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Comparative observation of the effect of electroacupuncture combined with heat-sensitive moxibustion and western medicine for premature ovarian failure
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·9·
Clinical Research Comparative observation of the effect of electroacupuncture combined with heat-sensitive moxibustion and western medicine for premature ovarian failure * 电针合热敏灸与西药治疗卵巢早衰疗效对照观察 * WXU Meng-bo (徐梦博)1, TIAN Hai-yan (田海燕) 1. School of Moxibustion, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi Province, China; 2. Department of Acupuncture-Moxibustion, Third Affiliated Hospital of Nanchang University (1. 江西中医药大学灸学院，江西南昌 330004；2. 南昌大学第三附属医院针灸科） ARTICLE INFO
ABSTRACT
First author: XU Meng-bo (1992-), male, postgraduate student. E-mail: [email protected]
Objective To compare the clinical efficacy between electroacupuncture combined with heat-sensitive moxibustion and western medicine for treatment of premature ovarian failure. Methods Eighty patients were randomly divided into an electroacupuncture combined with heat-sensitive moxibustion group (group A, n=40) and a western medicine group (group B, n=40). Zǐgōng (子 宫 EX-CA 1), Xuèhǎi (血海 SP 10), Gānshū (肝俞 BL 18) and Shènshū (肾俞 BL 23) were selected in group A, and acupuncture combined with heat-sensitive moxibustion were carried out. Climen was taken orally in group B. The score changes of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus, as well as the cured and markedly effective rate of the patients in the two groups before and after two courses of treatment were compared. Results The cured and markedly effective rate of group A was 72.5% (29/40), which was superior to that of group B (37.5%, 15/40) (P<0.05). The symptom scores were improved significantly in the two groups after treatment (all P<0.05), and the improvement in group A was superior to that in group B (all P<0.05). Conclusion The efficacy of electroacupuncture combined with heat-sensitive moxibustion is superior to that of conventional western medicine in treatment of premature ovarian failure.
Corresponding author: TIAN Hai-yan (1963-), female, chief physician. Research field: acupuncture-moxibustion for premature ovarian failure, herpes zoster, peripheral neuropathy, and other diseases. E-mail: [email protected]
* Supported by Nanchang Municipal Guiding Science and Technology Planning Project: H.K.Z. [2016] No. 96, item 19 Accepted on May 23, 2017
KEY WORDS: premature ovarian failure (kidney deficiency and liver constraint); electroacupuncture; heat-sensitive moxibustion; randomized controlled trial (RCT)
Premature ovarian failure is a kind of syndrome manifesting as persistent amenorrhea and sexual organs atrophy, concomitantly with elevation of follicle-stimulating hormone and luteinizing hormone and decrease in estrogen in women with normal secondary sex characteristic development before 40 years old [1]. In western medicine, the most used treatment method for premature ovarian failure is hormone replacement therapy with good efficacy but long-term administration, great side effect and high recurrence rate, and this method is not suitable for the patients with hysteromyoma, diabetes mellitus, and other diseases. However, electroacupuncture combined
with heat-sensitive moxibustion for treatment of premature ovarian failure is characterized by rapid effect onset, short treatment period and small adverse effect. The authors adopted electroacupuncture combined with heat-sensitive moxibustion for treatment of premature ovarian failure, and the details are reported as below.
CLINICAL DATA General data All the 80 patients were selected from the outpatients of obstetrics and gynecology department of
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·10· the Third Affiliated Hospital of Nanchang University from August 2015 to February 2017. Eighty-eight patients who conformed to the inclusion criteria were selected and then randomly divided into an electroacupuncture combined with heat-sensitive moxibustion group (group A, n=46) and western medicine group (group B, n=42) according to the visiting sequence and random number table [2]. At the end of observation, 6 patients were eliminated, and 2 dropped out from the study. The actual number of cases was 80 with 40 patients in each group. In group A, the youngest patient was 22 years old, and the oldest was 38 years old; the shortest course of disease was 96 days, and the longest was 120 days. In group B, the youngest patient was 24 years old, and the oldest was 39 years old; the shortest course of disease was 100 days, and the longest was 130 days. According to statistical analysis of age and course of disease in the two groups, the differences were not statistically significant (all P＞0.05), and the results were comparable. This study was approved ethically. The details can be seen in Table 1.
Diagnostic criteria The diagnostic criteria were developed by reference to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine [ 3 ] f o r mu lated b y th e S tate Administration of Traditional Chinese Medicine of the People’s Republic of China in 1994 and the contents related to premature ovarian failure in the amenorrhea chapter of Chinese Obstetrics and Gynecology[4]: with the symptoms of amenorrhea for at least 3 months and oligomenorrhea, concomitantly with tidal fever, night sweat, vexation and agitation and irascibility, poor sleep and other clinical perimenopausal symptoms, as well as soreness and weakness of waist and knees, dizziness and tinnitus and other symptoms of kidney deficiency and liver constraint before 40 years old. Serum FSH ＞40U/L, LH ＞30U/L, E2＜73.2 pmol/L.
Inclusion criteria ① With the age of 18–40 years old; ② conforming to the diagnostic criteria in western medicine and the pattern of kidney deficiency and liver constraint in traditional Chinese medicine; ③ discontinuing treatment for premature ovarian failure for more than 3 months, and the efficacy evaluation result will not be Table 1
affected; ④ signing the informed consent form by the patient oneself or family members.
Exclusion criteria ① Amenorrhea patients not caused by premature ovarian failure according to ultrasonic examination or other examinations; ② concomitantly with severe primary diseases such as cardiovascular, liver, kidney and hematopoietic system diseases, as well as mental disorders; ③ with premature ovarian failure not belonging to the pattern of kidney deficiency and liver constraint according to TCM diagnosis; ④ patients with organic diseases (such as hysteromyoma, etc.) and breast disorders.
Elimination criteria ① The patients who conformed to the inclusion criteria but didn’t accept treatment, or who accepted treatment but didn’t complete the courses; ② the patients who took medicine independently after inclusion.
Drop-out criteria ① The patients who suffered from adverse event and complication, and who was not suitable for further treatment; ② the patients who dropped out from the study voluntarily; ③ the patients who quit from the study due to other reasons; ④ the patients with incomplete data record which may affect the efficacy evaluation.
METHODS Electroacupuncture combined with heatsensitive moxibustion group (group A) Acupoint selection was conducted as the following two groups: one group: Zǐgōng (子宫 EXCA1), Xuèhǎi (血海 SP 10), Guānyuán (关元 CV 4), Sānyīnjiāo (三阴交 SP 6), Tàichōng (太冲 LR 3) , all points were selected bilaterally. Another group: Gānshū (肝俞 BL 18), Shènshū (肾俞 BL 23), Píshū (脾俞 BL 20), Géshū (膈俞 BL 17), and Cìliáo (次髎 BL 32), all points were selected bilaterally too. The two group of acupoints were punctured alternately. Manipulations: 0.30 mm×25 mm filiform needles were adopted for inserting for 20 mm at EX-CA1, SP 10, BL 18 and BL 23, and HANS-100A electroacupuncture device was connected. In group one, a group of electrodes were
Comparison of general information on the patients with premature ovarian failure in the two groups
Groups
Patients
Age (x±s, year)
Course of disease (x±s, d)
FSH (x±s, U/L)
LH (x±s, U/L)
E2 (x±s, pmol/L)
A
40
30.1±4.5
108.2±7.2
52.5±3.4
35.6±7.7
57.3±5.6
B
40
30.2±4.8
114.1±9.2
53.1±2.8
41.1±8.2
48.9±7.9
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
connected with EX-CA1 and SP 10 on the right side, and the other electrodes were connected with EXCA1 and SP 10 on the left side. In another group, a group of electrodes were connected with BL 18 and BL 23 on the right side, and the other electrodes were connected with BL 18 and BL 23 on the left side. The treatment was carried out for once every other day, 3 months was considered as 1 course of treatment, and 2 courses were needed. Heat-sensitive moxibustion treatment: the patients were asked in prone position with full exposure of the waist and back; two moxa sticks were adopted for moxibustion treatment at the heat-sensitive acupoints in the area 6 cun outwards away from the region inside both lateral lines of foot-taiyang bladder meridian and between the two horizontal lines of BL 17 and BL 23 on the back. The moxa sticks were lighted, and suspended moxibustion was implemented at the height of about 3cm away from the skin surface selected. When the patients felt heat penetration, heat expansion, heat transfer, non (micro) local heat but distant heat, non (micro) surface heat but deep heat, and one or more of the non thermal sensations, acupoint heat-sensitization occurred, and this acupoint was the heat-sensitive acupoint. The above procedures were repeated until all the heat-sensitive acupoints were found in the area, and the detailed locations were recorded. Then suspended moxibustion was conducted at these heatsensitive acupoints, and the ash was whisked every 2 min (no more than 10 s) and the distance between the moxa stick and the skin surface was controlled for maintaining enough heat. Moxibustion for once was defined as when heat penetration, heat expansion or the sensation of transmission disappeared in the area of heat-sensitive acupoints. The patients accepted treatment for 10 consecutive days at the first visit, once a day; treatment for 10 times should be completed in the later 20 days in the first month; treatment for 15 times per month should be completed in the later 2 months, treatment for 50 times was considered as 1 course of treatment, and 2 courses were needed.
Western medicine group (group B) Artificial cycle replacement therapy was adopted by using climen (Bayer HealthCare Co., Ltd., Guangzhou Branch, G.Y.Z.Z. No. J20130006). Usage: 1 pill/d, and administration for 21d was needed; then the drug was withdrawn for 7 d, and bleeding, with the menstruation characteristic, induced by drug withdrawal may be caused after withdrawal for 2-4 d. If the menses didn’t arrive after withdrawal for 7 d, the drug should be taken continuously. For the patients with menses, climen was taken for 1 pill/d since the 5 th day of the menstrual cycle, and administration for
·11· 21 d was needed; the drug should be taken periodically after withdrawal for 7 d. Administration for 3 months was considered as 1 course of treatment, and 2 courses were needed.
