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JiHong Ding
Abstract: In recent years, domestic and international research has found that patients with polycystic ovary syndrome (PCOS) often have varying degrees of mental disorders, with depression being the most common comorbidity. Depression significantly affects patients’ reproductive fertility, psychological health, and quality of life. To further explore the clinical symptoms of PCOS complicated with depression, identify possible causes and pathogenesis, and choose appropriate treatment methods, this article provides a review of the understanding of PCOS complicated with depression from the perspective of traditional Chinese medicine (TCM), clinical manifestations, relevant pathogenesis, and potential treatment strategies. This aims to provide a scientific basis for the clinical treatment of PCOS complicated with depression.
Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder in women of childbearing age, with over 15% of women of childbearing age suffering from PCOS［1,2］. The American Endocrine Society’s clinical practice guidelines［3］recommend using the Rotterdam criteria for diagnosis, which states that meeting any two or more of the criteria of excessive androgens, ovulatory dysfunction, and ovarian cystic changes can diagnose PCOS. Clinical manifestations of PCOS often include abnormal hair growth (hirsutism or hair loss), menstrual irregularities, pregnancy complications, and metabolic syndrome (such as obesity or insulin resistance). The occurrence of these symptoms increases the risk of depression in patients with PCOS; in fact, over 60% of PCOS patients are diagnosed with at least one mental disorder［2,4］.
Recent research has found an association between PCOS and mental health issues, with depression being a major concern［5］and considered one of the significant risk factors for PCOS. A 15-year follow-up study found that psychological distress is more common among reproductive-age and premenopausal women with PCOS［6］. Several studies have shown that women with PCOS have an increased risk of depression and negative body image compared to those without PCOS［7-9］.
On the other hand, patients with polycystic ovary syndrome (PCOS) have a higher risk of developing depression and face significant economic burdens. The risk of depression in PCOS patients is more than 2.5 times higher than in healthy women［10］, and another study indicated that the incidence of depression in PCOS patients is 3 to 8 times higher compared to the control group［11］, further highlighting the significantly increased risk of depression symptoms in women with PCOS. A domestic study pointed out that the prevalence of depression among PCOS patients in China is 30%, showing an increasing trend［12］. As of 2021, the direct annual medical costs associated with the most common mental health disorders related to PCOS (depression, anxiety, or eating disorders) in the US population alone exceeded $4 billion［13］. This demonstrates that the risk of depression caused by PCOS and the related mental health care costs continue to rise.
Therefore, this study, through databases such as China National Knowledge Infrastructure (CNKI) and PubMed, comprehensively analyzes relevant research on PCOS complicated with depression from domestic and international sources. The study will review four aspects: understanding of PCOS complicated with depression from the perspective of traditional Chinese medicine, clinical manifestations, possible related mechanisms, and potential treatment strategies. This is aimed at providing theoretical support for the treatment of PCOS complicated with depression.
Understanding of Polycystic Ovary SyndromeComplicated with Depression in Traditional Chinese Medicine
Based on the clinical manifestations of polycystic ovary syndrome (PCOS) complicated with depression, it can be categorized as “Yu Zheng,” “Zang Zao,” or “Baihe Bing” in traditional Chinese medicine (TCM) terms. The medical case records of Wang Mengying［14］state: “The liver governs the qi of the whole body, and diseases related to the seven emotions must start from the liver.” Emotional disturbances are most likely to impair qi and blood; women primarily use blood, and stagnation of liver qi and stasis of qi and blood can lead to abnormalities in physiological functions such as menstruation and fertility. For instance, the Wan family’s Obstetrics and Gynecology［15］describes: “Worrying, overthinking, anger, and resentment can lead to stagnation of qi and blood, resulting in irregular menstruation.” The Essentials of Gynecology［16］mentions: “If the seven emotions harm the body, it can lead to menstrual disorders and infertility.” Thus, emotional imbalance is considered a significant etiological factor in menstrual irregularities and infertility in women, making liver depression syndrome one of the common clinical patterns in PCOS complicated with depression.
TCM theory suggests that the occurrence and development of PCOS complicated with depression are closely related to emotional factors, with depressive emotions or stressful life events being risk factors for liver depression syndrome. The Secret Essentials of Gynecology［17］states: “Generally, women with strong emotions, stubbornness, anger, jealousy, and suspicion often damage liver qi.” According to TCM theory, women primarily rely on the liver for congenital essence; when the liver’s regulation and expression are affected by pathological emotions, and qi stagnation occurs, it can impair the functions of the liver, spleen, and kidneys. This, in turn, affects the kidney-Jing (essence)-chong (thoroughfare)-ren (conception)-bao (uterus) reproductive axis, leading to menstrual or pregnancy abnormalities and the development of this condition. The Essentials of the Yin School［18］states: “Female servants often have depression, leading to irregular menstruation and difficulty in conception.”
From the perspective of TCM differential diagnosis and treatment, patients with PCOS often exhibit liver dysfunction in regulating and expressing qi, qi stagnation, blood stasis, or phlegm-dampness obstruction, leading to dysfunction of organ physiology and clinical manifestations such as obesity, hirsutism, or menstrual irregularities. For example, the Jisheng Formula［19］states: “The essence of human qi lies in smooth flow; if it flows smoothly, there will be no phlegm or fluid-related disorders.” The Medical Canon［20］explains: “Emotional disturbances can lead to phlegm.” Prolonged liver dysfunction in regulating and expressing qi, abnormal spleen-stomach ascending and descending functions, improper distribution of body fluids, internal accumulation of phlegm turbidity, and the generation of greasy fats can lead to obesity. The Yellow Emperor’s Inner Canon: Basic Questions［21］records: “The lungs govern the skin and hair; they nourish the hair.” Prolonged liver depression can generate heat, and wood (liver) overacts on metal (lung), scorching the lung yin and affecting the head and face, leading to clinical signs such as hirsutism.
Common Clinical Manifestations of Polycystic Ovary Syndrome Complicated with Depression
Menstrual Irregularities
Polycystic ovary syndrome (PCOS) is one of the common endocrine disorders in women, characterized by changes in biochemical indicators such as sex steroids and neuroactive steroids［22］, leading to an increased risk of depression and occurrences of menstrual irregularities or infertility［23］. The clinical manifestations of menstrual abnormalities can exacerbate negative perceptions among PCOS patients, lower self-esteem, and have a negative impact on emotions［11］.
Among the related symptoms of PCOS, menstrual cycle irregularities are one of the most common［24］, such as anovulation, amenorrhea, or oligomenorrhea. A study by Syeda Sidra et al.［25］surveyed the clinical presentations, health risks, and impact on quality of life among 440 PCOS patients, finding that 71.8% of PCOS patients experienced menstrual irregularities and that depression was the primary cause of reduced quality of life. Similarly, domestic scholars have found a high incidence of emotional disorders among PCOS patients, with mental health issues (depression or anxiety) being the primary factors affecting quality of life［26］. Reproductive-age PCOS patients are prone to depression or anxiety, with menstrual irregularities being a risk factor for anxiety and depression symptoms, and infertility being a major source of stress leading to anxiety symptoms among reproductive-age PCOS patients［27］. Overall, both domestic and international studies confirm that menstrual abnormalities in PCOS patients can mutually influence depression, thereby reducing patients’ quality of life.
Infertility or Pregnancy Abnormalities
Polycystic ovary syndrome (PCOS) is considered a complex condition with psychological, reproductive, and metabolic manifestations, affecting women’s health throughout their lifetimes［28］.
Infertility or pregnancy abnormalities are among the primary clinical presentations of PCOS complicated with depression.
Recent research has found that PCOS is associated with an increased risk of pregnancy and childbirth complications among pregnant women［29］, and a longer duration of infertility is closely related to higher levels of clinically relevant depressive symptoms［5］.
Studies indicate that compared to infertile women without PCOS, infertile women with PCOS often experience higher levels of psychological stress［30］and have difficulty describing their feelings［31］.
These negative emotions may play a role in the progression of PCOS. Research by Li Sijiao et al. similarly shows that infertile PCOS patients have a higher incidence of depression and are more sensitive in interpersonal relationships compared to non-PCOS infertile patients.
Furthermore, PCOS patients with secondary infertility are more likely to experience anxiety or somatization disorders［32］. The prevalence of depression among women with PCOS causing infertility is significantly higher［33］, indicating that multiple complex etiological factors intertwine and may even be mutually reinforcing, exacerbating abnormalities in pregnancy function among PCOS patients.
Therefore, it is evident that the negative emotions of PCOS complicated with depression patients mutually influence the disease, affecting or exacerbating clinical characteristics, hormone levels, and metabolic disorders, leading to infertility and adverse effects on pregnancy outcomes［34］.
Possible Related Mechanisms of PolycysticOvary Syndrome Complicated with Depression
Neuroendocrine Mechanisms
Patients with polycystic ovary syndrome (PCOS) complicated with depression often experience endocrine and metabolic disturbances or chronic inflammation, leading to long-term chronic stressors (such as elevated androgens［35］, menstrual irregularities［36］, or changes in body composition［37］serving as chronic stressors), keeping them in a prolonged state of emotional stress［38］, resulting in symptoms of depression and other adverse emotions.
At the neuroendocrine level, PCOS complicated with depression may be associated with abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis［39］, neurotransmitter deficiencies or abnormalities［40］, or vitamin D deficiency［41,42］.
The hypothalamus plays a dual role in regulating reproductive function and emotional centers［43］. Studies suggest that the occurrence of PCOS complicated with depression may be related to abnormalities in the HPA axis［39］, indicating that PCOS may disrupt the HPA axis in some way leading to the onset of depression［44］.
On one hand, emotional stress can act on the hypothalamus, stimulating gonadotropin-releasing hormone secretion, thereby activating the HPA axis, leading to increased secretion of adrenocorticotropic hormone and cortisol［45］, affecting glucose and lipid metabolism processes, and may also induce insulin resistance or hyperinsulinemia［46］, forming a vicious cycle of intertwined factors.
On the other hand, negative emotions such as depression or anxiety in PCOS patients can affect hypothalamic endocrine function, leading to increased secretion of ovarian androgens［35,47］, inhibiting follicular development, thereby affecting the occurrence and development of PCOS.
Changes in neurotransmitters may be one of the causes of gonadotropin-releasing hormone secretion disorders, leading to PCOS complicated with depression. There is substantial evidence that alterations occur in catecholamine metabolism and brain serotonin or opioid activity among PCOS patients［48］.
Additionally, fluctuations in neurotransmitter and neuropeptide levels among PCOS patients may lead to mood swings. Research by Nirja Chaudhari et al. demonstrates that increased gonadotropin-releasing hormone and luteinizing hormone levels among PCOS patients may be due to cumulative effects of changes in gonadotropin-releasing hormone and inhibitory neurotransmitters in the hypothalamic-pituitary system, which may also be a contributing factor to depressive and anxiety-like mood disorders in women with PCOS［49］.
Therefore, the abnormal levels of gonadotropin-releasing hormone and luteinizing hormone in PCOS complicated with depression, leading to enhanced production of ovarian androgens and changes in cortisol metabolism resulting in increased adrenal androgen production, and mood swings affecting the release of these neurotransmitters, may help explain the clinical diversity observed in patients with PCOS complicated with depression.
Gut Microbiota Mechanisms
The dysregulation of gut microbiota plays a crucial role in the development of polycystic ovary syndrome (PCOS) complicated with depression. The gut microbiota, also known as the host’s “second genome,” is closely associated with chronic metabolic diseases. In recent years, the connection between PCOS and gut microbiota has garnered increasing attention［50］.
The dysbiosis of gut microbiota is related to hyperandrogenism, insulin resistance, chronic inflammation, and metabolic disorders associated with PCOS［51,52］, making it a potential contributing factor to PCOS complicated with depression.
Depression, as an inflammatory disorder, is characterized by elevated levels of inflammatory markers. On the other hand, PCOS is also considered a pro-inflammatory state, characterized by increased levels of pro-inflammatory markers［53］.
Meanwhile, the chronic low-grade inflammation seen in PCOS may interact with certain neuroregulators, leading to the onset of depression［54］. The imbalance in gut microbiota in PCOS patients may be characterized by a decrease in bacteria producing short-chain fatty acids and metabolizing bile acids, indicating a shift in gut microbiota balance that promotes the proliferation of pro-inflammatory bacteria, thus exacerbating inflammation levels in PCOS patients［55］.
There are alterations in the α-diversity of gut microbiota and the relative abundance of Proteobacteria in women with PCOS. Numerous studies indicate that Proteobacteria could be potential biomarkers of gut microbiota in PCOS complicated with depression［56］and may even have diagnostic value［57］.
On the other hand, many dietary components can impact the onset and progression of diseases by targeting gut microbiota［58］. PCOS patients often have vitamin D deficiency［59］, and it has been reported that inadequate vitamin D intake can lead to an increase in Proteobacteria［60］.
This has been indirectly supported by basic experiments, where animal models with imbalanced gut microbiota exhibited typical PCOS symptoms, including menstrual cycle disturbances, elevated testosterone levels, and ovarian morphological changes［61］.
Potential Treatment Strategies for Polycystic Ovary Syndrome (PCOS) Complicated with Depression
Lifestyle Management
A healthy lifestyle should be a primary focus of care for women with polycystic ovary syndrome (PCOS)［62］. Research by Natalia Ligocka et al. indicates that adopting a healthy lifestyle, balanced diet, and regular physical activity can help control PCOS symptoms, thereby improving overall quality of life for patients［63］. Evidence suggests that lifestyle management is a frontline intervention in the hierarchy of PCOS interventions, with multidimensional lifestyle interventions including diet, exercise, and behavioral strategies being core elements of PCOS management［64］.
Simultaneously, a commentary in The Lancet specifically points out［65］that the treatment of PCOS should combine lifestyle changes with medical management.
Lifestyle optimization includes maintaining a healthy balanced diet and regular exercise to prevent excessive weight gain. Medical management strategies involve using metformin to improve insulin resistance and abnormal metabolic features, along with combined oral contraceptives to regulate menstrual cycles and manage hyperandrogenism.
Additionally, the“2023 International Evidence-Based Guidelines for the Assessment and Management of Polycystic Ovary Syndrome” emphasizes the need for broader awareness and education about PCOS (such as metabolic risk factors, high prevalence of mental health issues, and adverse outcomes during pregnancy), along with continuous adjustment of lifestyle and emotional health to cope with changes in body weight and other physical characteristics［66］.
Therefore, recommending a healthy lifestyle to women with PCOS can optimize overall health, quality of life, body composition, and weight control. It may also promote improvement in emotional and mental well-being, thereby enhancing their quality of life as clinical features of PCOS lessen or improve.
Emotional Management and Regulation
Over the past decade, the risk of psychological health issues in PCOS patients has increased, particularly depression and anxiety, extending to other aspects of mental health such as body image concerns and eating disorders［67］.
Therefore, the treatment of PCOS must include assessment and treatment of psychological health symptoms.
Cognitive Behavioral Therapy (CBT) is a frontline psychological treatment method for clinical depression. CBT has significant advantages in alleviating depression and anxiety in PCOS patients, improving hirsutism, or increasing pregnancy rates［68］.
Most psychological interventions using CBT can effectively reduce depression scores in PCOS patients［69］.
Sheida Majidzadeh et al.’s study, using 8 sessions of 60-90 minutes each of cognitive behavioral training (including skill practice and cognitive challenges), found significant reductions in depression and anxiety symptoms in PCOS patients, along with improved quality of life［70］. Therefore, healthcare providers are advised to use this approach to improve the psychological health and quality of life of PCOS patients.
Aerobic exercise can also effectively alleviate the distress associated with depressive symptoms of polycystic ovary syndrome (PCOS). Aerobic exercise has been shown to improve clinical symptoms in patients with PCOS and also has some efficacy in reducing the incidence of depression and anxiety［71,72］. A study by Isis K. Santos et al.［73］employed a 12-week high-intensity interval training (HIIT) program with three sessions per week and 40-60 minutes per session. The PCOS patients in the HIIT group showed significant improvements in quality of life and depressive symptoms. Another large-sample study found that 16 weeks of exercise training, whether continuous aerobic exercise, interval aerobic exercise, or progressive resistance training, could improve depression scores in patients with PCOS. Moreover, among these three exercise types, interval aerobic exercise was found to be the most effective in improving quality of life and depressive symptoms in patients with PCOS［74］. Therefore, it is not difficult to see the potential of aerobic exercise in improving the mental health and quality of life of patients with PCOS. Aerobic exercise may be a feasible strategy to reduce depressive symptoms in patients with PCOS.
Acupuncture has significant advantages and remarkable efficacy in the treatment of PCOS comorbid with depression. Acupuncture may regulate hormone secretion, affect ovulation or menstrual cycles, thereby improving ovulation rates and pregnancy rates, reducing miscarriage rates, and reducing the production of negative stress; acupuncture can also effectively alleviate insulin resistance, regulate lipid metabolism, adjust body shape, and promote the physical and mental health development of patients with PCOS comorbid with depression; and acupuncture has few side effects and is relatively safe［75-77］. A study by Zhang Haolin et al.［78］found that electroacupuncture can effectively relieve patients’ depressive mood, and its mechanism may be related to the regulation of serum endorphin and androgen levels. Another study found that electroacupuncture treatment can reduce depression scores in patients with PCOS, has a mind-body coordination effect, and the therapeutic effect of electroacupuncture is superior to the drug Diane-35［79］. Therefore, acupuncture has a positive effect on the treatment of the main symptoms of PCOS (whether reproductive, metabolic or mental health). The action of acupuncture in the treatment of PCOS is related to the regulation of sex hormones, the improvement of ovulation and pregnancy rates, the regulation of insulin resistance and lipid metabolism, and the rebalancing of negative emotions.
It’s worth noting that some polycystic ovary syndrome (PCOS) patients in low-income countries may delay seeking professional help and treatment, leading to a delay in managing their condition［80］. The importance of support and acceptance from family and friends cannot be overlooked when PCOS patients experience emotional disturbances［63］. Therefore, timely diagnosis, cultural education related to lifestyle and weight management, and improving psychological and emotional support are crucial areas to address in clinical practice and future research for PCOS patients with comorbid depression.
The comorbidity of polycystic ovary syndrome (PCOS) and depression in Traditional Chinese Medicine (TCM) treatment and differentiation may be closely related to depressive patterns. Characteristic clinical manifestations such as menstrual irregularities or pregnancy complications may be closely associated with neuroendocrine abnormalities or disruption of intestinal microbiota balance. Alternatively, multiple complex factors may intertwine. In future research, it is necessary to delve deeper into the mechanisms between these factors. In treatment protocols, lifestyle management and emotional regulation should be the preferred treatment options for PCOS patients with comorbid depression, aiming to improve their overall health status and enhance their quality of life.
Author information:
Jihong Ding，Ph.D. candidate of FuJian University of Traditional Chinese Medicine.
參考文獻
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多囊性卵巢症候群合併憂鬱症的中西醫學研究進展
丁繼
摘要：近年來，國內外研究發現多囊性卵巢症候群患者常伴隨不同程度的精神障礙，其中最常見的合併症就是憂鬱症，其對病人的生殖生育，心理健康及生活品質均造成嚴重影響。為進一步探討多囊性卵巢症候群合併憂鬱症的臨床症狀，找出可能的病因及發病機制，從而選擇合適的治療手段，本文將對多囊性卵巢症候群合併憂鬱症患者的中醫認識，臨床表現，相關發病機轉及潛在的治療策略進行綜述，為多囊性卵巢症候群合併憂鬱症的臨床治療提供科學依據。
背景：囊性卵巢症候群（Polycystic Ovarian Syndrome，PCOS）是一種育齡期女性常見的內分泌及代謝性疾病，超過15%的育齡期女性患有多囊性卵巢症候群［1,2］。美國內分泌學會臨床實務指引［3］中建議使用鹿特丹標準進行診斷，即滿足雄性激素過多，排卵功能障礙和卵巢多囊改變中的任兩點或兩點以上即可診斷為多囊性卵巢綜合徵。多囊性卵巢症候群臨床上常表現為毛髮異常（多毛或脫髮等），月經紊亂，妊娠異常以及代謝症候群（肥胖症或胰島素抗性等）等症狀。 這些症狀的出現會導致多囊性卵巢症候群患者憂鬱風險增加，事實上，超過60%的多囊性卵巢症候群患者被診斷為至少患有一種精神疾病［2,4］。
近年來研究發現，多囊性卵巢症候群與心理健康問題之間存在關聯，其中憂鬱症備受關注［5］，被認為是多囊性卵巢症候群的重要危險因子之一。一項為期15年的追蹤研究發現，心理困擾在患有多囊性卵巢症候群的育齡和停經前女性中更為普遍［6］。多項研究發現，與沒有多囊性卵巢症候群的女性相比，患有多囊性卵巢症候群的女性憂鬱風險和身體形象負面感官增加［7-9］。
另一方面，多囊性卵巢症候群患者有較高的憂鬱症發病風險和經濟負擔。多囊性卵巢症候群患者罹患憂鬱症的風險比健康女性高2.5倍以上［10］，另一項研究則顯示多囊性卵巢症候群患者〖JP2〗的憂鬱症發生率是對照組的3-5倍［11］，進一步顯示患有多囊性卵巢症候群的女性出現憂鬱症狀的風險大大增加。國內的一項研究指出，我國多囊性卵巢症候群患者憂鬱的盛行率為30%，並呈現高發生率［12］。截止到2021年，僅在美國人口中與多囊性卵巢症候群相關的最常見的精神心理疾病（憂鬱、焦慮或飲食失調）的直接年度醫療費用就超過40億美元［13］。由此可見，由於多囊性卵巢症候群所造成的憂鬱疾病風險與精神衛生相關的醫療開支仍在增加。
因此，本研究透過中國知網（CNKI）和PubMed等文獻資料庫，綜合分析國內外有關多囊性卵巢症候群合併憂鬱症的相關研究，本研究將從多囊性卵巢症候群合併憂鬱症的中醫認識， 臨床表現，可能的相關機制以及潛在治療策略4個面向進行綜述，以期為多囊性卵巢症候群合併憂鬱症的治療提供理論支撐。
多囊性卵巢症候群合併憂鬱症的中醫認識
根據多囊性卵巢症候群合併憂鬱症的臨床表現，可將其歸類為“鬱證”，“臟躁”或“百合病”等範疇。《王孟英醫案》［14］中記載：“肝主一身之氣，七情之病必由肝起”。 七情內傷最易損及氣血，女性族群以血為用，肝氣鬱滯，氣滯血瘀，導致經由帶胎產的生理功能異常。
如《萬氏婦人科》［15］中記述：“憂慮思慮，惱怒怨恨，氣滯血瘀，而經不行”；《女科要旨》［16］中提及：“若七情損傷，經水失調，可致不孕”。
由此可知，情緒失調是女性月經不規則及不孕症的重要致病因素，肝鬱證亦成為多囊性卵巢症候群合併憂鬱症臨床常見證型之一。
中醫理論認為多囊性卵巢症候群合併憂鬱症的發生與發展主要與情緒因素密切相關，憂鬱情緒或壓力性生活事件等為肝鬱證的危險因素，如《女科秘要》［17］中所載：“大抵婦人，情多執拗，偏僻忿怒妒忌，多傷肝氣”。
中醫理論認為“女子以肝為先天”，因肝主疏洩，喜條達惡抑鬱，當情志致病，氣機受阻時，導致肝脾腎功能受損，從而影響腎-天癸-衝任 -胞宮生殖軸的功能，進而導致月經異常或懷孕異常而發為本病。 《濟陰綱目》［18］中記述：“婢妾多鬱，情不宣暢，經多不調，故難成孕”。
從辨識論治角度發現，多囊性卵巢症候群患者因肝失疏洩，氣滯血瘀或痰濕蘊結，導致臟腑生理功能失調可發為本病，出現肥胖，多毛或月經愆期等臨床表現。
如《濟生方》［19］中曰：“人之氣道貴乎順，順則津液流通，決無痰飲之患”；《醫貫》［20］中講述：“七情內傷， 鬱而生痰”。 肝失疏洩，脾胃升降失常，津液疏布不當，痰濁內蘊，膏脂內生，則為肥胖。《黃帝內經·素問》［21］中記載：“肺之合皮也，其榮毛也”。肝鬱日久化火，木火刑金，灼傷肺陰，上犯頭面，故可見多毛等體徵表現。
多囊性軟巢症候群合併憂鬱症的常見臨床表現
月經紊亂
多囊性軟巢症候群作為女性常見的內分泌疾病之一，透過性腺類固醇和神經活性類固醇等生化指標的變化［22］，導致憂鬱症風險升高和月經不規則或不孕等情況發生［23］。月經異常的臨床表現可能會加劇多囊性軟巢症候群患者的負面看法，降低自尊並對情緒產生負面影響［11］。
多囊性軟巢症候群的相關症狀中月經週期異常是最常見的症狀之一［24］，如無排卵，閉經或月經稀發等。Syeda Sidra等人的研究［25］，針對440名多囊性卵巢症候群患者的臨床表現和健康風險及其對生活品質的影響進行調查，發現多囊性卵巢症候群的患者中出現月經不調的患者佔71.8%，並發現憂鬱症是導致患者生活品質降低的最大原因。同時，國內學者也發現多囊性軟巢症候群患者情緒障礙的發生率較高，心理健康（憂鬱症或焦慮症）是影響生活品質的主要因素［26］。育齡期多囊性軟巢症候群患者容易出現憂鬱或焦慮，月經異常是導致患者出現焦慮和憂鬱症狀的危險因子之一，不孕症是導致育齡期多囊性軟巢症候群患者出現焦慮症狀的主要壓力 來源之一［27］。綜上，國內外研究均證實多囊性卵巢症候群患者月經異常表現與憂鬱症之間可以相互影響，進而降低患者的生活品質。
不孕或妊娠異常
多囊性卵巢症候群被認為是一種具有心理、生殖和代謝表現的複雜疾病，影響女性整個生命週期的健康［28］。不孕症或妊娠異常是多囊性卵巢症候群合併憂鬱症的主要臨床表現之一。近來研究發現，多囊性卵巢症候群與孕產婦妊娠和分娩併發症的風險增加有關［29］，且不孕症持續時間較長與臨床相關憂鬱症狀程度較高密切相關［5］。
研究表明，與未患有多囊性卵巢症候群的不孕症女性相比，患有多囊性卵巢症候群的不孕症女性通常會感受到更高程度的心理壓力［30］，並且無法描述自己的感受［31］，這些負面情緒可能在多囊性卵巢症候群的病程進展中發揮作用。李賽姣等人的研究同樣顯示多囊性卵巢症候群不孕患者較非多囊性卵巢症候群不孕患者的憂鬱發生率較高且人際關係較敏感等情況，且繼發不孕的多囊性卵巢綜合症患者更容易出現焦慮或軀體化等精神障礙［32］。多囊性卵巢症候群導致不孕的女性的憂鬱症盛行率顯著更高［33］，由此可見，多種複合致病原因交織與錯雜，甚至可能互為因果，加劇多囊性卵巢症候群患者的妊娠功能異常。
因此，不難發現，多囊性卵巢症候群合併憂鬱症患者的負性情緒與疾病相互影響，影響或加重多囊性卵巢症候群患者的臨床特徵、性荷爾蒙水平和醣脂代謝紊亂情況，進而導致不孕 的發生，並對妊娠結局造成不良影響［34］。
多囊性卵巢症候群合併憂鬱症的可能相關機制
神經內分泌機制
多囊性卵巢症候群合併憂鬱症患者因內分泌及代謝性疾病或慢性發炎等臨床表現，形成長期慢性刺激（如：高雄性激素［35］，月經失調［36］或體型改變［37］等因素可作為慢性壓力源），使多囊性卵巢症候群合併憂鬱症患者長期處於情緒壓力狀態［38］，產生憂鬱症狀等不良情緒。 在神經內分泌層面，多囊性卵巢症候群合併憂鬱症可能與下視丘-腦下垂體-腎上腺軸異常［39］（Hypothalamic Pituitary Adrenal，HPA axis），神經傳導物質缺乏或異常［40］或維生素D缺乏［41,42］等有關。
