Effects of exercise on depression in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials

doi:10.21203/rs.3.rs-4338122/v1

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Effects of exercise on depression in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials

https://doi.org/10.21203/rs.3.rs-4338122/v1

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Background: Exercise is a promising non-pharmacological therapy for depression; however, it is unclear whether exercise interventions are effective for postmenopausal women, and which ones work best.

Methods: Electronic searches in PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus were conducted to identify articles published through 1 March 2024, and included randomized controlled trials that examined the effectiveness of exercise interventions on depression in postmenopausal women. Mean changes (± standard deviations) in depression scores, assessed using various scales, were extracted to calculate standardized mean differences (SMDs). These SMDs were then pooled using a random effects model in a pairwise meta-analysis. Additionally, a Frequentist network meta-analysis employing a random effects model was conducted to evaluate the efficacy of different exercise types.

Results: This study included 26 studies involving 2,170 participants. In pairwise meta-analysis, exercise has shown a clinically significant positive impact on depression in postmenopausal women (SMD=-0.71, 95% confidence interval (95% CI)=-0.94–-0.48, P<0.001;I²=78%). In network meta-analysis, mind-body exercise (SMD=-0.98, 95% CI=-1.28–-0.68) and aerobic exercise (SMD=-0.58, 95% CI=-0.88–-0.29) significantly reduced the level of depression compared to the control group, and there was a significant trend for stretching, resistance exercise, and concurrent training. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety.

Conclusion: For postmenopausal women, exercise interventions are a clinically effective antidepressant therapy, with mind-body exercise most likely being the optimal type, followed by aerobic exercise.

Trial registration: This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).

exercise

depression

postmenopausal women

pairwise meta-analysis

network meta-analysis

Depression, recognized globally as a major cause of disability, is a severe mood disorder that profoundly impacts individuals' emotions, thoughts, and daily functionality^[1]. It often causes substantial suffering to patients and places a significant burden on families and society. Even subthreshold depression levels can result in distress or disability^[2], and severe cases may lead to suicide^[3]. Menopause is an inevitable and critical phase in the female life cycle^[4]. Although depression occurs in all age groups, the prevalence of depression is notably higher in women during and post-perimenopause^{[5, 6]}. This increase is often attributed to hormonal fluctuations in estrogen and progesterone, sleep disturbances, and heightened stress susceptibility^[2]. Additionally, aging, emerging health issues, and changes in family dynamics further contribute to depression^[7]. Despite its significant impact on the health-related quality of life among postmenopausal women^[8], the mental health concerns of this demographic remain largely unaddressed.

Common clinical treatments for depression typically encompass medication or hormone therapy and behavioral interventions^[9]. However, these interventions often exhibit both known and unknown side effects^[10], limited accessibility and acceptance, and are frequently stigmatized^[11]. Notably, about two-thirds of adults with depression do not receive adequate care^[12], largely due to the stigma associated with both pharmacological and psychological interventions, which deters many from seeking treatment^[13]. Furthermore, approximately one-third of patients with depression are unresponsive to multiple approved antidepressant medications^[14]. Research indicates that postmenopausal women tend to have a reduced response to antidepressants compared to younger women^[15]. Moreover, pharmacological and psychological interventions often fail to address the physical comorbidities associated with depression^[16]. While conventional treatments still require significant attention and further research, some novel therapies have demonstrated promising potential^[17].

Exercise intervention is often defined as an adjunctive therapy, noted for its high accessibility, acceptability, and safety. Due to its extensive physiological and psychological benefits, the World Health Organization recommends it for a diverse range of populations^[18]. A network meta-analysis, incorporating over two hundred randomized controlled trials (RCTs), demonstrated that the antidepressant effects of some exercise interventions might surpass those of selective serotonin reuptake inhibitors^[17]. Research has shown that being physically active, even at levels below public health recommendations, can yield significant mental health benefits^[19]. Given its varied benefits, several preliminary studies have been conducted to explore the effects of exercise interventions on postmenopausal women^[20–23]. Farzane et al.^[21] reported that eight weeks of Pilates significantly improved depression levels in the studied population. Similarly, Gutiérrez et al.^[22] found that exercise could improve depressive symptoms in patients experiencing either moderate or severe depression. Conversely, some researchers have different views. For instance, Williams et al.^[23] reported that 12 months of group exercise did not significantly reduce depression levels in patients compared to a control group. Additionally, Afonso et al.^[20] discovered that yoga could significantly improve patients' depression levels, whereas stretching exercises could not.

The reasons for the variability in outcomes may be attributed to several factors. First, differences in the physiological mechanisms among various exercise interventions can lead to varied effects on depression^[17]. Second, the severity of depression itself may result in significant differences in outcomes^[24]. For example, studies focusing on healthy postmenopausal women with lower baseline levels of depression may encounter a "floor effect"^[25]. Additionally, the use of different control groups in studies^[26], some of which may positively impact mental health, further complicates comparisons. Unfortunately, there is a dearth of research exploring the impact of exercise on depression among postmenopausal women. Furthermore, the potential moderating effects of baseline health status and intervention parameters in this context have not been sufficiently studied. Another concern is whether improvements (assuming effectiveness) for postmenopausal women justify recommendation (reaching the minimal clinically significant threshold) and whether the effects of various exercise interventions are comparable. The lack of comprehensive systematic reviews on the effects of exercise on depression in postmenopausal women impedes both understanding and the development of effective, evidence-based exercise prescriptions for this group.

In conclusion, there is an urgent need for a comprehensive systematic review to assess the effects of exercise on depression among postmenopausal women. Moreover, given the variability among exercise interventions and the limitations inherent in pairwise meta-analyses, employing a network meta-analysis is essential to discern the differential impacts of various types of exercise on this demographic. Therefore, the objectives of this study are: (1) To determine the efficacy of exercise interventions in reducing depression levels in postmenopausal women and to assess whether this efficacy is influenced by the duration of the intervention and population characteristics. (2) To identify the optimal exercise intervention if the initial intervention proves effective.

2.1. Data Source and Search Strategy

This systematic review and meta-analysis was prospectively registered with PROSPERO (CRD42024505425) and is reported according to the updated PRISMA statement^[27] and PERSiST guidance^[28].

The following online databases were searched from their inception to 1 March 2024: PubMed, Web of Science, SPORTDiscus, China National Knowledge Infrastructure (CNKI), The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus. The search strategy was constructed using the following keywords: postmenopause, senior woman, exercise, depression, and randomized controlled trial. Boolean logic operators were employed to link these terms, and the strategy was customized for each database's specific requirements. The complete search strategy, applied across all databases, is detailed in Supplemental Material 1. Additionally, a thorough search of references for meta-analyses on relevant topics was conducted to ensure the inclusion of all studies meeting the criteria.

2.2. Study Selection and Eligibility Criteria

Articles identified in the electronic databases were imported into the EndNote software (version 20.0; Clarivate, Philadelphia, PA, USA) to facilitate the removal of duplicates. Next, two researchers (BH and YYD) independently assessed their titles and abstracts for potential inclusion. Then, they screened the full texts of relevant articles against the study's specified inclusion and exclusion criteria to identify those to be included in the analyses. Any discrepancies in study selection between the two researchers were resolved through discussion.

To structure the eligibility criteria, the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) framework was used. Eligible for this meta-analysis included studies that: (1) Postmenopausal women without hormone therapy, any types of cancer, regular exercise habit or other comorbid conditions that may affect cognitive function. (2) At least one of the five exercise intervention arms of interest (stretching, aerobic, resistance training, mind-body exercise, and concurrent training) was examined and the duration of exercise intervention over 4 weeks. (3) Included a non-exercising control group (e.g., usual care, wait-list control conditions or health education) or two exercise interventions within the provision are contrasted with each other (only included in network meta-analysis). (4) Examined the pre-post effects of exercise interventions on depression using a validated scale. (5) Only RCTs published in English or Chinese.

2.3. Outcomes, coding and Data extraction

This study primarily assessed the mean change in depression from baseline to post-intervention. The secondary outcome evaluated was the mean change in anxiety before and after the intervention.

The characteristics of the interventions were appropriately coded based on physiological mechanisms and patterns. This article categorizes exercise into five broad types: stretching exercise, aerobic exercise, resistance training, mind-body exercise, and concurrent training. Detailed descriptions of each type of exercise intervention are available in Supplementary Appendix 2. The duration of the interventions was coded in weeks or months, with six months serving as the threshold to differentiate between long-term and short-term interventions.

Two researchers (BH and YYD) independently extracted the data. Any disagreements were resolved through discussion until a consensus was reached or by consulting a third researcher (PZZ). The following data were extracted: basic article information (first author, publication year, country, sample size for each arm, and dropout rate), participant characteristics (age and healthy status), intervention parameters (exercise intensity, frequency, duration per session, and overall length), and other information (comparator information, tools used to assess outcomes, and reported outcomes [mean ± standard deviation (SD)]). For each outcome, the pre- and post-intervention mean ± SD or mean differences and sample size were entered into the meta-analyses to generate forest plots. When relevant statistics were incompletely reported, we calculated the mean and SD using the sample size, standard error, confidence interval, range, and p-value. If the article lacks essential information, the corresponding author will be contacted to acquire the necessary details

2.4. Risk of bias

Two researchers (BH and YYD) used the Cochrane Collaboration tool^[29] for RCTs to assess the risk of bias for all included studies. Any disagreements were resolved through discussion. The quality of the included studies was assessed based on seven indicators: (1) the generation of random order; (2) allocation concealment; (3) blinding of participants; (4) blinding of outcome assessors; (5) completeness of outcome data; (6) possibility of selective reporting of study results; and (7) other bias. Each indicator has three risk levels: low, unclear, and high. Studies with baseline imbalances (differences), small sample size (n < 20), or other potential sources of bias were classified as 'high risk' under other bias.

2.5. Statistical Analysis

Pairwise and network meta-analysis were conducted using Revman 5.4 (Review Manager software version 5.4; Cochrane, London, UK) or STATA 15.0 (version 15.0; StataCorp, College Station, TX, USA). Since both measurement of depression and anxiety were continuous or sequential and measured on different scales, the effect estimates were represented using standardized mean differences (SMDs) and 95% confidence intervals (95% CIs). The statistical significance was set at P < 0.05.

For pairwise meta-analysis, heterogeneity among studies was evaluated using I² statistic and the Q test. A fixed-effects model was used when I² was ≤ 50%, and the random-effects model was used otherwise. Publication bias was detected using visual interpretation of funnel plots and Egger tests. Once significant publication bias was detected, the trim-and-fill method was employed to adjust the results, thus ensuring the robustness of the findings. The risk-of-bias graph was generated using the Revman 5.4. For subgroup analyses, participants age (< 60 and ≥ 60), health status (healthy, with depressive symptoms or other illness), and intervention duration (short-term and long-term intervention) was assessed as a categorical variable. The study conducted two types of sensitivity analyses: the leave-one-out method and the exclusion of studies that used health education as the control group, which facilitated a clearer observation of the effects of exercise interventions. If the results retained their significance following these analyses, they were deemed robust.

The network meta-analysis was performed according to the current operation guidelines^[30] and based on the frequentist framework. Evidence network diagrams, developed through network analysis, were designed to explore the comparative relationships among various interventions. Global inconsistency tests, utilizing inconsistency network models, were conducted to statistically assess whether the consistency assumptions of network meta-analysis were met. When interventions formed a closed loop, a loop inconsistency test was performed to evaluate the consistency between direct and indirect evidence within the loop. A league table was generated to illustrate the direct comparative effects of various exercise interventions. Interventions were ranked based on their superiority, as determined by the surface under the cumulative ranking curve (SUCRA) and mean rank. The SUCRA offline area map was plotted; the larger the area under the curve or SUCRA value (0–100%), the more effective the intervention, indicated greater effectiveness of the intervention in reducing depression.

3.1. Literature search and selection

A total of 1,248 articles related to this research topic were retrieved from the online databases, and an additional four articles were identified from the reference lists of previous review. After removing duplicate studies using Endnote (n = 390), 862 eligible records were identified. Following the initial screening of titles and abstracts, 92 records were considered potentially relevant. Subsequently, 66 studies (Supplementary Appendix 3) that did not meet this study's inclusion and exclusion criteria were excluded, resulting in the final inclusion of 22 studies in the pairwise meta-analysis and 26 studies in the network meta-analysis. The detailed study selection process is shown in Fig. 1.

