Ignite Creation Date:
2024-05-06 @ 4:00 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04838249
Status:
RECRUITING
Last Update Posted:
2023-12-14
First Post:
2021-03-18
Brief Title:
Effects of Cross-sex Hormone Therapy on Eating Behavior Metabolism Energy Balance and Cardiovascular System
Sponsor:
University of Leipzig
Organization:
University of Leipzig
Study Overview
Official Title:
Investigation of the Effects of Testosterone and Estrogen on Eating Behavior Metabolism Energy Balance and Cardiovascular System in Transsexual Patients Undergoing Cross-sex Hormone Therapy
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HHS
Brief Summary:
Current study aims to characterize five highly interconnected physiological systems in patients undergoing cross-sex hormone therapy - namely glucose and lipid metabolism energy balance eating behavior functional brain networks involved in the regulation of eating behavior and the cardiovascular system - to gain novel insights into the effects of sex hormones on the human body Gathered information will help to identify pathophysiological mechanisms for the development of overeatingobesity insulin resistance and cardiovascular disease Secondarily the relationships between the gut and oral microbiomes and metabolomes and circulating bacterial signatures will be investigated in relation to the other pervasive physiological systems
Current study is an observational study The decision if the patients request for cross-sex hormone therapy can complied with ie if cross-sex hormone therapy is medically indicated is made prior to the first contact with the study center and with the outpatients clinic for Endocrinology at the University Hospital in Leipzig Decision ifor treatment is made according to national and international guidelines Treatment of study participants with testosterone and estradiolantiandrogens is not affected by the study During the course of the study no invasive interventions are being performed
Current study is an observational study The decision if the patients request for cross-sex hormone therapy can complied with ie if cross-sex hormone therapy is medically indicated is made prior to the first contact with the study center and with the outpatients clinic for Endocrinology at the University Hospital in Leipzig Decision ifor treatment is made according to national and international guidelines Treatment of study participants with testosterone and estradiolantiandrogens is not affected by the study During the course of the study no invasive interventions are being performed
Detailed Description:
1 Introduction 11 Transsexualism Transsexualism is a condition in which an individuals gender identity is incongruent with the assigned sex at birth Many transsexuals suffer from severe psychological problems caused by this this incongruence referred to as gender dysphoria Supporting transsexuals in living in the sex with which they identify leads to amelioration of psychological problems and medical problems In sex reassignment therapy cross-sex hormone therapy is an essential element
12 Cross-sex hormone therapy in transsexual patients In many patients cross sex hormone therapy is used to conduct sex change In transmen biological women with perceived male sex testosterone is used for gender reassignment In transwomen biological men with perceived female sex the most commonly used medication is estrogen Successful therapy leads to the development of typical secondary sex characteristics Data and knowledge regarding the effects of cross-sex hormone therapy on the human body additionally to the desired sex affirming changes is scarce
13 Investigation of the effects of estrogen and testosterone on the human body Investigating the effects of cross-sex hormone therapy provides further information on the effects of testosterone and estradiol on the human body One of the most recognized differences between men and women regarding health is the increased cardiovascular risk of men as compared to women In transmen testosterone therapy leads to an increased risk for myocardial infarction Data from the diabetes prevention program suggest that in males the probability of developing diabetes mellitus type 2 a major risk factor for cardiovascular disease is positively correlated with serum concentrations of estradiol and negatively correlated with concentrations of testosterone Furthermore previous studies pointed to differences in the regulation of eating behavior of men and women potentially contributing to the development of obesity and type-2-diabetes
Moreover while the microbiota known to affect host homeostasis immunity and metabolism shows sex-related variations the impact of sex hormones and gender transition on the different microbiome niches and related metabolic processes remains largely unexplored
The above mentioned findings are just examples of plentiful dissimilarities in health and disease of the two sexes with unknown causes To date studies assessing eg markers of cardiometabolic disease in cross-sex hormone therapy remain inconclusive
14 Purpose of this study To gain novel insights into the effects of sex hormones on the human body current study aims to characterize four highly interconnected physiological systems in patients undergoing cross-sex hormone therapy glucose and lipid metabolism energy balance eating behavior and the cardiovascular system as well as several microbiome niches Gathered knowledge will help to identify pathophysiological mechanisms for the development of overeatingobesity insulin resistance and cardiovascular disease
2 Aims The study is designed to investigate the effects of testosterone and estradiolcyproteron acetate in patients with gender dysphoriatranssexualism undergoing cross-sex hormone therapy in comparison to a control group without hormone therapy
Effects of cross-sex hormone therapy on
Part A Glucose and lipid metabolism Part B Body composition and energy balance control microbiome Part C Psychobehavioral traits with a focus on eating behavior Part D Cardio- Vascular system
To best possibly attribute observed effects to the applied sex hormones baseline measurements before starting cross-sex hormone treatment will be performed V0 Measurements will be repeated at five time points during ongoing cross sex hormone treatment V1-5
V0 Baseline assessment before start of cross-sex hormone therapy V1 Three months after start of cross-sex hormone therapy V2 Six months after start of cross-sex hormone therapy V3 Twelve months after start of cross-sex hormone therapy V4 Two years after start of cross-sex hormone therapy V5 Five years after start of cross-sex hormone therapy To be able to exclude unspecific order effects of the measurements and to be able to compare obtained results with non-transsexual persons controls not undergoing cross-sex hormone therapy matched for age body mass index health status morbidity and education will be included
3 Research Design and Methods 31 Participants and recruitment This is a five year observational non-invasive study to evaluate the effect of cross-sex hormone therapy on metabolism eating behavior body composition energy expenditure oral and the gut microbiomes and the cardiovascular system Results will be compared longitudinally on an intra-individual level as well as on an inter-individual level by comparing transmen with transwomen and both groups with non-treated controls Transsexual patients will be recruited at the outpatient clinic for Endocrinology at the University Hospital Leipzig Patients seeking cross-sex hormone therapy will be asked before starting cross-sex hormone therapy for their willingness to participate in the study Patients willing to participate will be screened for study eligibility Eligible subjects will be informed about the study procedures and possible risks Upon receiving written informed consent the patient will be included into the study Willingness to participate in the study will not influence the medical treatment
A control group of men and women matched for age body mass index health status morbidity and education who are not undergoing cross-sex hormone therapy will be recruited via online advertisements
32 Study procedures Seven days prior to baseline assessment accelerometers will be handed to participants to measure physical activity Four days prior to baseline participants will be asked to complete a 96h activity log to objectify physical activity Food intake will be self-assessed four days prior to baseline assessment via questionnaire as instructed by a trained dietitian Dietary restraints will be assessed eg lactose intolerance etc to adjust procedures of ad libitum food intake measurement to individual needs A tour of our metabolic unit and the MRI facilities will be given to participants and procedures explained Subjects will be asked to fill out behavioral questionnaires at home within one hour of completing their breakfast to decrease variability of answers Participants will use provided kits to collect stool samples for the gut microbiome analysis
On the day of baseline assessment prior to initiation of cross-sex hormone therapyno therapy current medical history including current medication a physical exam including measurement of weight waist and hip circumferences blood pressure and heart rate will be performed In the fasted state blood will be drawn to measure fasting glucose HbA1c serum insulin triglycerides total- low- and high-density-lipoprotein concentrations Insulin sensitivity and HOMA-IR will be calculated The fasting blood draw will further include measurement of 17β-estradiol progesterone testosterone sex-hormone binding globulin SHBG blood cell count creatinine ALAT ASAT GGT TSH and FGF21 Saliva samples will be collected in a fasted state for analysis of oral microbiome All samples will be stored at -80 C and then sent for commercial sequencing and metabolome analysis In control women and transmen we will record whether menstrual cycle still persists From each blood draw serum will be stored at -80C for future analyses In order of procedures performed during baseline assessment subjects will receive
Assessment of body composition Fat mass and fat-free mass will be assessed using body impedance analysis BIA
Measurement of resting energy expenditure Baseline indirect calorimetry using a ventilated hood method will be performed in the fasted state resting energy expenditure REE prior to hormone substitution therapyno therapy The measurement will take 30 min In brief a clear plastic hood will be placed over the participants head with a soft collar around the neck to prevent any air leaks The hood will be securely ventilated with room air and over 30 min constant fractions of gases flowing out of the hood will be analyzed for carbon dioxide and oxygen concentrations Via measurement of the respiratory quotient calorimetric measurements will be performed during 5 min intervals and over a period of 30 min the subjects mean REE will be estimated Using the ventilated hood method adverse events are scarce and may include claustrophobia Thus subjects suffering from claustrophobia will be exempt from this measurement
