ORIGINAL RESEARCH—TR ANSGENDER AND GENDER NONCONFORMANCE

Cross-Sex Hormonal Treatment and Body Uneasiness in
Individuals with Gender Dysphoria
Alessandra D. Fisher, MD PhD,* Giovanni Castellini, MD PhD,*† Elisa Bandini, MD,*
Helen Casale, MA,* Egidia Fanni, BA,* Laura Benni, MD,*† Naika Ferruccio, MD,*†
Maria Cristina Meriggiola, MD PhD,‡ Chiara Manieri, MD,§ Anna Gualerzi, MD,§
Emmanuele Jannini, MD PhD,¶ Alessandro Oppo, MD,** Valdo Ricca, MD,** Mario Maggi, MD PhD,*
and Alessandra H. Rellini, PhD††
*Sexual Medicine and Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of
Florence, Florence, Italy; †Psychiatric Unit, Department of Neuropsychiatric Sciences, University of Florence, Florence,
Italy; ‡Center for Reproductive Health, Department of Obstetrics and Gynecology, S. Orsola Hospital, University of
Bologna, Bologna, Italy; §Interdepartmental Center for Gender Identity Disorders, Le Molinette Hospital, City of Health
and Science, Turin, Italy; ¶Endocrinology and Medical Sexology, Department of Experimental Medicine, University of
L’Aquila, L’Aquila, Italy; **Multispecialty Department of Endocrinology and Diabetology, University Hospital of Cagliari,
Cagliari, Italy; ††Department of Psychology, University of Vermont, Burlington, VT, USA
DOI: 10.1111/jsm.12413
A B S T R A C T
Introduction. Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well-being
without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects ofCHTalone.
Aims. This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients
taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT
treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms.
Methods. A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery
were considered.
Main Outcome Measures. Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different
areas of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R) to measure psychological
state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or
antiandrogens) were collected through an analysis of medical records.
Results. Among the male-to-female (MtF) individuals, those using CHT reported less body uneasiness compared
with individuals in the no-CHT group. No significant differences were observed between CHT and no-CHT groups
in the female-to-male (FtM) sample. Also, no significant differences in SCL score were observed with regard to
gender (MtF vs. FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two variables. Moreover,
a two-step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of
treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment)
predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI.
Conclusions. The differences observed between MtF and FtM individuals suggest that body-related uneasiness
associated with GD may be effectively diminished with the administration of CHT even without the use of genital
surgery for MtF clients. A discussion is provided on the importance of controlling both length and daily dose of
treatment for the most effective impact on body uneasiness. Fisher AD, Castellini G, Bandini E, Casale H, Fanni
E, Benni L, Ferruccio N, Meriggiola MC, Manieri C, Gualerzi A, Jannini E, Oppo A, Ricca V, Maggi M, and
Rellini AH. Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria. J Sex
Med 2014;11:709–719.
Key Words. Gender Identity Disorder; Cross-Sex Hormonal Treatment; Body Uneasiness
709
© 2013 International Society for Sexual Medicine J Sex Med 2014;11:709–719
Introduction
The emerging conceptualization of gender
nonconformity, as accepted by the World
Professional Association for Transgender Health,
is moving toward a definition of gender variance
that incorporates people who challenge social
norms of gender identity/role without necessarily
experiencing distress [1]. Moreover, the new view
proposes that passing for the opposite gender
should not be assumed as the final goal for all
nonconforming individuals [2,3]. Alternative
options, such as accepting the variant gender role
or identity, may also be a desired outcome. This
new perspective in conceptualizing gender incongruence
has two major implications for the way in
which treatment is applied to individuals with
gender dysphoria (GD). First, individuals withGD
need to be conceptualized as a subgroup within a
larger population of nonconforming individuals.
Based on the DSM IV-TR criteria, the experience
of distress becomes a key aspect of the diagnosis of
GD [4]. The distress experienced by these individuals
is the product of a discrepancy between
gender identity and sex assigned at birth, gender
role, and/or primary and secondary sex characteristics
[5,6]. Second, the treatment needs to be
designed to address the individual needs of the
patient who may not wish to live fully as an individual
of the opposite gender.
In line with this new conceptualization, individuals
with GD could benefit from flexibility in
treatment, depending on their final goals with
regard to aligning identity with body. While some
individuals may experience an amelioration of distress
by changing gender expression, others may
need different levels of body modifications [1,2].
Among interventions aimed at reducing the incongruence
between body and gender identity, a
medical approach includes cross-sex hormonal
treatment (CHT) alone or together with surgical
reassignment [1,2]. To date, studies have mostly
focused on the positive effects of sex reassignment
surgery on mental and sexual health and satisfaction,
omitting the potential benefit derived from
just CHT [7–22].
A meta-analysis of GD treatment published in
2011 [23] reported only five studies that described
the effects of CHT on psychological outcomes.
Findings from these individual studies showed
higher quality of life [24] and better psychological
[25] and psychosocial [26] adjustment for
individuals following CHT, perhaps because CHT
increased confidence in passing as a member of the
new gender and maintaining the new role [26].
Recently, only two additional studies have been
published on this topic, which essentially corroborated
the concept that CHT is associated with
higher quality of life [27], less social distress and
anxiety, and fewer depressive symptoms [28].
The interpretation of the available literature is
limited by several caveats that need to be considered.
First, only a paucity of studies took into
consideration the concurrent effects of both length
and dosage of hormonal treatment [25,27,28].
Second, data are rarely presented for both maleto-
female (MtF) and female-to-male (FtM) individuals,
thus preventing any inferences on the
differences between these two populations. Third,
in some studies the isolated effect of CHT was
confounded because individuals with and without
surgical sex reassignment were included in the
same group [28].
Finally, none of these studies focused on
the effects of CHT on body-related distress,
a dimension assumed to be at the core of GD
development.
There is a paucity of studies empirically testing
distress related to one’s body in individuals with
GD [29–31]. Initial evidence of the crucial role of
this type of distress comes from the fact that
medical GD treatment is not only effective in alleviating
dysphoria [1] but can also improve general
psychopathology and distress [32]. If treatment
for GD is moving toward a more flexible approach
in order to address subtle differences in the needs
of these people, a better understanding of the
potential benefits of CHT alone on body distress is
warranted.
Aims of Our Study
One of the aims of the present study was to assess
differences in body uneasiness and psychiatric
symptoms between GD individuals taking CHT
and those not taking hormones (no CHT). Secondary
analyses were conducted to better understand
if distress with specific parts of the body was
less pronounced among individuals taking CHT.
We also assessed whether length of CHT treatment
and daily hormone doses provided an explanation
for different levels of body uneasiness and
psychiatric symptoms.
Methods
Participants
Subjects referred for the first time to the centers
for GD assistance of the Universities of Florence,
710 Fisher et al.
J Sex Med 2014;11:709–719
Bologna, Turin, Cagliari, and L’Aquila between
July 2008 and January 2013 were enrolled in the
study, provided they met the following inclusion
criteria:
• Age older than 18 years.
• Diagnosis of GD based on formal psychiatric
classification criteria [1,4] and performed
through several sessions with two different
mental health professionals specializing in GD.
The exclusion criteria were as follows:
• Genital reassignment surgery.
• Use at any point in life of different CHT
therapy from the one reported at the time of
enrollment in the present study.
• Illiteracy.
• Mental retardation.
A total of 150 subjects were excluded from the
initial sample because of the following reasons:
changes in CHT treatment prior to the study
(n = 53), disorders of sexual development (n = 3),
internalized homophobia (n = 3), transvestite
fetishism (n = 6), mental retardation (n = 1),
incomplete assessment because of dropout during
the clinical assessment (n = 13), and completed
genital reassignment surgery (n = 69). The selected
sample (MtF patients, n = 66; FtM patients, n = 59)
included 53 participants from Florence, 55 from
Bologna, 14 from Turin, 2 from L’Aquila, and 1
from Cagliari. Participants were divided into
patients who had never taken CHT and patients
taking estrogens and/or antiandrogens at the
moment of the clinical interview.
Measures
The sociodemographic data were collected at the
beginning of the first visit, through a face-to-face
interview, by mental health professionals specialized
in this field (EB, GC, HC, VR). Subjects
reported their age, relationship status, morbidities,
preferred sexual orientation, and previous cosmetic
surgery interventions.
Anthropometric measurements were made by
expert endocrinologists using standard calibrated
instruments. Information was also collected
regarding estrogen and/or antiandrogen treatment,
including daily hormone dosage and the
duration of treatment (in days). In order to convert
ethinylestradiol dosage to a scale that allowed
comparison with estradiol, daily ethinylestradiol
doses (μg) were multiplied by 400 or 1000 based
on the cumulative hormone dose reported [33].
Cumulative dose of estrogens (CD-E) was calculated
as daily estradiol dose times days of treatment,
while cumulative dose of antiandrogens
(CD-CPA) was computed as daily androgen
blocker (cyproterone acetate) dose times days of
treatment.
Furthermore, levels of psychopathological distress
were specifically investigated by means of the
Italian version of the Symptom Checklist (SCL-
90-R [34,35]), which was answered for the week
preceding the clinical assessment. The 90 items
of the questionnaire are rated on a five-point
Likert-type scale (from 0 to 4) and are grouped
together into nine domains (somatization,
obsessive–compulsive thoughts, interpersonal sensitivity,
depression, anxiety, hostility, phobic
anxiety, paranoid conceptions, and psychotic
behavior). In this study we utilized the General
Severity Index (SCL-GSI), indicating the overall
psychological distress.
For the assessment of body uneasiness and dissatisfaction,
the Body Uneasiness Test (BUT [36])
was administered. This self-reported measure
comprises questions regarding 34 body experiences
(BUT-A) and dissatisfaction with 37 body
parts (BUT-B). BUT subscales include dissatisfaction
regarding the body and its weight (BUT-WP;
e.g., “I’m terrified of gaining weight,” “My physical
appearance is unsatisfying compared to my
ideal body image”); avoiding and compulsive selfmonitoring
behavior (BUT-AV, BUT-CSM; e.g.,
“When I get undressed I avoid looking,” “I spend
a lot of time in front of the mirror,” “I fear that my
appearance may suddenly change”); experience of
depersonalization, defined as separation and foreignness
regarding the body (BUT-D, e.g., “When
I look at myself in the mirror I feel a sense of
anxiety and alienation”); and body image concerns
(BUT-BIC). Answers are scored on a six-point
Likert-type scale (from “never” to “always”).
