Clinical trial NCT02026973: Impact of Endogenous E2 on SSI and GH Rebound
Official title: Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Normal Healthy Volunteers
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2014-01-03
Enrollment: 62
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Endogenous estrogens maintain growth hormone (GH) secretion in postmenopausal women by potentiating endogenous GH-releasing hormone (GHRH) drive and restraining somatostatin inhibition of GH release.

Detailed description: Systemic concentrations of testosterone (Te), estradiol (E2), GH, IGF-I and IGFBP-3 decline in healthy aging individuals (1-3). Sex-steroid deprivation accentuates GH and IGF-I depletion, since Te and E2 stimulate GH and IGF-I production in older adults, hypogonadal patients of all ages, and patients undergoing gender reassignment (1,2,4). Tamoxifen blocks the effect of Te, suggesting involvement of E2 in GH's stimulation in men (5). E2 also stimulates GH secretion in women, putatively via the nuclear estrogen receptor (ER-alpha) (1,2,6,7). Because Te, E2 and GH fall with menopause, and Te is converted to E2 by aromatization in the body (8-10), we postulate that diminished Te concentrations, Te→E2 concentrations and low E2 mediate low GH output in older women. What remains unknown is whether the low E2 levels in postmenopausal women retain GH-stimulating effects. To test this notion would require blocking: (i) aromatase-enzyme activity, which mediates E2 synthesis from Te, and/or (ii) estrogen receptor-alpha, which transduces most of E2's stimulation of the GH axis.

Eligibility criteria: Inclusion:

1. 60 healthy post-menopausal women (ages 55 to 80 y);
2. BMI 18-30 kg/m2
3. Community dwelling; and voluntarily consenting

Exclusion:

1. Recent use of psychotropic or neuroactive drugs (within five biological half-lives);
2. Obesity (outside weight range above);
3. Laboratory test results not deemed physician acceptable, cholesterol \>250, triglycerides \> 300, BUN \>30 or creatinine \> 1.5 mg/dL, liver function tests exceeding twice upper limit of normal, electrolyte abnormality, anemia;
4. Drug or alcohol abuse, psychosis, depression, mania or severe anxiety;
5. Systemic inflammatory disease;
6. Endocrinopathy, other than primary thyroidal failure receiving replacement;
7. Nightshift work or recent transmeridian travel (exceeding 3 time zones within 7 days of CRU admission);
8. Acute weight change (loss or gain of \> 2 kg in 6 weeks);
9. Systemic illness
10. Unwillingness to provide written informed consent.
11. Allergy to anastrozole or fulvestrant (treatment drugs).
12. History or suspicion of breast cancer.
13. History of carcinoma (excluding localized basal cell carcinoma removed or surgically treated with no recurrence).
14. History of thrombotic arterial disease (stroke, TIA, MI, angina) or deep-vein thrombophlebitis.
15. History of CHF, cardiac arrhythmias, congenital QT prolongation, and medications used to treat cardiac arrhythmias.
16. Pre-menopausal status as determined by screening hormone measurements.

Primary outcomes:
measure: The summed mass of GH over 10 hours.
timeFrame: 14-18 days: From date of randomization to overnight visit
Secondary outcomes:
measure: The summed mass of GH over a 2h Somatostatin infusion and 3h rebound window
timeFrame: 14-18 days: From date of randomization to overnight visit
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: