a fol-
low-up of fourteen male-to-female patients. Arch Sex Behav 18:145-153
Roth C 2002 Therapeutic potential of GnRH antagonists in the treatment of precocious puberty. Expert Opin Inves-
tig Drugs 11:1253-9
Ruble DN, Martin CL, Berenbaum SA 2006 Gender development. In: Damon W, Lerner RM, Eisenberg N, eds.
Handbook of Child Psychology, 6th edition. John Wiley & Sons, New York, NY; vol. 3, 858-932
Ruetsche AG, Kneubuehl R, Birkhaeuser MH, Lippuner K 2005 Cortical and trabecular bone mineral density in
transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study. Osteoporos Int 16:791-
8
Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA; UK Clinical Cytogenetics Group 2008
Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol
9:239-246
Schulze C 1988 Response of the human testis to long-term estrogen treatment: morphology of Sertoli cells, Leydig
cells, and spermatogonial stem cells. Cell Tissue Res 251:31-43
Seikowski K 2007 Psychotherapy and transsexualism. Andrologia 39:248-252
Seli E, Tangir J 2005 Fertility preservation options for female patients with malignancies. Curr Opin Obstet Gyne-
col 17(3):299-308
Selvaggi G, Ceulemans P, De Cuypere G, VanLanduyt K, Blondeel P, Hamdi M, Bowman C, Monstrey S
2005 Gender identity disorder: general overview and surgical treatment for vaginoplasty in male-to-female
transsexuals. Plast Reconstr Surg 116:135e-145e
Serri O, Noiseux D, Robert F, Hardy J 1996 Lactotroph hyperplasia in an estrogen treated male-to-female trans-
sexual patient. J Clin Endocrinol Metab 81:3177-3179
Smith RA, Cokkinides V, Eyre HJ 2006 American Cancer Society guidelines for the early detection of cancer,
2006. CA Cancer J Clin 56:11-25
Smith YL, van Goozen SH, Cohen-Kettenis PT 2001 Adolescents with gender identity disorder who were ac-
cepted or rejected for sex reassignment surgery: a prospective follow-up study. J Am Acad Child Adolesc
Psychiatry 40:472-481
Smith YL, van Goozen SH, Kuiper AJ, Cohen-Kettenis PT 2005 Sex reassignment: outcomes and predictors of
treatment for adolescent and adult transsexuals. Psychol Med 35:89-99
Spinder T, Spijkstra JJ, van den Tweel JG, Burger CW, van Kessel H, Hompes PG, Gooren LJ 1989 The ef-
fects of long term testosterone administration on pulsatile hormone section and on ovarian histology in
eugonadal female to male transsexual subjects. J Clin Endocrinol Metab 69:151-157
Symmers WS 1968 Carcinoma of the breast in trans-sexual individuals after surgical and hormone interference
with primary and secondary characteristics. Br Med J 2:82-85
Tangpricha V, Ducharme SH, Barber TW, Chipkin SR 2003 Endocrinologic treatment of gender identity disor-
ders. Endocr Pract 9:12-21
Tanner JM 1962 Growth at adolescence, 2
nd
edition. Oxford, UK: Blackwell Scientific Publications
Thiagaraj D, Gunasegaram R, Loganath A, Peh KL, Kottegoda SR, Ratnam SS 1987 Histopathology of the tes-
tes from male transsexuals on oestrogen therapy. Ann Acad Med Singapore 16:347-348
Distributed by: TransActive Education & Advocacy—www.TransActiveOnline.org
22
Thurston AV 1994 Carcinoma of the prostate in a transsexual. Br J Urol 73:217
Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, Rosing J 2003 Venous
thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual peo-
ple. J Clin Endocrinol Metab 88:5723-5729
Tugnet N, Goddard JC, Vickery RM, Khoosal D, Terry TR 2007 Current management of male-to-female gender
identity disorder in the UK. Postgrad Med J 83:638-642
Turner A, Chen TC, Barber TW, Malabanan AO, Holick MF, Tangpricha V 2004 Testosterone increases bone
mineral density in female-to-male transsexuals: a case series of 15 subjects. Clin Endocrinol (Oxf) 61:560-
566
Tuvemo T 2006 Treatment of central precocious puberty. Expert Opin Investig Drugs 15:495-505
U.S. Preventive Services Task Force (USPSTF) 2008 Screening for prostate cancer: US Preventive Services
Task Force recommendation statement. Ann Intern Med 149:185-191
Van Coeverden SC, De Ridder CM, Roos JC, Van't Hof MA, Netelenbos JC, Delemarre-Van de Waal HA 2001
Pubertal maturation characteristics and the rate of bone mass development longitudinally toward men-
arche. J Bone Miner Res16:774-781
van Haarst EP, Newling DW, Gooren LJ, Asscheman H, Prenger DM 1998 Metastatic prostatic carcinoma in a
male-to-female transsexual. Br J Urol 81:776
van Kesteren P, Kooistra T, Lansink M, van Kamp G, Asscheman H, Gooren L, Emeis J, Vischer U, Stehou-
wer C 1998 The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning.
Thromb Haemost 79:1029-1033
van Kesteren P, Lips P, Gooren LJ, Asscheman H, Megens J 1998 Long-term follow-up of bone mineral density
and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 48:347-354
van Kesteren P, Meinhardt W, van der Valk P, Geldof A, Megens J, Gooren L 1996 Effects of estrogens only
on the prostates of aging men. J Urol 156:1349-1353
van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ 1997 Mortality and morbidity in transsexual subjects
treated with cross-sex hormones. Clin Endocrinol (Oxf) 47:337-342
von Schoultz B 2007 Androgens and the breast. Maturitas 57:47-9
Wallien MSC, Cohen-KettenisPT 2008 Psychosexual outcome of gender dysphoric children. Am J Child Adolesc
Psychiatry, in press
Wallien MSC, Swaab H, Cohen-Kettenis PT 2007 Psychiatric comorbidity among children with gender identity
disorder. J Am Acad Child Adolesc Psychiatry 46:1307-1314
Wennink JM, Delemarre-van de Waal HA, Schoemaker R, Schoemaker H, Schoemaker J 1989 Luteinizing hor-
mone and follicle stimulating hormone secretion patterns in boys throughout puberty measured using highly
sensitive immunoradiometric assays. Clin Endocrinol (Oxf) 31:551-564
Wennink JM, Delemarre-van de Waal HA, Schoemaker R, Schoemaker H, Schoemaker J 1990 Luteinizing hor-
mone and follicle stimulating hormone secretion patterns in girls throughout puberty measured using highly
sensitive immunoradiometric assays. Clin Endocrinol (Oxf) 33:333-344
Westaby D, Ogle SJ, Paradinas FJ, Randell JB, Murray-Lyon IM 1977 Liver damage from long-term methyltes-
tosterone. Lancet 2(8032):262-3
Whitehead NE 2007 An antiboy antibody? Re-examination of the maternal immune hypothesis. J Biosoc Sci
39:905-21
Wilson JD, Roehrborn C 1999 Long-term consequences of castration in men: lessons from the Skoptzy and the
eunuchs of the Chinese and Ottoman courts. J Clin Endocrinol Metab 84:4324-4331
World Health Organisation Multiaxial Version of ICD10. 1992 Clinical Descriptions and Diagnostic Guidelines.
Geneva, World Health Organisation.
Zucker KJ 2004 Gender identity development and issues. Child Adolesc Psychiatric Clin N Am 13:551-568
Zucker KJ, Bradley SJ 1995 Gender Identity Disorder and Psychosexual Problems in Children and Adolescents.
New York: Guilford Press
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23
T
ABLE
1. D
EFINITIONS
OF
TERMS
USED
IN
THIS
GUIDELINE
Sex refers to attributes that characterize biological male- or femaleness;. the best known attributes in-
clude the sex-determining genes, the sex chromosomes, the H-Y antigen, the gonads, sex hormones,
internal and external genitalia and secondary sex characteristics
Gender identity is used to describe a person’s fundamental sense of being male, female or of indetermi-
nate sex.
Gender identity disorder (GID) is a DSM-IV-TR diagnosis. This psychiatric diagnosis is given
when a strong and persistent cross-gender identification, combined with a persistent discomfort
with one’s sex or sense of inappropriateness in the gender role of that sex causes clinically
significant distress.
Gender role is used to refer to behaviors, attitudes, and personality traits that a society, in a given cul-
ture and historical period, designates as masculine or feminine, that is, more “appropriate” to or typical of
the male or female social.
Gender dysphoria is the distress and unease experienced if gender identity and sex are not completely
congruent.
Sexual orientation can be defined by a person's relative responsiveness to sexual stimuli. The most sa-
lient dimension of sexual orientation is the sex of the person to whom one is attracted sexually; sexual
orientation is not entirely similar to sexual identity; a person may, for example, be predominantly aroused
by homoerotic stimuli, yet not regard himself or herself to be gay or lesbian.
Sex reassignment refers to the complete treatment procedure for those who want to adapt their bodies
to the desired sex.
Sex reassignment surgery refers only to the surgical part of this treatment.
Transsexual people identify as, or desire to live and be accepted as, a member of the gender opposite
to that assigned at birth; the term male-to-female (MTF) transsexual person is often used to refer to bio-
logical males who desire to be a member of the female gender, female-to-male (FTM) transsexual person
refers to a biological female who desires to be a member of the male gender.
Transition refers to the period of time during which a transsexual changes their physical, social and legal
characteristic to the gender opposite that of their biologic sex.
Note:
In this Guideline, we have chosen to use the term “transsexual” throughout as defined by the ICD10 Di-
agnostic Code (see Table 3). We recognize that “transsexual” and “transgender” are terms often used
interchangeably. However, since “transgender” may also be used to identify individuals whose gender
identity does not conform to the conventional gender roles of either male or female and who may not
seek endocrine treatment as described herein, we prefer to use “transsexual” as an adjective (e.g., when
referring to persons, individuals, men, or women and, when appropriate, referring to subjects in research
studies.)
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24
T
ABLE
2. DSM-IV-TR
D
IAGNOSTIC
CRITERIA
FOR
GENDER
IDENTITY
DISORDER
(American Psychiatric Association 2001)
A. A strong and persistent cross-gender identification (not merely a desire for
any perceived cultural advantages of being the other sex).
In children, the disturbance is manifested by four (or more) of the following:
1. repeatedly stated desire to be, or insistence that he or she is, the other
sex
2. in boys, preference for cross-dressing or simulating female attire; in girls,
insistence on wearing only stereotypical masculine clothing
3. strong and persistent preferences for cross-sex roles in make-believe
play or persistent fantasies of being the other sex
4. intense desire to participate in the stereotypical games and pastimes of
the other sex
5. strong preference for playmates of the other sex
In adolescents and adults, the disturbance is manifested by symptoms such
as a stated desire to be the other sex, frequent passing as the other sex,
desire to live or be treated as the other sex, or the conviction that he or she
has the typical feelings and reactions of the other sex.
B. Persistent discomfort with his or her sex or sense of inappropriateness in the
gender role of that sex.
In children, the disturbance is manifested by any of the following:
1. in boys, assertion that his penis or testes are disgusting or will disappear
or assertion that it would be better not to have a penis or aversion to-
ward rough-and-tumble play and rejection of male stereotypical toys,
games, and activities;
2. in girls, rejection of urinating in a sitting position, assertion that she has or
will grow a penis, assertion that she does not want to grow breasts or
menstruate, or marked aversion toward normative feminine clothing.
In adolescents and adults, the disturbance is manifested by symptoms such
as preoccupation with getting rid of primary and secondary sex characteris-
tics (e.g., request for hormones, surgery, or other procedures to physically
alter sexual characteristics to simulate the other sex) or belief that he or she
was born the wrong sex.
C. The disturbance is not concurrent with a physical intersex condition.
D. The disturbance causes clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
Code based on current age:
302.6 Gender Identity Disorder in Children
302.85 Gender Identity Disorder in Adolescents or Adults
Specify if (for sexually mature individuals):
Sexually Attracted to Males
Sexually Attracted to Females
Sexually Attracted to Both
Sexually Attracted to Neither
Section A:
Requiring male-bodied
children to merely indi-
cate a “preference for
crossdressing or simu-
lating female attire”
when female-bodied
children must express
an “insistence on wear-
ing stereotypical mas-
culine clothing” is in-
herently discriminatory,
and can result in a
“false positive” diagno-
sis of GID in male-
bodied children.
These criteria, in gen-
eral, depend on out-
dated gender role/
conformity expecta-
tions.
Section B:
1-2. While we agree
with the usefulness of
the first half of this sub-
section as a diagnostic
reference, TransActive
believes that the refer-
ences to “rough and
tumble play”,
“stereotypical toys” and
“normative feminine
clothing” is, at best,
antiquated as a diag-
nostic tool and at
worst, overtly subjec-
tive and discriminatory.
TransActive strongly
disagrees with the
need to specify the
sexual orientation of
trans adolescents.
Gender identity is inde-
pendent of sexual ori-
entation and sexual
orientation has not
been considered a
pathological condition
by the APA since 1973.
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25
T
ABLE
3. ICD-10
CRITERIA
FOR
TRANSSEXUALISM
AND
GENDER
IDENTITY
DISORDER
OF
CHILDHOOD
(W
ORLD
H
EALTH
O
RGANIZATION
M
ULTIAXIAL
V
ERSION
OF
ICD10 1992)
Transsexualism (F64.0) has three criteria:
1. The desire to live and be accepted as a member of
the opposite sex, usually accompanied by the
wish to make his or her body as congruent as pos-
sible with the preferred sex through surgery and
hormone treatments
2. The transsexual identity has been present persis-
tently for at least 2 years
3. The disorder is not a symptom of another mental
disorder or a genetic, intersex, or chromosomal
abnormality
Gender Identity Disorder of Childhood (F46.2) has separate criteria for girls
and for boys.
For girls:
1. The individual shows persistent and intense distress about being a girl
and has a stated desire to be a boy (not merely a desire for any per-
ceived cultural advantages of being a boy) or insistent that she is a
boy
2. Either of the following must be present:
a. persistent marked aversion to normative feminine clothing and
insistence of wearing stereotypical masculine clothing
b. persistent repudiation of female anatomical structures, as evi-
denced by at least one of the following:
i. an assertion that she has, or will grow, a penis
ii. rejection of urination in a sitting position
iii. assertion that she does not want to grow breasts or
menstruate
3. The girl has not yet reached puberty
4. The disorder must have been present for at least 6 months
For boys:
1. The individual shows persistent and intense distress about being a
boy and has a desire to be a girl or, more rarely, insists that he is a
girl
2. Either of the following must be present:
a. preoccupation with stereotypic female activities, as shown by a
preference for either cross-dressing or simulating female at-
tire or by an intense desire to participate in the games and
pastimes of girls and rejection of stereotypical male toys,
games and activities.
b. persistent repudiation of male anatomical structures, as evi-
dence by at least one of the following repeated assertions:
i. that he will grow up to become a woman (not merely
in the role)
ii. that his penis or testes are disgusting or will disap-
pear
iii. that it would be better not to have a penis or testes
3. The boy has not reached puberty
4. The disorder must have been present for at least 6 months
See Table 2 for
TransActive’s
(oppositional) position
on these gender
stereotypical diagnostic
requirements.
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26
T
ABLE
6. T
ANNER
STAGES
OF
BREAST
DEVELOPMENT
AND
MALE
EXTERNAL
GENITALIA
The description of Tanner stages
For breast development:
1. Preadolescent
2. Breast and papilla elevated as small mound; areolar diameter increased
3. Breast and areola enlarged, no contour separation
4. Areola and papilla form secondary mound
5. Mature; nipple projects, areola part of general breast contour
For penis and testes:
1. Preadolescent
2. Slight enlargement of penis; enlarged scrotum, pink texture altered
3. Penis longer, testes larger
4. Penis larger, glans and breadth increase in size; testes larger, scrotum dark
5. Penis and testes adult size
Adapted from Tanner JM: Growth at adolescence, 2
nd
edition. Oxford, England,
Blackwell Scientific Publications, 1962.
T
ABLE
7.
Estradiol levels (pmol/l) in female puberty during night and day
a
Median of hourly measurements during 2400 – 0600h and 1200 – 1800h:
Tanner stage Nocturnal estradiol Diurnal estradiol
B1 <37 <37
B2 38.5 56.3
B3 81.7 107.3
B4 162.9 132.3
B5 201.6 196.7
a
Adapted from Wennink JMB, Delemarre-van de Waal HA, Schoemaker R, Schoemaker H, Schoemaker
J. Luteinizing hormone and follicle stimulating hormone secretion patterns in girls throughout puberty
measured using highly sensitive immunoradiometric assays. Clin Endocrinology 1990 33 333-344
Testosterone levels (nmol/l) in male puberty during night and day
b
Median of hourly measurements during 2400 – 0600h and 1200 – 1800h:
Tanner stage Nocturnal testosterone Diurnal testosterone
G1 <0.25 <0.25
G2 1.16 0.54
G3 3.76 0.62
G4 9.83 1.99
G5 13.2 7.80
Adult 18.8 17.0
b
Adapted from Wennink JMB, Delemarre-van de Waal HA, Schoemaker R, Schoemaker H, Schoemaker
J. Luteinizing hormone and follicle stimulating hormone secretion patterns in boys throughout puberty
measured using highly sensitive immunoradiometric assays. Clin Endocrinology 1989 31 551-564
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27
T
ABLE
8. F
OLLOW
-
UP
PROTOCOL
DURING
SUPPRESSION
OF
PUBERTY
Every 3 months
Anthropometry: height, weight, sitting height, Tanner stages
Laboratory: LH, FSH, E2/T
Every year
Laboratory: renal- and liver function, lipids, glucose, insulin, HbA1c
Bone density using DXA
Bone age on X-ray of the left hand
T
ABLE
9. P
ROTOCOL
INDUCTION
OF
PUBERTY
Induction of female puberty with 17-beta estradiol, increasing the dose every 6 months:
5 µg/kg/day
10 µg/kg/day
15 µg/kg/day
20 µg/kg/day
adult dose=2 mg per day
Induction of male puberty with testosterone esters increasing the dose every 6 months:
25 mg/m
2
/2 weeks im
50 mg/m
2
/2 weeks im
75 mg/m
2
/2 weeks im
100 mg/m
2
/2 weeks im
T
ABLE
10. F
OLLOW
-
UP
PROTOCOL
DURING
INDUCTION
OF
PUBERTY
Every 3 months
Anthropometry: height, weight, sitting height, Tanner stages
Laboratory: endocrinology: LH, FSH, E2/T
Every year
Laboratory: renal- and liver function, lipids, glucose, insulin, HbA1c
Bone density using DXA
Bone age on X-ray of the left hand
These parameters should be measured also at long term. For bone development until the age of 25-30
years until peak bone mass has been reached.
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28
T
ABLE
11. M
EDICAL
CONDITIONS
THAT
CAN
BE
EXACERBATED
BY
CROSS
-
SEX
HORMONE
THERAPY
Transsexual Female (MTF) - Estrogen
Very high risk of serious adverse outcomes
• thromboembolic disease
Moderate to high risk of adverse outcomes
• macroprolactinoma
• severe liver dysfunction (transaminases > 3x upper limit of normal)
• breast cancer
• coronary artery disease
• cerebrovascular disease
• severe migraine headaches
Transsexual Male (FTM) - Testosterone
Very high risk of serious adverse outcomes
• breast or uterine cancer
• erythrocytosis (hematocrit >50%)
Moderate to high risk of adverse outcomes
• severe liver dysfunction (transaminases > 3x upper limit of normal)
T
ABLE
15. M
ONITORING
OF
TRANSSEXUAL
PERSONS
ON
CROSS
-
HORMONE
THERAPY
Male-to-female transsexual persons
1. Evaluate patient every 2-3 months in the first year and then 1-2 times per year to monitor for appro-
priate signs of feminization and for development of adverse reactions.
