Regulation Of Prostaglandin Levels In The Treatment Of Primary Dysmenorrhea With Traditional Chinese Medicine
Feb 21, 2025
Authors: HOU Xiaohu, HUO Lei, NIU Xingyu, ZHAO Ziqi
Affiliation: Henan University of Chinese Medicine, Zhengzhou, Henan, China, 450046
Abstract
Traditional Chinese Medicine (TCM) employs various approaches for treating primary dysmenorrhea, including:
Chinese medicinal monomer extracts
Single Chinese medicinal herbs
Chinese medicinal pairs
Commonly used Chinese medicinal compound formulas
Chinese patent medicine
Acupuncture and moxibustion
Massage therapy
Auricular points plaster therapy
Combination therapies
These methods are effective in improving primary dysmenorrhea through the regulation of prostaglandin (PG) levels. However, challenges remain:
Individual Differences:
Patients' constitutions and responses to the same treatment vary, making standardization and reproducibility of TCM treatments difficult.
Unpleasant Taste:
Decoctions, a common form of Chinese medicine, often taste unpleasant, leading to poor patient adherence. While modern technologies like granules and capsules improve taste, further research is needed to maintain efficacy and enhance patient acceptance.
Acupuncture Limitations:
Although acupuncture is effective, some patients struggle with acceptance or persistence due to pain, discomfort, or low tolerance levels.
Lifestyle Factors:
Irregular eating habits, disrupted routines, and lack of exercise not only exacerbate primary dysmenorrhea symptoms but also reduce the effectiveness of TCM treatments.
Future Directions
Optimization of Treatment Protocols:
Efforts should focus on ensuring safety, efficacy, and patient compliance while optimizing TCM treatment protocols.
Modern Technologies:
Utilizing big data analytics and artificial intelligence can enable precise assessments of patients' constitutions, symptoms, and habits, leading to individualized treatment plans.
Palatable Formulations:
Developing convenient, effective, and palatable Chinese medicinal formulations will improve patient compliance.
Integrated Therapy Systems:
Combining internal and external TCM therapies into an integrated system can improve outcomes and reduce recurrence rates for primary dysmenorrhea.
Keywords
Primary dysmenorrhea; Prostaglandin (PG); Chinese medicinal monomer; Single Chinese medicinal; Chinese medicinal pair; Chinese medicinal compound formula; Chinese patent medicine; Acupuncture and moxibustion therapy; Massage therapy; Auricular points plaster therapy
Traditional Chinese Medicine Herbal Cistanche For Primary dysmenorrhea
Definition and Clinical Manifestations
Primary dysmenorrhea is a condition characterized by lower abdominal pain and a sense of heaviness occurring during or around menstruation, without any organic lesions in the pelvic cavity. It is often accompanied by symptoms such as lower back soreness, nausea, vomiting, and loose stools [1]. In severe cases, it may cause fainting, significantly impacting the patient's daily life and work [2]. In China, the incidence of primary dysmenorrhea is high, accounting for 90% of dysmenorrhea cases [1, 3]. Given its cyclical recurrence and chronic nature, effective diagnosis and treatment are crucial to improving women's quality of life.
Pathogenesis in Modern Medicine
The pathogenesis of primary dysmenorrhea is not yet fully understood in modern medicine. However, abnormal fluctuations in prostaglandin (PG) levels in uterine tissues are widely regarded as one of the key factors inducing primary dysmenorrhea [4]. Currently, Western medicine predominantly relies on treatments such as oral nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and contraceptives [5-6]. While these medications can provide short-term pain relief, their long-term efficacy is limited, with significant side effects. This article systematically summarizes treatments for primary dysmenorrhea based on regulating PG levels, aiming to establish a theoretical foundation for the prevention and treatment of primary dysmenorrhea using Traditional Chinese Medicine (TCM).
1. TCM Understanding of Primary Dysmenorrhea
1.1 Etiology and Pathogenesis
In TCM, primary dysmenorrhea falls under the category of "menstrual abdominal pain" [7]. The Jing Yue Quan Shu (Complete Works of Jingyue) states that menstrual abdominal pain can arise from both deficiency and excess syndromes. Excess syndromes are caused by cold, blood stasis, qi stagnation, and heat, while deficiency syndromes result from blood deficiency and qi deficiency [8]. Based on this, the main pathogenesis of primary dysmenorrhea is summarized as "pain due to obstruction" and "pain due to lack of nourishment."
