The role of naturopathy in the management of women with polycystic ovary syndrome (PCOS) dataset

Polycystic ovary syndrome or PCOS was first described in 1935 by Irving F. Stein and Michael L. Leventhal as Stein Leventhal Syndrome; ‘women with ovarian hyperthecosis presenting with persistent anovulation, obesity and hirsutism.’ Today, PCOS is the most common reproductive endocrinopathy of women, the most common cause of ovarian infertility and the cause of psychological and emotional distress. PCOS is associated with serious health risks in the short and long term including significantly increased risks for diabetes, cancer and cardiovascular disease, independent to body weight. For the health care system, the annual cost of PCOS in Australia was conservatively estimated as AU$400 million.
The negative personal impact of PCOS on women’s quality of life and self-esteem is well defined and recognised. Evidence-based medical management emphasises a multidisciplinary approach with lifestyle intervention recommended as first-line treatment in international clinical guidelines. However, the strength of evidence for lifestyle intervention remains limited by high attrition in RCTs and clinical uptake is impeded by the lack of evidence for optimal dietary and exercise practices. Additional forms of management are often sought by women with PCOS and needed to achieve clinical outcomes, including fertility outcomes. Pharmaceuticals and surgery may be used to regulate menstruation, reduce androgens and treat infertility and hyperinsulinaemia, however these have limited capacity to address the range of PCOS symptoms, are often contra-indicated due to increased risk of co-morbidities or have high adverse effect profiles. In addition, women with PCOS have expressed preferences for alternatives.
Naturopathy is a type of complementary medicine with traditional origins in ancient western civilisations. Naturopathy is based on holistic philosophy, six principles of practice and theories with naturopaths provide health care for a wide range of conditions using natural treatment modalities to enhance well-being and support the innate healing capabilities of the body. The case for naturopathy for PCOS is presented here based on three rationales; a clinical gap in medical management; clinical potential for herbal medicine and nutritional supplements in PCOS, and the preferences and acceptability of complementary medicines by women. This thesis examined the role of naturopathy in women with PCOS by answering the following questions.
1. What is the prevalence of use and attitudes towards complementary medicine, self-help and lifestyle interventions by women with PCOS?
2. What is the evidence from randomised controlled trials for naturopathic herbal medicines and nutritional supplements for women with PCOS?
3. What is the pre-clinical and corroborating clinical evidence for the reproductive endocrine effects of herbal medicine for the treatment of oligo/amenorrhoea, hyperandrogenism and PCOS?
4. Does the addition of a Western herbal medicine combination (Tribulus terrestris, Glycyrrhiza glabra, Paeonia lactiflora, Hypericum perforatum and Cinnamomum cassia) to a lifestyle intervention compared with the lifestyle intervention alone improve menstrual regularity in overweight women PCOS?

Methods: These questions were addressed following the survey of women with PCOS, two separate literature reviews and through a randomised controlled trial examining the effectiveness of a naturopathic herbal formula plus lifestyle intervention on a broad range of outcomes in overweight women with polycystic ovary syndrome.
An electronic survey of 493 women with PCOS assessed women’s use and attitudes toward complementary medicine and self-care (diet and exercise). Women were recruited from the Polycystic Ovary Syndrome Association of Australia (POSAA) and through social media PCOS support groups on social media.
The evidence base for nutritional supplements and herbal medicine was examined through two literature reviews. The evidence from randomised controlled trials (RCT) for nutritional supplements and herbal medicine for clinical effects in women with PCOS was synthesised following a systematic review of the literature. Consistent pre-clinical and clinical evidence of reproductive endocrine effects in PCOS for herbal medicines used in naturopathic clinical practice explained the mechanisms of five herbal medicines that theoretically could contribute to regulating the menstrual pattern, reducing hyperandrogenism, and improving ovarian morphology in PCOS.
A randomised controlled trial (RCT) compared the clinical effectiveness and safety of the addition of a new herbal combination to lifestyle intervention against lifestyle intervention alone in 122 overweight women with medically diagnosed PCOS. The primary outcome was menstrual regularity. Secondary outcomes included pregnancy rates, serum hormone and blood glucose concentrations, anthropometry, and psychological health outcomes at three months and live birth rates at nine months after the intervention period.
Results: Over two-thirds of women surveyed reported regular use of nutritional and herbal supplements to manage their PCOS. Although most respondents reported regular engagement with lifestyle interventions (diet and exercise) few reported satisfaction, and most expressed a desire for transparent information about complementary medicines.
The systematic review of the literature revealed evidence from 18 RCTs (1109 women) for six types of nutritional supplements (vitamin D, Omega 3, calcium, chromium, vitamins and inositol) and four herbal medicines (Camellia sinensis, Cimicifuga racemosa Cinnamon cassia and Mentha spicata) for the management of symptoms associated with PCOS. The quality of studies was low to moderate, 11 meta-analyses were applied to 11 outcomes. The strongest evidence was found for inositol for the treatment of a hyperandrogenism, infertility, normalising metabolic hormones and for omega three fish oils for treatment of high cholesterol in women with PCOS. Findings highlighted the lack of robust evidence for many natural health supplements and that outcomes for inositol and omega three may contribute lower grade evidence to the evidence-based guidelines for the management of women with PCOS.
The literature review of the mechanisms of herbal medicines in oligo/amenorrhoea, hyperandrogenism and PCOS revealed consistent pre-clinical and clinical evidence for six herbal medicines (Cimicifuga racemosa, Cinnamomum cassia, Glycyrrhiza spp, Paeonia lactiflora, Tribulus terrestris and Vitex agnus-castus). Reproductive endocrinological effects were reduced LH (Cimicifuga racemosa, Paeonia lactiflora and Cinnamomum cassia), raised FSH (Tribulus terrestris), reduced testosterone (Glycorrhizza spp. and Paeonia lactiflora) and improved fasting insulin (Cinnamomum cassia). The mechanisms of herbal medicines and naturopathic clinical practices informed the development of a new herbal combination for investigation in the RCT.
One hundred and twenty-two women with PCOS were randomised to receive herbal medicine plus lifestyle intervention or lifestyle intervention alone. At three months there was a significant improvement in menstrual regularity for women taking the additional herbal medicine compared to women using lifestyle intervention alone with a moderate to large treatment effect. Significant improvements for secondary outcomes included fasting insulin, anthropometric characteristics (BMI, body weight, and waist circumference), quality of life (PCOSQ), depression, anxiety and stress (DASS 21) and pregnancy rates. Overall, the herbal medicine was well tolerated however two women were withdrawn due to non-serious side effects. Methodological strengths included sufficient power, low attrition and intention to treat analyses. Weaknesses included wide confidence intervals found for the primary outcome.
Conclusion: This thesis provides new evidence for the potential therapeutic role and safety of naturopathy as an adjunct to lifestyle intervention for the management of PCOS. It demonstrates that women with PCOS are frequent users of complementary medicine and the evidence of reproductive endocrine effects of Western herbal medicines includes lowered LH, and glucose and raised FSH and oestradiol. The evidence from published RCTs demonstrated the clinical efficacy of two nutritional supplements, inositol and omega-three fish oils, and two herbal medicines, Cimicifuga racemosa and Mentha spicata for an improved hormone profile, reproduction and reduced risk factors.
This thesis presents preliminary evidence for the enhanced effectiveness of lifestyle intervention following the addition of a new herbal formulation for overweight women with PCOS. Significantly improved outcomes included menstrual regularity, metabolic hormones, anthropometry, blood pressure, pregnancy rates, psychological profile and quality of life.

This entry includes 2 data-sets that were published in 3 papers.
1. Data collected from a randomised control trial that compared the effectiveness of a naturopathic herbal medicine supplement in addition to lifestyle intervention, compared to lifestyle alone for menstrual regularity in 122 overweight women with polycystic ovarian syndrome.
2. A survey of 496 women with PCOS describing their prevalence and patterns of complementary medicine use
3. A survey of 496 women with PCOS describing their experiences of lifestyle intervention.

The survey data-set could be used to further describe women with PCOS who are living in the community, and associated physical and psychological health characteristic ot other associations. It is a reasonably sized sample of 493 responses.

The RCT dataset could be used to generate a power calculation for a placebo-controlled efficacy RCT. The IP was commercialised by an Australian company Mediherb Pty Ltd, who manufactured a product called PCOSupport that is registered (listed) with the TGA

https://www.tga.gov.au/resources/artg/395997
The ANZCTR entry: Trial Id: ACTRN12612000122853 https://www.anzctr.org.au/trial/MyTrial.aspx
The effectiveness of naturopathic herbal medicine and a lifestyle intervention, compared to lifestyle intervention alone for oligomenorrhoea, serum hormones, anthropometric, reproductive, blood pressure, quality of life and adverse outcomes in overweight women with polycystic ovary syndrome (PCOS).

多囊卵巢综合征（Polycystic ovary syndrome, PCOS）最早于1935年由Irving F. Stein与Michael L. Leventhal提出，当时被命名为Stein-Leventhal综合征，其定义为「表现为持续性无排卵、肥胖与多毛症的卵巢膜细胞增生症女性」。如今，PCOS是女性最常见的生殖内分泌疾病，亦是卵巢性不孕的首要病因，并可引发心理与情绪困扰。无论体重水平如何，PCOS均与短期及长期的严重健康风险相关，包括糖尿病、癌症与心血管疾病风险的显著升高。就医疗保健系统而言，澳大利亚PCOS患者的年度医疗开销经保守估算可达4亿澳元。

PCOS对女性生活质量与自尊的负面影响已得到明确界定与广泛认可。基于循证医学的管理方案强调多学科联合诊疗，国际临床指南将生活方式干预推荐为一线治疗手段。然而，由于随机对照试验（randomised controlled trial, RCT）中高脱落率的存在，生活方式干预的证据强度仍较为有限；同时，因缺乏最优饮食与运动方案的相关证据，临床推广也受到阻碍。PCOS患者常寻求其他治疗方式以达成包括生育结局在内的临床目标。药物与手术可用于调节月经、降低雄激素水平、治疗不孕与高胰岛素血症，但这些手段仅能有限缓解部分PCOS症状，且常因合并症风险升高而存在禁忌，或伴随较高的不良反应发生率。此外，PCOS女性也表达了对替代疗法的偏好。

自然疗法（Naturopathy）是起源于古代西方文明的一类补充医学。该疗法以整体哲学为核心，遵循六项执业原则与相关理论，从业者通过自然治疗手段提升患者福祉、激发机体固有的自愈能力，以此为多种病症提供诊疗服务。本文基于三大核心理由阐述自然疗法用于PCOS管理的合理性：一是当前医学管理存在临床空白；二是草药与营养补充剂在PCOS治疗中具备临床潜力；三是女性患者对补充医学的偏好与接受度。本研究通过解答以下四个问题，探讨自然疗法在PCOS女性中的应用价值：
1. PCOS女性对补充医学、自助手段及生活方式干预的使用现状与态度如何？
2. 针对PCOS女性，现有随机对照试验中关于自然疗法草药与营养补充剂的研究证据有哪些？
3. 草药用于治疗排卵稀发/闭经（oligo/amenorrhoea）、高雄激素血症（hyperandrogenism）及PCOS的生殖内分泌效应，其临床前与佐证性临床证据如何？
4. 对于超重PCOS女性，在生活方式干预基础上联合使用西方复方草药（蒺藜Tribulus terrestris、甘草Glycyrrhiza glabra、芍药Paeonia lactiflora、贯叶连翘Hypericum perforatum及肉桂Cinnamomum cassia），相较于单纯生活方式干预，是否可改善月经规律度？

研究方法：本研究通过针对PCOS女性的问卷调查、两项独立的系统综述，以及一项评估自然疗法复方草药联合生活方式干预对超重PCOS女性多维度结局影响的随机对照试验，解答上述研究问题。
研究团队针对493名PCOS女性开展电子问卷调查，评估其使用补充医学与自我护理（饮食与运动）的情况及相关态度。受试者招募自澳大利亚多囊卵巢综合征协会（Polycystic Ovary Syndrome Association of Australia, POSAA）及社交媒体上的PCOS互助群组。
两项文献综述分别梳理了营养补充剂与草药的研究证据基础。其中一项系统综述整合了现有随机对照试验中，营养补充剂与草药用于PCOS女性的临床效应相关证据。针对自然疗法临床中常用的草药，已有一致的临床前与临床证据表明其可对PCOS产生生殖内分泌效应，本研究据此阐释了五种候选草药的作用机制——理论上，这些草药可帮助调节PCOS女性的月经模式、降低雄激素水平并改善卵巢形态。
一项随机对照试验纳入122名经医学确诊的超重PCOS女性，比较了在生活方式干预基础上添加新型复方草药与单纯生活方式干预的临床有效性与安全性。研究的主要结局为月经规律度，次要结局则包括干预后3个月时的妊娠率、血清激素与血糖浓度、人体测量学指标、心理健康结局，以及干预后9个月时的活产率。