2. Measure serum testosterone and estradiol every 3 months.
a. Serum testosterone levels should be <55 ng/mL;
b. Serum estradiol should not exceed the peak physiologic range for young healthy females,
with ideal levels approximately 200 ng/ml.
c. Doses of estrogen should be adjusted according to the serum levels of estradiol.
3. For individuals on spironolactone, serum electrolytes particularly potassium should be monitored
every 2-3 months initially in the first year.
4. Routine cancer screening recommended in non-transsexual individuals (breasts, colon, prostate)
5. Consider bone mineral density testing at baseline if risk factors for osteoporotic fracture are pre-
sent (e.g. previous fracture, family history, glucocorticoid use, prolonged hypogonadism). In indi-
viduals at low risk, screening for osteoporosis should be conducted at age 60 or in those who are
not compliant with hormone therapy.
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29
T
ABLE
16. M
ONITORING
OF
TRANSSEXUAL
PERSONS
ON
CROSS
-
HORMONE
THERAPY
Female to male transsexual persons
1. Evaluate patient every 2-3 months in the first year and then 1-2 times per year to monitor for appro-
priate signs of virilization and for development of adverse reactions;
2. Measure serum testosterone every 2-3 months until levels are in the normal physiologic male
range:*
a. For testosterone enanthate/cypionate injections, the testosterone level should be measured
mid-way between injections. If dose is >700 ng/dl or <350 ng/dl, adjust dose accordingly;
b. For testosterone undecanoate, testosterone should be measured just before the following
injection;
c. For transdermal testosterone, the testosterone level can be measured at any time after 1
week;
d. For oral testosterone undecanoate, the testosterone level should be measured 3-5 hours
after ingestion;
e. Note: During the first 3-9 months of testosterone treatment, total testosterone levels may be
high although free testosterone levels are normal due to high Sex Hormone Binding
Globulin (SHBG) levels in some biological women.
3. Measure estradiol levels during the first 6 months of testosterone treatment or until there has been
no uterine bleeding for six months. Estradiol levels should be < 50 pg/ml.
4. Measure CBC, LFTs at baseline and every 3 months for the first year then 1-2 times a year. Moni-
tor weight, blood pressure, lipids, fasting blood sugar is family history of diabetes and hemoglobin
A1c if diabetic at regular visits.
5. Consider bone mineral density testing at baseline if risk factors for osteoporotic fracture are pre-
sent (e.g. previous fracture, family history, glucocorticoid use, prolonged hypogonadism). In indi-
viduals at low risk, screening for osteoporosis should be conducted at age 60 or in those who are
not compliant with hormone therapy.
6. If cervical tissue is present, annual pap smear is recommended by American College of Obstetri-
cians and Gynecologists (ACOG).
7. If mastectomy is not performed, then consider annual mammograms recommended by American
Cancer Society (ACS)
Adapted from the Endocrine Society Guideline “Testosterone Therapy in Adult men with Androgen
Deficiency Syndromes”.
T
ABLE
17. S
EX
REASSIGNMENT
SURGERY
Eligibility and readiness criteria
Individuals treated with cross-sex hormones, are considered eligible for sex reassignment surgery if they
- are of legal age of majority in the patient's nation
- have used cross-sex hormones continuously and responsibly during 12 months (if they have no
medical contraindication)
- had a successful continuous full-time RLE (real-life experience) during 12 months
- (if required by the MHP) have regularly participated in psychotherapy throughout the RLE at a fre-
quency determined jointly by the patient and the MHP
- have shown demonstrable knowledge of all practical aspects of surgery (e.g. cost, required lengths
of hospitalizations, likely complications, post-surgical rehabilitation etc.)
Individuals, treated with cross-sex hormones, should fulfill the following readiness criteria prior to sex re-
assignment surgery:
- demonstrable progress in consolidating one’s gender identity; and,
- demonstrable progress in dealing with work, family, and interpersonal issues resulting in a signifi-
cantly better state of mental health
... But with the right reproductive therapy, many transgender people can have children in the future. This is why the Endocrine Society says that individuals undergoing gender reassignment should be provided reproductive counseling [40]. In addition, the ASRM ethics committee suggests providing all persons undergoing gender reassignment with the option of gamete freezing. ...