3.2. Studies' Characteristics

The quantitative analysis included the data of 2,170 participants (all female; 1,425 in the treatment group and 745 in the control group) from 26 RCTs^{[20–23, 31–52]}. The selected RCTs were originated from 11 countries, primarily Brazil (n = 5). Among the 26 studies, 22 compared the difference in effects between exercise interventions and control groups, while four studies compared the differences in effects among various types of exercises.

The included RCTs examined the effects of different exercise interventions: two (100 participants) examined the effects of stretching exercise, 13 (673 participants) examined the effects of aerobic exercise, four (220 participants) examined the effects of resistance training, 12 (334 participants) examined the effects of mind-body exercise, two (98 participants) examined the effects of concurrent training.

The participant characteristics differed across the studies included in this meta-analysis. Twelve studies targeted healthy postmenopausal women, four focused on postmenopausal women with depressive symptoms, and eight examined postmenopausal women with other health conditions, including obesity and heart failure. The mean age of participants from 52.5^[49] to 80.4^[33] years. The most common tool for measuring depression is Geriatric Depression Scale (N = 6^{[22, 33, 38, 39, 45, 46]}), followed by Beck Depression Inventory (n = 5^{[20, 34, 40, 44, 49]}) and Hospital Anxiety and Depression Scale (n = 4^{[21, 31, 32, 36]}), while the rest of the studies used various scales. The studies' detailed characteristics are provided in Supplementary Appendix 4.

3.3. Risk of bias

The results for each risk of bias indicator were as follows (low-, unclear-, and high-risk): (1) random order generation (73.1%, 26.9%, and 0%); (2) allocation concealment (38.5%, 53.8%, and 7.7%); (3) given the characteristics of exercise intervention, the blinding of participants was impossible and judged to be high risk for all RCTs; (4) blinding of outcome assessors (11.5%, 80.8%, and 7.7%); (5) outcome data completeness (65.4%, 0%, and 34.6%); (6) possibility of selective reporting of study results (53.8%, 30.8%, and 15.4%); and (7) other sources of bias (50.0%, 30.8%, and 19.2%). Most studies implemented and adequately described randomization procedures. The main source of bias was the inadequate reporting of allocation concealment and blinding of assessors. Risk of bias assessment is shown in Fig. 2.

3.4. Pairwise Meta-analysis

Twenty-five comparisons from twenty-two RCTs, involving 1,564 participants (Exercise group: 819; Control group: 745), were eligible for the pairwise meta-analysis on depression. Exercise interventions have demonstrated a clinically significant positive effect on depression in postmenopausal women (SMD=-0.71, 95% CI=-0.94–-0.48, P < 0.001; Fig. 3), with an overall I² value of 78%. The funnel plot appeared slightly asymmetric, and Egger's test indicated the presence of slight publication bias in the study (P = 0.047; Funnel plot see Supplementary Appendix 5.1). The study utilized the trim-and-fill method to account for potential unpublished studies. The results showed that no additional studies were necessary to balance the funnel plot, indicating strong stability of the outcomes.

The subgroup analyses (Table 1) revealed that exercise interventions significantly reduced depression levels in postmenopausal women, regardless of intervention duration, age, and health status. However, the effect size of the intervention varied across different subgroups, with short-term interventions (SMD=-0.99, 95% CI=-1.26–-0.71; I² = 66%) proving more effective than long-term intervention (SMD=-0.32, 95% CI=-0.54–-0.10; I² = 78%). And patients with depressive symptoms gaining greater health benefits (SMD=-0.95, 95% CI=-1.44–-0.45; I² = 78%). Early postmenopausal (N = 7, SMD=-0.70, 95% CI=-1.24–-0.16; I² = 85%) and late postmenopausal (N = 18, SMD=-0.71, 95% CI=-0.97–-0.45; I² = 75%) women derived similar benefits from exercise intervention. The results remained unchanged after two types of sensitivity analysis(Supplementary Appendix 5.2), whether using a leave-one-out approach or excluding studies with healthy education as the control group (SMD=-0.67, 95% CI=-0.93–-0.42; I² = 80%; P < 0.001).

