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Role of Endogenous Estrogen in Growth-Hormone Regulation in Postmenopausal Women

50 Years
80 Years
Not Enrolling

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Trial Information

Role of Endogenous Estrogen in Growth-Hormone Regulation in Postmenopausal Women

Hypotheses: Endogenous estrogen concentrations contribute significantly to maintaining
postmenopausal growth-hormone (GH) secretion and; (b) systemic vis-à-vis CNS actions of
endogenous estrogen differentially control the outflow of somatotropic hormones (viz., GH,

Approach: contrast regulation of the GH axis in postmenopausal women pretreated with the
CNS-excluded selective estrogen-receptor antagonist, fulvestrant, versus placebo.

Background: fulvestrant was released recently by the FDA for therapy of estrogen-sensitive
postmenopausal breast cancer. The drug acts as a mechanistically novel inhibitor of
estradiol-receptor dimerization, thereby depleting nuclear estrogen receptors. Fulvestrant
does not gain access to the CNS. Thus, inhibition of estrogen action will be restricted to
non hypothalamic sites of GH-axis control, such as the pituitary gland, liver and fat cells.
In contrast, endogenous estrogens have access to both CNS and peripheral sites.

Premise: selective blockade of peripheral estradiol receptors will reduce GH secretion if
endogenous estrogens maintain GH secretion via systemic effects.

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 < 20 pg/mL and verified by medical history and
screening blood work;

- normal hemoglobin of >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

- BMI < 19 or > 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

- 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).

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Outcome Measure:

BioStatistical Analysis

Outcome Description:

GH concentrations decrease with age gradually in premenopausal women and rapidly in ovariprival individuals. A prime focus of our clinical studies is how estradiol availability governs GH secretion via combined central and peripheral regulation of neuropeptide signaling. The present investigation extends this theme by assessing whether endogenous estrogen maintains GH output and, if so, whether estrogen acts via CNS or systemic mechanisms in postmenopausal individuals.

Outcome Time Frame:

Withdrawal of blood samples (2.5 mL each) every 10 min for 6 hr. Sampling will begin at 0800 h and conclude at 1400 h.

Safety Issue:


Principal Investigator

Johannes Veldhuis, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

June 2009

Completion Date:

June 2013

Related Keywords:

  • Healthy
  • Women
  • Fulvestrant Study
  • Post Menopausal Women
  • Hormones
  • Healthy Adult Women



Mayo Clinic Rochester, Minnesota  55905