Higher scores indicate greater body uneasiness. In
this study the BUT scores utilized were the total
score of the test (Global Severity Index, BUTGSI)
and the subscales. In addition, the number
of items from BUT-B with scores of 1 or higher
was summed to indicate overall dislike of body
parts (BUT-PST; e.g., skin, mouth, breasts, knees,
moustache, hair, smell, noise, sweating, flushing).
Finally, different body parts were considered individually
for exploratory purposes.
To measure gender role, a standard dichotomous
item was used: “Do you have a full-time male
gender role in daily life?” For the FtM group, a
rating of 0 corresponded to no full-time male
gender role and 1 to full-time male gender role, and
Cross-Sex Hormones and Body Uneasiness in Gender Dysphoria 711
J Sex Med 2014;11:709–719
for the MtF group, a rating of 0 corresponded to no
full-time female gender role and 1 to a full-time
female gender role. Answers were adjusted considering
clinical observations during the assessment.
For example, if a MtF subject answered that she had
a full-time female gender role, but the clinician’s
opinion during the interview was different, the
answer was coded as 0.
Procedure
The study was designed as a naturalistic crosssectional
survey, and it was planned and conducted
at the Interdepartmental Center for Gender Identity
Disorder Assistance (CIADIG), Sexual Medicine
and Andrology Unit, University of Florence,
and in other dedicated centers in Bologna, Turin,
L’Aquila, and Cagliari. Participants were recruited
from consecutive referrals by family doctors and
other clinicians. All the diagnostic procedures and
the psychometric tests were part of the routine
clinical assessment for GD at our clinics. Patients
were asked to provide their written informed
consent to participation in the study. The study
was carried out in accordance with the ethical standards
of the responsible institutional committees.
Data Analysis
A 2× 2 ancova (gender × CHT) was utilized to
assess differences in BUT-GSI. Control variables
used in this model were age, body mass index
(BMI), gender role, and cosmetic surgery. Also,
follow-up analyses for the BUT subscales and for
the BUT-B (individual body parts) were used to
provide a more comprehensive explanation of the
significant effects observed in the primary analyses.
A similar 2 × 2 ancova model was used to test
differences in overall psychiatric symptoms (SCL-
90-R). Follow-up univariate analyses were computed
for the MtF and FtM samples separately to
understand the interaction effects observed in the
main analyses.
When the CHT and no-CHT groups showed
significant differences (specifically, in BUT-GSI
between MtF groups), we conducted an analysis to
clarify the effects of cumulative hormone dose
(defined as daily dose of hormone times duration
of treatment) on BUT-GSI. Thus, for these secondary
analyses we included only MtF individuals
taking hormones, as only this group showed significant
differences for primary analyses comparing
CHT with no CHT. In this analysis, we
utilized a two-step hierarchical linear regression
where BMI, age, gender role, and cosmetic surgery
were entered in step 1. In step 2, cumulative
hormone dose was entered. We selected this
approach to assess whether cumulative hormone
dose provided a unique contribution to the explanation
of BUT-GSI above and beyond the effects
of the covariates included in step 1. Significant
changes in step 2 are an indication that cumulative
hormone dose added significantly to the prediction
of BUT-GSI, above and beyond the effects of
the variables entered in step 1.
Results
Differences Between the MtF and FtM Groups
In the MtF group (n = 66), 24 patients had never
taken CHT, and 42 were taking estrogens and
antiandrogens. Specifically, the breakdown of the
medications taken by these patients was as follows:
28.6% (n = 12), estradiol valerate; 28.6% (n = 12),
transdermal estradiol hemihydrate; 14.3% (n = 6),
estradiol gel; 92.9% (n = 39), oral cyproterone
acetate. It should be noted that self-medication
was often the reason for the mixed CHT profile of
some subjects (e.g., more than one type of estrogen
formulation at the same time).
For the FtM group (n = 59), 33 had never had
CHT and 26 were on CHT. Of those individuals
taking hormones, 54.5% (n = 12) were using testosterone
enanthate injections, 4.5% (n = 1) were
using parenteral testosterone undecanoate, and
40.9% (n = 9) used transdermal testosterone. For
four FtM patients in the CHT group, we did not
have information on the type of androgen taken.
On average, MtF and FtM subjects reported 467
days (SD = 323, median = 430, range 45 to 10,845)
and 1,940 days (SD = 2,595, median 799, range 33
to 1,021) of hormone therapy, respectively.
A description of the demographics of the MtF
and FtM patients is given in Table 1. MtF individuals
were on average 33.1 (SD = 10.25) years
old, and their BMI was 22.1 (SD = 3.9) kg/m2. It
was found that 53.8% (n = 35) of the individuals in
the MtF group reported an onset of GD during
adolescence. Similarly, FtM individuals were on
average 28.7 (SD = ± 6.5) years old, with BMI of
24.7 (SD = 4.5) kg/m2; 70.7% (n = 41) reported
GD onset during adolescence.
Differences in Body Uneasiness Based on Gender
(MtF vs. FtM) and CHT Use
Results from the 2 × 2 (gender × CHT) ancova
(age, BMI, gender role, and cosmetic surgery as
covariates) showed a significant main effect forCHT
712 Fisher et al.
J Sex Med 2014;11:709–719
(F(1,116) = 5.80, P < 0.05, η2 = 0.05) (Table 2).
When data were controlled for covariates, individuals
taking CHT (mean = 1.86, SEM = 0.12) had a
lower BUT-GSI than individuals in the no-CHT
group (mean = 2.28, SEM = 0.13). As illustrated in
Figure 1, there was also a significant interaction
effect for gender × CHT (F(1,116) = 5.24, P < 0.05,
η2 = 0.04).
To better understand the interaction, we stratified
the file by gender and computed one-way
ancovas for CHT using the same covariates as in
the principal analysis (Table 3). For the MtF
group, individuals using CHT (mean = 1.67,
SEM = 0.17) reported lower BUT-GSI
(F(1,60) = 7.14, P < 0.01, η2 = 0.11) compared
Table 1 Main clinical and sociodemographic features of our sample as derived from patient history and medical records
MtF (n = 66) FtM (n = 59) t (df) P d χ2 (df)
Age (years), mean ± SD 33.1 ± 10.3 28.7 ± 6.5 −2.93 (111.32) 0.004 0.53
BMI (kg/m2), mean ± SD 22.2 ± 3.9 24.7 ± 4.52 1.99 (43) 0.053 −0.6
Gender dysphoria onset during adolescence, % (n) 53.8 (35)* 70.7 (41)* 0.055 3.68 (1)
Non-Italian natives, % (n) 16.7 (11) 15.3 (9) 0.830 0.46 (1)
Marital status, % (n)
Stable relationship 6.2 (4) 1.8 (1)
Unmarried 89.2 (58) 91.1 (51)
Divorced 4.6 (3) 5.4 (3)
Cohabitation status, % (n) 0.278 3.85 (3)
With parents 30.3 (20) 35.6 (21)
With partner 19.7 (13) 30.5 (18)
With friends 18.2 (12) 10.2 (6)
Alone 31.8 (21) 23.7 (14)
Education, % (n) 0.129 5.66 (3)
Primary school 37.9 (25) 28.8 (17)
Secondary school 25.8 (17) 44.1 (26)
Professional diploma 16.7 (11) 16.9 (10)
University 19.7 (13) 10.2 (6)
Employment, % (n) 0.848 0.037 (1)
Student 10.6 (7) 11.9 (7)
Retired 3 (2) 0.0 (0)
Employed 57.6 (38) 67.8 (40)
Unemployed 28.8 (19) 20.3 (12)
Cosmetic surgery, % (n)
Facial cosmetic surgery 13.6 (9) 5.2 (3) 0.112 2.530 (1)
Breast cosmetic surgery 18.2 (12) 5.1 (3) 0.024 5.060 (1)
Any other cosmetic surgery 22.7 (15) 10.2 (6) 0.61 3.515 (1)
For the assessment of between-group differences (MtF and FtM), χ2 and Student’s t-test were applied for categorical and continuous variables, respectively.
*Data missing for 1 person.
Table 2 Summary of BUT-GSI and SCL differences
explained by 2 × 2 (gender × CHT) ANCOVA, controlling for
age, gender role, and surgery
Variable SS df F P η2
BUT-GSI
Age 0.03 1 0.04 0.841 <0.01
Gender role 0.72 1 0.90 0.345 0.01
Surgery 2.97 1 3.70 0.057 0.03
Gender 0.13 1 0.16 0.690 <0.01
CHT/no CHT 4.65 1 5.80 0.018 0.05
Gender × CHT 4.20 1 5.24 0.024 0.04
SCL
Age 1.46 1 1.65 0.202 0.01
Gender role 0.88 1 0.99 0.323 0.01
Surgery 0.24 1 0.27 0.601 <0.01
Gender 0.71 1 0.80 0.373 0.01
CHT/no CHT 0.81 1 0.91 0.341 0.01
Gender × CHT 1.28 1 1.44 0.233 0.01
BUT-GSI = Global Severity Index of Body Uneasiness Test; CHT = cross-sex
hormonal treatment, SCL = Symptom Checklist; SS = sum of squares
0.0
0.5
1.0
1.5
2.0
2.5
3.0
No CHT
MtF
CHT
MtF
No CHT
FtM
CHT
FtM
a
b
a,b a,b
BUT-GSI (0−5)
Figure 1 Differences in BUT-GSI according to gender (MtF
vs. FtM) and therapy (CHT vs. no CHT). Columns labeled
with different letters are significantly different from each
other (P < 0.05). BUT = Body Uneasiness Test; GSI =
Global Severity Index; MtF = male to female; FtM = female
to male; CHT = cross-sex hormonal treatment.
Cross-Sex Hormones and Body Uneasiness in Gender Dysphoria 713
J Sex Med 2014;11:709–719
with individuals in the no-CHT group
(Mean = 2.44, SEM = 0.23).1 As illustrated in
Table 3, no significant differences were observed
between CHT and no-CHT groups among the
FtM individuals (F(1,54) = 0.12, P = 0.736). As
BUT-GSI was significantly different for the MtF
group, we followed up with analyses of differences
in BUT subscales between CHT and no-CHT
patients within this group to better understand the
aspects of BUT implicated by the primary analyses.
Cosmetic surgery, age, BMI, and gender role
were included as covariates in these models. BUTGSI
was not associated with CHT for the FtM
group.We report follow-up analyses of differences
in BUT subscales between CHT and no-CHT
groups for the FtM group (Table 3) only for
reasons of completeness. In agreement with
primary analyses, BUT subscales did not significantly
differ between the CHT and the no-CHT
group among FtM patients (Table 3). The
subscales that showed significant differences
between MtF patients who did and did not use
CHT were BUT-BIC (F(1,63) = 10.47, P < 0.01,
η2 = 0.14), BUT-AV (F(1,63) = 14.22, P < 0.001,
η2 = 0.18), BUT-D (F(1,63) = 9.66, P < 0.01, η2 =
0.13), and BUT-PST (F(1,63) = 4.21, P < 0.05,
η2 = 0.06). The F-statistics, means, and standard
errors are illustrated in Table 3. Differences in the
other two subscales, BUT-WP and BUT-CSM,
were not significant.
The same models were utilized to assess differences
for each individual BUT-B item (body
part) to highlight potential patterns in aspects of
body image that were more strongly associated
with CHT for the MtF group, controlling for
age, BMI, gender role, and cosmetic surgery
when appropriate (i.e., an ancova testing satisfaction
with the face controlled for facial cosmetic
surgery, but an ancova testing satisfaction with
the hands did not). These analyses should be
considered secondary analyses conducted to
further explore the significant differences
observed in BUT-PST. Bonferroni corrections
were not utilized, as the results of the primary
analyses were significant. Given the descriptive
purpose of these analyses, a stronger emphasis
was placed on effect sizes (Cohen’s d) than on
statistical significance. Based on Cohen’s power
guidelines, an η2 between 0.01 and 0.04 was considered
small, one between 0.05 and 0.12 was
moderate, and one above 0.13 was large [37].
As highlighted in Table 4, MtF patients who
did and did not use CHT showed significant
differences (P < 0.05) in their dislike of their
body hair (η2 = 0.072), arms (η2 = 0.103), chest
(η2 = 0.115—but not breasts, η2 = 0.007), smell
(η2 = 0.008), and buttocks (η2 = 0.082). Surprisingly,
differences in dislike of eyes (η2 = 0.086)
also reached significance.
Differences in General Psychopathology Based on
Gender (MtF vs. FtM) and Use of CHT
The 2 × 2 (gender × CHT) ancova model used
above was utilized to assess differences in psychological
health between groups (Table 2).Nosignificant
differences in SCL score were observed
according to gender (MtF vs. FtM; F(1,113) = 0.80,
P = 0.373), hormones (CHT vs. no-CHT;
F(1, 113) = 0.91, P = 0.341), or the interaction of
these two variables (F(1, 113) = 1.44, P = 0.233).
1Note that means and SEM are provided for BUT-GSI
scores calculated after controlling for covariates.
Table 3 Summary of estimated means and standard errors for MtF and FtM participants by CHT group, including
results for differences tested with one-way ANOVA for all outcome variables
MtF
F(dfs)
FtM
F(dfs)
No CHT (n = 22) CHT (n = 42) No CHT (n = 32) CHT (n = 24)
Mean SEM Mean SEM Mean SEM Mean SEM
BUT-GSI 2.51 1.04 1.63 1.07 9.12 (1,63)** 2.13 0.69 2.04 0.69 0.09 (1,56)
SCL-90-R 0.74 0.15 0.70 0.11 0.04 (1,63) 0.50 0.21 0.84 0.23 1.11 (1,56)
BUT-BIC 3.07 1.30 1.96 1.32 10.47 (1,63)** 3.11 1.02 2.84 1.06 0.59 (1.56)
BUT-AV 2.16 1.25 0.95 1.11 14.22 (1,63)*** 1.55 0.92 1.60 1.15 0.11 (1,56)
BUT-D 2.40 1.05 1.34 1.35 9.66 (1,63)** 3.14 5.61 2.00 1.03 0.59 (1,56)
BUT-PST 21.75 8.71 16.14 9.53 4.21 (1,63)* 12.46 8.71 13.65 7.22 0.63 (1,56)
BUT-CSM 1.93 1.33 1.53 1.06 0.51 (1.63) 1.14 0.83 1.24 0.66 0.39 (1,56)
BUT-WP 2.56 1.01 2.04 1.11 3.02 (1,63) 2.04 0.89 2.21 0.78 0.18 (1,56)
*P < 0.05; **P < 0.01; ***P < 0.001.
MtF = male to female; FtM = female to male; CHT = cross-sex hormonal treatment, BUT = Body Uneasiness Test; GSI = Global Severity Index; SCL-90-
R = Symptom Checklist-90 Revised; BIC = body image concerns; AV = avoidance; D = depersonalization; PST = positive symptoms total (dislike for body parts);
CSM = compulsive self-monitoring; WP = weight phobia
714 Fisher et al.
J Sex Med 2014;11:709–719
Daily Hormone Dose and CHT Length and the Body
Uneasiness of MtF Subjects
The findings of a two-step hierarchical regression
showed that CD-E (daily estradiol dose times days
of treatment) and CD-CPA (daily androgen
blocker dose times days of treatment) added significantly
to the explanation of BUT-GSI above
and beyond the effects of age, gender role, cosmetic
surgery, and BMI (predictors in step 1;
ΔF(2,7) = 6.46, P < 0.05, ΔR2 = 0.48). An analysis
of beta coefficients revealed that only CD-E had a
significant and unique effect (β = −1.37, P < 0.05,
sr = −0.62). CD-CPA was not significant (β = 1.66,
P = 0.14, sr = 0.32). This relationship is illustrated
in Figure 2.
Table 4 Summary of means, standard deviations and statistical differences in dislike of body parts (BUT-B) between
MtF participants in no-CHT and CHT groups, with adjustment for age, body mass index, gender role, and cosmetic
surgery when appropriate
No CHT CHT
Mean SD Mean SD F(dfs) P η2
Height 1.23 0.31 0.70 0.24 1.69 (1,55) 0.200 0.030
Head shape 0.70 0.33 0.92 0.25 0.26 (1,55) 0.612 0.005
Face shape 1.50 0.38 1.26 0.29 0.25 (1,54) 0.619 0.005
Skin 0.91 0.23 0.54 1.80 1.44 (1,55) 0.235 0.025
Hair 2.14 0.43 1.05 0.33 3.7 (1,55) 0.057 0.064
Forehead 1.78 0.35 0.92 0.27 3.45 (1,55) 0.069 0.059
Brows 1.11 0.30 0.53 0.23 2.25 (1,55) 0.139 0.039
Eyes 0.84 0.21 0.21 0.17 5.10 (1,54) 0.028* 0.086
Nose 2.03 0.38 1.44 0.29 1.40 (1,54) 0.241 0.025
Lips 1.35 0.31 0.57 0.24 3.70 (1,54) 0.060 0.064
Mouth 0.79 0.22 0.33 0.17 2.60 (1,53) 0.113 0.047
Teeth 1.35 0.33 0.87 0.25 1.28 (1,54) 0.263 0.023
Ears 0.92 0.26 0.62 0.20 0.73 (1,55) 0.397 0.013
Neck 1.49 0.33 0.86 0.26 2.05 (1,45) 0.158 0.037
Chin 1.39 0.37 1.00 0.29 0.63 (1,54) 0.431 0.012
Moustache 4.22 0.46 3.36 0.36 2.01 (1,54) 0.158 0.037
Beard 4.58 0.42 3.64 0.33 2.91 (1,55) 0.094 0.05
Body hair 4.77 0.36 3.81 0.27 4.16 (1,54) 0.046* 0.072
Shoulder 2.03 0.41 1.42 0.32 1.28 (1.55) 0.262 0.023
Arms 1.67 0.31 0.66 0.24 6.35 (1,55) 0.015* 0.103
Hands 1.68 0.33 0.98 0.25 2.67 (1,55) 0.108 0.046
Chest 2.80 0.42 1.34 0.32 7.05 (1,54) 0.010* 0.115
Breast 1.28 0.43 1.62 0.33 0.36 (1,53) 0.552 0.007
Belly 1.55 0.38 0.71 0.30 2.81 (1,55) 0.099 0.049
Womb 1.24 0.36 0.85 0.28 0.71 (1,55) 0.404 0.013
Genitals 4.45 0.34 3.01 0.26 0.65 (1,55) 0.423 0.012
Buttocks 1.76 0.35 0.74 0.27 4.94 (1,55) 0.030* 0.082
Hips 1.12 0.34 1.01 0.27 0.67 (1,55) 0.800 0.001
Thighs 0.93 0.25 0.45 0.20 2.14 (1,53) 0.150 0.039
Knees 0.84 0.25 0.43 1.99 1.48 (1,54) 0.229 0.027
Legs 1.18 0.28 0.49 0.22 3.55 (1,55) 0.065 0.061
Ankles 1.02 0.27 0.64 0.211 1.11 (1,55) 0.297 0.020
Feet 2.27 0.42 1.75 0.32 0.89 (1,55) 0.348 0.016
Body scent 1.12 0.23 0.28 0.18 7.68 (1,55) 0.008* 0.123
Body sounds 1.41 0.32 0.68 0.24 3.18 (1,52) 0.080 0.058
Sweating 2.53 0.43 1.80 0.33 1.68 (1,55) 0.200 0.030
Blushing 1.04 0.31 1.08 0.24 0.01 (1,55) 0.914 0.000
*P < 0.05.
MtF = male to female; CHT = cross-sex hormonal treatment; SD = standard deviation; CHT = cross-sex hormonal treatment
0.0
0.5
1.0
1.5
2.0
0 20,000 40,000 60,000 80,000 100,000 120,000
CD-E
BUT-GSI (0−5)
P < 0.05
Figure 2 Representation of the regression predicting
the effects of cumulative dose of estradiol on BUT-GSI.
BUT-GSI = Global Severity Index of Body Uneasiness Test;
CD-E = cumulative dose of estradiol (daily dose times days
of treatment).
Cross-Sex Hormones and Body Uneasiness in Gender Dysphoria 715
J Sex Med 2014;11:709–719
Discussion
To our knowledge, this is the first published study
testing differences in body uneasiness according to
use of CHT in individuals with GD. In particular,
we have demonstrated that, among MtF subjects,
body uneasiness was lower in those in the CHT
group than in the no-CHT group. Also, interestingly,
we observed a negative relationship between
CHT and body uneasiness for the MtF group but
not for the FtM group. Even if some authors have
reported a more satisfied perception of the body
after sex reassignment surgery [38], to date no
empirical studies have focused on the effects of
CHT on body image. These findings are in line
with our clinical observations that modifying sexually
dimorphic body characteristics through hormones
can lead to a relief in body-related distress.
Also, this new empirical result implies that a more
flexible approach for treating individuals with GD
(i.e., not automatically including surgery) may be
better suited to address clients’ variety of needs.
Specifically, our results provide initial empirical
evidence that supports the last version of the
World Professional Association for Transgender
Health Standards of Care [1] advocating individualized
treatment goals.
Patterns in the body uneasiness subscales
emerged when we further investigated the differences
between the CHT and the no-CHT groups
of MtF subjects. In particular, less severe body
uneasiness and less avoidance of thoughts about
the body were observed in those MtF individuals
taking hormones as compared with those not
taking hormones. A significant difference was
present even after controlling for age, gender role,
BMI, and cosmetic surgery. This finding could be
explained by CHT-induced improvement in the
acceptance and appreciation of a body shape more
in line with patients’ ideal. Previous studies have
shown that depersonalization, a psychopathological
phenomenon defined as the feeling of being
outside of one’s body, was reduced after sex reassignment
surgery [31,39,40]; however, here we
provide evidence that MtF individuals taking hormones
also suffer less body dysphoria, adding
novel information for the field.
No significant differences were observed
between CHT and no-CHT patients in the MtF
group with regard to compulsive self-monitoring
and weight phobia. The lack of significant difference
in compulsive self-monitoring is not surprising
given that this scale captures cognitive
distortions usually produced by a pathological
view of the self, as observed in body dimorphic
disorder [36]. The pathology of compulsive selfmonitoring
is based on a view of the self that is
distorted from reality (i.e., individuals perceive
themselves differently from how they really
appear). For individuals with GD, the discrepancy
between mind and body results from a misalignment
between how they look and how they would
like to appear. However, their view of their body
remains aligned with reality (i.e., they really look
the way they perceive themselves). Weight concerns
were not significantly different between MtF
individuals taking hormones and those not taking
them. The relationship among hormones, weight
gain, and weight concerns may be more complex
than our design is able to explain. One potential
explanation can be derived from previous studies
showing that CHT increases weight in MtF clients
[41]. As in Western culture thinness is associated
with femininity and attractiveness [42], being thin
could represent a way to conform to femininity
[30,43,44]. Based on this logic, one could infer that
worries of MtF individuals about treatmentinduced
weight gain may counteract any satisfaction
that CHT may have introduced for the newly
gained womanly shape (i.e., accumulation of fat
around the hips). Thus, rather than no change,
CHT may lead both to positive changes and to
negative changes that may attenuate the actual
overall satisfaction. However, the present results
should be interpreted with caution in the light of
such complexity and the controversial physical
effects of CHT.
The absence of significant differences in body
uneasiness between CHT and no-CHT patients
among FtM subjects is unexpected and could be
explained in several different ways. One would
expect androgens to lead to more socially visible
alterations in the body. For example, the growth of
a beard may provoke a significant change in the
way the person is perceived by others and thus may
help the individual to pass as male. However, the
BUT scale is more concerned with the private
relationship between an individual and his/her
body [36], meaning that it asks how a person feels
about his/her own body and not the distress caused
by how one may appear to others. The scale
focuses on aspects that the individual faces when
undressed in front of the mirror, within the private
walls of the bathroom or bedroom [36]. Within
this context, the types of changes that CHT causes
in an FtM individual may not be enough to bring
about an amelioration in body uneasiness. For
example, CHT may ameliorate breast-related dis-
716 Fisher et al.
J Sex Med 2014;11:709–719
tress in MtF individuals by increasing breast size.
On the other hand, CHT-induced breast atrophy
is limited for FtM individuals, and thus CHT
alone may not be sufficient to ameliorate distress
caused by breasts in FtM subjects.
A second explanation of the CHT-related difference
in body uneasiness between MtF and FtM
individuals may be the objective difference in the
amount of change induced by the treatment. Specifically,
it is possible that changes induced by
androgens in body parts, such as breasts, may be
less drastic than the changes that estrogens
produce in the same area. Ideally, we would want
to compare body changes using objective measures
that allow use of the same scale for MtF and FtM
individuals. However, differences in hormones and
in the biological makeup of the two populations
does not allow such comparison.
In the secondary analyses that investigated individual
body parts listed in the BUT, we also found
evidence for a significant difference between CHT
and no-CHT groups for chest, arms, and buttocks
in the MtF sample. Specifically, the CHT group
reported less dislike for these body parts. These
findings could be the results of hormone-induced
body mass redistribution [41]. Also, we found
more satisfaction with body scent in the CHT
group, a finding in line with the literature showing
that androgen-related changes in physiological
mechanisms result in a less masculine scent, which
MtF individuals appear to appreciate [45–47].
As far as mental health is concerned, we did not
observe differences between CHT and no-CHT
individuals for either group (FtM or MtF), and
overall, subjects showed a low level of psychopathology.
It is possible that CHT may have a positive
effect on psychological well-being, but the
restricted range of psychopathology scores may
have prevented us from finding differences
between the two groups. This finding is in disagreement
with a previous study [28] reporting
less social distress and anxiety and fewer depression
symptoms among subjects receiving CHT.
However, these results cannot be directly compared
with ours, as in this previous study researchers
combined individuals taking CHT only with
individuals who received genital reassignment
surgery. The low level of psychopathology symptoms
in our subjects is in line with previous studies
reporting lower scores in psychopathology among
GD clients as compared with patients with eating
disorders [31] and similar scores to healthy controls
[31,48]. Moreover, we add to the extant literature
by showing a positive effect of CHT on
quality of life [27] and providing the first evidence
that body uneasiness is lower in MtF individuals
using hormonal treatment compared with those
not using hormones.
The analyses on cumulative hormone dose
showed that the cumulative dose of estrogens, but
not that of antiandrogens, provided a unique and
significant contribution to the prediction of lower
body uneasiness. The fact that antiandrogens did
not show a unique and independent effect should
not be interpreted as a lack of significant effect on
the part of these hormones but rather as indicating
that changes in levels of estrogens may be more
closely related to psychological state with regard
to the body, or that the effects of androgens are
produced through the interaction of androgens
with estrogens.
It should be noted that in our study we combined
length of therapy (days) with daily dose
level, and therefore the significant relationship
between body uneasiness and CHT needs to be
considered as the interaction between these two
variables. Administering higher daily doses of hormones
may not lead to the same positive effects
observed for cumulative hormone dose. Indeed,
high doses of estrogens have been reported to be
deleterious to body health [41]. Individuals selfmedicating
and taking hormones not medically
prescribed may be more likely to use higher daily
doses but may perhaps adopt a more discontinuous
pattern. Our data suggest that the combination of
number of days and daily dose matters, and thus a
lower-daily-dose but more stable and continuous
treatment may be more effective than a high-dailydose
and sporadic pattern of treatment.
Several limitations of the present study should
be recognized. The cross-sectional design of the
study does not allow for causal inferences with
regard to the relationship between the target variables
and CHT. Second, there are some potential
limitations in the way we collected data on CHT
treatment: while for some people we were able to
check self-reports against medical records, for the
majority of participants we had to rely on selfreport
information collected during a medical
history interview. Third, it should be taken into
account that the relatively small sample size in this
study could lead to a reduced power in detecting
significant differences; however, the fact that significant
effects were found for the MtF group but
not for the FtM group speaks to meaningful differences
between these two populations. Fourth,
our findings refer to patients seeking CHT and
cannot be generalized to the whole gender-variant
Cross-Sex Hormones and Body Uneasiness in Gender Dysphoria 717
J Sex Med 2014;11:709–719
population. However, given that the study was
conducted to provide clinically relevant information
to clinicians treating individuals with GD
seeking CHT, we feel that the findings in this
study provide novel information on CHT’s role
in alleviating distress. Fifth, the dichotomous
measure we used for gender role does not reflect
the real variability of GD phenomena. In fact, it
should be considered that a linear measure would
better honor the diversity of clients’ transitions.
However, it should be noted that in the
present study, gender role was utilized as a
covariate, not a main variable, and therefore does
not affect the outcome. Finally, given the crosssectional
design of the study, it is not possible to
ascertain a causal interpretation for our results.
However, this study is the first to test a possible
correlation between CHT and body uneasiness
in GD subjects and therefore provides a meaningful
insight into a topic that warrants further
exploration.
In conclusion, our findings are in line with the
hypothesis that cross-sex hormonal therapy can
alleviate body uneasiness, a core element of GD,
even without surgery. Such effects were observed
only for MtF subjects and were associated with
greater cumulative hormone dose, suggesting that
a continuous treatment with a set daily dose and
number of days may be an effective approach to
treat gender dysphoria in MtF clients, with or
without surgical intervention.
Acknowledgement
We would like to thank Enza Costantino, Center for
Reproductive Health, Department of Obstetrics and
Gynecology, S. Orsola Hospital, University of Bologna,
Italy.
Corresponding Author: Alessandra H Rellini, PhD,
University of Vermont, Department of Psychology, 2
Colchester Ave, John Dewey Hall room 240, Burlington,
VT 05401, USA. Tel: (802) 656-4110; Fax: (802)
656-8783; E-mail: arellini@uvm.edu
Conflict of Interest: The authors report no conflicts of
interest.
Statement of Authorship
Category 1
(a) Conception and Design
Alessandra H. Rellini; Alessandra D. Fisher; Mario
Maggi; Elisa Bandini; Giovanni Castellini
(b) Acquisition of Data
Egidia Fanni; Helen Casale; Elisa Bandini; Maria
Cristina Meriggiola; Naika Ferruccio; Laura Benni;
Chiara Manieri; Anna Gualerzi; Alessandro Oppo;
Valdo Ricca
(c) Analysis and Interpretation of Data
Alessandra H. Rellini; Alessandra D. Fisher; Mario
Maggi; Elisa Bandini; Valdo Ricca; Giovanni
Castellini
Category 2
(a) Drafting the Article
Alessandra H. Rellini; Alessandra D. Fisher; Mario
Maggi
(b) Revising It for Intellectual Content
Alessandra H. Rellini; Mario Maggi; Alessandra D.
Fisher; Elisa Bandini; Giovanni Castellini; Egidia
Fanni; Helen Casale; Valdo Ricca
Category 3
(a) Final Approval of the Completed Article
Alessandra D. Fisher; Mario Maggi; Alessandra H.
Rellini; Giovanni Castellini; Valdo Ricca
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