Impact of Estradiol Addback

June 5, 2019 updated by: Johannes D. Veldhuis, Mayo Clinic

Impact of Estradiol Addback on Somatostatin Rebound in Older Men

Repletion of testosterone (T) in older men drives Growth Hormone secretion after its aromatization to estradiol (E2) by potentiating endogenous GH drive.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Systemic concentrations of Te, E2, GH, Insulin-like Growth Factor-I and IGFBP-3 decline in healthy aging men. Relative sex-steroid deprivation accentuates GH and IGF-I depletion, since Te stimulates GH and IGF-I production in older men, hypogonadal males of all ages, and patients undergoing (genotypic female-to-male) gender reassignment. Tamoxifen blocks this effect of Te, suggesting involvement of E2 in GH's stimulation in men. E2 per se stimulates GH secretion in women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in men also. Moreover, we hypothesize that the decline of E2 in older men contributes to the fall in GH output. This has never been tested. From a clinical vantage, understanding the mechanistic basis of Te's drive of the somatotropic axis is especially relevant in boys with pubertal failure, adults with primary hypogonadism and men with aging-related hypoandrogenemia. In relation to aging in the male, testosterone and E2 bioavailabilities fall by 35-50% in the eighth compared with third decade of life. From a medical perspective, aging is accompanied by progressive osteopenia, sarcopenia and intra-abdominal obesity. These adverse outcomes are remediable by short-term replacement with Te and/or recombinant GH, thus linking GH/Te/E2 availability with key body-compositional features.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion:

  • 60 healthy men (ages 60 to 80 y);
  • BMI 18-30 kg/m2
  • Community dwelling; and voluntarily consenting

Exclusion:

  • Recent use of psychotropic or neuroactive drugs (within five biological half-live);
  • Obesity (outside weight range above);
  • Laboratory test results not deemed physician acceptable, cholesterol >250, triglycerides > 300, BUN >30 or creatinine > 1.5 mg/dL, liver functions tests twice upper limit of normal, electrolyte abnormality, anemia; hemoglobin <12.0 gm/dL
  • Drug or alcohol abuse, psychosis, depression, mania or severe anxiety;
  • Acute or chronic organ-system disease;
  • Endocrinopathy, other than primary thyroidal failure receiving replacement; untreated osteoporosis
  • Nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of admission);
  • Acute weight change (loss or gain of > 2 kg in 6 weeks);
  • Allergy to peanut oil (used in some injectable Te preparations)
  • Unwillingness to provide written informed consent.
  • PSA > 4.0 ng/mL
  • History or suspicion of prostatic disease (elevated PSA, indeterminate nodule or mass, obstructive uropathy.
  • History of carcinoma (excluding localized basal cell carcinoma removed or surgically treated with no recurrence.
  • History of thrombotic arterial disease (stroke, TIA, MI, angina) or deep vein thrombophlebitis.
  • History of CHF, cardiac arrhythmias, congential QT prolongation, and medications used to treat cardiac arrhythmias
  • Gynecomastia > 2 cm, untreated
  • Untreated gallbladder disease
  • History of smoking greater than one ppd.

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: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Degarelix/Te/placebo/ placebo
Degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
Drug: Degarelix
Drug: Testosterone
EXPERIMENTAL: degarelix/Te/anastrozole/ placebo
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
Drug: Degarelix
Drug: Anastrozole
Drug: Testosterone
EXPERIMENTAL: degarelix/Te/ anastrozole/E2 patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
Drug: Degarelix
Drug: Anastrozole
Drug: Testosterone
Drug: Estrogen patch
EXPERIMENTAL: degarelix/ placebo/placebo/no patch
degarelix 80 mg (given as two s.c. injections of 60 mg) once [called day 1]; placebo i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
Drug: Degarelix

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
BioStatistical Analysis
Time Frame: Subjects will undergo 15-h overnight (2200 - 1300 h) fasting, 10-min blood sampling
The primary analytical outcome is the summed mass of GH secreted in pulses over the 15 h of overnight blood sampling. The outcome measure is relevant, since sex-steroid hormones and regulatory peptides uniquely control GH secretory-burst mass.
Subjects will undergo 15-h overnight (2200 - 1300 h) fasting, 10-min blood sampling

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

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.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 27, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 7, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13-000047

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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