Strength and Aerobic Training Against Hot Flushes in Postmenopausal Women (START)

STrength and AeRobic Training Against Vasomotor Symptoms (START) in Postmenopausal Women

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.

Study Overview

• Status: Recruiting
• Conditions: Hot Flashes; Postmenopausal Symptoms
• Intervention / Treatment: Other: Strength training; Other: High-intensity aerobic training

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 Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna-Clara Spetz Holm, Ass prof, MD; Phone Number: +46101033130; Email: anna-clara.spetz.holm@liu.se

Study Locations

• Sweden
  • Kalmar, Sweden, S-39126
    • Recruiting
    • Region Kalmar län
    • Contact: Micaela Sundell, MD, PhD
  • Linköping, Sweden, S-58185
    • Recruiting
    • Region Östergötland
    • Contact: Anna-Clara Spetz Holm, Ass prof, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Strength training; Standardised programme with the following exercises: chest press, leg press, row, leg curl, latissimus dorsi pull down and leg extension in seated resistance machines. Training will be preceded by 7-10 minutes of warm-up and followed by two body-weight exercises for the abdominal and back muscles for two sets as many repetitions as possible, and thereafter cool down and stretches. The set-up of each machine will be recorded in the training diary. Weeks 1-3 will include two sets of training with 15-20 repetition-maximum (RM) and weeks 4-15 two sets with 8-12 RM. Throughout the intervention, loads will be adjusted to achieve muscle fatigue and approach training to failure during each set with the intent to maximize beta-endorphin release.	Other: Strength training; Both interventions (strength training and high intensity aerobic training) will be introduced with a 3-week adaptation period with lower loads (strength training) or intensity (aerobic training) followed by a 12-week period on the intended load/intensity. All participants in the intervention groups will be recommended to exercise three times per week (one hour per session) and in addition be active with everyday low-intensity physical activity. A structured and detailed training diary will be used in both groups to register frequency of each training session, as well as everyday physical activity. For the strength training, load and dose will also be registered for each training session.
Active Comparator: High-intensity aerobic training; Participants will be recommended to attend spinning classes three times per week. During their first visit to the training venue, they will meet a sports physiotherapist or personal trainer to be introduced to the spinning bike intervention. The intended intensity is ≥ 14 on the Borg rating of perceived exertion scale, equivalent to high intensity training (>70% of VO2max) with the aim of attaining sufficient stimulus for beta-endorphin release. During weeks 1-3 participants will attend spinning classes for beginners with lower intensity and predominantly seated cycling. They will progress to higher intensity classes with greater variation between seated and standing cycling during week 4-15.	Other: High-intensity aerobic training; Both interventions (strength training and high intensity aerobic training) will be introduced with a 3-week adaptation period with lower loads (strength training) or intensity (aerobic training) followed by a 12-week period on the intended load/intensity. All participants in the intervention groups will be recommended to exercise three times per week (one hour per session) and in addition be active with everyday low-intensity physical activity. A structured and detailed training diary will be used in both groups to register frequency of each training session, as well as everyday physical activity. For the strength training, load and dose will also be registered for each training session.
No Intervention: Control group; The control group will be recommended to carry on physical activity as usual and not to change their training or dietary habits during the 15-week study period. The control group will be contacted every fourth weeks by a research nurse to follow up on their general well-being and any questions they might have about menopause. After the study period they will be offered individual advise about training from a physiotherapist or personal trainer.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of moderate and severe hot flushes	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.	baseline to 6 months, 1, 2 and 5 years
Severity of hot flushes	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.	baseline to 15 weeks, 6 months, 1, 2 and 5 years
Generic health-related quality of life	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.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Women specific health-related quality of life	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.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Physical activity levels	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.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Sleep quality	Pittsburgh sleep quality index, 7 domains. For the total instrument, the lower score, the better, from 0 (best) to 21 (worst).	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Diet	Bespoke questionnaire, primarily to control for changes during the intervention period. Registration of amounts or portions. Results are presented question by question descriptively.	baseline to 15 weeks, 6 months, 1, 2 and 5 years
Accomplished physical activity	Bespoke training diary	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Bioimpedance	Fat mass (%) and fat-free (muscle) mass (%)	baseline to 15 weeks
Weight	kilogram (kg)	baseline to 15 weeks
Lenght	meters (m)	baseline to 15 weeks
Body mass index	kilograms/meters2 (kg/m2)	baseline to 15 weeks
Waist circumference	millimeters (mm)	baseline to 15 weeks
Systolic and diastolic blood pressure	Unit millimetre of mercury (mmHg)	baseline to 15 weeks
Hematologic and ironstatus changes	Hemoglobin full body count, Transferrin(gram/Litre), and Ferritin (microgram/Litre)	baseline to 15 weeks, and 1 year
Changes in blood-lipids	apolipoprotein A1, apolipoprotein B (gram/Litre) and total cholesterol, low-density lipoprotein, high-density lipoprotein (mmol/L) and leptin (ng/mL)	baseline to 15 weeks, and 1 year
Changes in sex hormones and gonadotrophins	Estradiol (pmol/Litre), Sex hormone bindning globulin, Testosterone (nmol/Litre), follicle-stimulating hormone, luteinizing hormone (IE/Litre)	baseline to 15 weeks, and 1 year
Changes in glucose profile	HbA1c (mmol/Litre) and fasting blood glucose (mmol/L)	baseline to 15 weeks, and 1 year
Changes in inflammatory biomarkers	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)	baseline to 15 weeks, and 1 year
Changes in the lenght of telomeres in white blood cells	Telomeres (kilobase) pair	baseline to 15 weeks, and 1 year
Change in exercise capacity	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.	baseline to 15 weeks
Experiences of the interventions, facilitators and barriers	Bespoke questionnaire, only for intervention groups. Results will be presented descriptively question by question.	baseline to 15 weeks
Adherence to the interventions	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.	baseline to 15 weeks
Muscle strength	For strength training group only, measured using 8 repetition-maximum tests.	baseline to 15 weeks
Adverse events	Adverse events of taking part in the study	baseline to 15 weeks
Changes in bone markers	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.	Baseline to 15 weeks, and 1 year
Change in body composition (DXA - dual energy x ray absorptiometry)	Fat mass, lean mass. Measurement added in January 2025 and data was only collected for participants entering the study from January 2025.	Baseline to 15 weeks
Change in bone mineral density (DXA - dual energy x ray absorptiometry)	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.	Baseline to 15 weeks

Collaborators and Investigators

• Sponsor: Linkoeping University
• Collaborators: Region Östergötland; Länssjukhuset i Kalmar län
• Investigators: Principal Investigator: Anna-Clara Spetz Holm, Ass prof, MD, Region Östergötland, Linköping university

Publications and helpful links

General Publications

• Berin E, Hammar M, Lindblom H, Lindh-Astrand L, Ruber M, Spetz Holm AC. Resistance training for hot flushes in postmenopausal women: A randomised controlled trial. Maturitas. 2019 Aug;126:55-60. doi: 10.1016/j.maturitas.2019.05.005. Epub 2019 May 14.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: strength training; aerobic training
• Additional Relevant MeSH Terms: Hot Flashes
• Other Study ID Numbers: START2022-05030-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in publications may be available upon reasonable request to the principal investigator
• IPD Sharing Time Frame: 1 year after publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No