... Reported average serum oestradiol levels will be Open access used to stratify and categorise articles into subphysiological, physiological and supraphysiological serum oestradiol reference ranges using target serum oestradiol levels of premenopausal cisgender women as the referent. 30 Measures of association for dichotomous variables will be reported as risk ratios, and measures of effect for continuous outcomes will be reported using weighted or standardised mean differences when common or different measurement instruments are used, respectively. If three or more studies reporting on the same outcome are included in the analysis, measures of heterogeneity (Cochrane Q and I 2 statistics) will be assessed to determine whether pooled analyses are appropriate to report. ...
Article
Full-text available
Introduction: The use of gender-affirming oestrogen therapy (GAOT) is an integral part of the gender-affirming transition process for transgender women (assigned male at birth who identify as women) and gender-diverse individuals. However, its use may present significant cardiovascular implications, which may be influenced by systemic oestradiol levels. Therefore, we aim to establish the association between serum oestradiol levels and incidence of adverse cardiovascular events in individuals using GAOT. Methods and analysis: We will conduct a systematic review addressing the association between serum oestradiol levels and risk of adverse cardiovascular events in individuals using GAOT. Our primary outcome is the incidence of adverse cardiovascular events, our secondary outcome is the incidence of cardiovascular-related mortality and our tertiary outcome is cardiovascular-related risk factors. Electronic databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE and Web of Science) will be searched from inception until September 2022. Two investigators will independently complete screening to determine appropriateness of inclusion. Extracted data will include information on serum sex hormone levels (oestradiol and testosterone), participants, GAOT (route of administration, formulations, dosages and duration of exposure), incidence of cardiovascular outcomes, study quality and risk of bias. Inter-reviewer reliability will be calculated at both phases. Data will be presented both descriptively and meta-analysed using a random effects model, if appropriate. Heterogeneity will be explored and meta-regressed if noted. Ethics and dissemination: Ethics approval is not needed. We will disseminate findings through international conferences, distributions to transgender and gender-diverse support organisations, decision-makers and key stakeholders. The final systematic review will be published in a peer-reviewed journal. Trial registration number: CRD42021247717.
... or higher for those assigned female at birth was reached, usually around age 12 years. If gender dysphoria remained present after treatment was started, and participants met all criteria as defined by the Endocrine Society's guideline for treatment of people with gender dysphoria, 16,17 gender affirming hor mones could be added to induce puberty in eligible adolescents 16 years or older. Genderaffirming hormone treatment consists of oestrogen in people assigned male at birth, and testosterone in those assigned female at birth. ...
Article
Full-text available
Background In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence. Methods In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment. Findings 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Interpretation Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment. Funding None.
... From the outset the Boston clinic offered GnRHa at Tanner stage 2 or 3 with no minimum age (Spack et al. 2012). Spack joined Cohen-Kettenis, Gooren, and Delemarre-van de Waal on the Endocrine Society's committee tasked with writing their first clinical guidelines for "transsexual persons," which recommended GnRHa for children at Tanner stage 2 or 3 (Hembree et al., 2009). "There was an attitudinal shift to be able to say that the Endocrine Society supports this," he later recalled (Ruttimann, 2013, p. 19). ...
Article
Full-text available
It has been a quarter of a century since Dutch clinicians proposed puberty suppression as an intervention for “juvenile transsexuals,” which became the international standard for treating gender dysphoria. This paper reviews the history of this intervention and scrutinizes the evidence adduced to support it. The intervention was justified by claims that it was reversible and that it was a tool for diagnosis, but these claims are increasingly implausible. The main evidence for the Dutch protocol came from a longitudinal study of 70 adolescents who had been subjected to puberty suppression followed by cross-sex hormones and surgery. Their outcomes shortly after surgery appeared positive, except for the one patient who died, but these findings rested on a small number of observations and incommensurable measures of gender dysphoria. A replication study conducted in Britain found no improvement. While some effects of puberty suppression have been carefully studied, such as on bone density, others have been ignored, like on sexual functioning.
Article
Aims: Feminizing gender-affirming hormone therapy (GAHT) can be utilized to help transfeminine transgender and gender diverse (TGD) individuals achieve the transformation of outward sex characteristics, thereby leading to improvements in psychological and social well-being. In this narrative review, we aim to summarize current guidelines for feminizing GAHT management as well as the available literature describing the associated health risks pertaining to cardiovascular disease, thromboembolic disease, bone health, and cancer risks. Methods: Relevant literature from January 2019 through July 2022 pertaining to feminizing GAHT was identified using PubMed, Cochrane Library, EMBASE, and MEDLINE. A narrative summary was performed with the inclusion of more recently published guidance from the World Professional Association for Transgender Health, Standards of Care Version 8. Results: Guidance regarding the prescribing of feminizing GAHT with estrogen, antiandrogen, and progesterone medications is summarized along with considerations of the cardiovascular, thromboembolic, bone health, and cancer risks associated with these therapies. Conclusions: Feminizing GAHT is a highly effective method for transfeminine TGD patients to achieve medically necessary changes in secondary sex characteristics. Knowledge of the health risks of feminizing GAHT is largely drawn from research in the cisgender population, with a growing body of literature in TGD-specific patient populations. Feminizing GAHT appears to carry a low risk profile for most patients; however, further research describing the risks of hormone management around the time of gender-affirming surgery and in the aging TGD population is needed to optimize GAHT in the context of the evolving health risks over a TGD patient's lifespan.
