Clinical trial NCT01862835: Impact of Estradiol Addback
Official title: Impact of Estradiol Addback on Somatostatin Rebound in Older Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Normal Healthy Volunteers
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2013-05-27
Enrollment: 43
Sex: MALE
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: BioStatistical Analysis
timeFrame: Subjects will undergo 15-h overnight (2200 - 1300 h) fasting, 10-min blood sampling
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Johannes Veldhuis, MD
role: PRINCIPAL_INVESTIGATOR
References: