Phase 1
N=30
Role of Endogenous Estrogen in Growth-Hormone Regulation in Postmenopausal Women
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT01186796 ↗Enrolled (actual)
30
Serious AEs
3.5%
Results posted
Mar 2015
Primary outcome: Primary: Mean Baseline GH Concentration — 0.23; 0.096 ug/L — p=<0.05
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Fulvestrant (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- Female
- Sponsor
- Mayo Clinic
- Primary completion
- Jun 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Baseline GH Concentration |
0.23; 0.096 | <0.05 sig |
| SECONDARY Mean GH Concentration (Pulsatile) in Response to Secretagogue |
22.6; 17.3; 46.6; 17.4; 66.9; 66.8 | <0.05 sig |
| SECONDARY Mean Mass of GH Released Per Burst in Response to Secretagogue |
12.6; 7.5; 48.4; 44.4; 64.7; 45.5 | <0.05 sig |
| SECONDARY Mean Duration of GH Bursts (Mode) in Response to Secretagogue |
18.0; 16.3; 17.6; 15.4; 12.8; 12.7 | <0.05 sig |
| SECONDARY Mean GH Half-Life in Response to Secretagogue |
15.4; 15.0; 17.2; 17.5; 19.4; 19.0 | <0.05 sig |
Summary
Participants are being asked to take part in this research study to learn why growth hormone(GH) levels decline when estrogen production falls at the time of menopause. GH is a hormone released from the pituitary gland that affects bone, muscle, and fat. Estrogen is a female hormone. Doctors believe that lower estrogen is one of the reasons that GH diminishes in postmenopausal women. However, estrogen does not fall completely. This raises the question whether the little bit of estrogen that is left is doing anything. Lack of GH makes bones thinner, muscles weaker, and fat stores larger. To learn whether the low amount of the body's own estrogen maintains GH secretion after menopause, the investigators need to stop any estrogen you might be taking and then partially block the effect, if any, of your own estrogen. The investigators will use a new estrogen-blocking drug (fulvestrant). Fulvestrant(which also goes by the tradename, Faslodex) was recently approved by the Food and Drug Administration (FDA) to treat breast cancer. Fulvestrant is being used in a non-FDA approved manner in this study (not to treat breast cancer, but to study the effect on Growth Hormone secretion). The drug interferes with how estrogen works in the body, except in the brain. The study that you are considering now tests whether your own estrogen works outside the brain to maintain GH secretion in postmenopausal women. This concept is important, because the brain controls how the pituitary gland secretes GH.
Eligibility Criteria
Inclusion Criteria
- healthy postmenopausal women (ages 50 to 80 y), wherein menopause is defined by the absence of spontaneous menses for 1 y and a serum concentration of FSH > 30 IU/L and of (ultrasensitive) estradiol 11.0 g/dL in women (a ferritin level will be drawn, and must be normal, if Hgb is 11.0 - 11.5) , Platelets greater than 200 x 109/L, AST 8-48 U/L.
- Subjects (age 50 and above) will have a screening baseline ECG if not on record from the past year.
Exclusion Criteria
- exposure to psychotropic or neuroactive drug within five biological half- lives;
- undesirability, disinclination or ill advisability of withholding estrogen supplements (e.g. under treatment for symptomatic hot flushes; primary physician recommendation);
- BMI 35
- drug or alcohol abuse; psychosis, depression, mania or anorexia nervosa;
- acute or chronic organ or systemic inflammatory disease;
- endocrinopathy, other than primary thyroidal failure receiving replacement;
- although fulvestrant has no known intrinsic estrogenicity, for safety reasons we include contraindication to short-term estrogen exposure; e.g.,estrogen-sensitive neoplasia, undiagnosed vaginal bleeding, deep-venous thrombosis, stroke or threatened stroke, clinical evidence of atherosclerotic heart disease, including myocardial infarction and/or angina, refractory high blood pressure, severe type IV hyperlipidemia:
- nightshift work or recent transmeridian travel (exceeding 3 time zones within 5 days of admission);
- systemic anticoagulation other than anti platelet therapy (in view of i.m. injections of fulvestrant); history of bleeding diathesis (ie; disseminated coagulation (DIC), clotting factor deficiency
- acute weight change (> 3 kg in 6 weeks); and/or
- unwillingness to provide written informed consent.
- Platelets less than 200 x 109 /L
- International normalization ratio(INR) (Prothrombin time) greater than 1.6
- Total bilirubin greater than 1.5 x ULRR
- ALT or AST greater than 2.5 xULRR if no demonstrable liver metastases or greater
- History or hypersensitivity to active or inactive excipients of fulvestrant (ie; castor oil or Mannitol).
Data sourced from ClinicalTrials.gov (NCT01186796). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.