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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science
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.
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.
Johannes Veldhuis, M.D.
United States: Food and Drug Administration
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