Table 1

The Result of Subgroup Analyses for Primary Outcomes
Outcomes	Subgroup	N	Z	SMD	95%CI	I² (%)	P	Weight
Duration of intervention	Short-term	15	7.00	-0.99	-1.26,-0.71	66	< 0.001	56.9
	Long-term	10	2.83	-0.32	-0.54,-0.10	56	0.02	43.1
	Test for subgroup differences: Chi² = 13.87, P < 0.001, I² = 92.8%
Health status	Healthy	12	4.77	-0.78	-1.09,-0.46	76	< 0.001	49.1
	DS	5	3.74	-0.95	-1.44,-0.45	78	< 0.001	21.2
	OI	8	2.17	-0.36	-0.69,-0.04	58	0.02	29.6
	Test for subgroup differences: Chi² = 4.97, P = 0.08, I² = 59.8%
Age	EPM	7	2.53	-0.70	-1.24,-0.16	85	< 0.001	27.6
	LPM	18	5.42	-0.71	-0.97,-0.45	75	< 0.001	72.4
	Test for subgroup differences: Chi² = 0.00, P = 0.97, I² = 0%

*DS, Depressive symptoms; OI, Other Illnesses; EPM, Early postmenopausal; LPM, Late postmenopausal.

3.5. Network Meta-analysis

Twenty-six RCTs involving 2,170 patients (Exercise group: 1,425; Control group: 745) were found to be eligible for the network meta-analysis. Figure 4 illustrates the network of pairwise comparisons across all RCTs. An inconsistency test based on network analysis revealed no significant global inconsistency (P > 0.05), which indicated that consistency assumption could be accepted at the overall level. Within the depression network, loop inconsistency test did not indicate inconsistency (inconsistency factors (IF) = 0.09 to 0.67) or loop-specific heterogeneity (τ² < 0.001). The results of the network meta-analysis reveal that, in both global and specific closed-loop contexts, there is no significant difference between direct and indirect evidence (Supplementary Appendix 5.3).

The predictive interval plot (Fig. 5) illustrates the pairwise comparison outcomes among interventions, along with their predictive intervals, result indicated that only mind-body exercise (SMD=-0.98, 95% CI=-1.28–-0.68) and aerobic exercise (SMD=-0.58, 95% CI=-0.88–-0.29) can significantly reduced depression compared with control conditions. The outcomes of pairwise comparisons between exercise interventions indicate that mind-body exercises are significantly more effective than aerobic exercise (SMD=-0.39, 95% CI=-0.77–-0.02). The rankings of the exercise interventions based on cumulative probability plots and SUCRA are shown in Fig. 6. Mind-body exercise had the highest probability (SUCRA = 94.7%, Supplementary Appendix 5.4) of being the most effective exercise type, followed by aerobic exercise and concurrent training.

3.6. Secondary outcomes

For anxiety, 13 RCTs involving 1,076 patients (Exercise group: 578; Control group: 498) were found to be eligible, pairwise meta-analysis revealed positive effects for exercise intervention (SMD=-0.53, 95% CI=-0.72 – -0.33, I² = 57.0%; P < 0.001). The network meta-analysis included 15 RCTs with 1,285 participants. The global inconsistency test indicated no significant global inconsistency in the results (p > 0.05). Within the anxiety network, loop inconsistency test did not indicate high inconsistency (IF = 0.05 to 0.30) or loop-specific heterogeneity (τ² < 0.001). Results demonstrate that aerobic exercise (SMD=-0.34, 95% CI=-0.63 – -0.05) and mind-body exercise (SMD=-0.69, 95% CI=-0.92–-0.47) significantly reducing the anxiety of postmenopausal women compared to controls, with mind-body exercise had the highest probability (SUCRA = 95.4%) of being the most effective exercise type. The specific results of the meta-analysis of anxiety are presented in Supplementary Appendix 6.

The meta-analysis was based on 26 RCTs and included 2,170 participants. To our knowledge, this is the first pairwise and network meta-analysis investigating the effects of exercise for depression in postmenopausal women, including a ranking of five prevalent exercise interventions. The study contributes to the ongoing debate about the efficacy of exercise interventions in reducing depression among this demographic, confirming that exercise significantly reduces depression levels. Among the five evaluated exercise interventions, only mind-body and aerobic exercises showed a significant reduction in depression levels, while the other three displayed notable trends. Mind-body exercise emerged as the most likely optimal type for alleviating depression in postmenopausal women. Furthermore, subgroup analysis demonstrated that exercise interventions significantly reduce depression levels in postmenopausal women, irrespective of the duration of the intervention, the participants' ages, or their health statuses.

