Testosterone and Its Metabolites in GID

March 19, 2018 updated by: Unita Complessa di Ostetricia e Ginecologia

Role of Testosterone and Its Metabolites Regarding Different Physiological Functions in Subjects Affected by Gender Identity Disorder (FtM Transsexuals)

The purposes of this study are:

  • to determine the role of testosterone versus dihydrotestosterone with respect to the following physiological functions: bone metabolism, body composition, insulin resistance and lipid profile
  • to determine the role of testosterone and dihydrotestosterone versus estradiol with respect to the following physiological functions: bone metabolism, body composition, insulin resistance and lipid profile

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND GID is a psychic disorder in which an otherwise normal person feels like he/she is a member of the opposite sex to which she/he belongs biologically. These patients require hormonal treatment to suppress the somatic characteristics of their own sex and to develop the somatic characteristics of the other sex. After psychotherapy and a period of hormonal treatment, they undergo surgical sex reassignment which, in the case of FtM subjects, consists of hystero-adnexectomy, reductive mastoplasty and possibly penile reconstruction. Thereafter, and for their entire life, they must be treated with testosterone (T) to maintain androgen-dependent physiological functions.

RATIONALE After sex-reassignment surgery, FtM subjects must be treated with T for their entire life in order to maintain androgen-estrogen dependent physiological functions.

These subjects represent an interesting model for the study of the effects of testosterone and its metabolites on different physiological functions. As of now, there is no information that the androgen receptors differ in males and females. Therefore, induction of the androgen effects in the FtM subjects can be considered similar to those in hypogonadal men and FtM subjects can serve as a model of the hypogonadal male.

Therefore, the aim of this trial is to evaluate the effects of selective steroid replacement on different physiological functions. In particular in this study we will evaluate the relative role of testosterone, DHT and estradiol on the different physiological functions. For these purposes, we will administer testosterone undecanoate alone (Group A) or in combination with letrozole, an aromatase inhibitor (Group B). A third group of FtM subjects will be treated with TU plus dutasteride (Group C).

In view of the development of selective androgen receptor modulators, the understanding of the relative role of each steroid on different physiological functions will provide useful information for future therapeutic indications. The information collected in this study will greatly help to optimize the long-term treatment of FtM subjects.

In particular, in this study, we will test the following questions:

  • what is the role of testosterone vs. DHT on the physiological functions evaluated in this study i.e. bone metabolism, body composition, insulin resistance and lipid profile (Group B vs. Group C)
  • what is the role of testosterone and DHT vs estradiol on the physiological functions evaluated in this study i.e. bone metabolism, body composition, insulin resistance and lipid profile (Group C vs. Group A)

DESIGN

For this purpose, in this study we will treat FtM castrated, subjects for 54 weeks with:

  • testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54)(n=5) (Group A)
  • testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54) mg/day plus letrozole 2.5 mg/day (n=5) (Group B)
  • testosterone undecanoate 1000 mg 6-12 weeks (injection at week 0, 6, 18, 30, 42 and 54) plus dutasteride 0.5 mg/day (n=5) (Group C)

Overall study design and plan-description Prospective, phase III, randomized study design will be used. The study consists of a control phase lasting 3 weeks and a 54-week treatment period.

Control phase: (will last 3 weeks: In this period, subjects will provide three fasting (at least 10 hours) blood samples and one urine sample. Subjects will undergo 2 visits to ensure fulfillment of inclusion criteria and, absence of exclusion criteria, to determine state of health and to be informed about the purposes of the study. During the two visits, they will undergo:

  • blood drawings for measurements of: LH, FSH, estradiol, testosterone DHEAS, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein, bone alkaline phosphate, PTH, osteocalcin, crosslaps, 25(OH) vit D, H RANKL, osteoprotegerin.
  • anthropometry: weight, measures
  • DEXA for bone mass determination and body composition
  • physical examination
  • a sexual and behavioral questionnaire
  • a pain questionnaire

Treatment phase All injections will be administered by the investigator or co-investigators for the entire study. Fasting (10 hours) blood samples will be taken (immediately before giving the injections) every time subjects come for injections (week 0, 6, 18, 30 and 42) and at the end of the treatment phase. On these occasions, a physical examination including weight, blood pressure and pulse rate checks will be performed. Volunteers will be asked to complete a sexual and behavioral questionnaire and a pain questionnaire during these visits.