The onset of primary dysmenorrhea is closely related to dysfunction in the liver, spleen, and kidney organs [7]. Liver qi stagnation obstructs menstrual blood flow, spleen deficiency with dampness disrupts qi movement, and kidney yang deficiency leads to a lack of warmth in the uterus, causing cold accumulation and blood stasis, which results in "pain due to obstruction." Meanwhile, insufficient liver blood, spleen qi deficiency, and kidney essence insufficiency lead to inadequate nourishment of the uterus, resulting in "pain due to lack of nourishment." Additionally, external pathogenic factors such as wind, cold, dampness, and heat, as well as emotional disturbances, dietary habits, and congenital factors, can influence the development of primary dysmenorrhea. The primary locations of the disease are the Chong and Ren meridians and the uterus [9–12].
1.2 Syndrome Classification
Historically, TCM scholars have proposed diverse perspectives on the classification of primary dysmenorrhea syndromes based on dimensions such as cold-heat, deficiency-excess, qi-blood, and organ involvement [13]. In recent years, textbooks and clinical research have gradually unified syndrome differentiation classifications.
The Standards for Diagnosis and Therapeutic Effectiveness in TCM Diseases classifies primary dysmenorrhea into five syndromes:
Qi and blood stagnation
Cold-damp obstruction
Liver depression with damp-heat
Qi and blood deficiency
Liver and kidney deficiency
The Gynecology of Traditional Chinese Medicine further subdivides dysmenorrhea into six syndromes:
Qi stagnation and blood stasis
Cold accumulation and blood stasis
Damp-heat obstruction with blood stasis
Qi deficiency with blood stasis
Kidney deficiency with blood stasis
Phlegm and blood stasis interacting
Among these, "cold accumulation and blood stasis" and "qi stagnation and blood stasis" are the most common TCM syndromes for primary dysmenorrhea and have received extensive attention and research [14–15].
2. Common TCM Methods for Treating Primary Dysmenorrhea by Regulating PG Levels
Modern medicine has identified multiple factors related to the onset of primary dysmenorrhea, including prostaglandins (PG), oxytocin (OT), arginine vasopressin (AVP), sex hormones, β-endorphins (β-EP), neurotransmitters, genetics, and psychological factors [16–23]. Among these, the imbalance of PG levels in uterine tissues is considered the key trigger of primary dysmenorrhea. PG is synthesized from arachidonic acid through the catalytic action of enzymes such as cyclooxygenase-2 (COX-2). The subtypes PGF₂α and PGE₂ are critical in the development of primary dysmenorrhea. PGF₂α promotes spasmodic contraction of uterine smooth muscles, causing pain, while PGE₂ inhibits spontaneous uterine smooth muscle activity. Clinically, an abnormality in PGF₂α, PGE₂, or their ratio is the direct cause of primary dysmenorrhea [24]. Therefore, regulating PG levels is a core strategy for treating primary dysmenorrhea.
Compared to Western medical treatments, such as oral contraceptives, NSAIDs, vitamins, and calcium channel blockers [25], Traditional Chinese Medicine (TCM) effectively regulates PG levels through multi-target and multi-pathway approaches, alleviating pain and preventing primary dysmenorrhea.
2.1 TCM Monomers and Extracts
TCM monomers and extracts, primarily derived from natural plants, are characterized by high safety and minimal side effects. Studies have shown that extracts such as sage volatile oil, ligusticum extract, angelica oil, and monomers like yuanhuacine, paeoniflorin and albiflorin, tetrahydropalmatine, ligustilide, and α-cyperone exhibit spasmolytic and analgesic effects on primary dysmenorrhea by regulating PG levels, thereby inhibiting abnormal uterine smooth muscle contractions.
Sage volatile oil [13], yuanhuacine [26], and paeoniflorin and albiflorin [27] can lower PGF₂α levels.
Tetrahydropalmatine reduces both PGF₂α levels and the PGF₂α/PGE₂ ratio [28].
Ligusticum extract [29] and ligustilide not only reduce PGF₂α levels but also increase PGE₂ levels, while angelica oil inhibits both PGF₂α and PGE₂ levels [30–31].
α-Cyperone reduces COX-2 protein expression, indirectly inhibiting PG synthesis and release [13, 32].
