Clinical trial NCT00435175: Acute Metabolic Effects of Estradiol
Official title: Acute Effects of Estradiol on Lipolysis in Subcutaneous Adipose Tissue and Muscle Assessed by Microdialysis and Tissue Biopsies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopause
Keywords: Estradiol
Lipolysis
Estrogen receptor
Adrenergic receptors
UCP2
Postmenopausal women
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2007-02-14
Enrollment: 8
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women assessed by FSH and estradiol levels
* Not taking any drugs
* Non-smokers

Exclusion Criteria:

* Obesity (BMI\>30)

Primary outcomes:
measure: Regional lipolysis assessed by microdialysis
measure: Systemic lipolysis assessed by the isotope dilution technique
measure: Lipoprotein lipase activity
measure: Adrenergic receptor mRNA expression
Secondary outcomes:
measure: Estrogen receptor mRNA expression
measure: UCP2 mRNA expression
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Medical Research Laboratories
Study officials:
affiliation: Aarhus University, Clinical Institute
name: Lars C Gormsen, MD
role: PRINCIPAL_INVESTIGATOR
References: