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<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
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<journal-title>Frontiers in Medicine</journal-title>
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<article-id pub-id-type="doi">10.3389/fmed.2026.1738629</article-id>
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<subject>Systematic Review</subject>
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<title-group>
<article-title>Acupuncture improves anxiety and depression in patients with polycystic ovary syndrome: a systematic evaluation and meta-analysis</article-title>
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<name><surname>Ye</surname><given-names>Rongzhen</given-names></name>
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<name><surname>Chen</surname><given-names>Jiao</given-names></name>
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<aff id="aff1"><label>1</label><institution>School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine</institution>, <city>Chengdu</city>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>Chengdu Pidu District Hospital of Traditional Chinese Medicine</institution>, <city>Chengdu</city>, <country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>The Third Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (West District)</institution>, <city>Chengdu</city>, <country country="cn">China</country></aff>
<aff id="aff4"><label>4</label><institution>Division of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University</institution>, <city>Chengdu</city>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Yu Liu, <email xlink:href="mailto:yliuchina@126.com">yliuchina@126.com</email>; Jiao Chen, <email xlink:href="mailto:chenjiao@cdutcm.edu.cn">chenjiao@cdutcm.edu.cn</email></corresp>
<fn fn-type="equal" id="fn0001"><label>&#x2020;</label><p>These authors have contributed equally to this work</p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-21">
<day>21</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>13</volume>
<elocation-id>1738629</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>11</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>02</day>
<month>01</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>09</day>
<month>01</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Ye, Sun, Yang, Peng, Tian, He, Yao, Liu, Liu and Chen.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Ye, Sun, Yang, Peng, Tian, He, Yao, Liu, Liu and Chen</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-21">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Acupuncture is increasingly utilized to address anxiety and depression in polycystic ovary syndrome (PCOS), yet evidence for non-pharmacological interventions remains limited. This study aimed to rigorously evaluate the efficacy and safety of acupuncture in alleviating anxiety and depression among women with PCOS, while exploring its potential mechanisms.</p>
</sec>
<sec>
<title>Methods</title>
<p>Eight Chinese/English databases (CNKI, Web of Science, PubMed, Embase, etc.) were searched from inception to March 1, 2025. Two investigators independently screened studies, extracted data, and assessed quality via the Cochrane risk-of-bias tool. The meta-analyses were performed with RevMan 5.4. Additionally, data mining methods were used, including frequency statistics to analyze the frequency of acupuncture points and the meridians involved.</p>
</sec>
<sec>
<title>Results</title>
<p>Twelve RCTs (<italic>n</italic>&#x202F;=&#x202F;2,127 patients; acupuncture&#x202F;=&#x202F;1,059, control&#x202F;=&#x202F;1,068) were included. Compared with the control, acupuncture significantly reduced anxiety scores [MD&#x202F;=&#x202F;&#x2212;6.42, 95% CI (&#x2212;8.91, &#x2212;3.56); <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001] and depression scores [MD&#x202F;=&#x202F;&#x2212;5.89, 95% CI (&#x2212;9.01, &#x2212;2.78); <italic>p</italic>&#x202F;=&#x202F;0.0002] versus controls. Acupuncture also improved testosterone [MD&#x202F;=&#x202F;&#x2212;0.05, 95% CI (&#x2212;0.11, 0.00); <italic>p</italic>&#x202F;=&#x202F;0.05], BMI [MD&#x202F;=&#x202F;&#x2212;0.70, 95% CI (&#x2212;1.19, &#x2212;0.21); <italic>p</italic>&#x202F;=&#x202F;0.005], and the waist-hip ratio [MD&#x202F;=&#x202F;&#x2212;0.06, 95% CI (&#x2212;0.11, &#x2212;0.01); <italic>p</italic>&#x202F;=&#x202F;0.03], with no significant adverse effects [OR&#x202F;=&#x202F;0.08, 95% CI (0.01, 0.81); <italic>p</italic>&#x202F;=&#x202F;0.03]. The effects on insulin resistance were not significant [MD&#x202F;=&#x202F;&#x2212;0.41, 95% CI (&#x2212;1.18, 0.37); <italic>p</italic>&#x202F;=&#x202F;0.31]. Data mining revealed that Foot Taiyin Spleen Meridian (SP), Conception Vessel (CV), and Foot Yangming Stomach Meridian (ST) were the most frequently used, and the most commonly used combination of points included SP6, LR3, and ST36.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Acupuncture, particularly manual and short-term protocols, is a safe and effective adjunct for reducing anxiety and depression in PCOS. These benefits may be mediated via modulation of androgen levels, adiposity, and neuroendocrine pathways. Nevertheless, conclusions are limited by sample size, methodological heterogeneity, and inadequate adverse event reporting. Higher-quality RCTs are needed to confirm the safety and efficacy of these methods.</p>
</sec>
<sec>
<title>Systematic review registration</title>
<p><uri xlink:href="https://www.crd.york.ac.uk/PROSPERO/view/CRD420251000646">https://www.crd.york.ac.uk/PROSPERO/view/CRD420251000646</uri>, Identifier CRD420251000646.</p>
</sec>
</abstract>
<kwd-group>
<kwd>acupuncture</kwd>
<kwd>anxiety</kwd>
<kwd>depression</kwd>
<kwd>meta-analysis</kwd>
<kwd>polycystic ovary syndrome</kwd>
<kwd>randomized controlled trial</kwd>
</kwd-group>
<funding-group>
<award-group id="gs1">
<funding-source id="sp1">
<institution-wrap>
<institution>The Technology Innovation R&#x0026;D Project of Chengdu Science and Technology Bureau</institution>
</institution-wrap>
</funding-source>
<award-id rid="sp1">2024-YF05-00521-SN</award-id>
</award-group>
<award-group id="gs2">
<funding-source id="sp2">
<institution-wrap>
<institution>The Medical Foundation of Sichuan Association</institution>
</institution-wrap>
</funding-source>
<award-id rid="sp2">S2024063</award-id>
</award-group>
<award-group id="gs3">
<funding-source id="sp3">
<institution-wrap>
<institution>The Natural Science Foundation of Sichuan Province</institution>
</institution-wrap>
</funding-source>
<award-id rid="sp3">2024NSFSC1861</award-id>
</award-group>
<award-group id="gs4">
<funding-source id="sp4">
<institution-wrap>
<institution>The &#x201C;Xinglin Scholar&#x201D; Discipline Talent Research Enhancement Program of Chengdu University of Traditional Chinese Medicine</institution>
</institution-wrap>
</funding-source>
<award-id rid="sp4">QJRC2024027</award-id>
</award-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This research was funded by the following programs: The &#x201C;Xinglin Scholar&#x201D; Discipline Talent Research Enhancement Program of Chengdu University of Traditional Chinese Medicine (Youth Foundation Talent Special Project, No. QJRC2024027); The Natural Science Foundation of Sichuan Province (No. 2024NSFSC1861).</funding-statement>
</funding-group>
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<ref-count count="61"/>
<page-count count="15"/>
<word-count count="8972"/>
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<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Obstetrics and Gynecology</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by clinical and/or biochemical hyperandrogenism, ovulatory dysfunction, and/or polycystic ovarian morphology, that predominantly affects reproductive-aged women (<xref ref-type="bibr" rid="ref1">1</xref>). With a global prevalence of 2&#x2013;26% (<xref ref-type="bibr" rid="ref2">2</xref>), the incidence of PCOS increased by 54.3% between 1990 and 2019 (<xref ref-type="bibr" rid="ref3">3</xref>). In China, it affects 5.61% of reproductive-aged women with increasing trends, constituting a major healthcare challenge (<xref ref-type="bibr" rid="ref4">4</xref>). Notably, PCOS patients face significantly elevated risks of psychological comorbidities (<xref ref-type="bibr" rid="ref5">5</xref>); the prevalence of anxiety and depression in this population is estimated to reach 22 and 30%, respectively (<xref ref-type="bibr" rid="ref6">6</xref>), potentially linked to insulin resistance (IR) and hyperandrogenaemia (<xref ref-type="bibr" rid="ref7">7</xref>). Hormonal dysregulation and concomitant symptoms (e.g., obesity, infertility, acne, hirsutism, and androgenetic alopecia) may trigger or exacerbate mood disorders (<xref ref-type="bibr" rid="ref8">8</xref>). These psychological burdens substantially impair quality of life and pose societal concerns, underscoring the imperative to address mental health in PCOS management.</p>
<p>The 2023 International Evidence-Based Guideline for PCOS (<xref ref-type="bibr" rid="ref9">9</xref>) points out that the etiology remains elusive with no curative treatment. For PCOS patients with comorbid moderate-to-severe anxiety/depression, psychotherapy or selected pharmacotherapy is recommended (<xref ref-type="bibr" rid="ref9">9</xref>). However, conventional pharmacological treatments demonstrate limited efficacy and may carry the risk of toxic side effects such as gastrointestinal reactions and cardiovascular disease (<xref ref-type="bibr" rid="ref10">10</xref>). Thus, investigating safe and effective alternative or complementary therapies is imperative.</p>
<p>Acupuncture, a cornerstone of complementary and alternative medicine (CAM), has been integrated into the management of neuropsychiatric conditions (<xref ref-type="bibr" rid="ref11">11</xref>). Evidence indicates that it alleviates emotional symptoms in cancer, Parkinson&#x2019;s disease, and gastrointestinal disorders by modulating neuroendocrine pathways and the gut-brain axis-mediated microbial balance (<xref ref-type="bibr" rid="ref12 ref13 ref14 ref15">12&#x2013;15</xref>). In addition, acupuncture may directly or indirectly ameliorate the anxiety-depression in individuals with PCOS via regulation of the neuropeptide Y, norepinephrine (NE), and serotonin (5-HT) systems (<xref ref-type="bibr" rid="ref15">15</xref>, <xref ref-type="bibr" rid="ref16">16</xref>), suggesting that it is a potential therapy for psychological symptoms (<xref ref-type="bibr" rid="ref17 ref18 ref19">17&#x2013;19</xref>). While existing meta-analyses have focused on the endocrine effects of acupuncture in individuals with PCOS (<xref ref-type="bibr" rid="ref20 ref21 ref22">20&#x2013;22</xref>), evidence regarding improvements in mood disorders remains scarce. This study presents the first meta-analysis specifically evaluating the efficacy of acupuncture for anxiety and depression in individuals with PCOS while investigating the mechanistic links to insulin resistance, hyperandrogenaemia, and obesity, thereby providing evidence-based guidance for clinical practice.</p>
</sec>
<sec id="sec2">
<label>2</label>
<title>Data and methods</title>
<p>This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist (<xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref24">24</xref>), with the protocol registered on PROSPERO (CRD420251000646).</p>
<sec id="sec3">
<label>2.1</label>
<title>Data sources and literature search strategy</title>
<p>Eight databases (CNKI, Wanfang, VIP, Duxiu, Web of Science, PubMed, Embase, and Medline) were searched up to March 1, 2025. We obtained RCTs of the use of acupuncture to improve anxiety and depression in patients with polycystic ovary syndrome, using the following terms: acupuncture, acupuncture therapy, electroacupuncture, ear acupuncture, polycystic ovary syndrome, micropolycystic ovary, stein-leventhal syndrome, and randomized controlled trial. For detailed search strategies, please refer to <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>.</p>
</sec>
<sec id="sec4">
<label>2.2</label>
<title>Inclusion and exclusion criteria</title>
<p>The inclusion criteria were as follows:</p><list list-type="order">
<list-item>
<p>Study type: randomized controlled trials (RCTs) published in Chinese or English.</p>
</list-item>
<list-item>
<p>Participants: Patients definitively diagnosed with PCOS (meeting the 2003 Rotterdam criteria or 2011 Chinese Medical Association diagnostic standards), regardless of age or disease duration.</p>
</list-item>
<list-item>
<p>Interventions: Treatment group: Acupuncture alone (including body acupuncture, electroacupuncture, or auricular acupuncture) or acupuncture combined with conventional drug therapy. Control group: Sham acupuncture, waitlist/no treatment control, conventional drug therapy, or lifestyle interventions.</p>
</list-item>
<list-item>
<p>At least one of the following outcome measures: primary outcomes: anxiety status (assessed via the Self-Rating Anxiety Scale (SAS)) and depression status (assessed via the Self-Rating Depression Scale (SDS)). The secondary outcomes included testosterone (T), homeostatic model assessment for insulin resistance (HOMA-IR), body mass index (BMI), waist&#x2013;hip ratio (WHR), and adverse reactions (e.g., bleeding, poor appetite, and abdominal pain).</p>
</list-item>
</list>
<p>Exclusion criteria:</p><list list-type="order">
<list-item>
<p>Study type: Non-randomized studies, protocol papers, conference abstracts, case reports, review articles, editorials, or animal studies.</p>
</list-item>
<list-item>
<p>Participants: Studies focusing on syndromes other than PCOS (e.g., simple ovarian cysts, other endocrine disorders) or studies where PCOS patients constituted a minority of a mixed population without separable data.</p>
</list-item>
<list-item>
<p>Intervention and Control: Studies where the experimental intervention was not acupuncture or where acupuncture was a minor adjunct to another primary therapy (e.g., surgery, intensive psychotherapy). Studies where the control group received an active acupuncture treatment (e.g., different acupuncture protocol) rather than a credible control (sham, no treatment/blank, drug, or lifestyle). Studies where the type of control (e.g., sham vs. blank) could not be clearly determined from the report.</p>
</list-item>
<list-item>
<p>Outcomes: Studies that did not report at least one of the pre-specified primary outcomes (anxiety assessed by SAS or depression assessed by SDS).</p>
</list-item>
<list-item>
<p>Data and Reporting: Studies with missing, incomplete, or obviously erroneous key data (e.g., mean, standard deviation, sample size for outcomes) that could not be obtained or reasonably imputed after contacting the authors. Duplicate publications or secondary analyses of already included trials without new primary data.</p>
</list-item>
</list>
</sec>
<sec id="sec5">
<label>2.3</label>
<title>Literature screening process</title>
<p>Two investigators (R.Z.Y. and Y.L.) independently (1) eliminated duplicate records via EndNote X9.1 software on the basis of eligibility criteria; (2) conducted preliminary screening by reviewing titles and abstracts to exclude nonconforming studies; and (3) performed full-text assessment for secondary screening to determine the final included trials. Key data, including researcher names, publication year, sample size, intervention protocols, outcome measures, and risk of bias assessments, were extracted into Excel spreadsheets. Disagreements during screening were resolved through consensus discussions or arbitration by a third researcher (J.C.).</p>
</sec>
<sec id="sec6">
<label>2.4</label>
<title>Quality evaluation</title>
<p>The Cochrane risk of bias tool was used to evaluate potential biases in the included studies. The assessment domains included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other sources of bias.</p>
<p>The quality of evidence for each outcome was assessed by two independent researchers (R.Z.Y. and Y.L.) using the evaluation (GRADE) system, with discrepancies resolved through consultation with a third expert (J.C.). Within the GRADE framework, evidence was rated as &#x201C;high&#x201D;, &#x201C;moderate&#x201D;, &#x201C;low&#x201D;, or &#x201C;very low&#x201D; based on the following criteria: risk of bias, inconsistency, imprecision, indirectness, and publication bias. Specifically, inconsistency was judged based on the direction and magnitude of effect estimates, the overlap of confidence intervals, and the I<sup>2</sup> statistic (where I<sup>2</sup>&#x202F;&#x003E;&#x202F;50% indicated substantial heterogeneity that could downgrade the evidence). Publication bias was considered based on the results of funnel plot inspection and statistical tests as detailed in the Statistical Analysis section below. The detailed GRADE assessments are summarized in <xref ref-type="supplementary-material" rid="SM1">Supplementary Table S3</xref>.</p>
</sec>
<sec id="sec7">
<label>2.5</label>
<title>Statistical analyses</title>
<p>RevMan 5.4.1 software was used for statistical analysis. All outcome data were continuous variables, expressed as the mean difference (MD) with 95% confidence interval (CI). Heterogeneity between studies was assessed via the I<sup>2</sup> statistic: I<sup>2</sup>&#x202F;&#x2264;&#x202F;50% and <italic>p</italic>&#x202F;&#x2265;&#x202F;0.05 indicated low heterogeneity, warranting a fixed-effects model; I<sup>2</sup>&#x202F;&#x003E;&#x202F;50% or <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05 indicated substantial heterogeneity, warranting a random-effects model. To explore potential sources of heterogeneity, pre-specified subgroup analyses were conducted based on acupuncture modality, treatment duration, and sample size. Sensitivity analysis was performed by sequentially removing each individual study to examine the stability of the pooled results, particularly for outcomes with high heterogeneity. Assessment of publication bias involved visual inspection of funnel plots for asymmetry. For outcomes that included 10 or more studies (i.e., anxiety and depression), Egger&#x2019;s linear regression test was performed using Stata software 18.0 to quantitatively assess small-study effects. Additionally, acupuncture prescription patterns were analyzed using frequency statistics, and meridian&#x2013;acupoint networks were visualized with Cytoscape software 3.9.0.</p>
</sec>
</sec>
<sec sec-type="results" id="sec8">
<label>3</label>
<title>Results</title>
<sec id="sec9">
<label>3.1</label>
<title>Results of the literature search</title>
<p>The initial search identified 2,306 records. After 1,137 duplicates were removed, 817 articles were excluded through title and abstract screening. The application of the inclusion/exclusion criteria resulted in the exclusion of 340 articles, yielding 12 RCTs (<xref ref-type="bibr" rid="ref25 ref26 ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34 ref35 ref36">25&#x2013;36</xref>) for final inclusion (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Literature screening process (PRISMA framework).</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Flowchart illustrating the literature review process for qualitative analysis. Identification involves database searches, totaling 2,306 articles, with no supplemental data added. After removing duplicates, 1,169 articles remain. Screening excludes 817 articles due to review articles, animal models, systematic reviews, and irrelevancies. Preliminary screening reduces the count to 352 articles, with 340 excluded for reasons like non-randomized trials and data issues. Twelve full articles are read and included in the final analysis.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec10">
<label>3.2</label>
<title>Basic characteristics of included studies</title>
<p>Twelve RCTs involving 2,127 patients (acupuncture group: <italic>n</italic>&#x202F;=&#x202F;1,059; control group: <italic>n</italic>&#x202F;=&#x202F;1,068) were included. The publication years ranged from 2013&#x2013;2024, with 3 English-language studies and 9 Chinese-language studies. The outcome measures included SAS scores [12 studies (<xref ref-type="bibr" rid="ref25 ref26 ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34 ref35 ref36">25&#x2013;36</xref>)], SDS scores [10 studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref27 ref28 ref29 ref30 ref31 ref32">27&#x2013;32</xref>, <xref ref-type="bibr" rid="ref34 ref35 ref36">34&#x2013;36</xref>)], testosterone (T) levels [5 studies (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32 ref33 ref34 ref35">32&#x2013;35</xref>)], HOMA-IR values [5 studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref36">36</xref>)], BMI values [7 studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33 ref34 ref35 ref36">33&#x2013;36</xref>)], WHR [4 studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33">33</xref>)], and adverse events [4 studies (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref36">36</xref>)]. Interventions primarily consisted of manual acupuncture (<xref ref-type="bibr" rid="ref27">27</xref>, <xref ref-type="bibr" rid="ref29">29</xref>, <xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref36">36</xref>) and electroacupuncture (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref35">35</xref>). The treatment duration spanned 3&#x2013;6 menstrual cycles, with 30-min sessions administered 2&#x2013;3 times weekly. The detailed characteristics are presented in <xref ref-type="table" rid="tab1">Tables 1</xref>, <xref ref-type="table" rid="tab2">2</xref> and <xref ref-type="fig" rid="fig2">Figure 2</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Characteristics of included studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Year of researcher</th>
<th align="center" valign="top" rowspan="2">Country</th>
<th align="center" valign="top">Sample size (<italic>n</italic>)</th>
<th align="center" valign="top">Mean age (years)</th>
<th align="center" valign="top" colspan="2">Intervention</th>
<th align="center" valign="top" rowspan="2">Course treatment (menstrual cycle)</th>
<th align="center" valign="top" rowspan="2">Outcome indicators</th>
<th align="left" valign="top" rowspan="2">Adverse events</th>
</tr>
<tr>
<th align="center" valign="top">T/C</th>
<th align="center" valign="top">T/C</th>
<th align="center" valign="top">T/C</th>
<th align="center" valign="top">T/C</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Chang H. 2023 (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">458/468</td>
<td align="center" valign="middle">27.97&#x202F;&#x00B1;&#x202F;3.33/27.97&#x202F;&#x00B1;&#x202F;3.33</td>
<td align="center" valign="middle">EA</td>
<td align="center" valign="middle">EA</td>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2463;&#x2464;&#x2465;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Lai Y. Q. 2019 (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">30/30</td>
<td align="center" valign="middle">27.91&#x202F;&#x00B1;&#x202F;4.41/28.36&#x202F;&#x00B1;&#x202F;4.52</td>
<td align="center" valign="middle">EA&#x202F;+&#x202F;TCM</td>
<td align="center" valign="middle">CC&#x202F;+&#x202F;TCM</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Li J. H. 2022 (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">45/45</td>
<td align="center" valign="middle">31.02&#x202F;&#x00B1;&#x202F;3.31/30.87&#x202F;&#x00B1;&#x202F;3.89</td>
<td align="center" valign="middle">MA&#x202F;+&#x202F;TCM&#x202F;+&#x202F;C</td>
<td align="center" valign="middle">CC&#x202F;+&#x202F;HMG</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Mao M. Y. 2021 (<xref ref-type="bibr" rid="ref28">28</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">54/54</td>
<td align="center" valign="middle">-</td>
<td align="center" valign="middle">EA&#x202F;+&#x202F;CPA/EE</td>
<td align="center" valign="middle">EA&#x202F;+&#x202F;CPA/EE</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2463;&#x2464;&#x2465;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Wang Z. 2019 (<xref ref-type="bibr" rid="ref29">29</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">27/27</td>
<td align="center" valign="middle">-</td>
<td align="center" valign="middle">MA</td>
<td align="center" valign="middle">SA</td>
<td align="center" valign="middle">2</td>
<td align="center" valign="middle">&#x2460;&#x2461;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Wu X. K. 2017 (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">250/249</td>
<td align="center" valign="middle">28.20&#x202F;&#x00B1;&#x202F;3.40/27.80&#x202F;&#x00B1;&#x202F;3.40</td>
<td align="center" valign="middle">EA&#x202F;+&#x202F;CC</td>
<td align="center" valign="middle">SA&#x202F;+&#x202F;CC</td>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2462;&#x2463;&#x2464;&#x2465;</td>
<td align="left" valign="middle">T: 34 cases; C: 16 cases</td>
</tr>
<tr>
<td align="left" valign="middle">Wu D. 2023 (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">30/30</td>
<td align="center" valign="middle">21.89&#x202F;&#x00B1;&#x202F;9.71/22.33&#x202F;&#x00B1;&#x202F;9.49</td>
<td align="center" valign="middle">MA&#x202F;+&#x202F;LET</td>
<td align="center" valign="middle">LET</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Xu X. L. 2024 (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">35/35</td>
<td align="center" valign="middle">29.39&#x202F;&#x00B1;&#x202F;4.54/28.79&#x202F;&#x00B1;&#x202F;4.67</td>
<td align="center" valign="middle">MA&#x202F;+&#x202F;TCM</td>
<td align="center" valign="middle">CPA/EE</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2462;</td>
<td align="left" valign="middle">T: no adverse reactions; C: 1 case of nausea</td>
</tr>
<tr>
<td align="left" valign="middle">Yao M. 2018 (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">50/50</td>
<td align="center" valign="middle">27.8&#x202F;&#x00B1;&#x202F;4.8/28.2&#x202F;&#x00B1;&#x202F;4.5</td>
<td align="center" valign="middle">EA</td>
<td align="center" valign="middle">MET</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">&#x2460;&#x2462;&#x2463;&#x2464;&#x2465;</td>
<td align="left" valign="middle">T: 1 case of bleeding at the acupuncture point after the needle was discharged; C: 2 cases of poor appetite, 7 cases of gastrointestinal reaction, 1 case of headache and 1 case of skin rash.</td>
</tr>
<tr>
<td align="left" valign="middle">Yue J. 2022 (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">30/30</td>
<td align="center" valign="middle">27&#x202F;&#x00B1;&#x202F;5/27&#x202F;&#x00B1;&#x202F;5</td>
<td align="center" valign="middle">MA</td>
<td align="center" valign="middle">SA</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2462;&#x2464;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang H. L. 2020 (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">20/20</td>
<td align="center" valign="middle">29&#x202F;&#x00B1;&#x202F;2/28&#x202F;&#x00B1;&#x202F;3</td>
<td align="center" valign="middle">EA&#x202F;+&#x202F;E</td>
<td align="center" valign="middle">E</td>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2462;&#x2464;</td>
<td align="left" valign="middle">Not reported</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang S. K. 2024 (<xref ref-type="bibr" rid="ref36">36</xref>)</td>
<td align="center" valign="middle">China</td>
<td align="center" valign="middle">30/30</td>
<td align="center" valign="middle">28.99&#x202F;&#x00B1;&#x202F;3.58/29.59&#x202F;&#x00B1;&#x202F;3.76</td>
<td align="center" valign="middle">MA&#x202F;+&#x202F;CPA/EE</td>
<td align="center" valign="middle">CPA/EE</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">&#x2460;&#x2461;&#x2463;&#x2464;</td>
<td align="left" valign="middle">T: 3 cases of bleeding at the acupoints after the needles were discharged; C: no adverse reactions occurred</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>T, Treatment group; C, Control group; MA, Manual acupuncture; EA, Electroacupuncture; SA, Sam acupuncture; TCM, Traditional Chinese Medicine cycle therapy/herbal tonics; E, Lifestyle management; CC, Clomiphene; MET, Metformin hydrochloride; CPA/EE, Cyproterone ethinylestradiol tablets; LET, Letrozole; HMG, Urotensin; WM, Western medical therapy. Outcome indicators: &#x2460; Anxiety status; &#x2461; Depression status; &#x2462; Testosterone T; &#x2463; Insulin resistance index HOMA-IR; &#x2464; Body mass index BMI; &#x2465; Waist-hip ratio WHR.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Acupuncture regimens were included in the literature.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Year of researcher</th>
<th align="left" valign="top">Acupuncture points (treatment group)</th>
<th align="left" valign="top">Acupuncture method</th>
<th align="left" valign="top">Treatment duration</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Chang H. 2023 (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="left" valign="middle">Not reported</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Tow</td>
</tr>
<tr>
<td align="left" valign="middle">Lai Y. Q. 2019 (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="left" valign="middle">Zhongji CV3, Guanyuan CV4, Sanyinjiao SP6, Ashigaru ST36, Ovary TF2, Uterus EX-CA1</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 20&#x202F;min, Qd</td>
</tr>
<tr>
<td align="left" valign="middle">Li J. H. 2022 (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="left" valign="middle">Taichong LR3, Xingma LR2, Sanyinjiao SP6, Foot Sanli ST36, Sea of Blood SP10, Guanyuan CV4, Uterus EX-CA1, Fenglong ST40</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 3&#x202F;day, thw</td>
</tr>
<tr>
<td align="left" valign="middle">Mao M. Y. 2021 (<xref ref-type="bibr" rid="ref28">28</xref>)</td>
<td align="left" valign="middle">Baihui GV20, Yintang EX-HN3, Spleen YU BL20, Stomach YU BL21, Heart YU BL15, Tianshu ST25, Guanyuan CV4, Qihai CV6, Guilai ST29, Zhongkou CV12, Hegu LI4, Taichong LR3, Adachi Sanli ST36, Sanyinjiao SP6</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Qod</td>
</tr>
<tr>
<td align="left" valign="middle">Wang Z. 2019 (<xref ref-type="bibr" rid="ref29">29</xref>)</td>
<td align="left" valign="middle">Baihui GV20, Zhongji CV3, Qihai CV6, Guilai ST29, Sanyinjiao SP6, Hegu LI4, Yinlingquan SP9</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Tow</td>
</tr>
<tr>
<td align="left" valign="middle">Wu X. K. 2017 (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="left" valign="middle">Not reported</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Tow</td>
</tr>
<tr>
<td align="left" valign="middle">Wu D. 2023 (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="left" valign="middle">Baihui GV20, Guanyuan CV4, Ren Yu BL23, Liver BL18, Spleen BL20, Uterus EX-CA1, Sanyinjiao SP6</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Qd, 14 consecutive days per month</td>
</tr>
<tr>
<td align="left" valign="middle">Xu X. L. 2024 (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="left" valign="middle">Guanyuan CV4, Zhongji CV3, Uterus EX-CA1, Sanyinjiao SP6, Tianshu ST25, Zhongkou CV12, Ashansanli ST36, Fenglong ST40, Liver BL18, Taichong LR3</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 3&#x202F;day, Qod, Tow</td>
</tr>
<tr>
<td align="left" valign="middle">Yao M. 2018 (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="left" valign="middle">Tanzhong CV7, Liver Yu BL18, Tianshu ST25, Uterus EX-CA1, Ashigang Sanli ST36, Ximen LR14, Zhongkou CV12, Guanyuan CV4, Sanyinjiao SP6, Taichong LR3</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Thw</td>
</tr>
<tr>
<td align="left" valign="middle">Yue J. 2022 (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="left" valign="middle">Supine position group: Guanyuan CV4, Zhongji CV3, Tianshu ST25, Daxiang SP15, Shenmen HT7 (left), Shusanli ST36, Sanyinjiao SP6<break/>Prone group: spleen yu BL20, kidney yu BL23, guanyuan yu BL26, ji-siao BL32</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Qd</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang H. L. 2020 (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="left" valign="middle">Baihui GV20, Zhongguancun CV12, Guanyuan CV4, Guilai ST29, Fubu ST32, Liangqiu ST34, Sanyinjiao SP6, Shusanli ST36, Shenmen HT7, Hegu LI4</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Qod, Thw</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang S. K. 2024 (<xref ref-type="bibr" rid="ref36">36</xref>)</td>
<td align="left" valign="middle">Auricular points (specific not reported)</td>
<td align="left" valign="middle">MA</td>
<td align="left" valign="middle">RNS 30&#x202F;min, Thw</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>MA, Manual acupuncture; EA, Electroacupuncture; RNS, Indwelling needle set; Qd, once a day; Qod, Once every other day; Tow, Twice weekly; Thw, three times weekly.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Network diagram of the meridian-acupoint usage frequency. SP6, Sanyinjiao; ST36, Foot Sanli; CV4, Guanyuan; LR3, Taichong; GV20, Baihui; EX-CA1, Uterus; ST25, Tianshu; CV3, Zhongji; BL20, Spleen Yu; BL18, Liver Yu; ST29, Guilai; LI4, Hegu; CV6, Qihai; CV12, Zhongkou; ST40, Fenglong; HT7, Shenmen; BL23, Kidney Yu; SP10, Sea of Blood; LR2, Xingma TF2, Ovary; EX-HN3, Indigo; BL21, Stomach; BL15, Heart; SP9, Yinlingquan; CV7, Tanzhong; LR14, Xiemen; SP15, Dahang; BL26, Guanyuan; BL32, Jiyu; ST32, Fubu; ST34, Liangqiu; SP, Spleen meridian; ST, Stomach meridian; CV, Ren meridian; BL, Bladder meridian; LR, Liver meridian; GV, Vessel meridian; LI, Large Intestine meridian; HT, Heart meridian; EX, Extra meridian points.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">A network diagram with yellow triangle nodes representing publications or studies interconnected by gray lines. Pink and green circles labeled with codes like BL15, CV, and ST36 surround the central nodes, indicating different categories or classifications.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec11">
<label>3.3</label>
<title>Quality assessment of literature</title>
<p>Ten RCTs (<xref ref-type="bibr" rid="ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34 ref35 ref36">27&#x2013;36</xref>) used random number tables for allocation, whereas two (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>) stated &#x201C;randomization&#x201D; without specifying methods. Three studies (<xref ref-type="bibr" rid="ref29">29</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref36">36</xref>) implemented double- or single-blinding; allocation concealment was not reported in the remaining trials. All studies reported complete outcome data with no evidence of selective reporting. Other potential sources of bias were unclear. The risk of bias assessments are summarized in <xref ref-type="fig" rid="fig3">Figures 3</xref>, <xref ref-type="fig" rid="fig4">4</xref>. According to GRADE (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S3</xref>), the quality of evidence ranged from very low to moderate.</p>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Risk of bias in the included studies.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Bar graph depicting risk of bias in various study areas. Categories include random sequence generation, allocation concealment, blinding of participants, and more. Risk levels are color-coded: green for low risk, yellow for unclear risk, and red for high risk. Most categories show predominantly low risk except blinding of participants and personnel, and blinding of outcome assessment, which have high risk sections. A key is provided for color reference.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Risk bias summary plot of the included studies.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g004.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">A bias assessment table for various studies, displayed with colored circles indicating risk levels: green for low risk, yellow for unclear risk, and red for high risk. Rows represent different types of biases, and columns list the studies.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec12">
<label>3.4</label>
<title>Data mining analysis of meridian and acupoint utilization patterns</title>
<p>To systematically elucidate acupoint selection patterns in acupuncture treatment for PCOS-related anxiety and depression, we performed data mining and visualization analyses on acupuncture prescriptions extracted from the 12 included RCTs.</p>
<p>Frequency analysis (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>) identified the Foot Taiyin Spleen Meridian (SP), Conception Vessel (CV), and Foot Yangming Stomach Meridian (ST) as the most frequently utilized meridians, collectively establishing the core meridian framework for acupuncture interventions in this context. At the acupoint level, the most frequently employed points were Sanyinjiao (SP6), Guanyuan (CV4), Zusanli (ST36), Taichong (LR3), and Zigong (EX-CA1), delineating a characteristic clinical acupoint combination profile.</p>
<p>The meridian-acupoint network diagram (<xref ref-type="fig" rid="fig2">Figure 2</xref>) constructed from these data further illustrated a selection pattern characterized by &#x201C;a core structure comprising the Foot Yin Meridians, Conception Vessel, and Stomach Meridian, with specific acupoints functioning as central hubs.&#x201D; Notably, Sanyinjiao (SP6)&#x2014;the confluence point of the three Yin meridians of the foot (Spleen, Liver, and Kidney)&#x2014;occupied a topologically central position within the network, exhibiting strong connections with Zusanli (ST36), Taichong (LR3), and Guanyuan (CV4).</p>
<sec id="sec13">
<label>3.4.1</label>
<title>TCM theoretical interpretation of the core acupoint synergy</title>
<p>SP6, the confluence point of the three Yin meridians (Spleen, Liver, Kidney), is pivotal for regulating the Chong and Ren Vessels, nourishing Blood, and calming the Mind, thereby addressing the fundamental Yin deficiency and reproductive axis dysfunction in PCOS. LR3, the Source (Yuan) point of the Liver meridian, is the primary point for soothing Liver Qi stagnation, a key TCM pathogenesis for depression, irritability, and menstrual irregularities. ST36, the Sea (He) point of the Stomach meridian, strongly tonifies Qi and strengthens the Spleen, addressing the root of phlegm-dampness accumulation (manifested as obesity and metabolic dysfunction) and providing the material basis for physiological and emotional balance. The frequent co-occurrence of these points in the network diagram reflects a clinical strategy to simultaneously regulate the Liver (LR3), fortify the Spleen (ST36), and tonify the Kidneys and regulate the Chong-Ren (SP6), creating a holistic therapeutic approach to break the cycle of emotional distress, endocrine imbalance, and metabolic disturbance characteristic of PCOS (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>).</p>
</sec>
<sec id="sec14">
<label>3.4.2</label>
<title>Interpretation of the network visualization</title>
<p>In the network diagram (<xref ref-type="fig" rid="fig2">Figure 2</xref>), circular nodes represent individual acupoints, with their size proportional to the frequency of use. Rectangular nodes represent meridians, color-coded for distinction. Solid lines connect acupoints to their parent meridian, while thicker lines between specific acupoints (e.g., connecting SP6, LR3, and ST36) indicate a higher frequency of co-occurrence within the same prescription, visually emphasizing their strong clinical association. This network topology not only confirms the quantitative findings from frequency analysis but also graphically underscores the principle of multi-point, multi-meridian synergy in TCM clinical practice for complex disorders like PCOS with psychological comorbidity.</p>
<p>In summary, this integrated data-driven and theory-informed analysis clarifies the preferred meridians and core acupoint combinations for acupuncture management of PCOS complicated by anxiety and depression. It demonstrates that contemporary clinical practice, as reflected in RCTs, aligns with classic TCM principles, providing an evidence-informed foundation for future clinical application and the development of standardized treatment protocols.</p>
</sec>
</sec>
<sec id="sec15">
<label>3.5</label>
<title>Meta-analysis results</title>
<sec id="sec16">
<label>3.5.1</label>
<title>Anxiety state</title>
<p>Twelve studies (<xref ref-type="bibr" rid="ref25 ref26 ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34 ref35 ref36">25&#x2013;36</xref>) assessed anxiety in women with PCOS via the Self-Rating Anxiety Scale (SAS). Significant heterogeneity was observed (I<sup>2</sup>&#x202F;=&#x202F;98%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001), indicating the need for a random effects model. Meta-analysis demonstrated that acupuncture significantly reduced anxiety scores compared with those of controls [MD&#x202F;=&#x202F;&#x2212;6.42, 95% CI (&#x2212;8.91, &#x2212;3.56); <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001]. Subgroup analyses by acupuncture modality, treatment duration, and sample size revealed reduced heterogeneity across all groups (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>). Notably, manual acupuncture [MD&#x202F;=&#x202F;&#x2212;8.78, 95% CI (&#x2212;11.62, &#x2212;5.94); <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001] showed significantly greater efficacy than electroacupuncture [MD&#x202F;=&#x202F;&#x2212;3.55, 95% CI (&#x2212;6.47, &#x2212;0.62); <italic>p</italic>&#x202F;=&#x202F;0.02], suggesting that treatment modality is a key source of effect heterogeneity (<xref ref-type="fig" rid="fig5">Figure 5</xref>). Funnel plot asymmetry indicated potential publication bias (<xref ref-type="fig" rid="fig6">Figure 6</xref>). Quantitative assessment via Egger&#x2019;s test did not indicate significant publication bias (<italic>p</italic>&#x202F;=&#x202F;0.445) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S5</xref>). The observed funnel plot asymmetry is likely attributable to the high heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;98%) among studies rather than systematic missing of negative trials.</p>
<fig position="float" id="fig5">
<label>Figure 5</label>
<caption>
<p>Forest plot of the effects of acupuncture on anxiety scores (subgroup analysis: EA vs. MA).</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g005.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot displaying a meta-analysis of studies comparing experimental and control groups. It shows mean differences with 95% confidence intervals for two subgroups, EA and MA. Each study is represented by a square, and diamonds indicate subgroup and overall mean differences. The plot includes individual weights and heterogeneity statistics. Results suggest an overall effect favoring the experimental group.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig6">
<label>Figure 6</label>
<caption>
<p>Funnel chart of anxiety states. Asymmetry was observed but Egger&#x2019;s test was not significant (<italic>p</italic>&#x202F;=&#x202F;0.445), possibly due to high heterogeneity.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g006.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">A funnel plot displaying standard error of mean difference (SE(MD)) on the vertical axis and mean difference (MD) on the horizontal axis. It includes red diamonds for acupuncture studies and black squares for electroacupuncture studies, both within a blue dashed funnel shape. The plot illustrates the distribution of study data points, indicating variability and potential publication bias.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec17">
<label>3.5.2</label>
<title>Depression states</title>
<p>Ten studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref27 ref28 ref29 ref30 ref31 ref32">27&#x2013;32</xref>, <xref ref-type="bibr" rid="ref34 ref35 ref36">34&#x2013;36</xref>) evaluated depression via the Self-Rating Depression Scale (SDS). High heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;98%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001) justified the use of a random effects model. Compared with the control condition, acupuncture significantly reduced depression scores [MD&#x202F;=&#x202F;&#x2212;5.89, 95% CI (&#x2212;9.01, &#x2212;2.78); <italic>p</italic>&#x202F;=&#x202F;0.0002]. Subgroup analyses (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>) similarly revealed reduced heterogeneity, with manual acupuncture [MD&#x202F;=&#x202F;&#x2212;7.95, 95% CI (&#x2212;10.56, &#x2212;5.33); <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001] demonstrating superior efficacy to electroacupuncture [MD&#x202F;=&#x202F;&#x2212;2.72, 95% CI (&#x2212;5.41, &#x2212;0.02); <italic>p</italic>&#x202F;=&#x202F;0.05], reinforcing modality as a determinant of treatment effects (<xref ref-type="fig" rid="fig7">Figure 7</xref>). The asymmetrical funnel plot distribution suggested a risk of publication bias (<xref ref-type="fig" rid="fig8">Figure 8</xref>). Similarly, Egger&#x2019;s test for depression did not show statistical significance (<italic>p</italic>&#x202F;=&#x202F;0.172) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S5</xref>). The funnel plot asymmetry may thus reflect the substantial heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;98%) across the limited number of included studies.</p>
<fig position="float" id="fig7">
<label>Figure 7</label>
<caption>
<p>Forest plot of the effects of acupuncture on depression scores (subgroup analysis: EA vs. MA).</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g007.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing electroacupuncture (EA) and manual acupuncture (MA) in various studies. Mean differences, confidence intervals, and weights are shown. Subtotals for EA and MA indicate heterogeneity and overall effects. The total combined effect favors the experimental group.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig8">
<label>Figure 8</label>
<caption>
<p>Funnel chart of depressive state. Asymmetry was noted; Egger&#x2019;s test, however, was non-significant (<italic>p</italic>&#x202F;=&#x202F;0.172).</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g008.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Funnel plot illustrating standard error against mean difference (MD) with subgroups electroacupuncture (squares) and acupuncture (diamonds), marked with dashed guide lines. Data points mainly cluster around an MD range from -10 to 0.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec18">
<label>3.5.3</label>
<title>Testosterone (T) levels</title>
<p>Five studies (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32 ref33 ref34 ref35">32&#x2013;35</xref>) reported testosterone levels. Low heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;0%, <italic>p</italic>&#x202F;=&#x202F;0.47) justified the use of a fixed-effects model. Compared with the control, acupuncture significantly reduced testosterone levels [MD&#x202F;=&#x202F;&#x2212;0.05, 95% CI (&#x2212;0.11, 0.00); <italic>p</italic>&#x202F;=&#x202F;0.05] (<xref ref-type="fig" rid="fig9">Figure 9</xref>).</p>
<fig position="float" id="fig9">
<label>Figure 9</label>
<caption>
<p>Effects of acupuncture on testosterone.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g009.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot from a meta-analysis comparing experimental and control groups across five studies: Wu XK2017, Xu.X.L2024, Yao.M2018, Yue.J2022, Zhang.H.L2020. Mean differences with confidence intervals are shown. Total participants are 374 in experimental and 375 in control. Heterogeneity is low with Chi-square of 3.56 and I-squared at 0%. Overall effect size is -0.05 with a confidence interval of [-0.11, 0.00], indicating the test for overall effect is significant with Z=1.96, p=0.05. The plot favors neither experimental nor control significantly.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec19">
<label>3.5.4</label>
<title>Homeostatic model assessment for insulin resistance</title>
<p>Five studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref36">36</xref>) assessed HOMA-IR. High heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;96%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001) was detected via a random effects model. No statistically significant difference was observed between the acupuncture and control groups [MD&#x202F;=&#x202F;&#x2212;0.41; 95% CI (&#x2212;1.18, 0.37), <italic>p</italic>&#x202F;=&#x202F;0.31] (<xref ref-type="fig" rid="fig10">Figure 10</xref>). Subgroup analyses (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>) did not substantially reduce heterogeneity, indicating limited reliability of the results.</p>
<fig position="float" id="fig10">
<label>Figure 10</label>
<caption>
<p>Effect of acupuncture on the insulin resistance index.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g010.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot illustrating a meta-analysis of five studies comparing experimental and control groups. Mean differences and 95% confidence intervals are shown for each study. The overall effect size is -0.41 with a 95% confidence interval of [-1.18, 0.37]. The plot includes study weights and heterogeneity statistics, indicating a high degree of heterogeneity with I-squared value at 96%. The test for the overall effect is not statistically significant with a p-value of 0.31, suggesting no clear difference between groups.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec20">
<label>3.5.5</label>
<title>Body mass index</title>
<p>Seven studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33 ref34 ref35 ref36">33&#x2013;36</xref>) reported BMI values. Moderate heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;60%, <italic>p</italic>&#x202F;=&#x202F;0.02) warranted a random effects model. Compared with the control diet, acupuncture significantly improved BMI [MD&#x202F;=&#x202F;&#x2212;0.70, 95% CI (&#x2212;1.19, &#x2212;0.21); <italic>p</italic>&#x202F;=&#x202F;0.005] (<xref ref-type="fig" rid="fig11">Figure 11</xref>). Subgroup analyses (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>) revealed that the acupuncture modality and treatment duration were the primary sources of heterogeneity.</p>
<fig position="float" id="fig11">
<label>Figure 11</label>
<caption>
<p>Effect of acupuncture on body mass index.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g011.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot displaying mean differences between experimental and control groups across seven studies. Each study's result is shown with a green square, with horizontal lines representing 95% confidence intervals. A diamond shape at the bottom indicates the overall effect estimate with a mean difference of -0.70, favoring the experimental group. Heterogeneity statistics include Tau&#x00B2;=0.23, Chi&#x00B2;=15.00, and I&#x00B2;=60%.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec21">
<label>3.5.6</label>
<title>Waist-to-hip ratio</title>
<p>Four studies (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref33">33</xref>) evaluated WHR. High heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;93%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001) necessitated a random effects model. Compared with the control, acupuncture significantly reduced the WHR [MD&#x202F;=&#x202F;&#x2212;0.06, 95% CI (&#x2212;0.11, &#x2212;0.01); <italic>p</italic>&#x202F;=&#x202F;0.03] (<xref ref-type="fig" rid="fig12">Figure 12</xref>). As all studies used electroacupuncture with large samples (<italic>n</italic>&#x202F;&#x003E;&#x202F;30), subgroup analysis was limited to treatment duration (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>). Heterogeneity persisted, compromising the reliability of the results.</p>
<fig position="float" id="fig12">
<label>Figure 12</label>
<caption>
<p>Effect of acupuncture on the waist-to-hip ratio.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g012.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot illustrating meta-analysis results of four studies comparing experimental and control groups. Each study shows mean, standard deviation, and total for both groups. The plot displays mean differences with confidence intervals and weights. Subtotal mean difference: -0.06, 95 percent CI: [-0.11, -0.01]. Test for heterogeneity: I-squared equals ninety-three percent. Overall effect: Z equals 2.16, P equals 0.03. Diamond represents total effect size.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec22">
<label>3.5.7</label>
<title>Adverse events</title>
<p>Four RCTs (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref36">36</xref>) reported adverse events, primarily subcutaneous hemorrhage and gastrointestinal reactions (<xref ref-type="table" rid="tab3">Table 3</xref>). The acupuncture group had a significantly lower incidence of adverse events [OR&#x202F;=&#x202F;0.08, 95% CI (0.01, 0.81); <italic>p</italic>&#x202F;=&#x202F;0.03] (<xref ref-type="fig" rid="fig13">Figure 13</xref>) with moderate heterogeneity (I<sup>2</sup>&#x202F;=&#x202F;81%, <italic>p</italic>&#x202F;=&#x202F;0.002).</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Coverage of adverse reactions.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Year of researcher</th>
<th align="center" valign="top" rowspan="2">Sample size (<italic>n</italic>) T/C</th>
<th align="center" valign="top" colspan="2">Intervention</th>
<th align="center" valign="top">Subcutaneous Hemorrhage</th>
<th align="center" valign="top" colspan="3">Gastrointestinal reaction</th>
<th align="center" valign="top" colspan="2">Other (rash, headache, dysmenorrhoea, etc.)</th>
</tr>
<tr>
<th align="left" valign="top">T</th>
<th align="left" valign="top">C</th>
<th align="center" valign="top">T</th>
<th align="center" valign="top">C</th>
<th align="center" valign="top">T</th>
<th align="center" valign="top">T</th>
<th align="center" valign="top">T</th>
<th align="center" valign="top">C</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Wu X. K. 2017 (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="center" valign="middle">250/249</td>
<td align="left" valign="middle">EA&#x202F;+&#x202F;CC</td>
<td align="left" valign="middle">SA&#x202F;+&#x202F;CC</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">14</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">12</td>
<td align="center" valign="middle">11</td>
</tr>
<tr>
<td align="left" valign="middle">Xu X. L. 2024 (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="center" valign="middle">35/35</td>