EFFICACY OBSERVATION Observational indices ① Menstrual cycle score: arrival of the menses for 3 consecutive months. The menstrual period was normal with normal quantity of menses, red color, scoring 0 point; arrival of the menses for 3 consecutive months with moderate quantity of menses, red color, scoring 1 point; arrival of the menses for 3 consecutive months with slightly less quantity of menses, light red color, scoring 2 points; arrival of the menses for 3 consecutive months with less quantity of menses, light color, scoring 3 points; infrequent menstruation for 3 consecutive months, scoring 4 points. ② Ti d a l f e v e r a n d s w e a t i n e s s s c ore: no fever, scoring 0 point; occasional fever on the head and face, and slight sweatiness, scoring 1 point; intermittent fever on the head and face concomitantly with sweatiness and slightly red face, scoring 2 points; occasional fever on the whole body concomitantly with sweatiness and flushed face, which can interfere with the attention, scoring 3 points; intermittent fever on the whole body concomitantly with sweatiness and red face, which can interfere with the attention and affect sleep, scoring 4 points. ③ Emotional excitement score: calm emotion, scoring 0 point; slightly excited emotion which can restore calm easily, scoring 1 point; excited emotion with depression and suspicion, scoring 2 points; vexation and agitation with depression and suspicion, which can interfere with the attention, scoring 3 points; vexation and agitation, irascibility which cannot be tolerated, and can affected sleep, scoring 4 points. ④ Soreness and weakness of waist and knees score: no soreness and weakness of waist and knees, scoring 0 point; slight soreness and weakness of waist and knees which can be ignored, without tenderness, scoring 1 point; obvious soreness and weakness of waist and knees which can be tolerated, with slight tenderness, scoring 2 points; obvious soreness and weakness of waist and knees which cannot be ignored, and can interfere with the attention, with tenderness, scoring 3 points; intolerable soreness and weakness of waist and knees which
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·12· can affect sleep, with obvious tenderness, scoring 4 points.
90%. Effective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were improved, the quantity of menses increased, and the reducing rate ≥30%, less than 60%. Ineffective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were not improved, infrequent menstruation for 3 consecutive months with light color, and the reducing rate ＜30%.
⑤ Dizziness and tinnitus score: no dizziness and tinnitus, scoring 0 point; occasional dizziness and tinnitus which can return to normal easily, scoring 1 point; intermittent dizziness and tinnitus, scoring 2 points; frequent dizziness and tinnitus which can interfere with the attention, scoring 3 points; continuous dizziness and tinnitus which can affect sleep, scoring 4 points.
Statistical analysis
The sum of each symptom score was the total score, and the symptom scores and total scores of patients in the two groups before and after treatment were observed.
After efficacy evaluation, SPSS 21.0 software was adopted by statisticians for statistical analysis. Measurement data were expressed as mean ± standard deviation (x±s), and intra-group comparison was performed via t-test. Intergroup comparison was conducted by using independent sample t-test, and enumeration data were analyzed through Chisquare test. P＜0.05 indicated that the difference was statistically significant.
Efficacy evaluation criteria By reference to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine [3] and the efficacy evaluation criteria of premature ovarian failure in the amenorrhea chapter of Chinese Obstetrics and Gynecology[4]: Reducing rate＝[(Total score before treatment－total score after treatment)÷total score before treatment]×100%.
RESULTS Comparison of symptom scores of patients with premature ovarian failure in the two groups before and after treatment (Table 2)
Clinically cured: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus disappeared, after drug withdrawal for 3 months, there was no relapse of menstrual cycle, the quantity of menses and menstrual period returned to normal, and the reducing rate ≥90%. Markedly effective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were improved obviously, the menstrual cycle and menstrual period returned to normal, the quantity of menses increased by 1/3 or over 20 mL, and the reducing rate ≥60%,less than
It was indicated from Table 2 that the difference in symptom scores of patients in the two groups before treatment was not statistically significant (all P＞0.05), and the results were comparable. The symptom scores were improved significantly in the two groups after treatment (group A: tmenstrual cycle＝14.970, ttidal fever and sweatiness＝10.873, temotional excitement＝22.375, tsoreness and weakness of waist and knees＝16.169, tdizziness and tinnitus＝13.270, ttotal score＝ 25.730; group B: tmenstrual cycle＝8.382, ttidal fever and sweatiness＝ 16.257, temotional excitement＝11.191, tsoreness and weakness of waist and knees＝11.048, tdizziness and tinnitus＝15.235, ttotal score＝16.257, all P＜0.05), and the effect of group A was superior to that of group B in menstrual cycle, tidal fever
Table 2 Comparison of symptom scores and total score of patients with premature ovarian failure in the two groups (x±s, point) before and after treatment Menstrual cycle Groups
Patients
Before treatment
After treatment
A
40
1.76±1.03
0.45±0.671)
1.76±1.08
1)
Tidal fever and sweatiness Difference value
B
40
0.79±0.81
Group
Patients
Before treatment
After treatment
A
40
3.19±0.71
0.76±0.851)
3.21±0.70
1)
1.31±0.782) 0.97±0.72
Before treatment
After treatment
2.71±0.64
1.17±0.821)
2 68±0.74
1)
Soreness and weakness of waist and knees