Ultrasound of vessels and microperfusion Ultrasound will be conducted to evaluate arterial stiffening abdominal aorta and carotid artery regional aortic strain and aortic impedance characteristics via LVOT doppler and aortic tonometry GE Healthcare Vivid E9 system Peripheral near-infrared spectroscopy combined with a vascular occlusion test will be used to evaluate microperfusion near-infrared spectroscopy Diaspective Vision Tivita tissue
Ad libitum food intake For breakfast subjects will undergo an ad libitum food intake situation in which they will be exposed to a buffet and asked to eat as much as they want The buffet addresses individual dietary retrains eg vegan diet Caloric and macronutrient intake will be measured Prior to and immediately after the buffet participants will rate their mood hunger and desire to eat on a 10 cm visual analogue scale
Snack Food Taste Test For assessment of taste preferences and as an additional measure of ad libitum food intake a snack food taste test will be performed This test will be administered within 30 min after lunch This will be a taste test where participants will be asked to rate four types of food that will be placed in front of them in large bowls potato chips 70 g peanuts 100 g Oreo cookies 100 g and MMs 100 g Participants will be asked to provide mood and appetite ratings They will then be instructed to consume as much or as little as they wish and to judge the taste of the food products using the provided rating scales The experimenter will then leave the room and return 10 min later remove the bowls of food and administer a final rating scale of mood and appetite The bowls of food will be weighed before and after the taste test as a measure of food and calorie intake
Response to thermic stimuli Via an electrode positioned below the base of the index finger C6 of the participants non-dominant hand thermic stimuli cold versus warm will be administered and subjects will be asked to indicate coldwarmth perception Perception of cold will be measured four times in a row followed by warmth perception Then thermal discomfort will be triggered via administration of one cold versus one warm stimulus
Measurement of taste perception and smell Administration of standardized gustatory and olfactory stimuli will enable the assessment of nonspecific taste perception and the subjects ability to perceive certain scents Taste perception will be assessed one at a time by placing paper slip on the participants tongue that had been coated with one specific known flavor Similarly the participants ability to perceive certain scents will be tested In this case specific known scents will be placed in front of the nose of the participant who will be asked to determine the scent and then asked to rate it
Sex hormone deposition in hair Using liquid chromatography-mass spectrometry deposition of sex hormones in hair will be measured time points V2-V4 For this purpose a small amount of hair will be removed from the occipital region of the subjects head and then analyzed
Gut oral microbiome circulating bacterial signature in the blood and metabolomics Participants in the study will collect stool samples at home using a provided kit and bring them to the study visit This kit includes a disposable tray and vials for metagenome sequencing Additionally saliva samples will be collected at the study center after fasting along with blood for microbiome and metabolome analyses Gut microbiome and oral microbiome will be sent for commercial library preparation and sequencing of whole genome metagenomics Bacterial DNA in the blood will be analyzed using 16S rRNA Amplicon sequencing and stool oral and circulating metabolomes will be subjected to commercial metabolomics via gas liquid chromatography-mass spectrometry GLC-MS
Visit to our clinical outpatient unit transgender subjects only Based on our unit-specific standards of care subjects will receive a prescription for hormones intended to induce transformation to the other sex cyproterone acetate testosteroneestradiol and advised to begin administration of their first dose of medication on day 1 of our study Patients will be advised to continue with treatment according to our unit-specific standards of care for subjects with gender dysphoria undergoing hormone substitution therapy
Upon baseline assessment cross-sex hormone treatment versus no treatment will commence Study procedures for V2 through V5 are the same as the above mentioned
12 Cross-sex hormone therapy in transsexual patients In many patients cross sex hormone therapy is used to conduct sex change In transmen biological women with perceived male sex testosterone is used for gender reassignment In transwomen biological men with perceived female sex the most commonly used medication is estrogen Successful therapy leads to the development of typical secondary sex characteristics Data and knowledge regarding the effects of cross-sex hormone therapy on the human body additionally to the desired sex affirming changes is scarce
13 Investigation of the effects of estrogen and testosterone on the human body Investigating the effects of cross-sex hormone therapy provides further information on the effects of testosterone and estradiol on the human body One of the most recognized differences between men and women regarding health is the increased cardiovascular risk of men as compared to women In transmen testosterone therapy leads to an increased risk for myocardial infarction Data from the diabetes prevention program suggest that in males the probability of developing diabetes mellitus type 2 a major risk factor for cardiovascular disease is positively correlated with serum concentrations of estradiol and negatively correlated with concentrations of testosterone Furthermore previous studies pointed to differences in the regulation of eating behavior of men and women potentially contributing to the development of obesity and type-2-diabetes