下視丘具有調節生殖功能和情緒中樞的雙重功能［43］。 研究發現，多囊性卵巢症候群合併憂鬱症發病可能與HPA軸異常相關［39］，顯示多囊性卵巢症候群可能透過某種方式引起HPA軸紊亂導致憂鬱症的發病［44］。一方面，異常情緒壓力可作用於下視丘，刺激性腺激素釋放激素分泌，進而活化下視丘-腦下垂體-腎上腺軸，導致促腎上腺皮質激素和皮質醇分泌增加［45］，進而影響糖代謝和脂 代謝過程，也可能誘發胰島素抗性或高胰島素血症等情況［46］，許多因素反覆交織，形成惡性循環。 另一方面，在多囊性卵巢症候群患者中，憂鬱或焦慮等負性情緒會影響下視丘內分泌功能，促使卵巢雄性激素分泌增加［35,47］，抑制卵泡發育，進而影響多囊性卵巢症候群的發生和發展。
神經傳導物質的改變可能是性腺激素釋放激素分泌失調的原因之一，導致多囊性卵巢症候群合併憂鬱症。因為有大量證據顯示多囊性卵巢症候群患者中兒茶酚胺代謝和大腦血清素或鴉片類藥物活性發生了變化［48］。此外，多囊性卵巢症候群患者中神經傳導物質和神經肽的水平波動也可能導致情緒波動。Nirja Chaudhari等人的研究證明，多囊性卵巢症候群患者性腺激素釋放激素和黃體生成素增加可能是由於下丘腦-垂體系統中性腺激素釋放激素和抑制性神經傳導物質改變的累積效應所致，這也可能是多囊性卵巢症候群女性中憂鬱和焦慮樣情緒障礙的原因之一［49］。因此，多囊性卵巢症候群合併憂鬱症與性腺激素釋放激素和黃體生成素水平異常，導致卵巢雄激素生成增強與皮質醇代謝的改變導致腎上腺雄激素的產生增強，情緒波動也會影響這些傳遞物質性腺激素釋放激素的釋放，這也可能幫助解釋了多囊性卵巢症候群合併憂鬱症患者的臨床多樣性表現。
腸道微生物機制
腸道微生物失調在多囊性卵巢症候群合併憂鬱症的發生與發展中起著至關重要的作用。腸道微生物又被稱為宿主的“第二基因組”，與慢性代謝性疾病密切相關。 近年來，多囊性卵巢症候群與腸道微生物之間的關聯越來越受到人們的關注［50］。
腸道微生物群失調與多囊性卵巢症候群相關的高雄激素血症，胰島素阻抗，慢性發炎和代謝紊亂有關［51,52］，可能是多囊性卵巢症候群合併憂鬱症的潛在致病因素之一 。憂鬱症作為一種發炎性疾病，其特徵是發炎標記物水平升高。另一方面，多囊性卵巢症候群也被認為是一種促發炎狀態，其特徵是促發炎標記物水平升高［53］。同時，在多囊性卵巢症候群中出現的慢性低劑量發炎可能與某些神經調節劑相互作用，導致憂鬱症的發生［54］。多囊性卵巢症候群患者的腸道微生物平衡失調，其特徵可能是產生短鏈脂肪酸和代謝膽汁酸的細菌減少，這表明腸道微生物平衡發生了轉變，而這種轉變卻能夠促進促炎細菌的增殖，進而加劇多囊性卵巢症候群患者的發炎程度［55］。
多囊性卵巢症候群女性腸道微生物群的α多樣性和擬桿菌科的相對豐度發生了變化。多項研究表明，擬桿菌是多囊性卵巢症候群合併憂鬱症的潛在腸道微生物生物標記［56］，甚至具有診斷價值［57］。 另一方面，許多飲食成分可以透過針對腸道微生物群來影響疾病的發作和進展［58］。 多囊性卵巢症候群患者常伴隨維生素D缺乏［59］。 據報導，維生素D攝取不足會導致擬桿菌數量增加［60］。基礎實驗也間接證明類似情況，動物模型腸道微生物失衡後也表現出典型的多囊性卵巢症候群症狀，包括動情週期紊亂，睪固酮水平升高和卵巢形態改變等［61］。
多囊性卵巢症候群合併憂鬱症的潛在治療策略
生活方式管理
健康的生活方式應該成為患有多囊性卵巢症候群的女性的護理重點［62］。Natalia Ligocka等人的研究表明，採用健康的生活方式，均衡的飲食和定期進行身體活動可以幫助控制多囊性卵巢症候群的症狀，從而提高患者的整體生活品質［63］。有證據表明，生活方式管理是多囊性卵巢綜合徵幹預層級中的一線管理方案，其中包括飲食，運動和行為策略在內的多組分生活方式乾預是多囊性卵巢綜合徵管理的核心要素［64］。
同時，柳葉刀的述評文章特別指出［65］，多囊性卵巢症候群的治療應該將改變生活方式和醫療管理相結合。生活方式優化包括健康均衡的飲食和定期鍛煉，以防止體重過度增加。醫療管理方案包括使用二甲雙胍以改善胰島素阻抗和異常代謝特徵，聯合口服避孕藥用於調節月經週期和高雄激素血症等。
同時，《2023年多囊性卵巢症候群評估與管理國際實證指引》中強調，應該加強對多囊性卵巢症候群更廣泛的認識與科普（如，代謝危險因素，精神心理的高盛行率以及懷孕期間不良結果等高風險因子），且應持續調整生活方式與情緒健康，合理面對體重等體表特徵的改變［66］。
因此，可以向患有多囊性卵巢綜合症的女性推薦健康的生活方式，以優化整體健康，生活質量，身體組成和體重控制，也許當多囊性卵巢綜合徵的患者其臨床特徵減輕或好轉後，也可以促進其情緒及精神狀態的提升，進而提高其生活品質。
情緒管理調控
在過去的十年中，多囊性卵巢症候群患者併發心理健康狀況的風險癒發升高，特別是憂鬱症和焦慮症，並可能延伸到精神健康的其他方面，包括身體形象困擾，飲食失調等 方面［67］。因此，多囊性卵巢症候群的治療必須包括心理健康症狀的評估和治療。
認知行為治療（Cognitive Behavior Therapy，CBT）是臨床憂鬱症的第一線心理治療方法。認知行為療法在緩解多囊性卵巢症候群患者憂鬱焦慮狀況，改善多毛症或提高懷孕率等方面有明顯優勢［68］。大多數應用認知行為療法的心理介入措施可有效降低多囊性卵巢症候群患者的憂鬱評分［69］。Sheida Majidzadeh等人的研究，採用8次，每次60-90分鐘的認知行為訓練（包括技能練習和思維挑戰等內容），發現可有效減輕多囊性卵巢綜合症患者的抑鬱和焦慮症狀，提高其生活品質［70］。因此，建議醫療保健提供者可以使用這種種方法來改善多囊性卵巢症候群患者的心理健康和生活品質。
有氧運動也可有效改善多囊性卵巢症候群的相關憂鬱症狀困擾。有氧運動對於改善多囊性卵巢症候群患者的臨床症狀，並且對於降低憂鬱和焦慮的盛行率也有一定的功效［71,72］。Isis K Santos等人的研究［73］，採用為期12週的高強度間歇訓練，每週訓練3天，每次課程40-60分鐘，高強度間歇訓練組的多囊性卵巢症候群患者在生活質量和憂鬱症狀方面顯著改善。另一項大樣本的研究發現，進行16週運動訓練，無論是連續性有氧訓練，間歇性有氧訓練或漸進式阻力訓練都能夠促進多囊性卵巢症候群患者憂鬱評分的改善。並且，研究發現這三種運動方式中間歇性有氧訓練對於多囊性卵巢症候群患者的生活品質提升和憂鬱症狀改善最有效［74］。因此，不難發現，有氧運動在改善多囊性卵巢症候群患者心理健康和生活品質方面的潛力，有氧運動可能成為減少多囊性卵巢症候群患者憂鬱症狀的可行策略之一。
針灸在治療多囊性卵巢症候群合併憂鬱症的優勢明顯且療效顯著，針灸可能會調控荷爾蒙分泌，影響排卵或月經週期，進而提高排卵率和懷孕率，降低流產率，減少負性壓力的產生； 針灸還可有效減輕胰島素阻抗，調節脂代謝，調整體態，促進多囊性卵巢症候群合併憂鬱症患者的身心健康發展；並且針灸療法的副作用少，且安全性較好［75-77］。張浩琳等人的研究發現［78］，電針療法可以有效緩解患者的憂鬱情緒，其機制可能與調節血清內啡肽和雄性激素的水平有關。另一項研究發現［79］，電針治療可降低多囊性卵巢症候群患者的憂鬱評分，具有身心同調作用，且電針的治療效果優於藥物達因-35。因此，針灸在治療多囊性卵巢症候群主要症狀（無論是生殖，代謝或心理健康）具有正面作用。針灸治療多囊性卵巢症候群的作用與調節性激素，改善排卵和懷孕率，胰島素阻抗和脂質代謝調節以及負性情緒的重新平衡有關。
另外，值得注意的是某些低收入國家的多囊性卵巢症候群患者會延遲尋求專業協助與治療［80］，使得病情延遲。當多囊性卵巢症候群患者情緒出現異常時，家人與朋友的支持與接納的重要性也不可忽視［63］。因此，對於多囊性卵巢症候群合併憂鬱症的患者應該及時診斷，提供與生活方式和體重管理相關的文化教育以及改善心理情緒支持是臨床實踐和未來研究中應解決的關鍵領域。
結論
多囊性卵巢症候群合併憂鬱症在中醫治療與辨識研究中可能與鬱證密切相關，其特徵性臨床表現，如月經紊亂或妊娠異常等，可能與神經內分泌異常或腸道微生物平衡被破壞密切相關，亦或多種複合因素交織，在未來的研究中，需要深入探討這些因素之間的機制。在治療方案中，生活方式的管理和情緒管理調控應成為多囊性卵巢症候群合併憂鬱症患者首選治療方案，以提高多囊性卵巢症候群合併憂鬱症患者的整體健康水平，促進其生活品質的提升 。
作者簡介：
丁繼紅，福建中醫藥大學中醫學院在讀博士。