At week 6, 18, 30 and 42 the following tests will be performed:

  • blood drawings for measurements of: LH, FSH, estradiol, testosterone, DHT, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein.
  • anthropometry: weight, measures
  • physical examination
  • sexual and behavioral questionnaire
  • pain questionnaire

At week 54 the following tests will be performed:

  • blood drawings for measurements of: LH, FSH, estradiol, testosterone, DHT, DHEAS, total cholesterol, HDL cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, uric acid, urea, creatinine, Na, K, Ca, P, Mg, Cl, total protein, bone alkaline phosphate, PTH, osteocalcin, crosslaps, 25(OH) vit D, H RANKL, osteoprotegerin.
  • anthropometry: weight, measures
  • DEXA for bone mass determination and body composition
  • physical examination
  • sexual and behavioral questionnaire
  • pain questionnaire

Measurements:

Blood samples(10 hours from last food intake). Blood collections will be carried out by venipuncture. After resting at room temperature for 30 min, the sample will be centrifuged at 3000 rpm for 10 min. Serum samples (about 10 ml) from each blood sample will be stored at -20°C for analysis.

Physical examinations:

They will include inspection of external genitalia (clitorides) and a visit to detect appearance of acne and gynecomastia.

Sexual function and behavior questionnaire:

In the sexual and behavior questionnaire the subjects will judge their sexual activity and behavior in the period between visits. The subjects have the possibility to making additional comments about important events and disturbances.

SELECTION OF STUDY POPULATION:

Healthy female FtM subjects, who have undergone SR surgery (hystero-adnexectomy) will be recruited to participate in this study. Healthy female subjects between 18 to 45 years of age will be enrolled in the study according to Inclusion/Exclusion Criteria listed below. They will be informed about the nature, aim and objectives of the study and will be required to give their written consent to participate in the study. The presence of the inclusion criteria and the absence of the exclusion criteria will be documented in the Case Report Forms (CRF).

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Clinic of Obstetrics and Gynecology - S. Orsola Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Healthy biological females, between 18 and 45 years of age:

  • SR surgery performed
  • Body Mass Index (BMI) between 20 and 29 kg/m²; (body weight in kilograms divided by body height in meters squared)
  • Clinical examination without pathological findings relevant to the study
  • Clinico-chemical laboratory values do not suggest an illness
  • Written Consent Form has been signed
  • High probability of a good compliance and termination of the study

Exclusion Criteria:

Subjects cannot be enrolled in this study if one or more of the following criteria apply:

  • Participation in another clinical trial within the 30 days preceding the first administration
  • Simultaneous participation in another clinical trial
  • Subjects institutionalized or imprisoned by order of the court
  • Subject who compete in sports which use IOC drug monitoring
  • Serious organic or psychic disease suspected from history and/or clinical examination
  • Diseases (especially tumors) that might represent an actual contraindication for testosterone
  • Past or present history of thrombotic or embolic diseases
  • Hypertension requiring therapy (BP 140/90 mmHg)
  • Diabetes mellitus requiring therapy
  • Acute or chronic hepatic diseases
  • Manifest renal diseases with renal dysfunction
  • Severe internal diseases as well as use of any medication to treat such
  • Biochemical and/or hematological laboratory values beyond normal ranges unless the Investigator confirms that the deviations are of no clinical relevance
  • Any indication of chronic use of drugs, alcohol, opiates or recreational drugs
  • Use of any drug known to affect biotransformation of testosterone and/or progestin, e.g. chlorcycline, phenobarbital, phenylbutazone, aminophenazone within the 30 days preceding the first administration of the test medication and during the study
  • Use of oral anticoagulatory drugs within the 30 days preceding the first administration of the test medication and during the study
  • Any oral or transdermal hormone medication within the 12 weeks preceding the first administration and during the study
  • Probability of poor compliance and termination of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
bone metabolism
Time Frame: baseline and end of the study
baseline and end of the study
insulin resistance
Time Frame: baseline and end of the study
baseline and end of the study
lipid profile
Time Frame: baseline and end of the study
baseline and end of the study

Secondary Outcome Measures

Outcome Measure
Time Frame
sexual function
Time Frame: baseline and end of the study
baseline and end of the study
mood
Time Frame: baseline and end of the study
baseline and end of the study
pain
Time Frame: baseline and end of the study
baseline and end of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Unita Complessa di Ostetricia e Ginecologia

Collaborators

Schering-Plough

Investigators

  • Principal Investigator: Cristina M Meriggiola, MD, University of Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

May 1, 2006

Study Completion (Actual)

January 1, 2008

Study Registration Dates

First Submitted

September 1, 2005

First Submitted That Met QC Criteria

September 1, 2005

First Posted (Estimate)

September 5, 2005

Study Record Updates

Last Update Posted (Actual)

March 21, 2018

Last Update Submitted That Met QC Criteria

March 19, 2018

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GID/2004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Transsexualism

Clinical Trials on testosterone undecanoate alone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in India

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe