This study aims to evaluate the efficacy of two traditional Chinese medicine (TCM) formulas, Danggui Shaoyao San (DSS) and Cuscuta Chinensis (Tu Si Zi), in treating primary dysmenorrhea (PD). Primary dysmenorrhea, a common condition characterized by painful menstrual cramps, affects many women of reproductive age and significantly impacts their quality of life. Conventional treatments, such as NSAIDs and oral contraceptives, often have limited efficacy or side effects, underscoring the need for alternative therapeutic options.

In this randomized, double-blind study, participants will be divided into four groups: DSS, Tu Si Zi, a combination of DSS and Tu Si Zi, and a placebo group. The study will measure treatment outcomes using the Visual Analogue Scale (VAS) for pain and the Menstrual Symptom Questionnaire (MSQ), which captures physical and emotional symptoms. Additionally, TCM-based tools like pulse diagnosis and constitution questionnaires will be employed to explore personalized treatment strategies.

This research seeks to determine whether these TCM formulas can alleviate pain and improve other menstrual symptoms, potentially providing broader benefits than conventional painkillers. The findings aim to support evidence-based integration of TCM in managing dysmenorrhea and inform clinicians and patients about effective therapeutic choices.

Study Overview This study investigates the efficacy of two traditional Chinese medicine (TCM) formulations, Danggui Shaoyao San (DSS) and Cuscuta Chinensis (Tu Si Zi), in managing primary dysmenorrhea (PD). PD is a prevalent condition characterized by painful menstrual cramps, often accompanied by physical and emotional symptoms such as fatigue, irritability, nausea, and breast tenderness. Existing treatment options, including NSAIDs and hormonal contraceptives, are effective for symptom relief but may cause side effects or fail to address associated non-pain symptoms, emphasizing the need for complementary or alternative therapies.

Study Design The trial is a randomized, double-blind, placebo-controlled study. Participants meeting the inclusion criteria will be randomly assigned to one of four groups: DSS, Tu Si Zi, a combination of DSS and Tu Si Zi, or placebo. Each treatment will be administered 3 to 7 days prior to menstruation and continued until 3 days post-menstruation. The intervention spans two consecutive menstrual cycles.

The primary outcomes will be changes in pain intensity measured by the Visual Analogue Scale (VAS) and improvements in menstrual symptoms evaluated using the Menstrual Symptom Questionnaire (MSQ). Secondary outcomes include an exploration of the correlation between TCM pulse diagnosis, TCM constitution types, and therapeutic responses, providing insights into the personalization of treatment based on TCM differentiation (辨證).

Rationale Danggui Shaoyao San, a classic TCM formula, is widely used for blood and qi regulation, reducing uterine contractions, and alleviating menstrual pain. Research suggests that it has anti-inflammatory properties and supports immune regulation, making it suitable for patients with blood stasis and qi stagnation patterns. Conversely, Cuscuta Chinensis, traditionally used to nourish kidney essence and yang, may be effective for individuals with kidney deficiency patterns associated with PD. The combination of these formulas could potentially enhance therapeutic outcomes by addressing multiple pathophysiological mechanisms simultaneously.

Methods Eligible participants are women aged 20-45 years with regular menstrual cycles (21-42 days) and a history of moderate to severe menstrual pain (VAS > 3) persisting for at least three cycles. Participants will be excluded if they have secondary dysmenorrhea caused by underlying conditions (e.g., endometriosis), use intrauterine devices, are pregnant or breastfeeding, or are taking anticoagulants or other conflicting medications.

Participants will undergo the following assessments:

Pain and Symptom Evaluation

VAS: Pain intensity will be measured before, during, and after treatment to assess changes.

MSQ: This tool evaluates menstrual symptoms such as mood changes, fatigue, nausea, diarrhea, and abdominal bloating, offering a comprehensive view of symptom burden.

TCM Diagnostic Tools

Pulse Diagnosis: Using a pulse diagnosis device, data from the radial artery will be collected to assess energy distribution across the pulse positions (cun, guan, chi).

TCM Constitution Questionnaire: Participants will complete a validated questionnaire to determine their constitution type, providing context for their treatment response.

Clinical and Demographic Data Collection

Baseline characteristics, including age, BMI, vital signs, and analgesic use, will be recorded.

Blinding and Randomization Randomization will be performed using a block randomization scheme. All participants, investigators, and outcome assessors will be blinded to group assignments. The study medications, prepared in identical capsules, will be indistinguishable from the placebo. The placebo group will serve as a control to isolate the specific effects of the TCM interventions.

Data Analysis The study will use repeated measures ANOVA to evaluate within-group and between-group differences in VAS and MSQ scores over time. Multivariate linear regression will identify variables influencing treatment outcomes, including constitution type and baseline symptom severity. Statistical significance will be set at p < 0.05.

Significance and Expected Outcomes This trial aims to determine whether DSS, Tu Si Zi, or their combination can effectively alleviate menstrual pain and associated symptoms, providing a holistic approach to managing PD. Additionally, it seeks to validate the scientific basis of TCM differentiation in treatment selection, enhancing its integration into modern clinical practice. The findings will inform clinicians and patients about effective, personalized therapeutic options and expand the evidence base for TCM in managing gynecological conditions.

Ethical Considerations The study has been approved by the Institutional Review Board (IRB) of Taichung Tzu Chi Hospital. Participants will provide written informed consent before enrollment. All data will be securely stored and anonymized to protect participant privacy.

Inclusion Criteria:

1. Female participants aged 20 to 45 years.
2. Regular menstrual cycles (21 to 42 days).
3. History of moderate to severe primary dysmenorrhea (Visual Analogue Scale (VAS) score > 3) persisting for at least three consecutive menstrual cycles.
4. Able to understand and complete the study questionnaires (e.g., MSQ).
5. Willing to comply with study protocols, including taking study medications and attending follow-up visits.

Exclusion Criteria:

1. Secondary dysmenorrhea caused by conditions such as endometriosis, pelvic inflammatory disease, or uterine fibroids.

2. Current use of an intrauterine contraceptive device (IUD).

3. Irregular menstrual cycles.

4. Pregnant, breastfeeding, or planning pregnancy within the study period.

5. Use of anticoagulant medications (e.g., aspirin, warfarin, or heparin).

6. Known allergies to any components of the study medications.

7. Severe uncontrolled systemic diseases (e.g., neurological disorders, immunodeficiency, or bleeding disorders).

8. Concurrent use of other herbal medicines or alternative treatments for premenstrual syndrome or dysmenorrhea.

9. Participation in another clinical trial during the study period.

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This study is open to individuals who self-identify as female and experience menstrual cycles. Eligibility is determined based on biological sex at birth, as the condition being studied, primary dysmenorrhea, specifically affects individuals with a uterus.

De-identified individual participant data (IPD) from this study will be made available to researchers upon reasonable request. The shared data will include all primary and secondary outcome measures as defined in the protocol, along with de-identified demographic and clinical information. Supporting documents, such as the study protocol, statistical analysis plan, and informed consent form, will also be shared to ensure transparency and reproducibility of results.

Start Date: Data will be available 6 months after the publication of primary results.

End Date: Data will remain accessible for up to 5 years following publication.

Researchers seeking access must submit a written request to the study director, Chung Chia Ying, at jiainwhh@tzuchi.com.tw. Requests must include a detailed research proposal that specifies the intended use of the data and has received approval from an independent ethics review board. Access to the data will require signing a data use agreement, which includes terms to ensure the data are used solely for the proposed purposes and maintained confidentially.

In this double-blind clinical trial, all participants, care providers, investigators, and outcomes assessors are masked to the group assignments. The study medications (Danggui Shaoyao San, Cuscuta Chinensis, combination therapy, and placebo) are prepared in identical medication containers with no distinguishable labeling. Randomization is conducted using a block randomization scheme, and the allocation sequence is securely managed by the study pharmacy. Neither the study team nor the participants have access to the randomization code until the trial concludes. This ensures unbiased treatment administration and assessment.