B
40
1.47±0.92
1)
Difference value
1.53±0.65
After treatment
2.71±1.02
0.71±0.841)
0.97±0.72
2.61±1.03
1)
Difference value
Before treatment
After treatment
10.38±2.48
3.07±2.131)
10.24±2.79
1)
1.31±0.782)
Dizziness and tinnitus
Difference value
Before treatment
After treatment
2.40±0.732)
2.56±0.43
1.07±0.551)
2.71±0.52
1)
1.74±0.76
Emotional excitement Before treatment
1.42±0.71 2)
Notes: compared with that before treatment, P＜0.05; compared with group B, P＜0.05
Difference value
1.18±0.96
2.05±0.762) 1.39±0.82
Total score
1.21±0.642) 0.98±0.82
Difference value
5.00±2.41
7.26±1.952) 5.21±1.98
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
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Table 3 Comparison of the effi cacy on patients with premature ovarian failure in the two groups (Case) Groups
Patients
Clinically cured
Markedly effective
Effective
Ineffective
Cured and markedly effective rate(%)
A
40
6
23
9
2
72.51)
B
40
2
13
19
6
37.5
1)
Note: compared with group B, P＜0.05
and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus (t menstrual cycle＝2.658, ttidal fever and sweatiness＝1.998, temotional excitement ＝3.607, t soreness and weakness of waist and knees ＝3.995, tdizziness and tinnitus＝2.774, all P＜0.05); the differences in the difference values of the total scores of patients in the two groups were also statistically significant (t＝ 4.949, P＜0.05), indicating that the efficacy of group A was superior to that of group B in improving the symptoms.
Comparison of clinical efficacy on patients in the two groups (Table 3) It was shown from Table 3 that the cured and markedly effective rate in group A was higher than that in group B ( χ2＝2.22, P＜0.05).
DISCUSSION Premature ovarian failure is a symptom of premature menopause caused by kidney essence depletion occurring before the age of menopause. Recent studies have shown that the incidence of premature ovarian failure was 1%-3% in the women of child-bearing age, 10%-28% in the patients with primary amenorrhea, and 4%-18% in the patients with secondary amenorrhea[5]. At present, hormone replacement therapy is commonly adopted in western medicine. Estradiol valerate, included in Climen, is a precursor of natural human 17 β-estradiol; another component cyproterone acetate is a kind of synthesized derivative of hydroxyprogesterone with the characteristics of progestational hormone and antigonadotropic hormone, thus achieving the purpose of treatment of premature ovarian failure. In spite of the good effect, the recurrence rate is higher after discontinuation, and it is not suitable for the patients with hysteromyoma and diabetes. It is believed in traditional Chinese medicine that premature ovarian failure is usually caused by kidney qi deficiency and kidney essence depletion, and related with liver, spleen, heart, thoroughfare vessel and conception vessel[6]. “The menstruation is from the kidney”. The kidney stores the essence, and governs reproduction, which is the foundation of congenital constitution, and the root of the five
viscera and six bowels. It has been verified in modern medicine that the kidney plays a leading role in the process of menstruation. Acupuncture-moxibustion for supplementing kidney can regulate the endocrine mechanism, and improve the ovarian response to FSH. The liver governs the free flow of qi, and stores the blood, which can be equivalent to all the neuroendocrine functions. The flow of qi of liver can maintain the amassment and regurgitation of SP 10, playing an important role in the maintaining of menstruation[7]. According to this, EX-CA1, SP 10, CV 4, SP 6 and LR 3 were selected as the main acupoints, and BL 18, BL 23, BL 20 were selected as the combined acupoints for jointly enriching and nourishing liver and kidney, balancing yin yang, soothing the liver qi, and regulating thoroughfare vessel and conception vessel. EX-CA1 and SP 10 can nourish the uterus, nourish blood and invigorate blood, jointly supplementing kidney and fortifying the spleen, as well as soothing the liver and invigorating blood; CV 4 and BL 23 can supplement kidney qi and enrich kidney yin; SP 6 can supplement kidney, fortify the spleen and soothe the liver; ST 36 and BL 18 can fortify the spleen and soothe the liver. Electroacupuncture stimulation at the acupoints can effectively activate the functions of related organs, make the menstruation pass and the symptoms disappear, improving the clinical efficacy to a great extent[8]. Under the disease state, the related acupoints of human body are heat-sensitive, and a series of strange moxibustion sensation phenomenons may be seen, such as heat penetration, heat expansion, heat transfer, and non (micro) local heat but distant heat. When the moxibustion sensations transfer to a lesion, the symptoms will be released accordingly. Heat-sensitive moxibustion is a new moxibustion therapy firstly researched and developed in Jiangxi University of Traditional Chinese Medicine [9], the hormonoid function of heat-sensitive moxibustion can significantly redeploy the whole functions, improve the ovarian response to gonadotropin, thus restoring and improving ovarian function, delaying senescence and regulating immunity, which is a safe and effective method for treatment of premature ovarian failure. When hormone replacement therapy is still used
·14· in most regions of the country, electroacupuncture combined with heat-sensitive moxibustion for treatment of premature ovarian failure has already broken through the conventional method, it is a new treatment idea, and an emerging technology in current China. This method is the inheritance of traditional medicine with satisfactory effect and no toxic neither side effect, which is safe and reliable, and easily accepted by patients. Heat-sensitive moxibustion is worthy of clinical popularization and application.
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Kalantaridou SN, Davis SR, Nelson LM. Premature ovarian failure.Endocrinol Metab Clin North Am 1998; 27(4): 989 1006. He SL, Wang J, Wang JJ. TCM Research Design & Statistics (Chin). Changsha: Hunan Science & Technology Press; 2003: 252 253. State Administration of Traditional Chinese Medicine of the People’s Republic of China. Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in
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[4] [5] [6]
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Traditional Chinese Medicine (Chin). Nanjing: Nanjing University Press; 1994: 234-235. Cao ZY. Chinese obstetrics and gynecology. Version 2. Beijing: People’s Medical Publishing House; 2004: 2568. Goswami D, Conway G S. Premature ovarian failure. Hormone Research 2015;68(4):196 202. Yu B, Wang JL, Zhao ZS, Chen J, Zhang YP, Wei Bo. Research progress of acupuncture-moxibustion treatment for premature ovarian failure. J Shandong Univ Tradit Chin Med (Chin) 2015; 39(2) 32 38. Yang XH, Lai XM, Huang ZB. Clinical observation of acupuncture-moxibustion treatment for 60 cases of premature ovarian failure. J Sichuan Tradit Chin Med (Chin) 2008; 26(5): 106 107. Luo X, Jin WT, Yang XM, Zhang B, Wang WZ, Shang LJ. Research progress of acupuncture-moxibustion treatment for premature ovarian failure. Chin Foreign Med Res (Chin) 2015; 13(35) 55 60. Chen RX, Kang MF. Practical Guidance of Heatsensitive Moxibustion (Chin). Beijing: People’s Medical Publishing House; 2009: 4.
ABSTRACT IN CHINESE
[摘 要] 目的：比较电针合热敏灸法与常规口服西药治疗卵巢早衰的临床疗效差异。方法：采用随机对 照的方法，将80例患者分为电针合热敏灸组（40例）和西药组（40例）。电针合热敏灸组给予子宫、血 海、肝俞、肾俞等穴位针刺配合热敏灸法治疗，西药组口服克龄蒙。比较治疗两个疗程前后两组患者月 经周期评分、潮热汗出评分、情绪激动评分、腰膝酸软评分、头晕耳鸣评分变化及愈显率。结果：电针 合热敏灸组的愈显率为72.5%（29/40），优于西药组的37.5%（15/40，P＜0.05）。两组治疗后各症状评 分较治疗前均明显改善（均P＜0.05），且电针合热敏灸组优于西药组（均P＜0.05）。结论：电针合热敏 灸法治疗卵巢早衰疗效优于常规西医疗法。 [关键词] 卵巢早衰（肾虚肝郁型） 电针 热敏灸 随机对照试验
·9·
Clinical Research Comparative observation of the effect of electroacupuncture combined with heat-sensitive moxibustion and western medicine for premature ovarian failure * 电针合热敏灸与西药治疗卵巢早衰疗效对照观察 * WXU Meng-bo (徐梦博)1, TIAN Hai-yan (田海燕) 1. School of Moxibustion, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi Province, China; 2. Department of Acupuncture-Moxibustion, Third Affiliated Hospital of Nanchang University (1. 江西中医药大学灸学院，江西南昌 330004；2. 南昌大学第三附属医院针灸科） ARTICLE INFO
ABSTRACT
First author: XU Meng-bo (1992-), male, postgraduate student. E-mail: [email protected]
Objective To compare the clinical efficacy between electroacupuncture combined with heat-sensitive moxibustion and western medicine for treatment of premature ovarian failure. Methods Eighty patients were randomly divided into an electroacupuncture combined with heat-sensitive moxibustion group (group A, n=40) and a western medicine group (group B, n=40). Zǐgōng (子 宫 EX-CA 1), Xuèhǎi (血海 SP 10), Gānshū (肝俞 BL 18) and Shènshū (肾俞 BL 23) were selected in group A, and acupuncture combined with heat-sensitive moxibustion were carried out. Climen was taken orally in group B. The score changes of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus, as well as the cured and markedly effective rate of the patients in the two groups before and after two courses of treatment were compared. Results The cured and markedly effective rate of group A was 72.5% (29/40), which was superior to that of group B (37.5%, 15/40) (P<0.05). The symptom scores were improved significantly in the two groups after treatment (all P<0.05), and the improvement in group A was superior to that in group B (all P<0.05). Conclusion The efficacy of electroacupuncture combined with heat-sensitive moxibustion is superior to that of conventional western medicine in treatment of premature ovarian failure.