Moreover while the microbiota known to affect host homeostasis immunity and metabolism shows sex-related variations the impact of sex hormones and gender transition on the different microbiome niches and related metabolic processes remains largely unexplored
The above mentioned findings are just examples of plentiful dissimilarities in health and disease of the two sexes with unknown causes To date studies assessing eg markers of cardiometabolic disease in cross-sex hormone therapy remain inconclusive
14 Purpose of this study To gain novel insights into the effects of sex hormones on the human body current study aims to characterize four highly interconnected physiological systems in patients undergoing cross-sex hormone therapy glucose and lipid metabolism energy balance eating behavior and the cardiovascular system as well as several microbiome niches Gathered knowledge will help to identify pathophysiological mechanisms for the development of overeatingobesity insulin resistance and cardiovascular disease
2 Aims The study is designed to investigate the effects of testosterone and estradiolcyproteron acetate in patients with gender dysphoriatranssexualism undergoing cross-sex hormone therapy in comparison to a control group without hormone therapy
Effects of cross-sex hormone therapy on
Part A Glucose and lipid metabolism Part B Body composition and energy balance control microbiome Part C Psychobehavioral traits with a focus on eating behavior Part D Cardio- Vascular system
To best possibly attribute observed effects to the applied sex hormones baseline measurements before starting cross-sex hormone treatment will be performed V0 Measurements will be repeated at five time points during ongoing cross sex hormone treatment V1-5
V0 Baseline assessment before start of cross-sex hormone therapy V1 Three months after start of cross-sex hormone therapy V2 Six months after start of cross-sex hormone therapy V3 Twelve months after start of cross-sex hormone therapy V4 Two years after start of cross-sex hormone therapy V5 Five years after start of cross-sex hormone therapy To be able to exclude unspecific order effects of the measurements and to be able to compare obtained results with non-transsexual persons controls not undergoing cross-sex hormone therapy matched for age body mass index health status morbidity and education will be included
3 Research Design and Methods 31 Participants and recruitment This is a five year observational non-invasive study to evaluate the effect of cross-sex hormone therapy on metabolism eating behavior body composition energy expenditure oral and the gut microbiomes and the cardiovascular system Results will be compared longitudinally on an intra-individual level as well as on an inter-individual level by comparing transmen with transwomen and both groups with non-treated controls Transsexual patients will be recruited at the outpatient clinic for Endocrinology at the University Hospital Leipzig Patients seeking cross-sex hormone therapy will be asked before starting cross-sex hormone therapy for their willingness to participate in the study Patients willing to participate will be screened for study eligibility Eligible subjects will be informed about the study procedures and possible risks Upon receiving written informed consent the patient will be included into the study Willingness to participate in the study will not influence the medical treatment
A control group of men and women matched for age body mass index health status morbidity and education who are not undergoing cross-sex hormone therapy will be recruited via online advertisements
32 Study procedures Seven days prior to baseline assessment accelerometers will be handed to participants to measure physical activity Four days prior to baseline participants will be asked to complete a 96h activity log to objectify physical activity Food intake will be self-assessed four days prior to baseline assessment via questionnaire as instructed by a trained dietitian Dietary restraints will be assessed eg lactose intolerance etc to adjust procedures of ad libitum food intake measurement to individual needs A tour of our metabolic unit and the MRI facilities will be given to participants and procedures explained Subjects will be asked to fill out behavioral questionnaires at home within one hour of completing their breakfast to decrease variability of answers Participants will use provided kits to collect stool samples for the gut microbiome analysis
On the day of baseline assessment prior to initiation of cross-sex hormone therapyno therapy current medical history including current medication a physical exam including measurement of weight waist and hip circumferences blood pressure and heart rate will be performed In the fasted state blood will be drawn to measure fasting glucose HbA1c serum insulin triglycerides total- low- and high-density-lipoprotein concentrations Insulin sensitivity and HOMA-IR will be calculated The fasting blood draw will further include measurement of 17β-estradiol progesterone testosterone sex-hormone binding globulin SHBG blood cell count creatinine ALAT ASAT GGT TSH and FGF21 Saliva samples will be collected in a fasted state for analysis of oral microbiome All samples will be stored at -80 C and then sent for commercial sequencing and metabolome analysis In control women and transmen we will record whether menstrual cycle still persists From each blood draw serum will be stored at -80C for future analyses In order of procedures performed during baseline assessment subjects will receive
Assessment of body composition Fat mass and fat-free mass will be assessed using body impedance analysis BIA
Measurement of resting energy expenditure Baseline indirect calorimetry using a ventilated hood method will be performed in the fasted state resting energy expenditure REE prior to hormone substitution therapyno therapy The measurement will take 30 min In brief a clear plastic hood will be placed over the participants head with a soft collar around the neck to prevent any air leaks The hood will be securely ventilated with room air and over 30 min constant fractions of gases flowing out of the hood will be analyzed for carbon dioxide and oxygen concentrations Via measurement of the respiratory quotient calorimetric measurements will be performed during 5 min intervals and over a period of 30 min the subjects mean REE will be estimated Using the ventilated hood method adverse events are scarce and may include claustrophobia Thus subjects suffering from claustrophobia will be exempt from this measurement
Ultrasound of vessels and microperfusion Ultrasound will be conducted to evaluate arterial stiffening abdominal aorta and carotid artery regional aortic strain and aortic impedance characteristics via LVOT doppler and aortic tonometry GE Healthcare Vivid E9 system Peripheral near-infrared spectroscopy combined with a vascular occlusion test will be used to evaluate microperfusion near-infrared spectroscopy Diaspective Vision Tivita tissue
Ad libitum food intake For breakfast subjects will undergo an ad libitum food intake situation in which they will be exposed to a buffet and asked to eat as much as they want The buffet addresses individual dietary retrains eg vegan diet Caloric and macronutrient intake will be measured Prior to and immediately after the buffet participants will rate their mood hunger and desire to eat on a 10 cm visual analogue scale
Snack Food Taste Test For assessment of taste preferences and as an additional measure of ad libitum food intake a snack food taste test will be performed This test will be administered within 30 min after lunch This will be a taste test where participants will be asked to rate four types of food that will be placed in front of them in large bowls potato chips 70 g peanuts 100 g Oreo cookies 100 g and MMs 100 g Participants will be asked to provide mood and appetite ratings They will then be instructed to consume as much or as little as they wish and to judge the taste of the food products using the provided rating scales The experimenter will then leave the room and return 10 min later remove the bowls of food and administer a final rating scale of mood and appetite The bowls of food will be weighed before and after the taste test as a measure of food and calorie intake
Response to thermic stimuli Via an electrode positioned below the base of the index finger C6 of the participants non-dominant hand thermic stimuli cold versus warm will be administered and subjects will be asked to indicate coldwarmth perception Perception of cold will be measured four times in a row followed by warmth perception Then thermal discomfort will be triggered via administration of one cold versus one warm stimulus
Measurement of taste perception and smell Administration of standardized gustatory and olfactory stimuli will enable the assessment of nonspecific taste perception and the subjects ability to perceive certain scents Taste perception will be assessed one at a time by placing paper slip on the participants tongue that had been coated with one specific known flavor Similarly the participants ability to perceive certain scents will be tested In this case specific known scents will be placed in front of the nose of the participant who will be asked to determine the scent and then asked to rate it
Sex hormone deposition in hair Using liquid chromatography-mass spectrometry deposition of sex hormones in hair will be measured time points V2-V4 For this purpose a small amount of hair will be removed from the occipital region of the subjects head and then analyzed
Gut oral microbiome circulating bacterial signature in the blood and metabolomics Participants in the study will collect stool samples at home using a provided kit and bring them to the study visit This kit includes a disposable tray and vials for metagenome sequencing Additionally saliva samples will be collected at the study center after fasting along with blood for microbiome and metabolome analyses Gut microbiome and oral microbiome will be sent for commercial library preparation and sequencing of whole genome metagenomics Bacterial DNA in the blood will be analyzed using 16S rRNA Amplicon sequencing and stool oral and circulating metabolomes will be subjected to commercial metabolomics via gas liquid chromatography-mass spectrometry GLC-MS
Visit to our clinical outpatient unit transgender subjects only Based on our unit-specific standards of care subjects will receive a prescription for hormones intended to induce transformation to the other sex cyproterone acetate testosteroneestradiol and advised to begin administration of their first dose of medication on day 1 of our study Patients will be advised to continue with treatment according to our unit-specific standards of care for subjects with gender dysphoria undergoing hormone substitution therapy
Upon baseline assessment cross-sex hormone treatment versus no treatment will commence Study procedures for V2 through V5 are the same as the above mentioned
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None