<td align="left" valign="middle">MA&#x202F;+&#x202F;TCM</td>
<td align="left" valign="middle">CPA/EE</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
</tr>
<tr>
<td align="left" valign="middle">Yao M. 2018 (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="center" valign="middle">50/50</td>
<td align="left" valign="middle">EA</td>
<td align="left" valign="middle">MET</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">2</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang S. K. 2024 (<xref ref-type="bibr" rid="ref36">36</xref>)</td>
<td align="center" valign="middle">30/30</td>
<td align="left" valign="middle">MA&#x202F;+&#x202F;CPA/EE</td>
<td align="left" valign="middle">CPA/EE</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>T, Treatment group; C, Control group; EA, Electroacupuncture; SA, Sham acupuncture; TCM, Traditional Chinese Medicine (TCM) cycle therapy/Chinese medicine (TCM) tonic; E, Lifestyle management; CC, Clomiphene; MET, Metformin hydrochloride; CPA/EE, Cyproterone ethinylestradiol.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="fig13">
<label>Figure 13</label>
<caption>
<p>Effect of acupuncture on adverse reactions.</p>
</caption>
<graphic xlink:href="fmed-13-1738629-g013.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot from a meta-analysis showing odds ratios with 95% confidence intervals for four studies: Zhang.S.K2024, Yao.M2018, Xu.X.L2024, and Wu XK2017. The diamond shape at the bottom represents the overall effect estimate. The total events for experimental and control groups are 20 and 76, respectively. Heterogeneity measures are provided, with Tau-squared at 4.05, chi-squared at 15.18, degrees of freedom at 3, and I-squared at 80%. Overall effect test shows Z equals 2.14 with a P value of 0.03.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="sec23">
<label>3.6</label>
<title>Sensitivity analysis</title>
<p>Sensitivity analysis was conducted using SAS, SDS, HOMA-IR, and WHR as indicators. After sequentially excluding individual studies, the results indicated that the heterogeneity did not significantly decrease compared to the initial analysis. This suggests that the findings of this study are robust.</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec24">
<label>4</label>
<title>Discussion</title>
<sec id="sec25">
<label>4.1</label>
<title>Key findings and mechanistic insights</title>
<p>This systematic review of 12 RCTs evaluated the efficacy of acupuncture in alleviating anxiety and depression in women with PCOS while exploring the mechanistic links to insulin resistance (IR), hyperandrogenaemia, and obesity-related negative effects. Validated international scales (SAS/SDS) quantify subjective mood states, directly reflecting mental health status&#x2014;a critical determinant of treatment adherence and quality of life in patients with PCOS. To investigate core pathological features, we analyzed key biomarkers, including testosterone (T), HOMA-IR, BMI, and the waist&#x2013;hip ratio (WHR), elucidating the integrated mechanisms of acupuncture through endocrine axis modulation, metabolic improvement, and the regulation of energy balance/adipose tissue distribution. Most outcomes exhibited substantial heterogeneity (<italic>I<sup>2</sup></italic> range: 0&#x2013;100%; wide <italic>Tau<sup>2</sup></italic> and <italic>Chi<sup>2</sup></italic> distributions), indicating significant effect size variations. These discrepancies likely originated from inconsistencies in acupuncture modalities, treatment durations, and sample sizes. Subgroup analyses of outcome measures revealed reduced intergroup heterogeneity for most endpoints (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S4</xref>).</p>
<p>Collectively, acupuncture demonstrated superior efficacy in improving anxiety/depression scores, reducing testosterone levels, decreasing body weight, and optimizing adiposity distribution compared with controls&#x2014;although not for HOMA-IR. Safety assessments, although limited by few adverse event reports, have consistently indicated a lower incidence and severity of acupuncture-related adverse events (primarily subcutaneous hemorrhage), supporting its favorable safety profile. Crucially, the risk of bias assessment necessitates caution in interpreting these findings because of potential publication bias in the included studies.</p>
<p>Women with PCOS exhibit elevated rates of depression (30&#x2013;50%) and anxiety disorders (22&#x2013;44%)&#x2014;significantly higher than those in the general population, particularly among infertile patients (<xref ref-type="bibr" rid="ref37">37</xref>, <xref ref-type="bibr" rid="ref38">38</xref>). Clinical symptoms overlap between depression and PCOS, with obesity, insulin resistance (IR), and hyperandrogenaemia constituting shared pathological underpinnings (<xref ref-type="bibr" rid="ref39">39</xref>, <xref ref-type="bibr" rid="ref40">40</xref>). IR, present in 50&#x2013;80% of PCOS patients, directly and/or indirectly promotes androgen synthesis and secretion (<xref ref-type="bibr" rid="ref41">41</xref>, <xref ref-type="bibr" rid="ref42">42</xref>). Subsequent hyperandrogenism stimulates visceral adipose tissue lipolysis, increasing free fatty acids that exacerbate IR (<xref ref-type="bibr" rid="ref42">42</xref>). Concurrently, IR aggravates hormonal dysregulation, inflammatory responses, and visceral adiposity&#x2014;key drivers of obesity (<xref ref-type="bibr" rid="ref43">43</xref>). These interconnected abnormalities establish a vicious cycle, worsening infertility, acne, and hirsutism, which profoundly impact self-image and amplify psychosocial stress (<xref ref-type="bibr" rid="ref38">38</xref>, <xref ref-type="bibr" rid="ref44">44</xref>).</p>
<p>Acupuncture demonstrates potential in alleviating PCOS symptoms, with its antidepressant effects already validated (<xref ref-type="bibr" rid="ref45">45</xref>, <xref ref-type="bibr" rid="ref46">46</xref>). This therapy physiologically regulates menstrual cycles, ovulation, and hyperandrogenism manifestations while mitigating adverse emotional impacts, all with minimal side effects (<xref ref-type="bibr" rid="ref11">11</xref>, <xref ref-type="bibr" rid="ref47">47</xref>). Animal studies confirm that acupuncture reduces anxiety-like behaviors in female rats separated from their offspring by modulating the amygdala neuropeptide Y system (<xref ref-type="bibr" rid="ref17">17</xref>). Qualitative research indicates that women with PCOS undergoing acupuncture treatment exhibit trends toward increased self-confidence, restored hope, and rebuilt autonomy (<xref ref-type="bibr" rid="ref18">18</xref>). Through metabolic regulation, acupuncture modulates glucose and lipid metabolism to reduce obesity while enhancing fertility. Mechanistically, endocrine dysregulation in PCOS patients (e.g., insulin resistance, hyperandrogenism, chronic inflammation) induces anxiety and depression by altering neurotransmitters like dopamine and serotonin (<xref ref-type="bibr" rid="ref48">48</xref>). Beyond regulating endocrine and metabolic markers, acupuncture&#x2019;s potential mechanisms for alleviating anxiety and depression in PCOS patients may involve modulating multiple interconnected neurobiological pathways. First, acupuncture regulates the HPA axis&#x2014;a core stress response system often hyperactive in mood disorders and PCOS. Preclinical studies indicate that electroacupuncture stimulation at specific points (e.g., ST36 Zusanli) reduces corticotropin-releasing hormone (CRH) expression and cortisol levels, thereby promoting HPA axis homeostasis and enhancing stress resilience (<xref ref-type="bibr" rid="ref49">49</xref>, <xref ref-type="bibr" rid="ref50">50</xref>). Second, acupuncture influences monoaminergic neurotransmitter systems, particularly serotonin (5-HT) and norepinephrine systems. Evidence suggests acupuncture increases serotonin availability and modulates 5-HT1A receptor sensitivity in limbic brain regions (e.g., hippocampus, prefrontal cortex) critical for emotional regulation (<xref ref-type="bibr" rid="ref15">15</xref>, <xref ref-type="bibr" rid="ref51">51</xref>). Furthermore, the insulin resistance and chronic low-grade inflammation prevalent in PCOS adversely affect neuroplasticity and neurotransmitter synthesis. Studies indicate that acupuncture improves insulin sensitivity and reduces levels of pro-inflammatory cytokines (e.g., TNF-<italic>&#x03B1;</italic>, IL-6), potentially creating a neurochemical environment conducive to emotional well-being (<xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref53">53</xref>). Moreover, emerging research indicates that acupuncture may influence central nervous system function by regulating the gut-brain axis and modulating the production of gut microbiota metabolites (<xref ref-type="bibr" rid="ref54 ref55 ref56">54&#x2013;56</xref>). Collectively, acupuncture exerts holistic effects on emotional disorders through integrated physiological, metabolic, and phenotypic regulation.</p>
</sec>
<sec id="sec26">
<label>4.2</label>
<title>Clinical significance and limitations</title>