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Transgender patients are seen in breast imaging centers for routine screening mammography and diagnostic imaging of the symptomatic breast. Radiology staff should be familiar with appropriate terminology and indications for breast imaging to provide culturally competent care. This comprehensive review of transgender breast imaging aims to update the radiologist on appropriate terminology, breast cancer risk in different patient populations, screening guidelines, and diagnostic scenarios. The chapter concludes with practical tips on how to optimize the patient experience, from the registration process to waiting room access.
Chapter
Until the past decade, clinicians and researchers assumed that the medical evaluation and treatment of both women and men were the same. This archaic and dangerous notion persisted in spite of the clear anatomic and physiologic differences between the genders. Today, we fully understand that this paradigm is false. In all specialties of medicine, practitioners and researchers are beginning to consider the influence of sex and gender and how it should inform the care of their patients. This book focuses on the issue of sex and gender in the evaluation and treatment of patients specifically in the delivery of acute medical care. It serves as a guide both to clinicians interested in the impact of sex and gender on their practice and to researchers interested in the current state of the art in the field and critical future research directions.
Chapter
A obra intitulada “Saúde e sociedade: perspectivas contemporâneas vol. 01”, publicada pela Brazilian Journals Publicações de Periódicos e Editora, apresenta um conjunto de vinte e cinco capítulos que reúnem diversas temáticas da área da saúde como um todo. Como um estudo com objetivo de descrever os impactos causados pelo uso excessivo de telas no desenvolvimento neuropsicomotor de crianças e adolescentes. Dessa forma, o presente trabalho foi elaborado a partir de pesquisas no mês de setembro de 2021 utilizando o site da Sociedade Brasileira de Pediatria (SBP), as bases de dados virtuais U.S National Library of Medicine (PUBMED) e Scientific Eletronic Library Online (SciELO). Também, um trabalho com intuito de compreender a relação da espiritualidade na percepção de pacientes com doença renal crônica em tratamento. Juntamente, uma pesquisa que apresenta os desafios do trabalho do nutricionista do NASF na Atenção Básica em Fortaleza e região metropolitana de Caucaia, municípios do Ceará por meio de um relato de experiência de nutricionistas atuantes no Núcleo Ampliado de Saúde da Família e Atenção Básica (NASF-AB). Também, uma pesquisa que tem como finalidade avaliar a correlação entre a frequência alimentar e o estado nutricional em pessoas com Estomia de eliminação (colostomia, ileostomiae urostomia). Trata-se de um estudo transversal e descritivo, com abordagem quantitativa, realizado com 77 estomizados (temporários e definitivos) no período de janeiro a março de 2020, na Unidade de Referência Especializada - URE’s. Além do mais, um trabalho que descreve o caso de sepse e abscesso cerebral por Serratia marcescens em um neonato, entre outros. Agradecemos os autores que com empenho e dedicação colaboraram para a construção dessa obra. Ansiamos que a mesma contribua de forma significativa no conhecimento das temáticas aqui abordadas.
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RESUME Les patients transgenres présentent des risques augmentés de cancers, de maladies sexuellement transmissibles, de complications post opératoires à court et long terme chez les patientes avec vaginoplastie, mais également de grossesse non désirée chez les hommes trans non hysterectomisés. Toutefois, l’accès aux soins est souvent difficile pour ces patients qui ne bénéficient le plus souvent pas d’un suivi gynécologique adapté notamment par peur de jugement ou discrimination. Au vu des risques pour la santé de ces patients il est indispensable de pouvoir leur proposer un suivi gynécologique spécifique et adapté. Il n’y a à ce jour pas de recommandations claires concernant le suivi gynécologique des patients transgenres. Nous nous sommes appuyés sur les recommandations de la W-PATH (World Professional Association of Transgender Health) et sur les Guideline de l’Endocrine Society et avons réalisé une revue de littérature. Nous avons effectué plusieurs recherches via pubmed afin d’explorer un par un les différents aspects du suivi gynécologique notamment des hommes transgenres non hystérectomisés et des femmes transgenres avec une vaginoplastie. Il en ressort un manque de suivi des personnes transgenres, avec une réticence à consulter un gynécologue, associée au manque de connaissances et d’expérience des professionnels de santé. De par les risques identiques à ceux de la population générale, additionnés de ceux spécifiques aux personnes transgenres, il est important de pouvoir proposer à ces patients un suivi gynécologique spécialisé et personnalisé, et de sensibiliser et de former les professionnels de santé à l’importance et aux spécificités du suivi gynécologique de ces patients.
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Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.
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A transsexual patient has the constant and persistent conviction that he or she belongs to the opposite sex, thus creating a deeply seated gender identity conflict. With psychotherapy being unsuccessful, it has been proven that in carefully selected patients, gender reassignment or adjusting the body to the mind (both with hormones and surgery) is the best way to normalize their lives. Optimal treatment of these patients requires the multidisciplinary approach of a gender team with the input of several specialties. Such a team consists of a nucleus of physicians who sees the patient more frequently: the psychiatrist, the endocrinologist, the plastic surgeon, the gynecologist and the urologist and a more peripheral group that sees the patients more incidentaly: the psychologist, the otorhinolaryngologist, the dermatologist, the speech therapist, the lawyer, the nurse and the social worker. Between 1987 and 1999, a total of 71 male-to-female (MTF) and 54 female-to-male transsexuals have undergone gender confirming surgery in our hospital. This article gives a review and an update on the different surgical procedures as well as on the outcome in our patient population. The results in this series of patients clearly demonstrate that a close cooperation of the different surgical specialties, within our multidisciplinary gender team, is the key to success in treating transsexual patients.
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Hyperinsulinemia is a common finding in hyperandrogenic women, during pregnancy, and in women using oral contraceptives. To test whether sex hormone treatment can induce insulin resistance in healthy subjects, we studied the effects of administration of testosterone to 13 female to male and of ethinyl estradiol to 18 male to female transsexuals. Utilization and production of glucose and levels of sex steroids were measured during a three-step hyperinsulinemic-euglycemic clamp before and after 4 months of hormone administration. Females were treated with im injections of testosterone esters (250 mg/2 weeks); males were treated with ethinyl estradiol alone (0.1 mg/day, orally) or a combination of ethinyl estradiol and cyproterone acetate (100 mg/day, orally). Similar insulin levels were achieved at each of the three steps of the clamp studies before and during hormone administration. During step 1 of each clamp, with insulin levels in the physiological range, glucose utilization decreased from 3.5 ± 1.2 to 2.6 ± 0.9 mmol/kg lean body mass (LBM).h in women treated with testosterone esters (P < 0.001) and from 3.2 ± 0.7 to 2.5 ± 0.5 mmol/kg lean body mass.h in men treated with ethinyl estradiol (P < 0.001). The effects of sex steroids during steps 2 and 3 of the clamp at higher (supraphysiological) insulin levels were less clear. Endogenous glucose production (measured by isotope dilution with tritiated glucose) was not affected by hormone administration, indicating that the observed changes in glucose requirement were determined by a diminished peripheral glucose uptake. We conclude that sex hormone administration, i.e. testosterone treatment in females and ethinyl estradiol treatment in males, can induce insulin resistance in healthy subjects.
Article
Objective To determine the influence of estrogens on male fertility. Design A 36-year-old eugonadal male was subjected to two different regimens of treatment with ethinyl estradiol (EE 2 ). Sperm quality, immunoreactive luteinizing hormone (LH) and follicle-stimulating Hormone (FSH), testosterone (T), estrone (E 1 ), estradiol (E 2 ), dehydroepiandrosterone sulfate (DHEAS), prolactin (PRL) and sex hormone-binding globulin were determined at intervals of 2weeks for 315days. Setting A gender dysphoria clinic. Patient A transsexual male nurse. Main Outcome Measures It was hypothesized (and confirmed) that by comparing the effects of increasing and constant dose of EE 2 on fertility parameters, differences in estrogen-sensitivity would show more clearly. Furthermore, this procedure served to find the minimal dose of EE 2 for complete testicular suppression. Results Low doses of EE 2 (20 μ g/d) had no negative effect on sperm motility and density for a period of approximately 4weeks, whereas high doses (60 μ g/d) reduced motility already after a few days and led to a pronounced decrease in sperm density after 2weeks. After discontinuation of therapy, motility normalized faster than sperm density. Under increasing doses of EE 2 there was a constant decrease of FSH that occurred several weeks earlier than that of LH. Under constant dose of EE 2 (60 μ g/d) the decrease of LH was delayed (with respect to FSH) by only a few days. The decrease in T showed a stronger correlation with that of FSH than with that of LH. Volume and fructose content of the seminal fluid correlated with the decrease in T. Rebound effects were observed for FSH, LH, T, and fructose during the therapy-free interval. Ethinyl estradiol therapy had no influence on the serum concentrations of E 1 , E 2 , and PRL. Estrone was the dominant estrogen before and after therapy with EE 2 . Adrenal gland activity was markedly suppressed by EE 2 , as reflected by the decrease in DHEAS. Conclusion The suppressive effect of EE 2 on FSH and sperm motility was more pronounced and consistent than on LH and sperm density. The T decrease appears to be mainly caused by a direct effect of EE 2 on the testes.
Article
Each January, the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, including guideline updates, emerging issues that are relevant to screening for cancer, and a summary of the most current data on cancer screening rates for US adults. In 2004, there were no updates to ACS guidelines. In this article, we summarize the current guidelines, discuss recent evidence and policy changes that have implications for cancer screening, and provide an update of the most recent data pertaining to participation rates in cancer screening by age, gender, and insurance status from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System.