As females age and transition through menopause, the decline in oestrogen level profoundly affects skeletal muscle mass and function. HER-MUSCLE aims to unravel the mechanisms by which oestrogen enhances muscle growth, providing insights for targeted therapies to improve the health and physical function of postmenopausal females. Focusing on postmenopausal females, an increasingly at-risk demographic, HER-MUSCLE addresses a critical gap in understanding how oestrogen influences muscle mass and function during anabolic (exercise) conditions. The project involves: 1. Clinical Trial: Postmenopausal females will receive either oestrogen or placebo, twelve weeks of exercise training to detect oestrogen regulatory role on muscle mass and function. 2. Molecular Analysis: Advanced techniques will study the muscle microenvironment, focusing on muscle stem cells (MuSCs), fibro-adipogenic progenitors (FAPs), and other cells critical for muscle regeneration and maintenance. 3. Mitochondrial Function assessed in vivo via magnetic resonance spectroscopy: The impact of oestrogen on mitochondrial health will be examined, exploring how it preserves mitochondrial function and ability to recovery and resist fatigue in response to muscle contractions. Our preliminary data indicate that oestrogen can promote muscle protein synthesis. HER-MUSCLE aims to pave the way for novel therapeutic strategies to manage sarcopenia in postmenopausal women, ultimately leading to better health outcomes and enhanced well-being for this growing population segment.
As females age and transition through menopause, the decline in oestrogen level profoundly affects skeletal muscle mass and function. HER-MUSCLE aims to unravel the mechanisms by which oestrogen enhances muscle growth, providing insights for targeted therapies to improve the health and physical function of postmenopausal females. Focusing on postmenopausal females, an increasingly at-risk demographic, HER-MUSCLE addresses a critical gap in understanding how oestrogen influences muscle mass and function during anabolic (exercise) conditions. The project involves: 1. Clinical Trial: Postmenopausal females will receive either oestrogen or placebo, twelve weeks of exercise training to detect oestrogen regulatory role on muscle mass and function. 2. Molecular Analysis: Advanced techniques will study the muscle microenvironment, focusing on muscle stem cells (MuSCs), fibro-adipogenic progenitors (FAPs), and other cells critical for muscle regeneration and maintenance. 3. Mitochondrial Function assessed in vivo via magnetic resonance spectroscopy: The impact of oestrogen on mitochondrial health will be examined, exploring how it preserves mitochondrial function and ability to recovery and resist fatigue in response to muscle contractions. Our preliminary data indicate that oestrogen can promote muscle protein synthesis. HER-MUSCLE aims to pave the way for novel therapeutic strategies to manage sarcopenia in postmenopausal women, ultimately leading to better health outcomes and enhanced well-being for this growing population segment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
30
The other group receive placebo treatment
Both groups will go through 12 weeks of supervised physical exercise, consisting of both strength training and cardiovascular training
Aarhus University
Aarhus, Jutland, Denmark
RECRUITINGMuscle mass
Magnetic resonance imaging of one leg before and after intervention
Time frame: 12 weeks
Mitochondria Function in vivo measured as phosphocreatine recovery rate
The dominant foot will be attached to a pedal mounted on the patient bed and a dedicated 31P surface coil will be secured over the tibialis anterior muscle. The pedal is designed to allow dynamic contractions of the tibialis anterior muscle while changes in metabolites from the tibialis anterior muscle are acquired non-invasively with the 31P coil. Two protocols will be performed: Firstly, 10 repeated contractions (one per 3 sec with a load representing 30% of maximal force) will result in a depletion (30-40%) of phosphocreatine (PCr). The rate constant for PCr recovery over 10 min will be used as an index of in vivo mitochondrial function. Secondly, a total of 80 repeated contractions (one per 3 sec with a load representing 30% of maximal force) will be used to quantify muscle fatigue and concurrent changes in muscle metabolites and intracellular pH (based on the chemical shift between inorganic phosphate and PCr).
Time frame: 12 weeks
Mitochondria Function in vitro measured as maximal oxygen consumption
All measurements were performed in duplicate using an Oxygraph-2k (Oroboros, Austria), in hyperoxygenated chambers (250-450 nmol O₂/mL). Respiratory Control Ratio was used to evaluate mitochondrial efficiency. It was calculated as the ratio of maximal ADP-supported respiration (with complex I + II substrates) to leak respiration. Leak respiration reflects oxygen consumption in the absence of ATP synthesis, when only substrates are present and no ADP is added.
Time frame: 12 weeks
Body composition
DXA
Time frame: 12 weeks
Satelitte cells
Histochemical Analysis of Muscle tisse
Time frame: 12 weeks
Muscle fiber cross-sectional Area
Histochemical Analysis of Muscle Tissue
Time frame: 12 weeks
Expression of Muscle proteins
Western blotting analysis
Time frame: 12 weeks
FACS Analysis
FACS analysis to quantify and isolate Muscle satelitte celss, fibro-adipogenic progenitors and macrofages
Time frame: 12 weeks
Muscle Strength
Includes measure of leg strength during isometric and dynamic maximal voluntary contractions in a dynamometer (Humac Norm, CSMi, Massachusetts, United States) with a hip angle of 90°. In addition, finger strength, hand grip strength
Time frame: 12 weeks
Functional test
Includes counter-movement jump on a speed force-platform (Swift performance, Australia). To measure dexterity, the nine-hole peg test will be applied.
Time frame: 12 weeks
Cardiovascular fitness
Vo2max test on a bike and estimated via Ventriject
Time frame: 12 weeks
Maximal fat oxidation rate
Bike test with increasing intensity steps
Time frame: 12 weeks
Resisting metabolic rate
Time frame: 12 weeks
Questionaires
The participant will be asked to fill out recognized questionnaires about menopause (Menopause Rating Scale), sleep, diet and training readiness (modified version of "The wellbeing review"
Time frame: 12 weeks
Physical Activity Level
Accelerometers
Time frame: 12 weeks
Flexibility
sit-and-reach test
Time frame: 12 weeks
Knee laxity
Lachmeter test
Time frame: 12 weeks
Protein expression in adipose tissue
Two adipose tissue biopsies will be obtained from each participant by a trained physician before and after 12 weeks from subcutaneous abdominal and gluteal regions. Western blotting analysis of expression of proteins related to lipolysis and lipogenesis
Time frame: 12 weeks
Blood pressure
Time frame: 12 weeks
Blood volume
Determination of blood volume and haemoglobin mass by the carbon-monoxide rebreathing method
Time frame: 12 weeks
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