<p>This study provides critical insights for the clinical application of acupuncture in managing anxiety and depression in polycystic ovary syndrome (PCOS) patients, establishing a theoretical foundation for standardized treatment protocols. Analysis of acupoints and meridians across the 12 included studies (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S2</xref>; <xref ref-type="fig" rid="fig2">Figure 2</xref>) revealed the most frequently used acupoints as Sanyinjiao (SP6), Guanyuan (CV4), Zusanli (ST36), Taichong (LR3), and Zigong (EX-CA1), with core meridians, including the Foot-Taiyin Spleen Meridian (SP), Conception Vessel (CV), Foot-Yangming Stomach Meridian (ST), and Foot-Jueyin Liver Meridian (LR). Traditional medicine emphasizes the regulatory roles of the Chong and Ren Meridians and the liver, spleen, and kidney organs in PCOS pathogenesis, demonstrating a mechanistic correspondence between the TCM &#x201C;Kidney&#x2013;Tian Gui&#x2013;Chong Ren&#x2013;Uterus&#x201D; reproductive axis and the modern hypothalamic&#x2013;pituitary&#x2013;ovarian (HPO) axis (<xref ref-type="bibr" rid="ref50">50</xref>). Through the synergistic effects of multiple targets and pathways mentioned above (<xref ref-type="bibr" rid="ref57">57</xref>), the acupoint combinations summarized herein achieve holistic regulation of physiological, metabolic, and psychological dimensions in PCOS, circumventing the adverse effects of Western pharmaceuticals and the limitations of monotherapy while offering a novel integrative approach for emotional disorders.</p>
<p>Subgroup analyses (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S4</xref>) revealed the superior efficacy of manual acupuncture over electroacupuncture in alleviating anxiety/depression, with a shorter treatment duration (&#x2264;3&#x202F;months) yielding more significant psychological improvement and larger effect sizes observed in smaller-sample studies (<italic>n</italic>&#x202F;&#x2264;&#x202F;30). This heterogeneity primarily stems from nonstandardized acupuncture protocols (e.g., variable stimulation parameters) and methodological quality variations. Notably, while electroacupuncture efficacy fluctuates with parameter consistency (frequency, waveform), both modalities significantly outperform conventional treatments. Manual acupuncture employs personalized point selection (e.g., LR3, CV4, SP6) combined with lifting-thrusting-twisting techniques to elicit &#x201C;Deqi&#x201D; sensations (soreness, numbness, distension), stimulating deep vagal nerve fibers to modulate limbic system function (<xref ref-type="bibr" rid="ref58">58</xref>). Its dual mechanisms of acupoint specificity and neuromodulation confer distinct advantages for emotional disorder intervention (<xref ref-type="bibr" rid="ref58">58</xref>, <xref ref-type="bibr" rid="ref59">59</xref>). The marked efficacy of short-term therapy (&#x2264;3&#x202F;months) in mild-to-moderate depression (<xref ref-type="bibr" rid="ref60">60</xref>, <xref ref-type="bibr" rid="ref61">61</xref>) may reflect heightened neural sensitivity during acute phases&#x2014;acupuncture rapidly alleviates symptoms by downregulating proinflammatory factors (e.g., TNF-<italic>&#x03B1;</italic>) and modulating the HPA axis (reducing ACTH and cortisol) (<xref ref-type="bibr" rid="ref60">60</xref>).</p>
<p>This study has several limitations that may impact the reliability of the findings. (1) Few high-quality RCTs have specifically targeted acupuncture for improving anxiety and depression in patients with PCOS. Only 12 studies met the inclusion criteria, predominantly featuring small sample sizes (mostly 20&#x2013;50 participants) and considerable size variation (range: 20&#x2013;468 participants). (2) Effective blinding was difficult to implement due to the nature of the acupuncture interventions. Only three studies mentioned single&#x2212;/double-blind designs. Overall study quality varied, introducing potential bias risk. (3) Acupuncture protocols vary significantly in terms of point selection and stimulation parameters. Most studies lacked standardized sham acupuncture controls, limiting the comparability of the results. (4) Most RCTs assessed outcomes only before and after treatment, and long-term follow-up data are lacking. This precludes the evaluation of treatment effects on sustainability and long-term mental health impacts. (5) Adverse effects have been underreported in some studies, and comprehensive safety evaluations are generally lacking. (6) The GRADE assessment of this study demonstrated that the evidence supporting acupuncture for improving anxiety and depression in patients with PCOS is of low quality, primarily due to the risk of bias in the primary studies and substantial heterogeneity among the results. Therefore, the conclusions drawn from this study require validation through future high-quality, large-scale RCTs incorporating long-term follow-up and standardized protocols.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec27">
<label>5</label>
<title>Conclusion</title>
<p>This meta-analysis confirms that acupuncture (particularly manual acupuncture and short-term protocols) demonstrates superior efficacy over conventional treatments in alleviating emotional symptoms among patients with PCOS. In alignment with the emphasis on nonpharmacological therapies in the 2023 International Evidence-Based Guideline for PCOS (<xref ref-type="bibr" rid="ref9">9</xref>), future clinical practice warrants exploration of an integrated acupuncture-psychology-lifestyle intervention model to improve patients&#x2019; physical and mental health outcomes holistically. Although acupuncture has promising therapeutic potential for treating PCOS, certain outcomes remain inconsistent, and its precise mechanisms have not yet been fully elucidated. Consequently, more rigorously designed, high-quality clinical studies are imperative to strengthen the credibility of these findings and further validate the long-term clinical efficacy of acupuncture in ameliorating anxiety and depression in patients with PCOS, thereby informing evidence-based clinical decision-making.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec28">
<title>Data availability statement</title>
<p>The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>.</p>
</sec>
<sec sec-type="author-contributions" id="sec29">
<title>Author contributions</title>
<p>RY: Methodology, Conceptualization, Validation, Visualization, Formal analysis, Writing &#x2013; original draft. YS: Writing &#x2013; original draft, Methodology, Conceptualization. HY: Data curation, Writing &#x2013; review &#x0026; editing, Formal analysis. JP: Writing &#x2013; review &#x0026; editing, Data curation, Software. QT: Writing &#x2013; review &#x0026; editing, Data curation, Methodology, Investigation, Software. SH: Data curation, Writing &#x2013; review &#x0026; editing, Formal analysis. SY: Writing &#x2013; review &#x0026; editing, Data curation, Software. YeL: Validation, Supervision, Writing &#x2013; review &#x0026; editing. YuL: Project administration, Methodology, Supervision, Resources, Writing &#x2013; review &#x0026; editing. JC: Resources, Writing &#x2013; review &#x0026; editing, Validation, Project administration, Funding acquisition.</p>
</sec>
<sec sec-type="COI-statement" id="sec30">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec31">
<title>Generative AI statement</title>
<p>The author(s) declared that Generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec32">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec33">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fmed.2026.1738629/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fmed.2026.1738629/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Supplementary_file_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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</ref-list>
<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0002">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3320740/overview">Bo Sun</ext-link>, The First People&#x2019;s Hospital of Lianyungang, China</p></fn>
<fn fn-type="custom" custom-type="reviewed-by" id="fn0003">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2292598/overview">Yuehan Ren</ext-link>, Graduate School of Beijing University of Chinese Medicine, China</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3333280/overview">Yaochen Wang</ext-link>, The First People&#x2019;s Hospital of Lianyungang, China</p></fn>
</fn-group>
<fn-group>
<fn fn-type="abbr" id="abbrev1">
<label>Abbreviations:</label>
<p>PCOS, polycystic ovary syndrome; RCTs, randomized controlled trials; CAM, complementary and alternative medicine; SAS, Self-Rating Anxiety Scale; SDS, Self-Rating Depression; T, Scale testosterone; HOMA-IR, homeostatic model assessment for insulin resistance; BMI, body mass index; WHR, waist&#x2013;hip ratio; HPA, hypothalamic&#x2013;pituitary&#x2013;adrenal; HPO, hypothalamic&#x2013;pituitary&#x2013;Ovarian; ACTH, adrenocorticotropic hormone; GnRH, hypothalamic gonadotropin-releasing hormone; LH, luteinizing hormone.</p>
</fn>
</fn-group>
</back>
</article>