Exercise Training, Menopause Related Conditions
Conditions
Keywords
Physical exercise, Strength training, Cardiovascular training, Muscle hypertrophy, Estrogen, Mitochondria function, Muscle strength, Menopause, Muscle mass
Brief summary
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.
Detailed description
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.
Interventions
DRUGEstrogel
The other group receive placebo treatment
BEHAVIORALPhysical exercise
Both groups will go through 12 weeks of supervised physical exercise, consisting of both strength training and cardiovascular training
Sponsors
Mette Hansen
Aalborg University
University of Copenhagen
Aarhus University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This is a model study where we manipulate with the estrogen level to study the consequences of low versus high estrogen status on physiological parameters during 12 weeks of physical exercise
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 1-10 years since last menstrual bleeding * Age \> 40 years old * BMI 20-30
Exclusion criteria
* Follicular stimulating hormone \< 30 mmol/L * Systematic strength training during the last year (\> 1 strength training session per week) * Injuries to the legs which may prevent participation in the physical training program * Magnetizable metals or electrical devices implanted in the body, such as a pacemaker * Use of medication that can influence the effect of immobilization and/or training * Muscular or joint disorders which may affect the results * Metabolic diseases (such as diabetes and cardiovascular diseases) * Previous or present liver or cancer disease * Current or previous thrombosis * Porphyria * Epilepsia * Systemic autoimmune disease * Edema * Smoking or use of other nicotine containing products * Claustrophobia * Addictive behavior, defined as abuse of cannabis, opioids, or other intoxicating substances. * Lack of ability to cooperate * Blood parameters out of normal range at the health check * Blood pressure above 140/90 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle mass | 12 weeks | Magnetic resonance imaging of one leg before and after intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mitochondria Function in vivo measured as phosphocreatine recovery rate | 12 weeks | 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). |
| Mitochondria Function in vitro measured as maximal oxygen consumption | 12 weeks | 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. |
| Body composition | 12 weeks | DXA |
| Satelitte cells | 12 weeks | Histochemical Analysis of Muscle tisse |
| Muscle fiber cross-sectional Area | 12 weeks | Histochemical Analysis of Muscle Tissue |
| Expression of Muscle proteins | 12 weeks | Western blotting analysis |
| FACS Analysis | 12 weeks | FACS analysis to quantify and isolate Muscle satelitte celss, fibro-adipogenic progenitors and macrofages |
| Muscle Strength | 12 weeks | 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 |
| Functional test | 12 weeks | Includes counter-movement jump on a speed force-platform (Swift performance, Australia). To measure dexterity, the nine-hole peg test will be applied. |
| Cardiovascular fitness | 12 weeks | Vo2max test on a bike and estimated via Ventriject |
| Maximal fat oxidation rate | 12 weeks | Bike test with increasing intensity steps |
| Resisting metabolic rate | 12 weeks | — |
| Questionaires | 12 weeks | 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" |
| Physical Activity Level | 12 weeks | Accelerometers |
| Flexibility | 12 weeks | sit-and-reach test |
| Knee laxity | 12 weeks | Lachmeter test |
| Protein expression in adipose tissue | 12 weeks | 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 |
| Blood pressure | 12 weeks | — |
| Blood volume | 12 weeks | Determination of blood volume and haemoglobin mass by the carbon-monoxide rebreathing method |
Countries
Denmark
Contacts
CONTACTMette Hansen, PhD
PRINCIPAL_INVESTIGATORMette Hansen, PhD
Aarhus University, Department of Public Health
Outcome results
None listed