Strength and Aerobic Training Against Hot Flushes in Postmenopausal Women

Not Applicable

Recruiting

• Conditions: Postmenopausal Symptoms; Hot Flashes

• Registration Number: NCT06030388
• Lead Sponsor: Linkoeping University

Brief Summary

The goal of this randomised controlled trial is to investigate the effects of and compare two modes of physical exercise (strength training and high-intensity aerobic exercise) to unchanged physical activity on vasomotor symptoms (hot flushes) in postmenopausal women. The main question it aims to answer is the effect of 15 weeks of strength training vs high intensity aerobic training vs unchanged physical activity on frequency and severity of hot flushes. Participants will be randomised to:

1. strength training

2. high-intensity aerobic training

3. untreated control group.

Researchers will compare strength training, high-intensity aerobic training and untreated control group to see if training can reduce hot flushes.

Detailed Description

The overall aim is to investigate the efficacy of and compare two modes of physical exercise (strength training and high-intensity aerobic exercise) to unchanged physical activity on vasomotor symptoms (VMS), as well as secondary outcomes such as health-related quality of life, sleep quality, physical activity levels, clinical outcomes, biomarkers, bone markers (outcome added January 2025), bone mineral density (outcome added January 2025), perceptions of and adherence to the interventions. In a longer perspective, the goal is to find evidence-based treatment options for VMS in postmenopausal women that are safe and effective, and have positive effects on health and quality of life after menopause.

Our hypothesis is that strength training and high-intensity aerobic exercise will reduce VMS in postmenopausal women and improve quality of life as well as clinical outcomes more than in a control group with unchanged physical activity. We also hypothesize that strength training and high-intensity aerobic training will have the same effect on the primary outcome (change in VMS) and that most of the changes in secondary outcomes will be superior in the high-intensity aerobic training group compared to the strength training group.

This is an open, two-centre, parallel, randomized controlled study performed according to the SPIRIT and CONSORT statements

Recruitment will take place by advertising on social media, in local newspapers and in the Women's clinics and primary care centers in Linköping and Kalmar. Women who respond to the advertisements will be contacted by a member of the research group or research nurse to receive information about the study and screen for inclusion and exclusion criteria. Women who are possibly eligible will be invited to a screening visit for further information and informed consent. At the visit, inclusion and exclusion criteria will be checked by a physician, and a clinical examination will be performed. Eligible participants will receive a VMS screening diary and invited to a second visit 2-3 weeks later where inclusion and randomization will be performed if the VMS inclusion criteria are fulfilled.

Randomization An allocation sequence using a computerized random number generator will be prepared by a statistician not involved in recruitment. Opaque sealed and sequentially numbered envelopes with group allocation will be prepared and opened in the presence of the participant upon inclusion and randomization.

Power analysis: A sample size calculation was made based on the results of our previous study on strength training for VMS (Berin et al 2019) and showed that to detect a 50% difference in moderate and severe hot flushes with 80% power and expected dropout rate of 20% 40 participants in total would be needed. For this three-armed set-up we estimate that 20 participants in each group will be needed, i.e. 60 in total. To also achieve sufficient power for some of the secondary outcomes the intended sample size is increased to 30 per group, 90 in total.

Data analysis: The primary analysis will be performed according to the intention-to-treat principle, including all participants who provided more than baseline data for the primary outcome. For quantitative interval data mixed design ANOVAs will be used to analyze the effect over time between and within groups. For the between-group comparisons effect sizes will be calculated. For ordinal data, such as the questionnaires, Kruskal-Wallis and Friedman test will be used for statistical analysis of the effect. Participants who complete two or more training sessions per week will be considered adherent with their assigned intervention and included in a per-protocol analysis. Detailed description of adherence, such as the fidelity with the training interventions, will be presented descriptively.

Study Timeline

• Study First Submitted: 2023-06-15
• Study First Submitted QC: 2023-09-08
• Study First Posted: 2023-09-11
• Study Start: 2023-09-12
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-20
• Last Update Posted: 2025-01-22
• Primary Completion: 2027-06
• Study Completion: 2032-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

• Postmenopausal women (one of: ≥ 12 months since last menstruation; amenorrhea due to intrauterine device or hysterectomy and Follicle Stimulating Hormone (FSH) >30 mIU/ml; bilateral oophorectomy; induced menopause due to chemotherapy or radiation and ≥2 years amenorrhea);
• ≥ 28 moderate to severe hot flushes per week during a 2-week screening period, registered through a daily VMS diary;
• Age ≥45 years;
• Physical ability to participate in strength training or high intensity aerobic exercise for 60 minutes, 3 times/week during 15 weeks;
• Understand Swedish orally and in writing

Exclusion Criteria

• Regular physical activity >30 minutes per week of vigorous intensity or ≥150 minutes of moderate intensity or combined activities representing maximum 150 minutes of moderate intensity;
• Use of systemic menopausal hormone therapy the last 2 months;
• Use of natural preparations such as herbal preparations for VMS, or other medications for VMS the last 2 months;
• Capillary hemoglobin <110 g/l;
• Blood pressure >160 mmHg systolic or >100 mmHg diastolic;
• Unstable medical condition with a potential to affect VMS (like unregulated thyroid disease);
• Medical condition that by a physician is judged not appropriate (because of potential to affect VMS or risk of injury with vigorous exercise)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Frequency of moderate and severe hot flushes	baseline to 15 weeks	Frequency of hot flushes per 24 h daily recorded in hot flush diary from baseline throughout 15 weeks of intervention.

Secondary Outcome Measures

Name	Time	Method
Frequency of moderate and severe hot flushes	baseline to 6 months, 1, 2 and 5 years	Frequency of hot flushes per 24 h daily recorded in hot flush diary 2 weeks at baseline and 2 weeks at each of the time points.
Severity of hot flushes	baseline to 15 weeks, 6 months, 1, 2 and 5 years	Severity of hot flushes per 24 hours recorded in hot flush diary from baseline throughout 15 weeks of intervention and two weeks during follow-up.
Generic health-related quality of life	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention	Short-form 36, 36 questions in 8 scales. Scores for each domain range from 0-100, and a high score represents a higher health-related quality of life.
Women specific health-related quality of life	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention	Women's health questionnaire nine sub-scales with four-point scales (yes definitely, yes sometimes, not not much, no not at all) that are reduced to binary options (0/1). The subscale items are summated and divided by the number of items in each subscale.A higher score represents worse outcome.
Physical activity levels	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention	International Physical Activity Questionnaire short form, the participant describes the amount of time (minutes and hours) that is spent on different physical activities each week, the more time, the better, except for the question about the amount of time spent in sitting.
Sleep quality	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention	Pittsburgh sleep quality index, 7 domains. For the total instrument, the lower score, the better, from 0 (best) to 21 (worst).
Diet	baseline to 15 weeks, 6 months, 1, 2 and 5 years	Bespoke questionnaire, primarily to control for changes during the intervention period. Registration of amounts or portions. Results are presented question by question descriptively.
Accomplished physical activity	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention	Bespoke training diary
Weight	baseline to 15 weeks	kilogram (kg)
Lenght	baseline to 15 weeks	meters (m)
Body mass index	baseline to 15 weeks	kilograms/meters2 (kg/m2)
Waist circumference	baseline to 15 weeks	millimeters (mm)
Systolic and diastolic blood pressure	baseline to 15 weeks	Unit millimetre of mercury (mmHg)
Hematologic and ironstatus changes	baseline to 15 weeks, and 1 year	Hemoglobin full body count, Transferrin(gram/Litre), and Ferritin (microgram/Litre)
Changes in blood-lipids	baseline to 15 weeks, and 1 year	apolipoprotein A1, apolipoprotein B (gram/Litre) and total cholesterol, low-density lipoprotein, high-density lipoprotein (mmol/L) and leptin (ng/mL)
Changes in sex hormones and gonadotrophins	baseline to 15 weeks, and 1 year	Estradiol (pmol/Litre), Sex hormone bindning globulin, Testosterone (nmol/Litre), follicle-stimulating hormone, luteinizing hormone (IE/Litre)
Changes in inflammatory biomarkers	baseline to 15 weeks, and 1 year	high-sensitive C-reactive Protein (microgram/Litre), Brain-derived neutrophic factor, Matrix metalloproteinase-2 and -9 (ng/mL), Interleukin -4, -6, -7, -8, 10, -15, tumour necrosis factor, monocyte chemoattractant protein-1 (pg/mL)
Changes in the lenght of telomeres in white blood cells	baseline to 15 weeks, and 1 year	Telomeres (kilobase) pair
Changes in bone markers	Baseline to 15 weeks, and 1 year	25-hydroxyvitamin D (25OHD) (nmol/L), Parathyroid hormone (PTH) (pmol/L), C-terminal telopeptide cross-links of collagen type I (CTX) (ng/L), Tartrate-resistant acid phosphatase isoform 5B (TRACP5B) (U/L), Type I procollagen intact N-terminal propeptide (PINP) (µg/L), Bone-specific alkaline phosphatase (BALP) (µg/L or U/L (assay dependent)), Bioactive sclerostin (pmol/L), Osteoprotegerin (OPG) (pmol/L), Free soluble receptor activator of nuclear factor κB ligand (RANKL) (pmol/L), Intact fibroblast growth factor 23 (FGF23) (pg/mL), Irisin (µg/L). Measurement added in January 2025 and data was only collected for participants entering the study from January 2025.
Change in body composition (DXA - dual energy x ray absorptiometry)	Baseline to 15 weeks	Fat mass, lean mass. Measurement added in January 2025 and data was only collected for participants entering the study from January 2025.
Change in bone mineral density (DXA - dual energy x ray absorptiometry)	Baseline to 15 weeks	Bone mineral density (g/area) and T-score in spine and hip. Measurement added in January 2025 and data was only collected for participants entering the study from January 2025.
Change in exercise capacity	baseline to 15 weeks	Change in exercise capacity is primarily used as a measure of adherence and obtained through cardiopulmonary exercise testing assessing maximum oxygen uptake milliliter/kilogram/minute (ml/kg/minute) and analysed according to local clinical routines.
Experiences of the interventions, facilitators and barriers	baseline to 15 weeks	Bespoke questionnaire, only for intervention groups. Results will be presented descriptively question by question.
Adherence to the interventions	baseline to 15 weeks	Assessed through bespoke training diary where each training session is registered and the total number of training sessions as well as training sessions/week will be calculated.
Muscle strength	baseline to 15 weeks	For strength training group only, measured using 8 repetition-maximum tests.
Adverse events	baseline to 15 weeks	Adverse events of taking part in the study
Changes in glucose profile	baseline to 15 weeks, and 1 year	HbA1c (mmol/Litre) and fasting blood glucose (mmol/L)
Bioimpedance	baseline to 15 weeks	Fat mass (%) and fat-free (muscle) mass (%)

Trial Locations

Locations (2)

Region Kalmar Län; 🇸🇪 Kalmar, Sweden

Region Östergötland; 🇸🇪 Linköping, Sweden