Corresponding author: TIAN Hai-yan (1963-), female, chief physician. Research field: acupuncture-moxibustion for premature ovarian failure, herpes zoster, peripheral neuropathy, and other diseases. E-mail: [email protected]
* Supported by Nanchang Municipal Guiding Science and Technology Planning Project: H.K.Z. [2016] No. 96, item 19 Accepted on May 23, 2017
KEY WORDS: premature ovarian failure (kidney deficiency and liver constraint); electroacupuncture; heat-sensitive moxibustion; randomized controlled trial (RCT)
Premature ovarian failure is a kind of syndrome manifesting as persistent amenorrhea and sexual organs atrophy, concomitantly with elevation of follicle-stimulating hormone and luteinizing hormone and decrease in estrogen in women with normal secondary sex characteristic development before 40 years old [1]. In western medicine, the most used treatment method for premature ovarian failure is hormone replacement therapy with good efficacy but long-term administration, great side effect and high recurrence rate, and this method is not suitable for the patients with hysteromyoma, diabetes mellitus, and other diseases. However, electroacupuncture combined
with heat-sensitive moxibustion for treatment of premature ovarian failure is characterized by rapid effect onset, short treatment period and small adverse effect. The authors adopted electroacupuncture combined with heat-sensitive moxibustion for treatment of premature ovarian failure, and the details are reported as below.
CLINICAL DATA General data All the 80 patients were selected from the outpatients of obstetrics and gynecology department of
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·10· the Third Affiliated Hospital of Nanchang University from August 2015 to February 2017. Eighty-eight patients who conformed to the inclusion criteria were selected and then randomly divided into an electroacupuncture combined with heat-sensitive moxibustion group (group A, n=46) and western medicine group (group B, n=42) according to the visiting sequence and random number table [2]. At the end of observation, 6 patients were eliminated, and 2 dropped out from the study. The actual number of cases was 80 with 40 patients in each group. In group A, the youngest patient was 22 years old, and the oldest was 38 years old; the shortest course of disease was 96 days, and the longest was 120 days. In group B, the youngest patient was 24 years old, and the oldest was 39 years old; the shortest course of disease was 100 days, and the longest was 130 days. According to statistical analysis of age and course of disease in the two groups, the differences were not statistically significant (all P＞0.05), and the results were comparable. This study was approved ethically. The details can be seen in Table 1.
Diagnostic criteria The diagnostic criteria were developed by reference to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine [ 3 ] f o r mu lated b y th e S tate Administration of Traditional Chinese Medicine of the People’s Republic of China in 1994 and the contents related to premature ovarian failure in the amenorrhea chapter of Chinese Obstetrics and Gynecology[4]: with the symptoms of amenorrhea for at least 3 months and oligomenorrhea, concomitantly with tidal fever, night sweat, vexation and agitation and irascibility, poor sleep and other clinical perimenopausal symptoms, as well as soreness and weakness of waist and knees, dizziness and tinnitus and other symptoms of kidney deficiency and liver constraint before 40 years old. Serum FSH ＞40U/L, LH ＞30U/L, E2＜73.2 pmol/L.
Inclusion criteria ① With the age of 18–40 years old; ② conforming to the diagnostic criteria in western medicine and the pattern of kidney deficiency and liver constraint in traditional Chinese medicine; ③ discontinuing treatment for premature ovarian failure for more than 3 months, and the efficacy evaluation result will not be Table 1
affected; ④ signing the informed consent form by the patient oneself or family members.
Exclusion criteria ① Amenorrhea patients not caused by premature ovarian failure according to ultrasonic examination or other examinations; ② concomitantly with severe primary diseases such as cardiovascular, liver, kidney and hematopoietic system diseases, as well as mental disorders; ③ with premature ovarian failure not belonging to the pattern of kidney deficiency and liver constraint according to TCM diagnosis; ④ patients with organic diseases (such as hysteromyoma, etc.) and breast disorders.
Elimination criteria ① The patients who conformed to the inclusion criteria but didn’t accept treatment, or who accepted treatment but didn’t complete the courses; ② the patients who took medicine independently after inclusion.
Drop-out criteria ① The patients who suffered from adverse event and complication, and who was not suitable for further treatment; ② the patients who dropped out from the study voluntarily; ③ the patients who quit from the study due to other reasons; ④ the patients with incomplete data record which may affect the efficacy evaluation.
