Menopause
DOI: 10.1111/1471-0528.13193 www.bjog.org
The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial AJ Daley,a A Thomas,b AK Roalfe,a H Stokes-Lampard,a S Coleman,a M Rees,c MS Hunter,d C MacArthure a
Primary Care Clinical Sciences, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK b Macquarie University, Macquarie Park, NSW, Australia c Women’s Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK d Institute of Psychiatry, King’s College London, London, UK e Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK Correspondence: Dr AJ Daley, Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham B15 2TT, UK. Email [email protected] Accepted 14 September 2014. Published Online 17 December 2014.
Objective To investigate the effectiveness of exercise as treatment
Main outcome measure The primary outcome was frequency of
for vasomotor menopausal symptoms.
hot flushes/night sweats at 6-month up.
Design Three-group randomised controlled trial, two exercise
Results Two hundred and sixty-one women were randomised (n = 87 per group). Neither of the exercise intervention groups reported significantly less frequent hot flushes/night sweats per week than controls (exercise-DVD versus control: 8.9, 95% CI 20.0 to 2.2; exercise-social support versus control: 5.2, 95% CI 16.7 to 6.3).
interventions and a control group. Setting Primary Care, West Midlands UK. Population Perimenopausal and postmenopausal women
experiencing at least five hot flushes/night sweats per day and not taken MHT in previous 3 months were recruited from 23 general practices. Methods Participants in both exercise interventions groups were
offered two face-to-face consultations with a physical activity facilitator to support engagement in regular exercise. In addition, one exercise group received a menopause-specific information DVD and written materials to encourage regular exercise and the other exercise group was offered the opportunity to attend exercise social support groups in their communities. Interventions lasted 6 months.
Conclusions This trial indicates that exercise is not an effective
treatment for hot flushes/night sweats. Contrary to current clinical guidance, women should not be advised that exercise will relieve their vasomotor menopausal symptoms. Keywords Exercise, hot flushes, menopause, night sweats, primary
care. Linked article This article is commented on by G Bachmann,
p. 576 in this issue. To view this mini commentary visit http://dx. doi.org/10.1111/1471-0528.13207.
Please cite this paper as: Daley AJ, Thomas A, Roalfe AK, Stokes-Lampard H, Coleman S, Rees M, Hunter MS, MacArthur C. The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial. BJOG 2015;122:565–575.
Introduction Many perimenopausal and postmenopausal women experience hot flushes/night sweats that negatively impact on their health and quality of life.1 Menopausal hormone therapy (MHT) is an effective treatment and, until recently, popular among patients and doctors. Research and media scares, however, have raised questions about the safety of MHT.2,3 Many women are now reluctant to consider MHT as treatment and doctors are more cautious about prescribing it.4–6
ª 2014 Royal College of Obstetricians and Gynaecologists
As many women are choosing to avoid MHT it is increasingly important to identify other evidence-based interventions.7 One possible treatment option is exercise, and the Scientific Advisory Committee of The Royal College of Obstetricians and Gynaecologists, and their Patient Information Committee have already advised that regular sustained aerobic exercise (e.g. running and swimming) may be an effective intervention.8,9 Likewise, The North American Menopause Society states that women who are overweight (most menopausal women) have more hot flushes, so it is
565
Daley et al.
important for them to maintain a healthy weight and exercise regularly to decrease bothersome hot flushes.10 Although exercise has been recommended as a treatment for hot flushes/flushes/night sweats, available evidence is inconclusive. The recently updated Cochrane review of exercise for the management of vasomotor menopausal symptoms in symptomatic women concluded that existing evidence suggests exercise is not an effective treatment for vasomotor menopausal symptoms but a definitive statement could not be made until more evidence was available.11 The trials had also typically included relatively short interventions and follow up. This is important because the effects of exercise on hot flushes/night sweats may not be immediate, particularly if the mechanism of effect is via a reduction in adiposity.12 The RCT reported here aimed to investigate the feasibility/acceptability of two exercise interventions identified from our previous pilot study relative to a control group,13 and if feasible and acceptable, to continue to recruit sufficient women to examine the effectiveness of these interventions on hot flushes/night sweats compared with a control group. In the feasibility phase we randomised 165 women to one of the three trial groups.14 The interventions were deemed feasible and acceptable, with high recruitment and good adherence, therefore the trial continued to investigate the effectiveness of the exercise interventions in reducing hot flushes and night sweats.14
Methods Setting and participants This study is a randomised controlled trial (RCT) with 261 participants allocated to one of two 6-month exercise interventions or a control group. The published protocol provides more detail regarding the feasibility phase, which indicated that the trial was feasible with no protocol changes needed.14 Women aged 48–57 years were identified from general practice records and the practices sent the study invitation letter, information leaflet and screening questionnaire to these patients and asked them to return their screening questionnaire to the research team. A reminder was sent to non-responders 3 weeks later. The screening questionnaire assessed frequency of hot flushes/night sweats,15 menopausal status, MHT use, menstrual cycle length, contraception/medication use and current levels of exercise to ascertain eligibility. General practices (n = 23) across the West Midlands assisted with recruitment. Recruitment began in April 2011 and final follow up was completed in September 2014.
Eligibility Perimenopausal and postmenopausal women who were currently experiencing five or more hot flushes/night sweats
566
each day of any severity and had not used MHT in the previous 3 months to baseline were eligible. Only women who were inactive (not currently meeting the public health guidelines for physical activity16) were eligible. Women using oral or injectable hormonal contraception, tamoxifen, tibolone and raloxifene in the previous 3 months, who were unable to provide written informed consent or who were unable to understand English sufficiently to complete the research questionnaires were excluded, as were women whom the GP considered unsuitable.
Outcomes and process measures The primary outcome was the frequency of hot flushes/ night sweats measured by hot flush rating scale15 at 6month up. Secondary outcomes included hot flushes/night sweats frequency at 12-month’up. Problem rating of hot flushes/flushes,15 menopause-specific quality of life subscales from the Women’s Health Questionnaire (WHQ),17 and generic QoL(SF-12),18 depression and anxiety,19 subjective vitality,20 self efficacy for exercise,21 social support for exercise22 and self reported physical activity measured using the International Physical Activity Questionnaireshort23 scores at 6 and 12 months follow up were also secondary outcomes. Adverse events were recorded.
Demographic data Demographic information on health behaviours, reproductive history and use of complementary and alternative medicine for symptom control were collected at baseline and follow up. Current medication use was collected at baseline and follow up.
Randomisation, concealment and blinding Participants were randomised to one of two 6-month exercise interventions or a control group on a 1:1:1 ratio. Group allocation was stratified by menopausal status (perimenopausal or post menopausal) and BMI (underweight/ normal weight or overweight/obese using self-reported height and weight). The allocation sequence was generated by the trial statistician using NQUERY ADVISOR 7.0 (Statistical Solutions, Cork, Ireland) with mixed blocked randomisation within strata. The methods of sequence generation were concealed (computer-generated and web-based) from researchers involved in recruiting and randomising participants. Participants, researchers and those delivering the intervention could not be blinded to group allocation.
Data collection Outcome measures were assessed at baseline and 6 months (immediately post intervention) and 12 months post randomisation. Outcome questionnaires were mailed to participants at follow-up times.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Participants in all groups were asked to complete prospective 7-day hot flush/night sweat diaries at weeks 7, 14, and 21 of the intervention to provide an indication of the profile of their symptoms throughout the intervention period, recording both frequency and severity of their symptoms. In the same weeks those randomised to intervention groups also completed 7-day prospective exercise logs that detailed the amount and type of exercise they had completed. The hot flush diaries and physical activity logs were sent and returned by freepost. A 50% random sample of all participants were asked to wear an Actiheart (CamNtech Ltd., Cambridge, UK) monitor for five consecutive days at baseline and 6-month up, to provide objective data about physical activity patterns over time to corroborate the self-reported physical activity data. The Actiheart device measures both exercise intensity and amount of physical activity achieved.
Interventions The development of the two exercise interventions and their rationale are described in detail in elsewhere.14 The intervention exercise goal was incremental over time with an initial goal (weeks 1–12) of progressing towards achieving 30 minutes of moderate intensity exercise on at least 3 days per week. During weeks 13–24, participants in the intervention groups were encouraged to accumulate at least 30 minutes of moderate intensity exercise on 3– 5 days per week. The definition of moderate intensity exercise that was given to participants was that they should aim for an increase in their breathing rate, an increase in their heart rate to the level where they could feel their pulse and an increase in body temperature. Participants were given examples of what types of activities were likely to constitute moderate intensity exercise (i.e. brisk walking, jogging, aerobics, swimming, cycling and tennis). Both interventions involved two-one-to-one consultations which typically lasted 40–60 minutes (during months 1 and 2). The consultations focused on equipping women with the skills, knowledge and confidence needed to participate in regular exercise and were delivered by a physical activity facilitator in the participant’s home. The first consultation focused on uptake of exercise and on enhancing motivation and self-efficacy for exercise. Participants were given a pedometer as a motivational tool. In addition to the one-to-one consultations one intervention group (herein referred to as the exercise-DVD group) were also sent a DVD, a booklet and five study leaflets at various times throughout the intervention; the intention was that these leaflets would act as regular reminders that prompted and encouraged exercise. These materials provided information about the menopause, benefits of exercise during menopause, and outlined strategies that could be used to motivate participants to exercise. Information
ª 2014 Royal College of Obstetricians and Gynaecologists
on the importance of healthy eating was also included. The DVD was developed specifically for this study and contained case studies of women who had recently experienced hot flushes/night sweats and discussed strategies that they had used to motivate themselves to exercise and the impact it had on their health. The second intervention, in addition to the consultations, involved participants being invited to take part in three exercise support groups in their local community (e.g. at community centres, general practices) (herein referred to as the exercisesocial support group). The primary purpose of these groups was to bring women together to share experiences about exercising during the menopause and offer regular encouragement to each other. The support groups focused on giving information about the symptoms of menopause and the importance of exercise and healthy eating during menopause and covered all the topics within the materials received by the exercise-DVD intervention group. These social support groups typically last 75–90 minutes.
Control group The control group were offered the opportunity to have an exercise consultation and were given a pedometer at the end of their involvement in the study.