Similar to findings in other studies across diverse populations^{[17, 24, 53–55]}, our study demonstrated that exercise intervention significantly reduced depression levels in postmenopausal women. Encouragingly, this improvement was clinically meaningful, which exceeds the minimal clinically important difference (SMD = -0.24)^{[24, 56]}. The robustness of our results is supported by two sensitivity analyses. After excluding the "health education" control condition, although there was a slight reduction in effect size, the results remained statistically significant. The antidepressant mechanisms of exercise are manifold and, although not fully elucidated, can be categorized into biological and psychosocial mechanisms^[7]. Regarding biological mechanisms, exercise potentially alleviates depression by enhancing neuroplasticity^[57], promoting anti-inflammatory responses^[58], and regulating oxidative stress^[57], as well as modulating the neuroendocrine system, including attenuation of the hypothalamic–pituitary–adrenal (HPA) axis response to stress^[59]. Psychosocial mechanisms appear to be more varied. Research suggests that exercise fosters mental health by improving self-esteem^[40], self-efficacy^[7], social support^[60], and body image, and by increasing social interaction^[19].

Our subgroup analysis of the primary outcomes revealed several significant phenomena or conclusions that warrant further discussion. Firstly, short-term interventions demonstrate a stronger impact on reducing depression compared to long-term interventions, aligning with the results of numerous previous studies^{[24, 26, 54]}. Most long-term follow-up studies^{[41, 52]} fail to adjust exercise interventions to the duration of the intervention or the conditions of the participants, failing to adhere to the principle of 'progression^[61]' in exercise prescription formulation. And studies^{[22, 44]} of long intervention cycles that conform to the principle of progressivity-increasing the volume or changing the form of exercise as the intervention progresses-have achieved better results. Consequently, a plausible explanation is that unaltered exercise regimen over an extended period may reduce participants' motivation to exercise, subsequently diminishing the intervention's benefits. Secondly, patients with depression derive greater benefits from exercise, potentially due to the lower baseline level of depression in healthy populations, which illustrates a "floor effect." Thirdly, our findings indicate that exercise interventions provide similar benefits across different age stages in postmenopausal women. This consistency may stem from the significant changes, such as hormonal fluctuations and shifts in social roles, that primarily occur during menopause^[4]. Once this critical phase is surpassed, age appears to have a minimal impact on the efficacy of exercise interventions for depression. However, it is crucial to recognize that the age categorizations derived from the average age in study reports may not adequately reflect the diversity of ages; therefore, caution is advised when interpreting these results.

Mind-body exercise focuses on promoting the unity of mind, body, and behaviour, and is characterised by gentle and slow movements^[62]. The results of network meta-analysis showed that mind-body exercise and aerobic exercise have a significant effect on reducing depression in postmenopausal women, while the other three types demonstrate a significant trend. The confidence intervals for the effect sizes of stretching, resistance, and combined exercises, compared to the control group, are relatively wide, likely due to the limited number of studies on these exercises. Mind-body exercise may be the most suitable form of exercise intervention for reducing depression in postmenopausal women, akin to findings in elderly populations^{[55, 63]}. This preference may stem from the gentler nature of mind-body exercises, which are often favored by postmenopausal women. Unlike other exercise forms, mind-body exercises uniquely foster 'interoceptive states^[64],' potentially explaining their superior antidepressant effects. Furthermore, considering that the intensity of mind-body and aerobic exercises is generally lower, it is noteworthy that when exercise intensities are comparable, certain exercise modalities^[63] may be more effective in alleviating depression in postmenopausal women and potentially in a wider demographic.

Anxiety is a common co-morbidity of depression, and not only do they share some similar symptoms, but there may also be a causal relationship between them^[65]. Our study found that exercise intervention can have a moderate mitigating effect on the anxiety levels of postmenopausal women. Individuals with anxiety tend to withdraw from social situations, and engaging in exercise represents a change in social behavior^[66]. Exercise interventions can also exert anti-anxiety effects by eliciting specific physiological responses that may mimic sensations associated with anxiety or panic, such as a rapid heartbeat^[67]. Certain potential mechanisms of exercise in combating depression (such as enhancing self-efficacy through progressive positive feedback^[7]) are also used to explain the anti-anxiety effects of exercise. Additionally, network meta-analysis found that mind-body exercises shows the highest probability of being the most effective exercise type for alleviating anxiety, which further supports our recommendation of mind-body exercises.

Some limitations of our review warrant mention. First, heterogeneity is difficult to avoid due to the experimental design (e.g., different exercise intervention modalities) used in the included studies. To enhance the reliability of our findings, we conducted subgroup and sensitivity analyses across multiple dimensions. Moreover, we utilized network meta-analysis to rank and compare exercise intervention modalities, identifying these modalities as a likely significant source of heterogeneity. Second, the use of diverse scales to measure depression may also contribute to heterogeneity, although we prioritized the most commonly used scales. Third, the predominant pre-post intervention design of the included studies limited our analysis to data extracted solely from intervention endpoints, due to the absence of long-term follow-up data. Lastly, interventions like stretching exercise, resistance and concurrent training, represented by fewer original studies, resulted in broader confidence intervals. Consequently, non-significant results should be interpreted with caution. Future research should include larger samples to more thoroughly assess the efficacy of these exercise interventions.

This pairwise and network meta-analysis provides valuable insights and recommendations for clinical professionals and researchers. Most importantly, it confirms the clinically significant antidepressant effects of exercise interventions in postmenopausal women, highlighting the particular efficacy of mind-body exercise. These should be considered as complementary therapies in clinical settings due to their significant benefits for depression and anxiety. Notably, consistent with prior research^{[24, 26, 54]}, we observed that long-term interventions did not yield results as favorable as short-term interventions. While several hypotheses are proposed to explain this phenomenon, detailed investigation falls outside the scope of this review and should be addressed in future research. Despite our findings support the superior efficacy of mind-body exercises, it is important to emphasize that the value of other exercise interventions remains undiminished. To enhance adherence in clinical settings, postmenopausal women should be given the choice of their preferred exercise type, although mind-body exercises likely being the most favored.

This pairwise and network meta-analysis synthesized 26 RCTs highlights the efficacy of exercise in postmenopausal women and provided some important findings about exercise treatment for clinical professionals and researchers. Exercise interventions have a clinically significant effect in reducing depression levels in postmenopausal women, with mind-body exercises being the most likely to be the best form of exercise intervention. The analysis of anxiety also supports our recommendation for exercise, particularly mind-body exercises. Future research should develop more acceptable exercise intervention models and conduct additional multi-arm RCTs to provide robust direct evidence.

CI, confidence interval;

IF, inconsistency factors;

RCT, randomized controlled trials;

HPA, hypothalamic–pituitary–adrenal;

PERSiST, Prisma in Exercise, Rehabilitation, Sport medicine and Sports science;

PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses;

SD, standard deviation;

SMD, standardized mean difference;

SUCRA, surface under the cumulative ranking curve;

WHO, World Health Organization.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

This research was supported by the National Key R&D Program of China (Grant No. 2022YFC2010201).

Authors' contributions

All authors contributed substantially to this paper. BH and PZZ involved in conceptualization, methodology, writing-original draft; BH, YYD and PZZ involved in writing-review & editing; BH, YYD and GLD involved in Data curation and investigation; BH and JPC involved in formal analysis; PZZ involved in supervision, validation, funding acquisition and project administration; BH, PP and LQZ involved in software; BH and YYD involved in visualization and resources. All authors have read and approved the manuscript for publication.

Acknowledgements

We extend our heartfelt gratitude to the authors and researchers of all the original studies that have contributed to this meta-analysis. Their invaluable work forms the foundation upon which our analysis is built, and their dedication to advancing knowledge in our field is deeply appreciated. Without their rigorous efforts and pioneering research, this comprehensive synthesis of evidence would not have been possible.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Effects of exercise on depression in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials

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Abstract

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1. Introduction

2. Methods

2.1. Data Source and Search Strategy

2.2. Study Selection and Eligibility Criteria

2.3. Outcomes, coding and Data extraction

2.4. Risk of bias

2.5. Statistical Analysis

3. Results

3.1. Literature search and selection

3.2. Studies' Characteristics

3.3. Risk of bias

3.4. Pairwise Meta-analysis

3.5. Network Meta-analysis

3.6. Secondary outcomes

4. Discussions

5. Conclusions

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Supplementary Files

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Version 1