Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06291675 |
| Other study ID # |
2083/2022 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 3, 2023 |
| Est. completion date |
March 3, 2033 |
Study information
| Verified date |
February 2024 |
| Source |
Medical University of Vienna |
| Contact |
Carola Deischinger, MD PHD |
| Phone |
+43140400 |
| Email |
carola.deischinger[@]meduniwien.ac.at |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background: Gender affirming hormone therapy (GAHT) leads to profound changes in sex hormone
levels, carrying a wide range of implications for major physiological processes in the body.
GAHT has been shown to be associated with changes in cardiovascular parameters, the insulin
system, body composition, and the psychological state. However, despite the fact that GAHT is
usually a long-term intervention, the majority of the research concerns itself with an
overall short duration of the therapy and the data on the mid- to long-term effects of GAHT
is scarce.
Objectives: The study aims to investigate the effects of gender affirming hormone therapy on
the cardiovascular risk profile, insulin system, body composition, various metabolic
parameters, and the psychological state after 2, 5, and 10 years of the treatment.
Study design: The study is designed as an observational longitudinal monocentric study, which
includes transgender men and transgender women who have been taking gender affirming hormone
therapy during the past 2 years and took part in our pilot study. Our probands will undergo a
magnetic resonance scan, extensive bloodwork, an oral glucose tolerance test, and a
psychological self-assessment after 2, 5, and 10 years of the treatment.
Materials and methods: The magnetic resonance imaging and spectroscopy will be performed with
a 3-Tesla magnetic resonance device. We will also perform an extensive blood analysis and an
75g- 2h oral glucose tolerance test. Additionally, the psychological state of the probands
will be assessed with 3 questionnaires.
Study population: 30 transgender men 30 transgender women who participated in our pilot study
and have been taking the gender affirming hormone therapy for the past 2 years.
Relevance and implications of the study: The majority of previous research has focused on the
short-term effects of gender affirming hormone therapy. Contrastingly, our study aims to
focus on the effects of hormone therapy at 2, 5 and 10 years after the beginning of the
treatment. Moreover, our study group utilizes measurements of myocardial, hepatic, and
pancreatic fat content as well as an MR-assisted measurement of cardiac function, which is a
topic that has not been present in research into the effects of gender affirming hormone
therapy outside of our pilot study.
Description:
Background Gender affirming hormone therapy is a treatment used by many transgender
individuals aiming for physical transition. During this treatment, the endogenous production
of sex hormones is reduced, and they are supplemented by the sex hormones of the gender with
which the person identifies. These profound changes in the hormonal profiles of transgender
people have been shown to be associated with changes in cardiovascular parameters, the
insulin system, body composition, and the psychological state.
In the case of transgender men under GAHT, the treatment seems to be associated with the
development of a less favorable, more atherogenic lipid profile, with an increase in
triglycerides and low-density lipoprotein (LDL) levels, while also experiencing a decrease in
high-density lipoprotein (HDL). On the other hand, transgender women under GAHT seem to
develop higher levels of triglycerides, with little to no changes in LDL and HLD levels.
Additionally, GAHT seems to have an effect on body composition - in transgender men, GAHT is
associated with a decrease in fat mass, on the other hand, in transgender women GAHT is
connected to an increase in total body fat. These changes do not seem to be associated with a
significant change in the visceral fat mass in either group (Klaver et al., 2022).
Despite the documented effects of GAHT on cardiovascular risk factors, it is still not
entirely clear whether these effects are significant enough to cause significant changes in
cardiovascular morbidity and mortality. However, the prior findings suggest that transgender
women have a higher risk of suffering an ischemic stroke or a myocardial infarction compared
to cisgender women, while there is no consistent evidence documenting an increase of
cerebrovascular and cardiovascular disease transgender men compared to cisgender men.
The research into changes in glucose homeostasis has not delivered conclusive long-term
findings so far. Nevertheless, there is a documented tendency towards a slight worsening of
insulin sensitivity in transgender women, while the effects of GAHT on insulin resistance in
transgender men are associated with either no change or a small improvement.
Gender affirming hormone treatment also seems to have an impact on the psychological and
cognitive state of the patients, for example, it has been brought into connection with an
alleviation of depressive symptoms. Furthermore, there are documented morphological and
functional changes in the brains of people taking GAHT. These changes might be accompanied by
changes in neuropsychological processes, including, for example, emotional regulation.
Additionally, there is a lack of data on the possible changes in executive function in
transgender people, especially in regard to longitudinal changes under GAHT.
Long-term studies are still lacking in the realm of sequelae of GAHT. Thus, we aim at
observing and investigating psychological and cardiovascular effects of GAHT in the
long-term.
3.3. Study design The study is designed as a prospective longitudinal mono-centric
observational study comparing cardiovascular and psychological effects of GAHT after 2, 5,
and 10 years of GAHT with the patient's status before GAHT. We aim at enrolling all
participants of our pilot study (EK 1629/2017) who started GAHT in the last two years and
have, thus, completed the psychological assessments before the start of GAHT.
At each visit, our probands will undergo a magnetic resonance scan, an oral glucose tolerance
test, as well as an extensive blood analysis and an assessment of the anthropometric
parameters. Additionally, the patient history and self-assessment with standardized
psychological tests will be performed at each visit. The study will include 3 separate study
visits, after 2, 5, and 10 years of treatment.
3.4. Subject section Our study aims to enroll transgender probands who took part in our pilot
study. 30 transgender women and 30 transgender men will be recruited from the pool of
participants in the previous pilot study (EK 1629/2017). The study will include transgender
participants between 18 and 99 years of age, who have been taking gender affirming hormone
therapy for the past 2 years. The study will not include a placebo group or a control group,
and it will not interfere with the gender affirming hormone therapy in any way regarding
composition and time course of the treatment.
3.5. Hormones/treatment protocols The gender affirming hormone treatment protocols of our
probands are based on the protocols as used by the outpatient clinic specializing in gender
affirming hormone treatment at the Departments of Endocrinology and Metabolism and Gynecology
and Obstetrics of the Vienna General Hospital/Medical University of Vienna. The GAHT of our
probands is prescribed and managed independently of the study, and the study has no effect on
the treatment.
Transgender women included in this study receive estrogen, either transdermally
(Estrogel-Gel®, Estradot® or Estramon®) or orally (Estrofem®). If needed, the treatment can
be supplemented by cyproterone acetate (Androcur®), and/or an alpha-5-reductase inhibitor
(Finasterid Actavis/Arcana/Aurobindo®).
Transgender men included in this study receive testosterone either intramuscularly (Nebido®)
or transdermally (Testogel® or Testavan®). If necessary, the treatment might be supplemented
by lynestrenol (Orgametril®).
Furthermore, the treatment in both cohorts can, if necessary, be complemented by GnRH
analogues, such as triptorelin acetate (Decapeptyl® or leuprorelin acetate every 3 months
(Trenantone®).
4. Methods and materials All measurements and assessments will be performed after an
overnight fast of minimum 8 hours.
4.1. Magnetic resonance imaging and spectroscopy Magnetic resonance spectroscopy is a
possible non-invasive method for quantifying ectopic accumulation of lipids. Intramyocardial,
hepatic and pancreatic fat content, as well as subcutaneous and visceral fat and parameters
of cardiac function will be measured using magnetic resonance imaging and magnetic resonance
spectroscopy in a 3-Tesla Magnetom PrismaFit magnet (Siemens Healthliners, Erlangen,
Germany). Magnetic resonance imaging and spectroscopy will be conducted in accordance with
established protocols, which have previously been used in our pilot study.
For the measurements of visceral and subcutaneous adipose tissue, T1-weighted visualizations
in an axial slice in the L2/L3 area will be used. Pancreatic fat content will be quantified
following a protocol similar to one previously published by Al-Mrabeh et al., which utilizes
fat fraction images derived from multi-echo Dixon imaging sequences. Additionally, hepatic
and myocardial fat content will be assessed by short time single voxel spectroscopy and
electrocardiogram-gated spectroscopy respectively.
4.2. Bloodwork and oral glucose tolerance test Our study will include extensive bloodwork
with an analysis of metabolic parameters, cardiovascular risk factors, and various other
biomarkers. After the initial blood draw, an oral glucose tolerance test will be performed.
After taking the baseline sample, the probands will be asked to ingest 75 grams of glucose
dissolved in 200ml of water. Subsequently, blood samples will be taken 30, 60, 90, and 120
minutes after the glucose ingestion, and the concentrations of glucose, insulin and c-peptide
will be measured from the samples. For the repeated blood draws, an intravenous cannula will
be placed preferably into the cubital vein. The measured concentrations will be used to
calculate the surrogate markers for insulin sensitivity/insulin resistance (HOMA-IR,
Matsuda-Index, Stumvoll first and second phase indices).
The samples will be analyzed at an ISO 9001 certified laboratory of the Vienna General
Hospital, according to the established protocols of the Institute of Laboratory Medicine.
Adiponectin and betatrophin will be measured by human ELISA kits from the company Biovendor.
4.3. Assessment of psychological and cognitive state The patients will be asked to fill out 3
standardized questionnaires for an assessment of their psychological and cognitive state.
Depressive symptoms will be evaluated by the Becks depression inventory self-rating scale
(BDI-II) which consists of 21 items. Emotion control, processing, avoidance, and repression
will be quantified with the 25-item Emotional Process Scale (EPS-D). Additionally, the Trier
personality questionnaire (TPF) will be used for evaluating psychological wellbeing. The
questionnaires will be handed to the probands during the OGTT and are intended to be filled
out during the waiting times between the blood draws. The questionnaires will then be
analyzed by the psychologist involved in this study, Mag. Maria-Christine Mautner. Should a
patient show an increased risk for endangerment of self or others in a psychological
questionnaire, the patient will be informed and they will immediately be referred to the
crisis intervention center of the Vienna General Hospital.
4.4. Other parameters Blood pressure and heart rate will be measured with an OMRON 705 device
on the left arm after a minimum of 10 minutes at rest. Weight will be measured on calibrated
electronic scales (SECA 877/888) to the nearest 0,1 kg wearing light clothes and no shoes.
The body mass index will be calculated from the measured weight and self-reported height.
Waist circumference will be measured at the midpoint between the lower border of the rib cage
twice, and the average of the two measurements will be recorded.
5. Statistical and data analysis After the completion of the study, we will have data at
several time points. To be exact, we will have measured systolic and diastolic heart
function, hepatic, pancreatic, and myocardial fat content, subcutaneous to visceral fat
ratio, variables on the functionality of the insulin system, information on depression,
emotion and behavioral control as well as adiponectin and betatrophin concentration after 2,
5, and 10 years of the treatment. Initially, the data will be tested for normal distribution
using the Kolmogorov-Smirnov and Shapiro-Wilks tests. If necessary, logarithmic
transformation will be performed. The comparisons between the different time points will be
performed using a repeated measure ANOVA. Possible correlations will be tested using
Pearson's or Spearman's correlation coefficients. The data will also be presented as mean ±
standard deviation, or median ± interquartile range, as appropriate. The level of
significance will be set at α < 0,05. The data will be tested using the IBM SPSS Statistics
Software (Version 29, IBM, New York, USA).
6. Ethical section The study will be performed under the Declaration of Helsinki (1964) and
the Good Clinical Practice guidelines.
The gender affirming hormone therapy of the probands is clinically indicated and completely
independent from our study. The study does not influence the composition, start, duration, or
end of the treatment. All subjects will receive a thorough patient information and will sign
informed consent forms prior to the inclusion in the study. The probands will be able to
withdraw from the study at any time. Additionally, the study team has the right to remove
participants from the study if the exclusion criteria have been met, or if the participation
in the study is not in the best interest of the proband.
No significant side effects are expected from any of the procedures included in the study. In
the case of possible concerning findings made during the examinations, the probands will be
offered a consultation and will be referred to the appropriate diagnostic or therapeutic
procedures. Should a patient show an increased risk for endangerment of self or others in a
psychological questionnaire, they will immediately be referred to the crisis intervention
center of the Vienna General Hospital.
7. Human resources, study sites, cooperations The proposed study will be conducted at the
Department of Endocrinology and Metabolism (head: Univ. Prof. Dr. Alexandra Kautzky-Willer;
collaborators: Dr. Carola Deischinger, Dr. Jürgen Harreiter, Dr. Dorota Sluková, Mag.
Maria-Christine Mautner, Dr. Lana Kosi-Trebotic), the Department of Obstetrics and
Gynecology, Division of Gynecologic Endocrinology and Reproductive Medicine, Unit for Gender
Identity Disorder (Ulrike Kaufmann, MD) of the Medical University of Vienna / General
Hospital of Vienna. and the High Field MR Centre (collaborators: Ivica Just, MSc PhD; Mag.
Radka Klepochova, PhD; Assoc. Prof. Dr. Martin Krššák).
8. Relevance and implications of the study Despite the fact that gender affirming hormone
therapy is usually a long-term intervention, the majority of the research into its effects
concerns itself with only the short-term effects. Thus, there is an obvious need for more
longitudinal research into the longer-term effects of GAHT in order to assess the potential
effects of gender affirming hormone therapy more appropriately and to provide better
personalized patient care. Our study aims to provide more insight into the mid- to long-term
effects of gender affirming hormone treatment in both transgender women and transgender men.
Furthermore, apart from our pilot study, we are not aware of a study including MRI and
MRS-assisted measurements of SAT, VAT, hepatic, pancreatic and myocardial fat content and
cardiac function in people taking gender affirming hormone therapy.