These findings enrich our understanding of the pharmacological effects of TCM and provide new strategies for treating primary dysmenorrhea.
2.2 Single Chinese Medicinal Herbs
Given the diverse syndrome types of primary dysmenorrhea, a wide variety of Chinese medicinal herbs are used for treatment. Studies have shown that herbs such as motherwort, ginger, peony pollen, cinnamon, daphne, mugwort, mint, zedoary, and polygonatum exhibit potential in treating primary dysmenorrhea by regulating PG levels.
Motherwort [33–34], ginger [35–36], peony pollen [37], and cinnamon [35, 38] regulate COX-2 protein expression, thereby inhibiting PG synthesis.
Peony pollen and cinnamon focus on suppressing PGF₂α and PGE₂ levels, while ginger mainly reduces PGF₂α levels.
Motherwort reduces PGF₂α while increasing PGE₂ levels and lowering the PGF₂α/PGE₂ ratio, blocking PG from binding to its receptors.
Daphne lowers PGF₂α by inhibiting the synthesis pathway from arachidonic acid to PG [26].
Mugwort [39], mint [40], zedoary [41], and polygonatum [42] directly regulate PG levels. For example, mint and zedoary primarily lower PGF₂α levels, while mugwort reduces PGE₂ levels to alleviate symptoms. Polygonatum lowers PGF₂α, raises PGE₂ levels, and reduces the PGF₂α/PGE₂ ratio.
In summary, single Chinese medicinal herbs not only inherit the wisdom of traditional medicine but also complement modern medical advancements in treating primary dysmenorrhea.
2.3 Common Herbal Pairs
Angelica and Ligusticum: Angelica nourishes blood, promotes circulation, and relieves pain, while ligusticum activates blood, dispels stasis, and alleviates pain. This pair enhances menstrual pain relief and protects vital energy, often used for qi stagnation and blood stasis-type dysmenorrhea. Studies [43] have shown that this pair alleviates uterine smooth muscle spasms in dysmenorrhea models by inhibiting PGF₂α production and increasing PGE₂ levels.
Galangal and Cyperus: This pair significantly reduces serum PGF₂α levels and inhibits COX-2 expression [44].
White Peony and Licorice: Commonly used for pain relief, this pair reduces PGE₂ levels, 6-keto-PGF₁α levels, and prostaglandin activity while increasing glutathione peroxidase, effectively alleviating symptoms in dysmenorrhea models [45]. The optimal ratio is 2:1.
These studies reveal the analgesic mechanisms of herbal pairs and provide a scientific basis for optimizing their ratios.
2.4 Chinese Herbal Formulas
Classical formulas, treasures of TCM clinical practice, have been extensively explored and validated for their efficacy in treating primary dysmenorrhea. Formulas such as Gegen Tang, Wenjing Tang, Sini Tang, Danggui Sini Tang, Tugua Gen San, Chaigui Tang, Danggui Shaoyao San, and Guizhi Fuling Wan have been proven to regulate PG levels and effectively treat primary dysmenorrhea.
Gegen Tang alleviates cold-dampness-induced dysmenorrhea by inhibiting abnormal PGF₂α secretion [46].
Wenjing Tang [47], Sini Tang [48], and Danggui Sini Tang [49–50] reduce PGF₂α levels and increase PGE₂ levels.
Tugua Gen San [51] and Chaigui Tang [52] reduce both PGF₂α and PGE₂ levels and lower the PGF₂α/PGE₂ ratio.
Danggui Shaoyao San [53] and Guizhi Fuling Wan [54] downregulate COX-2 protein expression, indirectly reducing PGF₂α production.
Additionally, Qing Dynasty physician Wang Qingren's formulas, such as Xuefu Zhuyu Tang, Shaofu Zhuyu Tang, and Gexia Zhuyu Tang, remain research hotspots for treating primary dysmenorrhea [55–58]. Xuefu Zhuyu Tang emphasizes lowering PGF₂α and increasing PGE₂ to balance their levels, while Gexia Zhuyu Tang promotes PGE₂ secretion. Custom formulas like Tongxiao Yin and Aiqi Tang have also shown potential in regulating PG levels [59–60]. Aiqi Tang excels at reducing PGF₂α, while Tongxiao Yin lowers PGF₂α and raises PGE₂ levels.