Sample size and statistical analyses A sample size of 87 participants per group (n = 261) was sufficient to detect a 50% reduction in the mean number of hot flushes/night sweats per week (e.g. 40 reduced to 20 SD = 31.6)8 with 80% power and 5% significance level, allowing for 20% drop out between the intervention and control groups. Comparisons were made between the mean number of symptoms per week between the control group and each exercise intervention group. Pre-specified adjustments were made for baseline symptom frequency, menopausal status, BMI as well as antidepressant and MHT use recorded at 6month up. Paired comparisons were made between controls and each intervention group with P values adjusted for multiple testing. To identify any longer term effects of the intervention on symptoms, repeated measures mixed modelling of hot flushes/night sweats was conducted to compare groups across all time points, adjusting for covariates and multiple comparisons as previously described. Secondary outcomes were all compared at the 6- and 12month follow up using the same method as previously stated. The frequency, intensity, type and duration of exercise is summarised in MET/minutes/week. Bland–Altman plots were used to compare the agreement between the selfreported physical activity data and objectively measured physical activity. The number of adverse events that occurred during the intervention period is summarised by
567
Daley et al.
group. Bootstrapped estimates were calculated where there was evidence of non-normality in the residuals. The impact of missing primary data was explored by sensitivity analysis including multiple imputation. All analyses were by intention-to-treat.
significant differences between groups in flushes/night sweats problem rating scores at 6 or 12 months (Tables 2 and 3).
Results
The exercise-social support group reported significantly lower somatic symptoms scores at the 6-month (mean difference = 0.10, 95% CI 0.18 to 0.02) and 12-month (mean difference = 0.08, 95% CI 0.15 to 0.002) follow up, and significantly lower sleep problem scores (mean difference = 0.11, 95% CI 0.21 to 0.01) compared with the control group at the 6-month follow up. The results for anxiety were marginally different (mean difference = 1, 95% CI 2.0 to 0.02), favouring the exercisesocial support group at the 12-month follow up (Table 3).
Patients and recruitment Study invitation letters and screening questionnaires were sent by practices to 9409 women and 1715 (18%) were returned. Of these, 353/1715 (21%) were eligible and sent a participant information sheet, baseline questionnaires and consent form; the remainder were either ineligible (n = 1055) or not interested in participating (n = 307). Of those eligible and interested, 261 completed and returned the baseline questionnaires (n = 261/353, 74%) (see Figure 1).
Randomisation and participant’s baseline characteristics In all, 261 participants were randomised to one of the two exercise (n = 87 per group) or control groups (n = 87). Table 1 contains the baseline characteristics of randomised participants, which demonstrate a good balance between the groups on these variables. On average women were experiencing 9.1 hot flushes/night sweats per day and mean problem ratings were 6/10, suggesting moderately troublesome symptoms. The average age of participants was 52.3 years. Most participants lived in the two highest deprivation quartiles (55.3%), 10% were of non-white ethnicity, 67.4% were overweight/obese, 70.1% postmenopausal and 29.9% perimenopausal, and 16.8% were smokers. Baseline measures were also well balanced across the groups (Table 1, Table S1).
Follow-up rates and data At 6 months, 83.4% (n = 219/261) of randomised participants completed follow up (primary) and at 12 months the follow-up rate was 85.1% (n = 222/261). By the 6-month follow up, five participants had started to take MHT; this increased to 12 by the 12-month follow up. At both time points the number of participants using MHT was balanced across the groups. No adverse events were recorded.
Hot flushes and night sweats Neither exercise group reported significantly less frequent hot flushes/night sweats per week than controls at the 6month follow up (exercise-DVD group versus controls: mean difference = 8.9, 95% CI 20.0 to 2.2) (exercisesocial support group versus controls: mean difference = 5.2, 95% CI 16.7 to 6.3). The magnitude of the effect was reduced at 12 months. Similarly, there were no
568
Other menopausal symptoms (WHQ) and quality of life outcomes
Exercise for social support The exercise-DVD group reported they experienced significantly more support from their families to exercise compared with controls at the 6-month follow up (mean difference = 2.8, 95% CI 0.03–5.6). A similar increase was observed in the exercise-social support group compared with controls (mean difference = 2.8, 95% CI 0.1 to 5.7) (Tables 2 and 3).
Physical activity The exercise-social support group reported participating in significantly more MET/minutes/week of vigorous physical activity than controls at the 6-month follow up (mean difference = 403, 95% CI 78–727). There was a nonsignificant trend showing the exercise-DVD group reported completing more MET/minutes/week of vigorous physical activity compared with controls (mean difference = 336, 95% CI 27 to 669). The exercise-DVD group reported significantly lower walking (MET/minute/week) and total MET minutes/week mean scores compared with controls at the 12-month follow up (see Tables S1 and S2). Of those randomised to wear the Actiheart device, only 85/130 provided follow-up data/useable data. Although a Bland– Altman test to consider the agreement between selfreported and objectively measured physical activity data (moderate and vigorous intensity combined) showed a low mean discrepancy (98 MET/minutes/week, 95% CI 354 to 159), the limits of agreement were wide ( 2200 to 2037). The accelerometry data are available from the first author on request.
Prospective hot flushes/night sweats diaries (process outcome) A total of 393/783 (50%) (i.e. 261 participants 9 three diaries) of the hot flushes/night sweats symptom diaries were completed and returned, with 131/261 (50%) completing at
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Information letter and screening questionnaire sent to menopausal aged women aged 48-57 years by general practices (n = 9409)
Returned screening questionnaire (n = 1715)
Did not respond (n = 7694)
Experiencing five or more HF/NS and otherwise eligible and sent baseline questionnaire n = 353
Experiencing less than 5 HF/NS or otherwise ineligible (n = 1055) or not interested (n = 307)
Returned baseline questionnaire and randomised (n = 261)
Exercise-DVD intervention (Two exercise
Exercise–social support intervention (Exercise consultations
consultations plus leaflets & DVD) (n = 87)
plus support groups)
Control (n = 87)
(n = 87)
Completed follow up at 6 months for primary outcome Exercise-DVD (n = 75) Exercise–social support (n = 67) Usual care (n = 77) Intention to treat analysis was adopted
Completed follow up at 12 months for primary outcome Exercise-DVD (n = 74) Exercise–social support (n = 72) Usual care (n = 76) Intention to treat analysis was adopted
Figure 1. Trial flow.
least two of three diaries. A total of 83/261 (32%) participants did not complete even one diary. The average number of hot flushes/night sweats reported across the three diaries by the exercise-DVD, exercise-social support and control groups were 27.7, 36.7 and 38.7 per week, respectively, and average severity scores (1–10) were 5.1,
ª 2014 Royal College of Obstetricians and Gynaecologists
5.0 and 4.7 for each group, respectively. The data recorded in the prospective diaries during the intervention period for all groups corresponded very closely with the primary outcome of hot flushes rating scale scores at the 6-month follow up.
569
Daley et al.
Table 1. Comparability of baseline characteristics Exercise–DVD (n = 87) n (%)
Exercise–social support (n = 87) n (%)
Control (n = 87) n (%)
52.3 (2.4)
52.7 (2.5)
52.0 (2.4)
27 (31) 60 (69)
26 (30) 61 (70)
25 (29) 62 (71)
BMI* mean (SD) Under/normal Over/obese (>25 kg/m2)
28.2 (5.7) 28 (32) 59 (68)
27.8 (5.4) 29 (33) 58 (67)
28.0 (5.8) 28 (32) 59 (68)
Weight (kg) mean (SD)
75.9 (16.8)
72.6 (14.7)
73.9 (15.1)
Characteristics
Age (years) mean (SD) Menopausal* status Peri–menopausal Menopausal
IMD quartile 1 (least deprived) 2 3 4 (most deprived)
13 26 19 28
(14) (31) (23) (32)
12 26 19 28
(14) (30) (22) (32)
19 18 18 29
(22) (21) (21) (33)
Unknown
1 (1)
2 (2)
3 (3)
Non white ethnic origin
8 (9)
7 (8)
11 (13)
Non smokers
78 (90)
62 (71)
66 (77)
Education level Primary Secondary left at min age Secondary left after min age University or College of HE
2 36 13 36
(2) (41) (15) (42)
1 44 11 31
(1) (51) (13) (36)
0 34 17 36
(0) (39) (20) (41)
Employment status Paid/self–employed Unemployed/retired/student Looking after home/family Sick/disabled Other/not known
75 2 2 7 1
(86) (2) (2) (8) (1)
67 3 9 7 1
(77) (3) (10) (8) (1)
70 6 8 2 1
(80) (7) (9) (2) (1)
Number of children, mean (SD)
2.1 (1.4)
2.0 (1.4)
2.0 (1.4)
Illness limiting activities/work
28 (32)
18 (20)
24 (28)
6 (7)
10 (11)
7 (8)
42 (48)
51 (59)
42 (53)
Taking antidepressants Using complementary/alternative therapies *Stratification variable at randomisation.
Adherence to the exercise intervention and intervention implementation A total of 244/522 (47%) (i.e. 174 intervention participants 9 three diaries) of the exercise diaries were completed and returned by women in the exercise intervention groups, with 83/174(48%) completing at least two diaries. Sixty-five (37%) participants failed to complete a single diary. In the diaries received, the exercise-social support and exercise-DVD groups reported completing an average of 281 and 297 min of at least moderate intensity exercise per week (40.1 and 42.4 minutes/day) respectively. Both groups
570
reported consistent levels of exercise across the three diary measurement points. The most common types of exercise were walking, aerobics/keep fit classes and swimming. Adherence to the various intervention contacts/components was high; 83% (n = 144/174) participants received both exercise consultations, 93% (n = 162/174) received at least one exercise consultation. In the exercise-DVD group, 90% (n = 78/87) received all the materials/leaflets that were part of this intervention. In the exercise-social support group, 55% (n = 48/87) attended at least one of the three support groups.
