Postmenopause Clinical Trial
Official title:
Acute Effects of Estradiol on Lipolysis in Subcutaneous Adipose Tissue and Muscle Assessed by Microdialysis and Tissue Biopsies
Estradiol promotes and maintains the typical female phenotype characterized by subcutaneous fat accumulation. There is evidence to suggest that this effect relies on the ability of estradiol to increase the amount of anti-lipolytic α2A-adrenergic receptors, but whether this requires long-term exposure to estradiol or is the result of an immediate effect is not clear. Objective: To study acute effects of a single dose (4 mg) of 17β-estradiol on regional and systemic lipolysis.
Estradiol affects muscle and fat distribution, and thereby lipid metabolism. A reduction in
muscle power is seen after menopause, readily counteracted by female hormone therapy (HT).
Treatment with HT through months to previously untreated postmenopausal women, or hormone
replacement therapy (HRT) to women with Turner syndrome, increases muscle mass and reduces
fat mass. HT in postmenopausal women furthermore prevents fat accumulation and increases
lipoprotein lipase activity and lipolysis to an extent comparable to premenopausal women. In
contrast, it has also been shown that estradiol may actually attenuate lipolysis during
basal as well as catecholamine stimulated conditions. In addition, one study found whole
body fat metabolism to be lower during treatment with estradiol than without, and reduced
lipolysis is present in postmenopausal women during treatment with estradiol, along with an
increased number of α-adrenergic receptors and a decreased number of β-adrenergic receptors.
It is not clear whether the lipolytic effect of estradiol happens acutely or is dependent on
chronic exposure. Moreover, regional differences in the pharmacodynamics of estradiol have
not been assessed. Finally, effects on skeletal muscle have never been examined.
The purpose of the present study was 1) by microdialysis to quantify the regional production
of glycerol in two tissues (muscle and fat), and in two regions (abdominal and femoral). 2)
To quantify the whole-body lipolytic effect of estradiol, and 3) in biopsies to study
intracellular mechanisms behind the action of estradiol.
;
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind, Primary Purpose: Treatment
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