研究结果：超三分之二的受访女性表示会定期使用营养补充剂与草药来管理PCOS。尽管多数受访者称会规律进行生活方式干预（饮食与运动），但仅有少数人表示对此满意，且大部分女性都希望获取关于补充医学的透明化信息。
系统综述结果显示，纳入18项随机对照试验（共1109名女性）的研究证据表明，六种营养补充剂（维生素D、Omega-3、钙、铬、复合维生素与肌醇）及四种草药（茶树Camellia sinensis、升麻Cimicifuga racemosa、肉桂Cinnamomum cassia与留兰香Mentha spicata）可用于改善PCOS相关症状。研究整体质量为低至中等水平，共针对11项结局开展了11项荟萃分析。其中，肌醇用于治疗PCOS女性的高雄激素血症、不孕及调节代谢激素水平的证据强度最高，Omega-3鱼油用于改善PCOS女性高胆固醇血症的证据亦较为充分。本研究结果同时指出，多数天然健康补充剂仍缺乏高质量研究证据，且肌醇与Omega-3的相关研究结果仅能为PCOS管理的循证指南提供低等级证据。
针对草药治疗排卵稀发/闭经、高雄激素血症及PCOS的作用机制的文献综述显示，六种草药（升麻Cimicifuga racemosa、肉桂Cinnamomum cassia、甘草属Glycyrrhiza spp、芍药Paeonia lactiflora、蒺藜Tribulus terrestris及牡荆Vitex agnus-castus）均具备一致的临床前与临床证据支持其生殖内分泌效应。具体而言，这些草药的生殖内分泌作用包括：降低促黄体生成素（LH，升麻、芍药与肉桂）、升高促卵泡生成素（FSH，蒺藜）、降低睾酮水平（甘草属与芍药）及改善空腹胰岛素水平（肉桂）。基于上述草药作用机制与自然疗法临床实践，本研究开发了一款新型复方草药，用于后续随机对照试验的评估。
本随机对照试验共纳入122名PCOS女性，随机分为复方草药联合生活方式干预组与单纯生活方式干预组。干预3个月后，联合用药组女性的月经规律度较单纯干预组出现显著改善，且治疗效应为中到大程度。次要结局方面，联合用药组在空腹胰岛素水平、人体测量学指标（体质量指数BMI、体重及腰围）、生活质量（PCOSQ量表）、抑郁、焦虑与压力（DASS-21量表）及妊娠率上均出现显著提升。整体而言，该复方草药耐受性良好，仅2名受试者因非严重不良反应退出研究。本研究的方法学优势包括充足的检验效能、低脱落率及意向性治疗分析；局限性则包括主要结局的置信区间较宽。

结论：本研究为自然疗法作为生活方式干预的辅助手段用于PCOS管理的潜在治疗价值与安全性提供了新的证据。研究证实，PCOS女性是补充医学的高频使用者，且西方草药的生殖内分泌效应包括降低LH、葡萄糖水平，升高FSH与雌二醇水平。已发表的随机对照试验证据显示，两种营养补充剂（肌醇与Omega-3鱼油）及两种草药（升麻Cimicifuga racemosa与留兰香Mentha spicata）可有效改善激素谱、生殖结局并降低风险因素。
本研究还为超重PCOS女性在生活方式干预基础上添加新型复方草药可提升干预效果提供了初步证据，其改善的结局包括月经规律度、代谢激素水平、人体测量学指标、血压、妊娠率、心理状态及生活质量。

本条目包含2组数据集，相关成果已发表于3篇论文：
1. 一项随机对照试验的相关数据：该试验比较了复方草药补充剂联合生活方式干预与单纯生活方式干预，对122名超重多囊卵巢综合征女性月经规律度的影响。
2. 一项针对496名PCOS女性的问卷调查数据：描述了其使用补充医学的现状与模式。
3. 一项针对496名PCOS女性的问卷调查数据：描述了其接受生活方式干预的相关体验。

该问卷调查数据集可用于进一步描述社区居住的PCOS女性群体及其相关生理与心理健康特征，以及其他关联因素。本研究共回收有效问卷493份，样本量较为可观。
本随机对照试验数据集可用于为安慰剂对照的疗效性随机对照试验计算检验效能。该研究的知识产权已由澳大利亚公司Mediherb Pty Ltd进行商业化开发，该公司生产了一款名为PCOSupport的产品，已在澳大利亚治疗用品管理局（Therapeutic Goods Administration, TGA）完成注册备案。
相关链接：https://www.tga.gov.au/resources/artg/395997
澳大利亚新西兰临床试验注册中心（ANZCTR）登记信息：试验编号ACTRN12612000122853，详见https://www.anzctr.org.au/trial/MyTrial.aspx
研究主题：比较自然疗法草药联合生活方式干预与单纯生活方式干预，对超重多囊卵巢综合征女性的排卵稀发、血清激素水平、人体测量学指标、生殖结局、血压、生活质量及不良反应的影响。