ª 2014 Royal College of Obstetricians and Gynaecologists
ª 2014 Royal College of Obstetricians and Gynaecologists
28.0 (0.4)
0.40 0.65 0.63 0.42 0.34 0.67
BMI
Women’s Health Questionnaire Depressed mood Somatic symptoms Memory/concentration Anxiety/fears Sexual behaviour Sleep problems
50.9 (1.9) 41.5 (2.4)
(0.06) (0.06) (0.44) (0.07) (0.13) (0.08)
51.5 (1.8) 42.5 (2.3)
6.5 (0.8) 9.0 (0.8)
28.2 (3.2) 13.5 (1.4)
19.3 (2.1) 3.9 (0.4) 14.6 (2.3)
3.8 (0.28)
0.34 0.56 0.60 0.39 0.29 0.56
28.1 (0.4)
74.3 (1.0)
35.8 (9.1) 3.8 (0.6)
Mean (SE)
Exercise–social support
(0.06) (0.06) (0.47) (0.07) (0.13) (0.08)
49.4 (1.8) 44.1 (2.3)
6.8 (0.8) 8.8 (0.8)
25.6 (3.2) 12.8 (1.4)
16.5 (2.1) 3.9 (0.4) 14.2 (2.3)
3.5 (0.28)
0.34 0.66 0.62 0.39 0.34 0.67
28.3 (0.4)
74.9 (1.0)
41.0 (9.3) 4.4 (0.6)
Control
( ( ( ( ( (
0.02 0.10 0.09 0.07 0.11 0.10
to to to to to to
0.14) 0.06) 0.11) 0.12) 0.10) 0.11)
1.4 ( 1.0 to 3.9) 2.5 ( 5.6 to 0.5)
0.4 ( 0.6 to 1.5) 0.7 ( 0.4 to 1.8)
2.5 ( 1.0 to 6.0) 0.8 ( 0.8 to 2.5)
2.8 (0.03 to 5.6) 0.2 ( 0.4 to 0.8) 0.9 ( 3.9 to 2.1)
0.05 ( 0.42 to 0.32)
0.06 0.02 0.01 0.03 0.005 0.005
0.2 ( 0.7 to 0.3)
0.5 ( 1.7 to 0.8)
8.9 ( 20.0 to 2.2) 0.2 ( 0.6 to 0.9)
Adjusted* mean (95% CI)
0.31 0.11
0.55 0.27
0.19 0.41
0.047 0.68 0.75
0.94
0.16 0.83 0.94 0.73 0.99 0.99
0.52
0.62
0.14 0.76
P–value
Comparison Exercise–DVD versus control
( ( ( ( ( (
0.09 0.18 0.13 0.10 0.16 0.21
to to to to to to
0.07) 0.02) 0.08) 0.09) 0.05) 0.01)
2.0 ( 0.4 to 4.5) 1.6 ( 4.7 to 1.5)
0.3 ( 1.3 to 0.8) 0.1 ( 1.0 to 1.3)
2.7 ( 1.1 to 6.5) 0.8 ( 1.0 to 2.5)
2.8 ( 0.1 to 5.7) 0.01 ( 0.6 to 0.6) 0.4 ( 2.7 to 3.5)
0.25 ( 0.13 to 0.64)
0.01 0.10 0.02 0.002 0.05 0.11
0.2 ( 0.7 to 0.3)
0.6 ( 1.8 to 0.7)
5.2 ( 16.7 to 6.3) 0.6 ( 1.3 to 0.1)
0.12 0.42
0.79 0.96
0.20 0.52
0.06 0.99 0.95
0.24
0.98 0.01 0.84 0.99 0.41 0.04
0.64
0.53
0.50 0.13
P–value
Comparison Exercise–social support versus control Adjusted* mean (95% CI)
*Adjusted by baseline value, BMI (≤25, >25 kg/m2), menopausal status, hormone replacement therapy/anti–depression medication recorded at follow up.
SF–12 Physical component score Mental component score
7.2 (0.8) 9.6 (0.9)
28.1 (3.3) 13.6 (1.5)
Exercise confidence Sticking to it [8–40] Making time for it [4–20]
HADS Depression Anxiety
19.3 (2.2) 4.1 (0.5) 13.3 (2.3)
3.5 (0.29)
Social support and exercise Family participation [10–50] Family rewards [3–15] Friend participation [10–50]
Vitality
74.4 (1.0)
Weight
(0.06) (0.06) (0.48) (0.07) (0.13) (0.08)
32.1 (9.3) 4.6 (0.6)
Exercise–DVD
Hot Flush Rating Scale Frequency hot flushes/night sweats per week Hot flush problem– rating [1–10]
Outcome
Table 2. Comparison of primary and secondary outcomes at 6–month follow up
Exercise and hot flushes and night sweats
571
572 0.32 0.60 0.61 0.41 0.53 0.63
WHQ Depressed mood Somatic symptoms Memory/concentration Anxiety/fears Sexual behaviour Sleep problems
SF–12 Physical component score Mental component score 49.6 (0.8) 45.9 (1.0)
5.8 (0.3) 8.1 (0.4)
26.7 (1.0) 13.6 (0.5)
Exercise confidence Sticking to it [8–40] Making time for it [4–20]
HADS Depression Anxiety
19.7 (0.9) 3.5 (0.2) 16.2 (0.9)
3.6 (0.1)
Social support & exercise Family participation [10–50] Family rewards [3–15] Friend participation [10–50]
Vitality
27.7 (0.3)
BMI
(0.03) (0.03) (0.03) (0.03) (0.03) (0.04)
73.5 (0.7)
Weight
(3.5) (2.5) (1.5) (0.2)
34.6 21.0 13.7 4.1
Exercise–DVD
Hot Flush Rating Scale Frequency hot flushes/night sweats per week Frequency hot flushes per week Frequency night sweats per week Hot flush problem–rating [1–10]
Outcome
(3.6) (2.6) (1.6) (0.2)
(0.03) (0.03) (0.03) (0.03) (0.03) (0.04)
49.7 (0.8) 46.9 (1.0)
5.3 (0.3) 7.4 (0.4)
25.2 (1.2) 13.4 (0.6)
20.3 (1.0) 3.9 (0.2) 17.6 (1.0)
3.9 (0.1)
0.28 0.55 0.62 0.36 0.53 0.60
28.5 (0.3)
75.6 (0.7)
34.3 22.1 12.3 4.1
Mean (SE)
Exercise–social support
Table 3. Comparison of primary and secondary outcomes at 12–month follow up
(3.4) (2.5) (1.5) (0.2)
(0.03) (0.03) (0.03) (0.03) (0.03) (0.03)
49.4 (0.8) 45.6 (1.0)
5.9 (0.3) 8.4 (0.4)
26.9 (1.1) 13.4 (0.5)
18.0 (0.9) 3.6 (0.2) 16.6 (0.9)
3.6 (0.1)
0.34 0.63 0.64 0.38 0.57 0.65
28.0 (0.3)
74.2 (0.7)
37.8 23.3 14.4 4.4
Control
( ( ( (
12.7 to 6.4) 9.2 to 4.7) 5.0 to 3.4) 1.0 to 0.3)
( ( ( ( ( (
0.09 0.10 0.13 0.05 0.13 0.11
to to to to to to
0.05) 0.05) 0.06) 0.11) 0.06) 0.08)
0.2 ( 2 to 2.4) 0.2 ( 2.4 to 2.9)
0.05 ( 0.9 to 0.8) 0.4 ( 1.4 to 0.7)
0.2 ( 3.2 to 2.7) 0.2 ( 1.2 to 1.7)
1.7 ( 0.9 to 4.3) 0.2 ( 0.6 to 0.3) 0.4 ( 2.9 to 2.1)
0.04 ( 0.36 to 0.29)
0.02 0.03 0.04 0.03 0.03 0.02
0.3 ( 1.1 to 0.4)
0.8 ( 2.7 to 1.2)
3.2 2.3 0.8 0.4
Adjusted* mean (95% CI)
0.87 0.86
0.92 0.49
0.87 0.77
0.19 0.52 0.74
0.83
0.57 0.48 0.44 0.49 0.49 0.73
0.38
0.43
0.52 0.53 0.72 0.25
P–value
Comparison Exercise–DVD–versus control
( ( ( (
13.2 to 6.1) 8.3 to 5.9) 6.4 to 2.1) 1.0 to 0.3)
( ( ( ( ( (
0.13 0.15 0.12 0.11 0.13 0.14
to to to to to to
0.01) 0.002) 0.07) 0.06) 0.07) 0.05)
0.3 ( 1.9 to 2.5) 1.2 ( 1.5 to 3.9)
0.6 ( 1.5 to 0.3) 1.0 ( 2.0 to 0.02)
1.7 ( 4.9 to 1.4) 0.03 ( 1.5 to 1.5)
2.3 ( 0.3 to 5.0) 0.2 ( 0.2 to 0.7) 1.0 ( 1.6 to 3.6)
0.30 ( 0.03 to 0.63)
0.06 0.08 0.02 0.02 0.03 0.04
0.5 ( 0.2 to 1.3)
1.3 ( 0.6 to 3.3)
3.5 1.2 2.2 0.3
Adjusted* mean (95% CI)
0.77 0.36
0.17 0.053
0.28 0.97
0.09 0.32 0.46
0.08
0.11 0.04 0.62 0.60 0.52 0.38
0.16
0.18
0.47 0.74 0.32 0.33
P–value
Comparison Exercise–social support versus Control
Daley et al.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Discussion Main findings Neither of the exercise interventions resulted in women reporting significantly fewer hot flushes/night sweats per week compared with controls at the 6- and 12-month follow ups. The 95% confidence intervals did not include the minimum 50% reduction in symptoms that we planned to detect. This finding is further supported by the prospective symptom diary reports completed throughout the intervention period, participants across all groups recording very similar frequencies of hot flushes/night sweats and severity scores. The self-reported data showed that women in both exercise groups reported participating in more (double the rate) vigorous intensity exercise than controls at the 6-month follow up, demonstrating the interventions were effective in increasing this type of activity. Total physical activity scores also favoured the exercise intervention groups, particularly the exercise-social support group, compared with controls at the 6-month follow up. The exercise-social support group reported significantly lower somatic symptoms and sleep problem scores, as well as lower anxiety scores, which were clinically meaningful;24 this intervention therefore had a greater effect on general symptoms of menopause than on hot flushes/night sweats specifically.
Strength and limitations of the study This study is one of the largest trials to date to examine the effectiveness of exercise as a treatment for hot flushes/ night sweats compared with controls in symptomatic women and is the only trial to recruit from general practices. A major strength of this study is that only women who were experiencing five or more hot flushes/night sweats per day (at least 35 per week) were eligible. On average, participants were in fact experiencing substantially more hot flushes/night sweats than the inclusion criteria, about nine per day (62–65 per week) at baseline, meaning we recruited women who were experiencing very frequent symptoms and rated these as problematic for them. Other studies25,26 have recruited women with relatively low frequencies of symptoms at baseline. Trials that recruit women with infrequent symptoms may be prone to a ‘floor effect’, an inability to detect an effect if it exists, which was not a concern for this trial. There was very low loss to follow up at both 6 (primary) and 12 months. It is possible that other types of exercise intervention might be effective, although the interventions tested here were based on extensive pilot work13 that assessed the exercise preferences of menopausal women. We assessed outcomes at 12 months; no study to date in this population has included trial follow up for this length of time. Only ~18% of women within the age eligibility criteria
ª 2014 Royal College of Obstetricians and Gynaecologists
responded to the invitation from their GP to complete the screening questionnaire, although it is likely that many of these non-responders would have been asymptomatic and thus chose not to respond. A broad range of women were recruited from 23 general practices across the West Midlands, UK. We recruited women who varied in deprivation status and 10% were of non-White ethnicity, meaning that the results in these respects should have good generalisability.
Interpretation Observational studies27–29 have reported lower frequency and severity of hot flushes/night sweats in women who exercise regularly compared with their less active counterparts. This trial showed that symptomatic women randomised to receive community-based exercise interventions did not report experiencing significantly fewer hot flushes/night sweat, or that these were less bothersome, compared with controls. This study adds to the findings of the recent Cochrane review,11 which was unable to make a definitive conclusion due to insufficient (high quality) evidence. These results are also consistent with a trial of women with breast cancer experiencing treatment-induced vasomotor symptoms which found that a home-based exercise intervention did not significantly reduce the frequency of hot flushes/night sweats or problem rating score compared with the control group.30 A substantial number of menopausal women typically experience somatic symptoms and difficulties sleeping. The finding here that the exercise-social support group significantly improved sleep and reduced somatic symptoms is consistent with other exercise studies involving menopausal women and other populations.31,32 In line with the behavioural goals of the interventions, both exercise groups reported participating in more vigorous intensity exercise than controls. It has been postulated that the effects of exercise upon hot flushes/night sweats may be mediated by exercise intensity.33 It has been suggested the concentration of beta endorphins (which are decreased as estrogen production declines, enhancing the release of norepinephrine and serotonin), is more likely to occur during higher intensity than lower intensity exercise and that basal levels of beta endorphins are higher in active individuals than in those who are less active.34,35 Intervention participants were informed of the principles of this hypothesis and the importance of exercise intensity to reduce their symptoms. The increase in vigorous intensity exercise indicates that the intervention participants put this message into practice, and that women were achieving sufficient amounts of exercise to impact their symptoms should exercise have been an effective intervention. Contrary to current guidance, women should not be advised that exercise will reduce hot flushes/night sweats.
573
Daley et al.
This study was statistically powered to detect a 50% reduction in symptoms (i.e. frequency of 40 down to 20 hot flushes/night sweats per week). We cannot rule out the possibility that exercise may lead to a smaller effect on hot flushes/night sweats than this study was powered to detect. However, even if regular exercise reduced symptoms by a smaller amount than we were able to detect, a question remains about whether women would be prepared to commit to doing so, in return for little relief from their symptoms. It also remains questionable whether doctors/ physicians would be prepared to recommend exercise to women seeking treatment for their vasomotor symptoms if the impact on symptoms was likely to be small. Regardless, there are many other good reasons why doctors should encourage women to exercise regularly around the time of the menopause when they might need the health gains from exercise the most (i.e. reduce risks of osteoporosis and cardiovascular disease, improved muscle strength), all evidenced-based effects of exercise.16
Conclusion In conclusion, this study indicates that exercise is not an effective treatment for hot flushes/night sweats. Contrary to current guidance, women seeking treatment for their hot flushes/night sweats should not be advised that exercise is an effective treatment.
Trial registration ISRCTN registration: ISRCTN06495625.
Study sponsor University of Birmingham acted as sponsor for the study. The writing of the report and the decision to submit the article for publication rested with the authors from the University of Birmingham.
Data sharing Additional data can be obtained from the corresponding author for the purposes of secondary research.
Disclosure of interests None.
Contributions to authorship AD developed the initial idea for the study with assistance from CM, HSL and MR. AT, SC and MH also contributed to the development of the trial protocol at a later stage. AD wrote the initial draft of the manuscript with assistance from all the authors. AR is the trial statistician and performed the power calculations and wrote the analysis plan. All authors have seen and agreed the final version of the manuscript. AD is the guarantor.
574
The corresponding author (AD) confirms that everyone who contributed significantly to the work is in the Acknowledgments.
Ethics approval Favourable ethical opinion for this study was granted by the West Midlands Research Ethics Committee in March 2010 (ref: 10/H1208/3).
Funding This study was funded by the National Institute for Health Research School for Primary Care Research. AD is supported by a National Institute for Health Research Senior Research Fellowship. CM is part funded by the NIHR through the Collaborations for Leadership in Applied Health Research and Care for West Midlands (CLAHRCWM) programme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Acknowledgements We would like to thank patients and staff who participated in the study. We would also like to thank the Primary Care Clinical Research and Trials Unit at the University of Birmingham for their help in developing the study.
Supporting Information Additional Supporting Information may be found in the online version of this article: Table S1. Baseline questionnaires and physical activity. Table S2. Self reported physical activity data at follow up. &
References 1 Greendale GA, Lee N, Arriola E. The menopause. Lancet 1999;353:571–80. 2 Rossouw JE, Anderson G, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomised controlled trial. JAMA 2002;288:321–33. 3 Usher C, Teeling M, Bennett K, Feely J. Effect of clinical trial publicity on HRT prescribing in Ireland. Eur J Clin Pharmacol 2006;62:307–10. 4 Lawton B, Rose S, McLeod D, Dowell A. Change in use of hormone replacement therapy after the report from the women’s health initiative: cross sectional survey of users. BMJ 2003;327:845–6. 5 Hersh A, Stefanick M, Stafford R. National use of postmenopausal hormone replacement therapy: annual trend and response to recent evidence. JAMA 2004;291:47–53. 6 UK Committee for Safety of Medicines. HRT: update on the risk of breast cancer and long-term safety. Curr Prob Pharmacovigil 2003;29:1–3.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
7 Daley AJ, MacArthur C, McManus R, Stokes-Lampard H, Wilson S, Roalfe A, et al. Factors associated with the use of complementary medicine and non-pharmacological interventions in symptomatic menopausal women. Climacteric 2006;9:336–46. 8 Royal College of Obstetricians and Gynaecologists. Scientific Advisory Committee. Alternatives to HRT for the management of symptoms of the menopause. Scientific Impact paper 6. 2010 [https://www.rcog.org.uk/en/guidelines-research-services/guidelines/ sip6/]. Accessed 3 August 2012. 9 Royal College of Obstetricians and Gynaecologists. Alternatives to hormone replacement therapy for symptoms of the menopause. 2011 [https://www.rcog.org.uk/en/patients/patient-leaflets/alternatives-to-hrtfor-symptoms-of-the-menopause/]. Accessed 3 August 2012. 10 North American Menopause Society. Consumer Education Committee. Treating hot flushes. 2012 [http://www.menopause.org/ docs/for-women/mnflushes.pdf]. Accessed 15 June 2014. 11 Daley A, Stokes-Lampard H, MacArthur C. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007;17: CD006108. 12 Huang AJ, Subka L, Wing R, West DS, Hernandez AL, Macer J, et al. An intensive behavioural weight loss intervention and hot flushes in women. Arch Intern Med 2010;12:1161–7. 13 Daley AJ, Stokes-Lampard H, Wilson S, Rees M, Roalfe A, MacArthur C. What women want? Exercise preferences of menopausal women. Maturitas 2011;68:174–8. 14 Daley AJ, Stokes-Lampard H, Thomas A, Rees M, Coleman S, Roalfe A, et al. Aerobic exercise as a treatment for vasomotor menopausal symptoms: randomised controlled trial protocol. Maturitas 2013;76:350–6. 15 Hunter MS, Liao KLM. A psychological analysis of menopausal hot flushes. Br J Clin Psychol 1995;34:589–99. 16 Chief Medical Officers of England, Scotland, Wales, and Northern Ireland. Start Active, Stay Active. A report on physical activity for health from the four home countries’ Chief Medical Officers. Department of Health, 2011 [https://www.gov.uk/government/ publications/start-active-stay-active-a-report-on-physical-activity-fromthe-four-home-countries-chief-medical-officers]. Accessed 11 September 2012. 17 Hunter MS. The women’s health questionnaire: a measure of midaged women’s perceptions of their emotional and physical health. Psychol Health 1992;7:45–54. 18 Ware JE, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33. 19 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 20 Bostic TJ, Rubio DM, Hood M. A validation of the subjective vitality scale using structural equation modeling. Soc Indic Res 2000;52: 313–24.
ª 2014 Royal College of Obstetricians and Gynaecologists
21 Sallis JF, Pinski RB, Grossman RM, Patterson TL, Nader PR. The development of self-efficacy scales for health-related diet and exercise behaviours. Health Educ Res 1988;3:283–92. 22 Sallis JF, Grossman RM, Pinski RB, Patterson TL, Nader PR. The development of scales to measure social support for diet and exercise behaviours. Prev Med 1987;16:825–36. €stro €m M, Bauman AE, Booth ML, 23 Craig CL, Marshall AL, Sjo Ainsworth BE, et al. International physical activity questionnaire: 12country reliability and validity. Med Sci Sports Exerc 2003;35:1381– 95. 24 Hunter MH. The Women’s Health Questionnaire (WHQ): frequently asked questions (FAQ). Health Qual Life Outcomes 2003;1:41. 25 Luoto R, Moilanen J, Heinonen R, Mikkola T, Raitanen J, Ojala TE, et al. Effects of aerobic training on hot flushes and quality of life-a randomized controlled trial. Ann Med 2012;44:616–26. 26 Sternfeld B, Guthrie KA, Ensrud KE, LaCroix AZ, Larson JC, Dunn AL, et al. Efficacy of exercise for menopausal symptoms: a randomized controlled trial. Menopause 2014;21:330–8. 27 Gold EB, Sternfeld B, Kelsey JL. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. Am J Epidemiol 2000;152:463–73. 28 Progetto Menopausa Italia Study Group. Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy. Maturitas 2005;52:181–9. 29 Ivarsson T, Spetz AC, Hammar M. Physical exercise and vasomotor symptoms in postmenopausal women. Maturitas 1998; 29:139–46. 30 Duijits SF, van Beurden M, Oldenberg HS, Hunter MS, Kieffer JM, Stuiver MM, et al. Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial. J Clin Oncol 2012;30:4124–33. 31 Tworoger SS, Yasui Y, Vitiello MV, Schwartz RS, Ulrich CM, Aiello EJ, et al. Effects of a yearlong moderate-intensity exercise and stretching intervention on sleep quality in postmenopausal women. Sleep 2003;26:830–6. 32 King AC, Oman RF, Brassington GS, Bliwise DL, Haskell WL. Moderate-intensity exercise and self-rated quality of sleep in older adults: a randomised controlled trial. JAMA 1997;277:32–7. 33 Daley AJ, MacArthur C, Stokes-Lampard H. Exercise to reduce vasomotor and other menopausal symptoms: a review. Maturitas 2009;63:176–80. 34 Bortz WM, Angwin P, Mefford IN. Catecholamines, dopamine and endorphin levels during extreme exercise. N Engl J Med 1981;305:466–7. 35 Heitkamp HC, Huber W, Scheib K. Beta-endorphin and adrenocorticotropin after incremental exercise and marathon running – female response. Eur J Appl Physiol Occup Physiol 1996;72:417–24.
575
Copyright of BJOG: An International Journal of Obstetrics & Gynaecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
DOI: 10.1111/1471-0528.13193 www.bjog.org
The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial AJ Daley,a A Thomas,b AK Roalfe,a H Stokes-Lampard,a S Coleman,a M Rees,c MS Hunter,d C MacArthure a
Primary Care Clinical Sciences, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK b Macquarie University, Macquarie Park, NSW, Australia c Women’s Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK d Institute of Psychiatry, King’s College London, London, UK e Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK Correspondence: Dr AJ Daley, Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham B15 2TT, UK. Email [email protected] Accepted 14 September 2014. Published Online 17 December 2014.
Objective To investigate the effectiveness of exercise as treatment
Main outcome measure The primary outcome was frequency of
for vasomotor menopausal symptoms.
hot flushes/night sweats at 6-month up.
Design Three-group randomised controlled trial, two exercise
Results Two hundred and sixty-one women were randomised (n = 87 per group). Neither of the exercise intervention groups reported significantly less frequent hot flushes/night sweats per week than controls (exercise-DVD versus control: 8.9, 95% CI 20.0 to 2.2; exercise-social support versus control: 5.2, 95% CI 16.7 to 6.3).
interventions and a control group. Setting Primary Care, West Midlands UK. Population Perimenopausal and postmenopausal women
experiencing at least five hot flushes/night sweats per day and not taken MHT in previous 3 months were recruited from 23 general practices. Methods Participants in both exercise interventions groups were
offered two face-to-face consultations with a physical activity facilitator to support engagement in regular exercise. In addition, one exercise group received a menopause-specific information DVD and written materials to encourage regular exercise and the other exercise group was offered the opportunity to attend exercise social support groups in their communities. Interventions lasted 6 months.
Conclusions This trial indicates that exercise is not an effective
treatment for hot flushes/night sweats. Contrary to current clinical guidance, women should not be advised that exercise will relieve their vasomotor menopausal symptoms. Keywords Exercise, hot flushes, menopause, night sweats, primary
care. Linked article This article is commented on by G Bachmann,
p. 576 in this issue. To view this mini commentary visit http://dx. doi.org/10.1111/1471-0528.13207.
Please cite this paper as: Daley AJ, Thomas A, Roalfe AK, Stokes-Lampard H, Coleman S, Rees M, Hunter MS, MacArthur C. The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial. BJOG 2015;122:565–575.
Introduction Many perimenopausal and postmenopausal women experience hot flushes/night sweats that negatively impact on their health and quality of life.1 Menopausal hormone therapy (MHT) is an effective treatment and, until recently, popular among patients and doctors. Research and media scares, however, have raised questions about the safety of MHT.2,3 Many women are now reluctant to consider MHT as treatment and doctors are more cautious about prescribing it.4–6
ª 2014 Royal College of Obstetricians and Gynaecologists
As many women are choosing to avoid MHT it is increasingly important to identify other evidence-based interventions.7 One possible treatment option is exercise, and the Scientific Advisory Committee of The Royal College of Obstetricians and Gynaecologists, and their Patient Information Committee have already advised that regular sustained aerobic exercise (e.g. running and swimming) may be an effective intervention.8,9 Likewise, The North American Menopause Society states that women who are overweight (most menopausal women) have more hot flushes, so it is
565
Daley et al.
important for them to maintain a healthy weight and exercise regularly to decrease bothersome hot flushes.10 Although exercise has been recommended as a treatment for hot flushes/flushes/night sweats, available evidence is inconclusive. The recently updated Cochrane review of exercise for the management of vasomotor menopausal symptoms in symptomatic women concluded that existing evidence suggests exercise is not an effective treatment for vasomotor menopausal symptoms but a definitive statement could not be made until more evidence was available.11 The trials had also typically included relatively short interventions and follow up. This is important because the effects of exercise on hot flushes/night sweats may not be immediate, particularly if the mechanism of effect is via a reduction in adiposity.12 The RCT reported here aimed to investigate the feasibility/acceptability of two exercise interventions identified from our previous pilot study relative to a control group,13 and if feasible and acceptable, to continue to recruit sufficient women to examine the effectiveness of these interventions on hot flushes/night sweats compared with a control group. In the feasibility phase we randomised 165 women to one of the three trial groups.14 The interventions were deemed feasible and acceptable, with high recruitment and good adherence, therefore the trial continued to investigate the effectiveness of the exercise interventions in reducing hot flushes and night sweats.14
Methods Setting and participants This study is a randomised controlled trial (RCT) with 261 participants allocated to one of two 6-month exercise interventions or a control group. The published protocol provides more detail regarding the feasibility phase, which indicated that the trial was feasible with no protocol changes needed.14 Women aged 48–57 years were identified from general practice records and the practices sent the study invitation letter, information leaflet and screening questionnaire to these patients and asked them to return their screening questionnaire to the research team. A reminder was sent to non-responders 3 weeks later. The screening questionnaire assessed frequency of hot flushes/night sweats,15 menopausal status, MHT use, menstrual cycle length, contraception/medication use and current levels of exercise to ascertain eligibility. General practices (n = 23) across the West Midlands assisted with recruitment. Recruitment began in April 2011 and final follow up was completed in September 2014.
Eligibility Perimenopausal and postmenopausal women who were currently experiencing five or more hot flushes/night sweats
566
each day of any severity and had not used MHT in the previous 3 months to baseline were eligible. Only women who were inactive (not currently meeting the public health guidelines for physical activity16) were eligible. Women using oral or injectable hormonal contraception, tamoxifen, tibolone and raloxifene in the previous 3 months, who were unable to provide written informed consent or who were unable to understand English sufficiently to complete the research questionnaires were excluded, as were women whom the GP considered unsuitable.
Outcomes and process measures The primary outcome was the frequency of hot flushes/ night sweats measured by hot flush rating scale15 at 6month up. Secondary outcomes included hot flushes/night sweats frequency at 12-month’up. Problem rating of hot flushes/flushes,15 menopause-specific quality of life subscales from the Women’s Health Questionnaire (WHQ),17 and generic QoL(SF-12),18 depression and anxiety,19 subjective vitality,20 self efficacy for exercise,21 social support for exercise22 and self reported physical activity measured using the International Physical Activity Questionnaireshort23 scores at 6 and 12 months follow up were also secondary outcomes. Adverse events were recorded.
Demographic data Demographic information on health behaviours, reproductive history and use of complementary and alternative medicine for symptom control were collected at baseline and follow up. Current medication use was collected at baseline and follow up.
Randomisation, concealment and blinding Participants were randomised to one of two 6-month exercise interventions or a control group on a 1:1:1 ratio. Group allocation was stratified by menopausal status (perimenopausal or post menopausal) and BMI (underweight/ normal weight or overweight/obese using self-reported height and weight). The allocation sequence was generated by the trial statistician using NQUERY ADVISOR 7.0 (Statistical Solutions, Cork, Ireland) with mixed blocked randomisation within strata. The methods of sequence generation were concealed (computer-generated and web-based) from researchers involved in recruiting and randomising participants. Participants, researchers and those delivering the intervention could not be blinded to group allocation.
Data collection Outcome measures were assessed at baseline and 6 months (immediately post intervention) and 12 months post randomisation. Outcome questionnaires were mailed to participants at follow-up times.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Participants in all groups were asked to complete prospective 7-day hot flush/night sweat diaries at weeks 7, 14, and 21 of the intervention to provide an indication of the profile of their symptoms throughout the intervention period, recording both frequency and severity of their symptoms. In the same weeks those randomised to intervention groups also completed 7-day prospective exercise logs that detailed the amount and type of exercise they had completed. The hot flush diaries and physical activity logs were sent and returned by freepost. A 50% random sample of all participants were asked to wear an Actiheart (CamNtech Ltd., Cambridge, UK) monitor for five consecutive days at baseline and 6-month up, to provide objective data about physical activity patterns over time to corroborate the self-reported physical activity data. The Actiheart device measures both exercise intensity and amount of physical activity achieved.
Interventions The development of the two exercise interventions and their rationale are described in detail in elsewhere.14 The intervention exercise goal was incremental over time with an initial goal (weeks 1–12) of progressing towards achieving 30 minutes of moderate intensity exercise on at least 3 days per week. During weeks 13–24, participants in the intervention groups were encouraged to accumulate at least 30 minutes of moderate intensity exercise on 3– 5 days per week. The definition of moderate intensity exercise that was given to participants was that they should aim for an increase in their breathing rate, an increase in their heart rate to the level where they could feel their pulse and an increase in body temperature. Participants were given examples of what types of activities were likely to constitute moderate intensity exercise (i.e. brisk walking, jogging, aerobics, swimming, cycling and tennis). Both interventions involved two-one-to-one consultations which typically lasted 40–60 minutes (during months 1 and 2). The consultations focused on equipping women with the skills, knowledge and confidence needed to participate in regular exercise and were delivered by a physical activity facilitator in the participant’s home. The first consultation focused on uptake of exercise and on enhancing motivation and self-efficacy for exercise. Participants were given a pedometer as a motivational tool. In addition to the one-to-one consultations one intervention group (herein referred to as the exercise-DVD group) were also sent a DVD, a booklet and five study leaflets at various times throughout the intervention; the intention was that these leaflets would act as regular reminders that prompted and encouraged exercise. These materials provided information about the menopause, benefits of exercise during menopause, and outlined strategies that could be used to motivate participants to exercise. Information
ª 2014 Royal College of Obstetricians and Gynaecologists
on the importance of healthy eating was also included. The DVD was developed specifically for this study and contained case studies of women who had recently experienced hot flushes/night sweats and discussed strategies that they had used to motivate themselves to exercise and the impact it had on their health. The second intervention, in addition to the consultations, involved participants being invited to take part in three exercise support groups in their local community (e.g. at community centres, general practices) (herein referred to as the exercisesocial support group). The primary purpose of these groups was to bring women together to share experiences about exercising during the menopause and offer regular encouragement to each other. The support groups focused on giving information about the symptoms of menopause and the importance of exercise and healthy eating during menopause and covered all the topics within the materials received by the exercise-DVD intervention group. These social support groups typically last 75–90 minutes.
Control group The control group were offered the opportunity to have an exercise consultation and were given a pedometer at the end of their involvement in the study.
Sample size and statistical analyses A sample size of 87 participants per group (n = 261) was sufficient to detect a 50% reduction in the mean number of hot flushes/night sweats per week (e.g. 40 reduced to 20 SD = 31.6)8 with 80% power and 5% significance level, allowing for 20% drop out between the intervention and control groups. Comparisons were made between the mean number of symptoms per week between the control group and each exercise intervention group. Pre-specified adjustments were made for baseline symptom frequency, menopausal status, BMI as well as antidepressant and MHT use recorded at 6month up. Paired comparisons were made between controls and each intervention group with P values adjusted for multiple testing. To identify any longer term effects of the intervention on symptoms, repeated measures mixed modelling of hot flushes/night sweats was conducted to compare groups across all time points, adjusting for covariates and multiple comparisons as previously described. Secondary outcomes were all compared at the 6- and 12month follow up using the same method as previously stated. The frequency, intensity, type and duration of exercise is summarised in MET/minutes/week. Bland–Altman plots were used to compare the agreement between the selfreported physical activity data and objectively measured physical activity. The number of adverse events that occurred during the intervention period is summarised by
567
Daley et al.
group. Bootstrapped estimates were calculated where there was evidence of non-normality in the residuals. The impact of missing primary data was explored by sensitivity analysis including multiple imputation. All analyses were by intention-to-treat.
significant differences between groups in flushes/night sweats problem rating scores at 6 or 12 months (Tables 2 and 3).
Results
The exercise-social support group reported significantly lower somatic symptoms scores at the 6-month (mean difference = 0.10, 95% CI 0.18 to 0.02) and 12-month (mean difference = 0.08, 95% CI 0.15 to 0.002) follow up, and significantly lower sleep problem scores (mean difference = 0.11, 95% CI 0.21 to 0.01) compared with the control group at the 6-month follow up. The results for anxiety were marginally different (mean difference = 1, 95% CI 2.0 to 0.02), favouring the exercisesocial support group at the 12-month follow up (Table 3).
Patients and recruitment Study invitation letters and screening questionnaires were sent by practices to 9409 women and 1715 (18%) were returned. Of these, 353/1715 (21%) were eligible and sent a participant information sheet, baseline questionnaires and consent form; the remainder were either ineligible (n = 1055) or not interested in participating (n = 307). Of those eligible and interested, 261 completed and returned the baseline questionnaires (n = 261/353, 74%) (see Figure 1).
Randomisation and participant’s baseline characteristics In all, 261 participants were randomised to one of the two exercise (n = 87 per group) or control groups (n = 87). Table 1 contains the baseline characteristics of randomised participants, which demonstrate a good balance between the groups on these variables. On average women were experiencing 9.1 hot flushes/night sweats per day and mean problem ratings were 6/10, suggesting moderately troublesome symptoms. The average age of participants was 52.3 years. Most participants lived in the two highest deprivation quartiles (55.3%), 10% were of non-white ethnicity, 67.4% were overweight/obese, 70.1% postmenopausal and 29.9% perimenopausal, and 16.8% were smokers. Baseline measures were also well balanced across the groups (Table 1, Table S1).
Follow-up rates and data At 6 months, 83.4% (n = 219/261) of randomised participants completed follow up (primary) and at 12 months the follow-up rate was 85.1% (n = 222/261). By the 6-month follow up, five participants had started to take MHT; this increased to 12 by the 12-month follow up. At both time points the number of participants using MHT was balanced across the groups. No adverse events were recorded.
Hot flushes and night sweats Neither exercise group reported significantly less frequent hot flushes/night sweats per week than controls at the 6month follow up (exercise-DVD group versus controls: mean difference = 8.9, 95% CI 20.0 to 2.2) (exercisesocial support group versus controls: mean difference = 5.2, 95% CI 16.7 to 6.3). The magnitude of the effect was reduced at 12 months. Similarly, there were no
568
Other menopausal symptoms (WHQ) and quality of life outcomes
Exercise for social support The exercise-DVD group reported they experienced significantly more support from their families to exercise compared with controls at the 6-month follow up (mean difference = 2.8, 95% CI 0.03–5.6). A similar increase was observed in the exercise-social support group compared with controls (mean difference = 2.8, 95% CI 0.1 to 5.7) (Tables 2 and 3).
Physical activity The exercise-social support group reported participating in significantly more MET/minutes/week of vigorous physical activity than controls at the 6-month follow up (mean difference = 403, 95% CI 78–727). There was a nonsignificant trend showing the exercise-DVD group reported completing more MET/minutes/week of vigorous physical activity compared with controls (mean difference = 336, 95% CI 27 to 669). The exercise-DVD group reported significantly lower walking (MET/minute/week) and total MET minutes/week mean scores compared with controls at the 12-month follow up (see Tables S1 and S2). Of those randomised to wear the Actiheart device, only 85/130 provided follow-up data/useable data. Although a Bland– Altman test to consider the agreement between selfreported and objectively measured physical activity data (moderate and vigorous intensity combined) showed a low mean discrepancy (98 MET/minutes/week, 95% CI 354 to 159), the limits of agreement were wide ( 2200 to 2037). The accelerometry data are available from the first author on request.
Prospective hot flushes/night sweats diaries (process outcome) A total of 393/783 (50%) (i.e. 261 participants 9 three diaries) of the hot flushes/night sweats symptom diaries were completed and returned, with 131/261 (50%) completing at
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Information letter and screening questionnaire sent to menopausal aged women aged 48-57 years by general practices (n = 9409)
Returned screening questionnaire (n = 1715)
Did not respond (n = 7694)
Experiencing five or more HF/NS and otherwise eligible and sent baseline questionnaire n = 353
Experiencing less than 5 HF/NS or otherwise ineligible (n = 1055) or not interested (n = 307)
Returned baseline questionnaire and randomised (n = 261)
Exercise-DVD intervention (Two exercise
Exercise–social support intervention (Exercise consultations
consultations plus leaflets & DVD) (n = 87)
plus support groups)
Control (n = 87)
(n = 87)
Completed follow up at 6 months for primary outcome Exercise-DVD (n = 75) Exercise–social support (n = 67) Usual care (n = 77) Intention to treat analysis was adopted
Completed follow up at 12 months for primary outcome Exercise-DVD (n = 74) Exercise–social support (n = 72) Usual care (n = 76) Intention to treat analysis was adopted
Figure 1. Trial flow.
least two of three diaries. A total of 83/261 (32%) participants did not complete even one diary. The average number of hot flushes/night sweats reported across the three diaries by the exercise-DVD, exercise-social support and control groups were 27.7, 36.7 and 38.7 per week, respectively, and average severity scores (1–10) were 5.1,
ª 2014 Royal College of Obstetricians and Gynaecologists
5.0 and 4.7 for each group, respectively. The data recorded in the prospective diaries during the intervention period for all groups corresponded very closely with the primary outcome of hot flushes rating scale scores at the 6-month follow up.
569
Daley et al.
Table 1. Comparability of baseline characteristics Exercise–DVD (n = 87) n (%)
Exercise–social support (n = 87) n (%)
Control (n = 87) n (%)
52.3 (2.4)
52.7 (2.5)
52.0 (2.4)
27 (31) 60 (69)
26 (30) 61 (70)
25 (29) 62 (71)
BMI* mean (SD) Under/normal Over/obese (>25 kg/m2)
28.2 (5.7) 28 (32) 59 (68)
27.8 (5.4) 29 (33) 58 (67)
28.0 (5.8) 28 (32) 59 (68)
Weight (kg) mean (SD)
75.9 (16.8)
72.6 (14.7)
73.9 (15.1)
Characteristics
Age (years) mean (SD) Menopausal* status Peri–menopausal Menopausal
IMD quartile 1 (least deprived) 2 3 4 (most deprived)
13 26 19 28
(14) (31) (23) (32)
12 26 19 28
(14) (30) (22) (32)
19 18 18 29
(22) (21) (21) (33)
Unknown
1 (1)
2 (2)
3 (3)
Non white ethnic origin
8 (9)
7 (8)
11 (13)
Non smokers
78 (90)
62 (71)
66 (77)
Education level Primary Secondary left at min age Secondary left after min age University or College of HE
2 36 13 36
(2) (41) (15) (42)
1 44 11 31
(1) (51) (13) (36)
0 34 17 36
(0) (39) (20) (41)
Employment status Paid/self–employed Unemployed/retired/student Looking after home/family Sick/disabled Other/not known
75 2 2 7 1
(86) (2) (2) (8) (1)
67 3 9 7 1
(77) (3) (10) (8) (1)
70 6 8 2 1
(80) (7) (9) (2) (1)
Number of children, mean (SD)
2.1 (1.4)
2.0 (1.4)
2.0 (1.4)
Illness limiting activities/work
28 (32)
18 (20)
24 (28)
6 (7)
10 (11)
7 (8)
42 (48)
51 (59)
42 (53)
Taking antidepressants Using complementary/alternative therapies *Stratification variable at randomisation.
Adherence to the exercise intervention and intervention implementation A total of 244/522 (47%) (i.e. 174 intervention participants 9 three diaries) of the exercise diaries were completed and returned by women in the exercise intervention groups, with 83/174(48%) completing at least two diaries. Sixty-five (37%) participants failed to complete a single diary. In the diaries received, the exercise-social support and exercise-DVD groups reported completing an average of 281 and 297 min of at least moderate intensity exercise per week (40.1 and 42.4 minutes/day) respectively. Both groups
570
reported consistent levels of exercise across the three diary measurement points. The most common types of exercise were walking, aerobics/keep fit classes and swimming. Adherence to the various intervention contacts/components was high; 83% (n = 144/174) participants received both exercise consultations, 93% (n = 162/174) received at least one exercise consultation. In the exercise-DVD group, 90% (n = 78/87) received all the materials/leaflets that were part of this intervention. In the exercise-social support group, 55% (n = 48/87) attended at least one of the three support groups.
