Impact of Estradiol Addback

Normal Healthy Volunteers Clinical Trial

Official title:

Impact of Estradiol Addback on Somatostatin Rebound in Older Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01862835
• Other study ID #: 13-000047
• Status: Completed
• Phase: Phase 1
• Start date: May 2013
• Est. completion date: December 30, 2018

Study information

• Verified date: June 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: December 30, 2018
• Est. primary completion date: September 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 60 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Normal Healthy Volunteers

Intervention

Drug:
• Degarelix

• Testosterone

• Anastrozole

• Estrogen patch

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BioStatistical Analysis	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

External Links

•   Mayo Clinic Clinical Trials