Xue Xiao (薛晓), Liu Xin (刘鑫), Liu Yu (刘余), Peng Guo-ran (彭果然), Wang Qian (汪茜), Chen Chun (陈纯), Li Yun (李云), Wang Pan-an (王磐安)

1 The First Affiliated Hospital of University of South China, Hunan 421001, China

2 Hunan University of Chinese Medicine, Hunan 410208, China

Abstract

Keywords: Moxibustion Therapy; Moxa Stick Moxibustion; Mild Moxibustion; Dose Response Relationship, Acupuncture-moxibustion: Pain Measurement; Cold-dampness; Dysmenorrhea

Primary dysmenorrhea (PD), among the most common gynecological diseases, has been negatively influencing the life and work of women[1]. It is a focus for modern medicine to prevent PD, slow the development progression and treat this disease. As for the currently, treatment, Western medicine mainly adopts non-steroidal anti-inflammatory drugs (NSAIDs) to treat PD, which are not suitable for long-term use because of the side effects. In traditional Chinese medicine (TCM), moxibustion therapy shows promising potential and presents its strengths in simple operation, affirmative efficacy, affordable costs, easily available material, wide indications, guaranteed safety and reliability, and less adverse reactions. The efficacy of moxibustion is closely related to its duration, and thus certain duration is a must to achieve certain efficacy. In our previous clinical research, we have found that different courses of acupuncture, duration of needle retention and amount of electroacupuncture (EA) stimulation produce various clinical effects in patients with dysmenorrhea. Moreover, the time factor has a correlation with the changes of serum prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and β-endorphin (β-EP)[2-5]. In clinical practice, we have found that the majority of PD patients fall under the syndrome of stagnation and congelation of cold-damp. We hold that this disease is attributed to cold coagulating meridians, stasis and obstruction in the Thoroughfare Vessel and Conception vessel, and inhibited circulation of qi and blood, consequently, resulting in ‘pain due to blockage’. Therefore, based on the pathogenesis of the disease, we formulated such treatment principle as warming the meridian to dissipate cold. And we employed moxibustion at Guanyuan (CV 4) as the treatment method according to clinical experience and point features[6-9]. Moxibustion duration may also be a factor that influences clinical efficacy. Based on the hypothesis that different moxibustion durations may produce different therapeutic effects under the same stimulating frequency and intervention time of moxibustion, we gave the patients moxibustion treatment at Guanyuan (CV 4) for 20 min, 40 min and 60 min, respectively. Then we observed the effect of moxibustion duration on the pain measurement score and clinical efficacy for PD, and made further explorations.

1 Clinical Materials

1.1 Diagnostic criteria

1.1.1 Diagnostic criteria in Western medicine

The diagnostic criteria referred the following criteria described in theEvidence-based Guidelines of Clinical Practice with Acupuncture and Moxibustion: Primary Dysmenorrhea[10]: dysmenorrhea most often begins within 1-2 years after the initial menstruation; the pain comes along with menstruation; gynecological examination and B-mode ultrasonography exclude pain caused by organic lesions, such as inflammation, tumor, and endometriosis, etc.

1.1.2 Diagnostic criteria in TCM

The following diagnostic criteria were formulated based on the criteria for PD due to stagnation and congelation of cold-damp described in theGuiding Principles for Clinical Study of New Chinese Medicines[11]as well as theGynecology of Traditional Chinese Medicine[12]: 1 or 2 of such symptoms occur periodically during or around menstruation (usually within 1 week) as lower abdominal cold pain and distension, accompanied by heavy or light menstrual flow, with dark blood clots, cold limbs, diarrhea, breast distension, dizziness and fatigue, lower back soreness, pale complexion, sweating and even a shock; gynecological examination and B-mode ultrasonography exclude organic lesions of reproductive organs.

The syndrome differentiation of stagnation and congelation of cold-damp referred the following criteria. The main symptoms include ① lower abdominal cold pain or distending pain refusing to pressure and relieved by heat; ② the menstrual flow is light or normal, and not smooth; ③ the color of menstruation is dull purple, with blood clots, and the pain is relieved after the blood clots are expelled; ④ the tongue is purple with stasis speckles and white coating, and the pulse is string-like or deep and tight. The secondary symptoms include ① aversion to cold or lack of warmth in the extremities; ② nausea, vomiting or clear abundant urine; ③ delayed menstruation. One could be diagnosed with PD due to stagnation and congelation of cold-damp if she presented all the main symptoms and any one secondary symptom.

1.2 Inclusion criteria

Met the above diagnostic criteria for PD; fell under the syndrome of stagnation and congelation of cold-damp; were conscious with stable vital signs; aged 18-25 years old; with regular menstrual cycle (28±7) d, did not receive other treatment for dysmenorrhea in the past one month and not take NSAIDs and painkillers in the past two weeks; were willing to cooperate with treatment, examination and efficacy evaluations; signed informed consent.

1.3 Exclusion criteria

Those with unstable vital signs; those with serious cardiovascular and cerebrovascular diseases, serious heart disease, serious diabetes, malignant hypertension, serious infection, liver and kidney dysfunction, hematopoietic system diseases, mental illness, AIDS, and tuberculosis, hepatitis or other infectious diseases.

1.4 Elimination and dropout criteria

Those who did not meet the inclusion criteria but went astray; received other relevant treatment during this study, such as taking painkillers, etc.; had poor compliance and required withdrawal during the study; adopted other therapies that were prohibited by this study; whose indicators could not be observed due to their changing treatment methods halfway without consent or failing to complete treatment within the specified time; presented serious adverse reactions or complications; were believed not suitable to continue the treatment in this study.

1.5 Statistical methods

The SPSS version 18.0 statistical software was adopted for data analysis. Chi-square test was adopted for counting data and the measurement data which did not meet the normal distribution. Measurement data which met the normal distribution were expressed as mean ± standard deviation (±s). Pairedt-test was used for intra-group comparison, and one way analysis of variance (ANOVA) for inter-group comparison.P＜0.05 indicated statistical significance.

1.6 General data

We recruited 90 cases in this study. They were inpatients or outpatients from the Departments of TCM, Acupuncture-moxibuston and Tuina, Gynecology, and Reproduction in the First Affiliated Hospital of University of South China, as well as the nulliparous students with PD in the University of South China. According to the order of visit, they were divided into groups A, B and C by random number table method, with 30 cases in each group. All the patients in the three groups were given moxibustion treatment at Guanyuan (CV 4), for 20 min, 40 min and 60 min respectively. There were no significant inter-group differences in age and disease duration of patients (allP＞0.05), indicating that the three groups were comparable (Table 1).

Table 1. Comparison of general data

2 Therapeutic Methods

2.1 Health education

All the patients should pay attention to food hygiene, and work and rest regularly; should keep a good mood, especially one week before and after menstruation; should pay attention to health care during menstruation and not have sex to avoid bacterial infection; should take foods that are easy to digest and rich in vitamins and minerals 3-4 d before menstruation and during menstruation, avoid raw or cold foods, overeating, and hot spicy and greasy foods; should keep regular bowel movements; should moderately participate in physical exercises, such as walking, mild-pace square dancing, Tai Chi, mild-aerobics, etc. which is conducive to relieving dysmenorrhea symptoms. Moreover, we introduced them as much knowledge as possible about menstrual physiology and pathology to help them speculate on the possible causes of this disease and avoid inducements.

2.2 Emergency drugs and concomitant drugs

In principle, patients should not take drugs or other treatment during the study, but if the patient suffered from severe dysmenorrhea and required treatment measures, she could take the emergency painkillers diclofenac sodium enteric-coated tablets (25 mg/tablet, State Food and Drug Administration Approval No.: H11021640) distributed to all patients before the study. The maximum daily dose of the drug was no more than 8 tablets taken over 2-3 doses. Patients were required to make detailed records after taking this drug. We took back the drug from them once a month and distributed again for the next month. At the end of the study, we took back and checked all unused drugs, and recorded on the case report form.

2.3 Moxibustion treatment

Acupoint: Guanyuan (CV 4).

Methods:The patients were asked to take a supine position after urination. Hwato Brand moxa sticks of 1.5 cm in diameter and 20 cm in length were used for mild moxibustion for 20 min, 40 min or 60 min in each group, respectively. The timing started when the patient felt the heat. Moxibustion temperature depended on patient’s tolerance. When the patient felt burning pain, we would lift the moxa stick slightly to keep it away from the skin for a moment, then approached again to continue until the specified time in this group.

Treatment time: Moxibustion was applied 5-7 d before menstruation, once a day, until the menstruation began. One menstrual cycle was a course of treatment. After 3 courses, we observed the changes in patients' pain measurement scores and evaluated the clinical efficacy.

3 Observation of Clinical Efficacy

3.1 Observed items

The pain measurement score referred the pain evaluation criteria of dysmenorrhea in theObstetrics and Gynecology[1].

Five points (basic points) for lower abdominal pain during menstruation and before and after menstruation; 1 point for unbearable abdominal pain; 0.5 point for obvious abdominal pain; 1 point for the pain that could not be relieved by common measures, and 0.5 point for that could be relieved; 0.5 point for pallid complexion; 1 point for profuse cold sweating; 1 point for cold; 2 points for shock; 1 point for fidgetiness while sitting or lying; 1 point for the pain that influenced work and study; 1 point for patient needing to stay in bed; the pain accompanied by aching lower back, nausea and vomiting, heavy sagging sensation in the anus accounted for 0.5 point each; 0.5 point for pain within one day, and 0.5 point for each additional day. The sum of the above scores was the pain measurement score.

3.2 Efficacy evaluation criteria

This criteria referred theGuiding Principles for Clinical Study of New Chinese Medicines[11].

Recovery: After treatment, the pain measurement score was 0 point, and abdominal pain and other symptoms all disappeared.

Markedly effective: After treatment, the score was reduced to less than 1/2 of the pre-treatment score; abdominal pain was significantly relieved; other symptoms improved; and work could be maintained without continuing treatment.

Effective: After treatment, the score was reduced to 1/2-3/4 of the pre-treatment score, abdominal pain was relieved; other symptoms were improved, and work could be maintained without continuing treatment.in group A (bothP＜0.05), and that in group B was better than that in group C (P＜0.05). These results demonstrated that various moxibustion durations all had clear therapeutic effects on PD due to stagnation and congelation of cold-damp, but the efficacy could be influenced by the moxibustion duration. We held that the duration for 40 min could achieve relatively better efficacy in treating this disease. Check Table 2 for details.Invalid: Neither abdominal pain nor other symptoms got improved.

Table 2. Comparison of the clinical efficacy (case)

3.3 Results

All patients had completed the treatment with no dropout or termination halfway.

3.3.1 Comparison of the clinical efficacy

Chi-square test suggested significant differences in clinical efficacy among the three groups (P＜0.05). The clinical efficacy was better in group B and group C than

3.3.2 Comparison of the pain measurement score Before treatment, there was no significant inter-group difference in this score (allP＞0.05). After treatment, the scores in the three groups were significantly reduced (allP＜0.01), and the inter-group differences were significant (P＜0.05). The scores were lower in group B and group C than in group A (bothP＜0.05), and that in group B was lower than that in group C (P＜0.05). These results demonstrated that various moxibustion durations all had analgesic effects on PD, but the efficacy could be influenced by the moxibustion duration. We held that the duration for 40 min could achieve relatively better efficacy. Check Table 3 for details.

Table 3. Comparison of the pain measurement score (±s, point)

Table 3. Comparison of the pain measurement score (±s, point)

Note: A=20-minute moxibustion; B=40-minute moxibustion; C=60-minute moxibustion

Group n Before treatment After treatment A 30 12.71±2.33 4.30±2.47 B 30 12.22±2.67 2.42±1.96 C 30 12.83±2.42 4.10±1.95

4 Discussion

PD due to stagnation and congelation of cold-damp is mostly attributed to weak constitution and exposure to wind-cold. Moxibustion has the functions of warming and dredging meridians, dispelling cold and dampness, and warming uterus. Its efficacy is closely related to the duration, and thus a proper duration is a must to achieve certain efficacy[12]. The duration should be determined based on the patient's constitution, age, severity of the disease, moxibustion location, depth of disease lesions, disease nature (cold, heat, deficiency and excess) and the patient's actual feelings during moxibustion. Studies have found that different time of intervention and needle retention have various efficacy in treating dysmenorrhea[13-17]. If the patient receives acupuncture-moxibustion treatment before the occurrence of the disease, her meridian qi will be stimulated to enhance disease resistance and enrich healthy qi as prevention. Therefore, in this study we decided to offer moxibustion treatment for this disease 5-7 d before menstruation.

Guanyuan (CV 4), as the crossing point of the Conception Vessel and the three yin meridians of foot, features warming yang to tonify the kidney, consolidating the body, and regulating and supplementing the Thoroughfare Vessel and the Conception Vessel. The Conception Vessel is related to reproductive function, and experimental studies in large numbers show that Guanyuan (CV 4) can regulate uterine function[18-20]; the three yin meridians of foot pass through the lower abdomen. Therefore, moxibustion at Guanyuan (CV 4) can regulate the circulation of qi and blood in the uterus and relieve pain via the Conception Vessel and the three yin meridians of foot.

This study suggested that moxibustion with the three various durations all can improve the clinical symptoms in the patients, especially abdominal pain, and group B, the 40 min group showed the most significant efficacy. This may be attributed to that the thermal effect of moxibustion on meridians, nerves and uterus increases blood flow and improves the endocrine environment of the body. Then the spastic contraction of uterine smooth muscle and blood vessels is inhibited, and the local ischemia and hypoxia state is improved, thus giving birth to the analgesic function[21]. The result showed that the dose-response relationship in moxibustion treatment is not that the longer the moxibustion duration, the better the curative effect.

In this study, we took PD patients with syndrome of stagnation and congelation of cold-damp as the research subjects, instead of recruiting various syndrome types but strictly following the criteria of both syndrome differentiation and inclusion, which ensured the consistency of syndrome type in the observation subjects. Besides, we only took one point Guanyuan (CV 4) for moxibustion, which is easy to expose and high safety, the treatment is low costs and high safety, which presents relatively high economic efficiency and social benefits. In further study, we will increase the sample size and observation items to better evaluate the curative effect of moxibustion, and optimize the stimulation duration of moxibustion to obtain the best efficacy.

Conflict of Interest

The authors declare that there is no conflict of interest.

Acknowledgments

This work was supported by National Natural Science Foundation of China (国家自然科学基金项目, No. 82004490); Key Project of University of South China (南华大学校级重点项目课题, No. USCKF201902K02).

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received: 3 March 2020/Accepted: 15 April 2020