ª 2014 Royal College of Obstetricians and Gynaecologists
ª 2014 Royal College of Obstetricians and Gynaecologists
28.0 (0.4)
0.40 0.65 0.63 0.42 0.34 0.67
BMI
Women’s Health Questionnaire Depressed mood Somatic symptoms Memory/concentration Anxiety/fears Sexual behaviour Sleep problems
50.9 (1.9) 41.5 (2.4)
(0.06) (0.06) (0.44) (0.07) (0.13) (0.08)
51.5 (1.8) 42.5 (2.3)
6.5 (0.8) 9.0 (0.8)
28.2 (3.2) 13.5 (1.4)
19.3 (2.1) 3.9 (0.4) 14.6 (2.3)
3.8 (0.28)
0.34 0.56 0.60 0.39 0.29 0.56
28.1 (0.4)
74.3 (1.0)
35.8 (9.1) 3.8 (0.6)
Mean (SE)
Exercise–social support
(0.06) (0.06) (0.47) (0.07) (0.13) (0.08)
49.4 (1.8) 44.1 (2.3)
6.8 (0.8) 8.8 (0.8)
25.6 (3.2) 12.8 (1.4)
16.5 (2.1) 3.9 (0.4) 14.2 (2.3)
3.5 (0.28)
0.34 0.66 0.62 0.39 0.34 0.67
28.3 (0.4)
74.9 (1.0)
41.0 (9.3) 4.4 (0.6)
Control
( ( ( ( ( (
0.02 0.10 0.09 0.07 0.11 0.10
to to to to to to
0.14) 0.06) 0.11) 0.12) 0.10) 0.11)
1.4 ( 1.0 to 3.9) 2.5 ( 5.6 to 0.5)
0.4 ( 0.6 to 1.5) 0.7 ( 0.4 to 1.8)
2.5 ( 1.0 to 6.0) 0.8 ( 0.8 to 2.5)
2.8 (0.03 to 5.6) 0.2 ( 0.4 to 0.8) 0.9 ( 3.9 to 2.1)
0.05 ( 0.42 to 0.32)
0.06 0.02 0.01 0.03 0.005 0.005
0.2 ( 0.7 to 0.3)
0.5 ( 1.7 to 0.8)
8.9 ( 20.0 to 2.2) 0.2 ( 0.6 to 0.9)
Adjusted* mean (95% CI)
0.31 0.11
0.55 0.27
0.19 0.41
0.047 0.68 0.75
0.94
0.16 0.83 0.94 0.73 0.99 0.99
0.52
0.62
0.14 0.76
P–value
Comparison Exercise–DVD versus control
( ( ( ( ( (
0.09 0.18 0.13 0.10 0.16 0.21
to to to to to to
0.07) 0.02) 0.08) 0.09) 0.05) 0.01)
2.0 ( 0.4 to 4.5) 1.6 ( 4.7 to 1.5)
0.3 ( 1.3 to 0.8) 0.1 ( 1.0 to 1.3)
2.7 ( 1.1 to 6.5) 0.8 ( 1.0 to 2.5)
2.8 ( 0.1 to 5.7) 0.01 ( 0.6 to 0.6) 0.4 ( 2.7 to 3.5)
0.25 ( 0.13 to 0.64)
0.01 0.10 0.02 0.002 0.05 0.11
0.2 ( 0.7 to 0.3)
0.6 ( 1.8 to 0.7)
5.2 ( 16.7 to 6.3) 0.6 ( 1.3 to 0.1)
0.12 0.42
0.79 0.96
0.20 0.52
0.06 0.99 0.95
0.24
0.98 0.01 0.84 0.99 0.41 0.04
0.64
0.53
0.50 0.13
P–value
Comparison Exercise–social support versus control Adjusted* mean (95% CI)
*Adjusted by baseline value, BMI (≤25, >25 kg/m2), menopausal status, hormone replacement therapy/anti–depression medication recorded at follow up.
SF–12 Physical component score Mental component score
7.2 (0.8) 9.6 (0.9)
28.1 (3.3) 13.6 (1.5)
Exercise confidence Sticking to it [8–40] Making time for it [4–20]
HADS Depression Anxiety
19.3 (2.2) 4.1 (0.5) 13.3 (2.3)
3.5 (0.29)
Social support and exercise Family participation [10–50] Family rewards [3–15] Friend participation [10–50]
Vitality
74.4 (1.0)
Weight
(0.06) (0.06) (0.48) (0.07) (0.13) (0.08)
32.1 (9.3) 4.6 (0.6)
Exercise–DVD
Hot Flush Rating Scale Frequency hot flushes/night sweats per week Hot flush problem– rating [1–10]
Outcome
Table 2. Comparison of primary and secondary outcomes at 6–month follow up
Exercise and hot flushes and night sweats
571
572 0.32 0.60 0.61 0.41 0.53 0.63
WHQ Depressed mood Somatic symptoms Memory/concentration Anxiety/fears Sexual behaviour Sleep problems
SF–12 Physical component score Mental component score 49.6 (0.8) 45.9 (1.0)
5.8 (0.3) 8.1 (0.4)
26.7 (1.0) 13.6 (0.5)
Exercise confidence Sticking to it [8–40] Making time for it [4–20]
HADS Depression Anxiety
19.7 (0.9) 3.5 (0.2) 16.2 (0.9)
3.6 (0.1)
Social support & exercise Family participation [10–50] Family rewards [3–15] Friend participation [10–50]
Vitality
27.7 (0.3)
BMI
(0.03) (0.03) (0.03) (0.03) (0.03) (0.04)
73.5 (0.7)
Weight
(3.5) (2.5) (1.5) (0.2)
34.6 21.0 13.7 4.1
Exercise–DVD
Hot Flush Rating Scale Frequency hot flushes/night sweats per week Frequency hot flushes per week Frequency night sweats per week Hot flush problem–rating [1–10]
Outcome
(3.6) (2.6) (1.6) (0.2)
(0.03) (0.03) (0.03) (0.03) (0.03) (0.04)
49.7 (0.8) 46.9 (1.0)
5.3 (0.3) 7.4 (0.4)
25.2 (1.2) 13.4 (0.6)
20.3 (1.0) 3.9 (0.2) 17.6 (1.0)
3.9 (0.1)
0.28 0.55 0.62 0.36 0.53 0.60
28.5 (0.3)
75.6 (0.7)
34.3 22.1 12.3 4.1
Mean (SE)
Exercise–social support
Table 3. Comparison of primary and secondary outcomes at 12–month follow up
(3.4) (2.5) (1.5) (0.2)
(0.03) (0.03) (0.03) (0.03) (0.03) (0.03)
49.4 (0.8) 45.6 (1.0)
5.9 (0.3) 8.4 (0.4)
26.9 (1.1) 13.4 (0.5)
18.0 (0.9) 3.6 (0.2) 16.6 (0.9)
3.6 (0.1)
0.34 0.63 0.64 0.38 0.57 0.65
28.0 (0.3)
74.2 (0.7)
37.8 23.3 14.4 4.4
Control
( ( ( (
12.7 to 6.4) 9.2 to 4.7) 5.0 to 3.4) 1.0 to 0.3)
( ( ( ( ( (
0.09 0.10 0.13 0.05 0.13 0.11
to to to to to to
0.05) 0.05) 0.06) 0.11) 0.06) 0.08)
0.2 ( 2 to 2.4) 0.2 ( 2.4 to 2.9)
0.05 ( 0.9 to 0.8) 0.4 ( 1.4 to 0.7)
0.2 ( 3.2 to 2.7) 0.2 ( 1.2 to 1.7)
1.7 ( 0.9 to 4.3) 0.2 ( 0.6 to 0.3) 0.4 ( 2.9 to 2.1)
0.04 ( 0.36 to 0.29)
0.02 0.03 0.04 0.03 0.03 0.02
0.3 ( 1.1 to 0.4)
0.8 ( 2.7 to 1.2)
3.2 2.3 0.8 0.4
Adjusted* mean (95% CI)
0.87 0.86
0.92 0.49
0.87 0.77
0.19 0.52 0.74
0.83
0.57 0.48 0.44 0.49 0.49 0.73
0.38
0.43
0.52 0.53 0.72 0.25
P–value
Comparison Exercise–DVD–versus control
( ( ( (
13.2 to 6.1) 8.3 to 5.9) 6.4 to 2.1) 1.0 to 0.3)
( ( ( ( ( (
0.13 0.15 0.12 0.11 0.13 0.14
to to to to to to
0.01) 0.002) 0.07) 0.06) 0.07) 0.05)
0.3 ( 1.9 to 2.5) 1.2 ( 1.5 to 3.9)
0.6 ( 1.5 to 0.3) 1.0 ( 2.0 to 0.02)
1.7 ( 4.9 to 1.4) 0.03 ( 1.5 to 1.5)
2.3 ( 0.3 to 5.0) 0.2 ( 0.2 to 0.7) 1.0 ( 1.6 to 3.6)
0.30 ( 0.03 to 0.63)
0.06 0.08 0.02 0.02 0.03 0.04
0.5 ( 0.2 to 1.3)
1.3 ( 0.6 to 3.3)
3.5 1.2 2.2 0.3
Adjusted* mean (95% CI)
0.77 0.36
0.17 0.053
0.28 0.97
0.09 0.32 0.46
0.08
0.11 0.04 0.62 0.60 0.52 0.38
0.16
0.18
0.47 0.74 0.32 0.33
P–value
Comparison Exercise–social support versus Control
Daley et al.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
Discussion Main findings Neither of the exercise interventions resulted in women reporting significantly fewer hot flushes/night sweats per week compared with controls at the 6- and 12-month follow ups. The 95% confidence intervals did not include the minimum 50% reduction in symptoms that we planned to detect. This finding is further supported by the prospective symptom diary reports completed throughout the intervention period, participants across all groups recording very similar frequencies of hot flushes/night sweats and severity scores. The self-reported data showed that women in both exercise groups reported participating in more (double the rate) vigorous intensity exercise than controls at the 6-month follow up, demonstrating the interventions were effective in increasing this type of activity. Total physical activity scores also favoured the exercise intervention groups, particularly the exercise-social support group, compared with controls at the 6-month follow up. The exercise-social support group reported significantly lower somatic symptoms and sleep problem scores, as well as lower anxiety scores, which were clinically meaningful;24 this intervention therefore had a greater effect on general symptoms of menopause than on hot flushes/night sweats specifically.
Strength and limitations of the study This study is one of the largest trials to date to examine the effectiveness of exercise as a treatment for hot flushes/ night sweats compared with controls in symptomatic women and is the only trial to recruit from general practices. A major strength of this study is that only women who were experiencing five or more hot flushes/night sweats per day (at least 35 per week) were eligible. On average, participants were in fact experiencing substantially more hot flushes/night sweats than the inclusion criteria, about nine per day (62–65 per week) at baseline, meaning we recruited women who were experiencing very frequent symptoms and rated these as problematic for them. Other studies25,26 have recruited women with relatively low frequencies of symptoms at baseline. Trials that recruit women with infrequent symptoms may be prone to a ‘floor effect’, an inability to detect an effect if it exists, which was not a concern for this trial. There was very low loss to follow up at both 6 (primary) and 12 months. It is possible that other types of exercise intervention might be effective, although the interventions tested here were based on extensive pilot work13 that assessed the exercise preferences of menopausal women. We assessed outcomes at 12 months; no study to date in this population has included trial follow up for this length of time. Only ~18% of women within the age eligibility criteria
ª 2014 Royal College of Obstetricians and Gynaecologists
responded to the invitation from their GP to complete the screening questionnaire, although it is likely that many of these non-responders would have been asymptomatic and thus chose not to respond. A broad range of women were recruited from 23 general practices across the West Midlands, UK. We recruited women who varied in deprivation status and 10% were of non-White ethnicity, meaning that the results in these respects should have good generalisability.
Interpretation Observational studies27–29 have reported lower frequency and severity of hot flushes/night sweats in women who exercise regularly compared with their less active counterparts. This trial showed that symptomatic women randomised to receive community-based exercise interventions did not report experiencing significantly fewer hot flushes/night sweat, or that these were less bothersome, compared with controls. This study adds to the findings of the recent Cochrane review,11 which was unable to make a definitive conclusion due to insufficient (high quality) evidence. These results are also consistent with a trial of women with breast cancer experiencing treatment-induced vasomotor symptoms which found that a home-based exercise intervention did not significantly reduce the frequency of hot flushes/night sweats or problem rating score compared with the control group.30 A substantial number of menopausal women typically experience somatic symptoms and difficulties sleeping. The finding here that the exercise-social support group significantly improved sleep and reduced somatic symptoms is consistent with other exercise studies involving menopausal women and other populations.31,32 In line with the behavioural goals of the interventions, both exercise groups reported participating in more vigorous intensity exercise than controls. It has been postulated that the effects of exercise upon hot flushes/night sweats may be mediated by exercise intensity.33 It has been suggested the concentration of beta endorphins (which are decreased as estrogen production declines, enhancing the release of norepinephrine and serotonin), is more likely to occur during higher intensity than lower intensity exercise and that basal levels of beta endorphins are higher in active individuals than in those who are less active.34,35 Intervention participants were informed of the principles of this hypothesis and the importance of exercise intensity to reduce their symptoms. The increase in vigorous intensity exercise indicates that the intervention participants put this message into practice, and that women were achieving sufficient amounts of exercise to impact their symptoms should exercise have been an effective intervention. Contrary to current guidance, women should not be advised that exercise will reduce hot flushes/night sweats.
573
Daley et al.
This study was statistically powered to detect a 50% reduction in symptoms (i.e. frequency of 40 down to 20 hot flushes/night sweats per week). We cannot rule out the possibility that exercise may lead to a smaller effect on hot flushes/night sweats than this study was powered to detect. However, even if regular exercise reduced symptoms by a smaller amount than we were able to detect, a question remains about whether women would be prepared to commit to doing so, in return for little relief from their symptoms. It also remains questionable whether doctors/ physicians would be prepared to recommend exercise to women seeking treatment for their vasomotor symptoms if the impact on symptoms was likely to be small. Regardless, there are many other good reasons why doctors should encourage women to exercise regularly around the time of the menopause when they might need the health gains from exercise the most (i.e. reduce risks of osteoporosis and cardiovascular disease, improved muscle strength), all evidenced-based effects of exercise.16
Conclusion In conclusion, this study indicates that exercise is not an effective treatment for hot flushes/night sweats. Contrary to current guidance, women seeking treatment for their hot flushes/night sweats should not be advised that exercise is an effective treatment.
Trial registration ISRCTN registration: ISRCTN06495625.
Study sponsor University of Birmingham acted as sponsor for the study. The writing of the report and the decision to submit the article for publication rested with the authors from the University of Birmingham.
Data sharing Additional data can be obtained from the corresponding author for the purposes of secondary research.
Disclosure of interests None.
Contributions to authorship AD developed the initial idea for the study with assistance from CM, HSL and MR. AT, SC and MH also contributed to the development of the trial protocol at a later stage. AD wrote the initial draft of the manuscript with assistance from all the authors. AR is the trial statistician and performed the power calculations and wrote the analysis plan. All authors have seen and agreed the final version of the manuscript. AD is the guarantor.
574
The corresponding author (AD) confirms that everyone who contributed significantly to the work is in the Acknowledgments.
Ethics approval Favourable ethical opinion for this study was granted by the West Midlands Research Ethics Committee in March 2010 (ref: 10/H1208/3).
Funding This study was funded by the National Institute for Health Research School for Primary Care Research. AD is supported by a National Institute for Health Research Senior Research Fellowship. CM is part funded by the NIHR through the Collaborations for Leadership in Applied Health Research and Care for West Midlands (CLAHRCWM) programme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Acknowledgements We would like to thank patients and staff who participated in the study. We would also like to thank the Primary Care Clinical Research and Trials Unit at the University of Birmingham for their help in developing the study.
Supporting Information Additional Supporting Information may be found in the online version of this article: Table S1. Baseline questionnaires and physical activity. Table S2. Self reported physical activity data at follow up. &
References 1 Greendale GA, Lee N, Arriola E. The menopause. Lancet 1999;353:571–80. 2 Rossouw JE, Anderson G, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomised controlled trial. JAMA 2002;288:321–33. 3 Usher C, Teeling M, Bennett K, Feely J. Effect of clinical trial publicity on HRT prescribing in Ireland. Eur J Clin Pharmacol 2006;62:307–10. 4 Lawton B, Rose S, McLeod D, Dowell A. Change in use of hormone replacement therapy after the report from the women’s health initiative: cross sectional survey of users. BMJ 2003;327:845–6. 5 Hersh A, Stefanick M, Stafford R. National use of postmenopausal hormone replacement therapy: annual trend and response to recent evidence. JAMA 2004;291:47–53. 6 UK Committee for Safety of Medicines. HRT: update on the risk of breast cancer and long-term safety. Curr Prob Pharmacovigil 2003;29:1–3.
ª 2014 Royal College of Obstetricians and Gynaecologists
Exercise and hot flushes and night sweats
7 Daley AJ, MacArthur C, McManus R, Stokes-Lampard H, Wilson S, Roalfe A, et al. Factors associated with the use of complementary medicine and non-pharmacological interventions in symptomatic menopausal women. Climacteric 2006;9:336–46. 8 Royal College of Obstetricians and Gynaecologists. Scientific Advisory Committee. Alternatives to HRT for the management of symptoms of the menopause. Scientific Impact paper 6. 2010 [https://www.rcog.org.uk/en/guidelines-research-services/guidelines/ sip6/]. Accessed 3 August 2012. 9 Royal College of Obstetricians and Gynaecologists. Alternatives to hormone replacement therapy for symptoms of the menopause. 2011 [https://www.rcog.org.uk/en/patients/patient-leaflets/alternatives-to-hrtfor-symptoms-of-the-menopause/]. Accessed 3 August 2012. 10 North American Menopause Society. Consumer Education Committee. Treating hot flushes. 2012 [http://www.menopause.org/ docs/for-women/mnflushes.pdf]. Accessed 15 June 2014. 11 Daley A, Stokes-Lampard H, MacArthur C. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007;17: CD006108. 12 Huang AJ, Subka L, Wing R, West DS, Hernandez AL, Macer J, et al. An intensive behavioural weight loss intervention and hot flushes in women. Arch Intern Med 2010;12:1161–7. 13 Daley AJ, Stokes-Lampard H, Wilson S, Rees M, Roalfe A, MacArthur C. What women want? Exercise preferences of menopausal women. Maturitas 2011;68:174–8. 14 Daley AJ, Stokes-Lampard H, Thomas A, Rees M, Coleman S, Roalfe A, et al. Aerobic exercise as a treatment for vasomotor menopausal symptoms: randomised controlled trial protocol. Maturitas 2013;76:350–6. 15 Hunter MS, Liao KLM. A psychological analysis of menopausal hot flushes. Br J Clin Psychol 1995;34:589–99. 16 Chief Medical Officers of England, Scotland, Wales, and Northern Ireland. Start Active, Stay Active. A report on physical activity for health from the four home countries’ Chief Medical Officers. Department of Health, 2011 [https://www.gov.uk/government/ publications/start-active-stay-active-a-report-on-physical-activity-fromthe-four-home-countries-chief-medical-officers]. Accessed 11 September 2012. 17 Hunter MS. The women’s health questionnaire: a measure of midaged women’s perceptions of their emotional and physical health. Psychol Health 1992;7:45–54. 18 Ware JE, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33. 19 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 20 Bostic TJ, Rubio DM, Hood M. A validation of the subjective vitality scale using structural equation modeling. Soc Indic Res 2000;52: 313–24.
ª 2014 Royal College of Obstetricians and Gynaecologists
21 Sallis JF, Pinski RB, Grossman RM, Patterson TL, Nader PR. The development of self-efficacy scales for health-related diet and exercise behaviours. Health Educ Res 1988;3:283–92. 22 Sallis JF, Grossman RM, Pinski RB, Patterson TL, Nader PR. The development of scales to measure social support for diet and exercise behaviours. Prev Med 1987;16:825–36. €stro €m M, Bauman AE, Booth ML, 23 Craig CL, Marshall AL, Sjo Ainsworth BE, et al. International physical activity questionnaire: 12country reliability and validity. Med Sci Sports Exerc 2003;35:1381– 95. 24 Hunter MH. The Women’s Health Questionnaire (WHQ): frequently asked questions (FAQ). Health Qual Life Outcomes 2003;1:41. 25 Luoto R, Moilanen J, Heinonen R, Mikkola T, Raitanen J, Ojala TE, et al. Effects of aerobic training on hot flushes and quality of life-a randomized controlled trial. Ann Med 2012;44:616–26. 26 Sternfeld B, Guthrie KA, Ensrud KE, LaCroix AZ, Larson JC, Dunn AL, et al. Efficacy of exercise for menopausal symptoms: a randomized controlled trial. Menopause 2014;21:330–8. 27 Gold EB, Sternfeld B, Kelsey JL. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. Am J Epidemiol 2000;152:463–73. 28 Progetto Menopausa Italia Study Group. Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy. Maturitas 2005;52:181–9. 29 Ivarsson T, Spetz AC, Hammar M. Physical exercise and vasomotor symptoms in postmenopausal women. Maturitas 1998; 29:139–46. 30 Duijits SF, van Beurden M, Oldenberg HS, Hunter MS, Kieffer JM, Stuiver MM, et al. Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial. J Clin Oncol 2012;30:4124–33. 31 Tworoger SS, Yasui Y, Vitiello MV, Schwartz RS, Ulrich CM, Aiello EJ, et al. Effects of a yearlong moderate-intensity exercise and stretching intervention on sleep quality in postmenopausal women. Sleep 2003;26:830–6. 32 King AC, Oman RF, Brassington GS, Bliwise DL, Haskell WL. Moderate-intensity exercise and self-rated quality of sleep in older adults: a randomised controlled trial. JAMA 1997;277:32–7. 33 Daley AJ, MacArthur C, Stokes-Lampard H. Exercise to reduce vasomotor and other menopausal symptoms: a review. Maturitas 2009;63:176–80. 34 Bortz WM, Angwin P, Mefford IN. Catecholamines, dopamine and endorphin levels during extreme exercise. N Engl J Med 1981;305:466–7. 35 Heitkamp HC, Huber W, Scheib K. Beta-endorphin and adrenocorticotropin after incremental exercise and marathon running – female response. Eur J Appl Physiol Occup Physiol 1996;72:417–24.
575
Copyright of BJOG: An International Journal of Obstetrics & Gynaecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