METHODS Electroacupuncture combined with heatsensitive moxibustion group (group A) Acupoint selection was conducted as the following two groups: one group: Zǐgōng (子宫 EXCA1), Xuèhǎi (血海 SP 10), Guānyuán (关元 CV 4), Sānyīnjiāo (三阴交 SP 6), Tàichōng (太冲 LR 3) , all points were selected bilaterally. Another group: Gānshū (肝俞 BL 18), Shènshū (肾俞 BL 23), Píshū (脾俞 BL 20), Géshū (膈俞 BL 17), and Cìliáo (次髎 BL 32), all points were selected bilaterally too. The two group of acupoints were punctured alternately. Manipulations: 0.30 mm×25 mm filiform needles were adopted for inserting for 20 mm at EX-CA1, SP 10, BL 18 and BL 23, and HANS-100A electroacupuncture device was connected. In group one, a group of electrodes were
Comparison of general information on the patients with premature ovarian failure in the two groups
Groups
Patients
Age (x±s, year)
Course of disease (x±s, d)
FSH (x±s, U/L)
LH (x±s, U/L)
E2 (x±s, pmol/L)
A
40
30.1±4.5
108.2±7.2
52.5±3.4
35.6±7.7
57.3±5.6
B
40
30.2±4.8
114.1±9.2
53.1±2.8
41.1±8.2
48.9±7.9
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
connected with EX-CA1 and SP 10 on the right side, and the other electrodes were connected with EXCA1 and SP 10 on the left side. In another group, a group of electrodes were connected with BL 18 and BL 23 on the right side, and the other electrodes were connected with BL 18 and BL 23 on the left side. The treatment was carried out for once every other day, 3 months was considered as 1 course of treatment, and 2 courses were needed. Heat-sensitive moxibustion treatment: the patients were asked in prone position with full exposure of the waist and back; two moxa sticks were adopted for moxibustion treatment at the heat-sensitive acupoints in the area 6 cun outwards away from the region inside both lateral lines of foot-taiyang bladder meridian and between the two horizontal lines of BL 17 and BL 23 on the back. The moxa sticks were lighted, and suspended moxibustion was implemented at the height of about 3cm away from the skin surface selected. When the patients felt heat penetration, heat expansion, heat transfer, non (micro) local heat but distant heat, non (micro) surface heat but deep heat, and one or more of the non thermal sensations, acupoint heat-sensitization occurred, and this acupoint was the heat-sensitive acupoint. The above procedures were repeated until all the heat-sensitive acupoints were found in the area, and the detailed locations were recorded. Then suspended moxibustion was conducted at these heatsensitive acupoints, and the ash was whisked every 2 min (no more than 10 s) and the distance between the moxa stick and the skin surface was controlled for maintaining enough heat. Moxibustion for once was defined as when heat penetration, heat expansion or the sensation of transmission disappeared in the area of heat-sensitive acupoints. The patients accepted treatment for 10 consecutive days at the first visit, once a day; treatment for 10 times should be completed in the later 20 days in the first month; treatment for 15 times per month should be completed in the later 2 months, treatment for 50 times was considered as 1 course of treatment, and 2 courses were needed.
Western medicine group (group B) Artificial cycle replacement therapy was adopted by using climen (Bayer HealthCare Co., Ltd., Guangzhou Branch, G.Y.Z.Z. No. J20130006). Usage: 1 pill/d, and administration for 21d was needed; then the drug was withdrawn for 7 d, and bleeding, with the menstruation characteristic, induced by drug withdrawal may be caused after withdrawal for 2-4 d. If the menses didn’t arrive after withdrawal for 7 d, the drug should be taken continuously. For the patients with menses, climen was taken for 1 pill/d since the 5 th day of the menstrual cycle, and administration for
·11· 21 d was needed; the drug should be taken periodically after withdrawal for 7 d. Administration for 3 months was considered as 1 course of treatment, and 2 courses were needed.
EFFICACY OBSERVATION Observational indices ① Menstrual cycle score: arrival of the menses for 3 consecutive months. The menstrual period was normal with normal quantity of menses, red color, scoring 0 point; arrival of the menses for 3 consecutive months with moderate quantity of menses, red color, scoring 1 point; arrival of the menses for 3 consecutive months with slightly less quantity of menses, light red color, scoring 2 points; arrival of the menses for 3 consecutive months with less quantity of menses, light color, scoring 3 points; infrequent menstruation for 3 consecutive months, scoring 4 points. ② Ti d a l f e v e r a n d s w e a t i n e s s s c ore: no fever, scoring 0 point; occasional fever on the head and face, and slight sweatiness, scoring 1 point; intermittent fever on the head and face concomitantly with sweatiness and slightly red face, scoring 2 points; occasional fever on the whole body concomitantly with sweatiness and flushed face, which can interfere with the attention, scoring 3 points; intermittent fever on the whole body concomitantly with sweatiness and red face, which can interfere with the attention and affect sleep, scoring 4 points. ③ Emotional excitement score: calm emotion, scoring 0 point; slightly excited emotion which can restore calm easily, scoring 1 point; excited emotion with depression and suspicion, scoring 2 points; vexation and agitation with depression and suspicion, which can interfere with the attention, scoring 3 points; vexation and agitation, irascibility which cannot be tolerated, and can affected sleep, scoring 4 points. ④ Soreness and weakness of waist and knees score: no soreness and weakness of waist and knees, scoring 0 point; slight soreness and weakness of waist and knees which can be ignored, without tenderness, scoring 1 point; obvious soreness and weakness of waist and knees which can be tolerated, with slight tenderness, scoring 2 points; obvious soreness and weakness of waist and knees which cannot be ignored, and can interfere with the attention, with tenderness, scoring 3 points; intolerable soreness and weakness of waist and knees which
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·12· can affect sleep, with obvious tenderness, scoring 4 points.
90%. Effective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were improved, the quantity of menses increased, and the reducing rate ≥30%, less than 60%. Ineffective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were not improved, infrequent menstruation for 3 consecutive months with light color, and the reducing rate ＜30%.
⑤ Dizziness and tinnitus score: no dizziness and tinnitus, scoring 0 point; occasional dizziness and tinnitus which can return to normal easily, scoring 1 point; intermittent dizziness and tinnitus, scoring 2 points; frequent dizziness and tinnitus which can interfere with the attention, scoring 3 points; continuous dizziness and tinnitus which can affect sleep, scoring 4 points.
Statistical analysis
The sum of each symptom score was the total score, and the symptom scores and total scores of patients in the two groups before and after treatment were observed.
After efficacy evaluation, SPSS 21.0 software was adopted by statisticians for statistical analysis. Measurement data were expressed as mean ± standard deviation (x±s), and intra-group comparison was performed via t-test. Intergroup comparison was conducted by using independent sample t-test, and enumeration data were analyzed through Chisquare test. P＜0.05 indicated that the difference was statistically significant.
Efficacy evaluation criteria By reference to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine [3] and the efficacy evaluation criteria of premature ovarian failure in the amenorrhea chapter of Chinese Obstetrics and Gynecology[4]: Reducing rate＝[(Total score before treatment－total score after treatment)÷total score before treatment]×100%.
RESULTS Comparison of symptom scores of patients with premature ovarian failure in the two groups before and after treatment (Table 2)
Clinically cured: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus disappeared, after drug withdrawal for 3 months, there was no relapse of menstrual cycle, the quantity of menses and menstrual period returned to normal, and the reducing rate ≥90%. Markedly effective: the symptoms of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus were improved obviously, the menstrual cycle and menstrual period returned to normal, the quantity of menses increased by 1/3 or over 20 mL, and the reducing rate ≥60%,less than
It was indicated from Table 2 that the difference in symptom scores of patients in the two groups before treatment was not statistically significant (all P＞0.05), and the results were comparable. The symptom scores were improved significantly in the two groups after treatment (group A: tmenstrual cycle＝14.970, ttidal fever and sweatiness＝10.873, temotional excitement＝22.375, tsoreness and weakness of waist and knees＝16.169, tdizziness and tinnitus＝13.270, ttotal score＝ 25.730; group B: tmenstrual cycle＝8.382, ttidal fever and sweatiness＝ 16.257, temotional excitement＝11.191, tsoreness and weakness of waist and knees＝11.048, tdizziness and tinnitus＝15.235, ttotal score＝16.257, all P＜0.05), and the effect of group A was superior to that of group B in menstrual cycle, tidal fever
Table 2 Comparison of symptom scores and total score of patients with premature ovarian failure in the two groups (x±s, point) before and after treatment Menstrual cycle Groups
Patients
Before treatment
After treatment
A
40
1.76±1.03
0.45±0.671)
1.76±1.08
1)
Tidal fever and sweatiness Difference value
B
40
0.79±0.81
Group
Patients
Before treatment
After treatment
A
40
3.19±0.71
0.76±0.851)
3.21±0.70
1)
1.31±0.782) 0.97±0.72
Before treatment
After treatment
2.71±0.64
1.17±0.821)
2 68±0.74
1)
Soreness and weakness of waist and knees
B
40
1.47±0.92
1)
Difference value
1.53±0.65
After treatment
2.71±1.02
0.71±0.841)
0.97±0.72
2.61±1.03
1)
Difference value
Before treatment
After treatment
10.38±2.48
3.07±2.131)
10.24±2.79
1)
1.31±0.782)
Dizziness and tinnitus
Difference value
Before treatment
After treatment
2.40±0.732)
2.56±0.43
1.07±0.551)
2.71±0.52
1)
1.74±0.76
Emotional excitement Before treatment
1.42±0.71 2)
Notes: compared with that before treatment, P＜0.05; compared with group B, P＜0.05
Difference value
1.18±0.96
2.05±0.762) 1.39±0.82
Total score
1.21±0.642) 0.98±0.82
Difference value
5.00±2.41
7.26±1.952) 5.21±1.98
World Journal of Acupuncture-Moxibustion (WJAM) Vol. 27, No.3, 30th Sep. 2017
·13·
Table 3 Comparison of the effi cacy on patients with premature ovarian failure in the two groups (Case) Groups
Patients
Clinically cured
Markedly effective
Effective
Ineffective
Cured and markedly effective rate(%)
A
40
6
23
9
2
72.51)
B
40
2
13
19
6
37.5
1)
Note: compared with group B, P＜0.05
and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus (t menstrual cycle＝2.658, ttidal fever and sweatiness＝1.998, temotional excitement ＝3.607, t soreness and weakness of waist and knees ＝3.995, tdizziness and tinnitus＝2.774, all P＜0.05); the differences in the difference values of the total scores of patients in the two groups were also statistically significant (t＝ 4.949, P＜0.05), indicating that the efficacy of group A was superior to that of group B in improving the symptoms.
Comparison of clinical efficacy on patients in the two groups (Table 3) It was shown from Table 3 that the cured and markedly effective rate in group A was higher than that in group B ( χ2＝2.22, P＜0.05).
DISCUSSION Premature ovarian failure is a symptom of premature menopause caused by kidney essence depletion occurring before the age of menopause. Recent studies have shown that the incidence of premature ovarian failure was 1%-3% in the women of child-bearing age, 10%-28% in the patients with primary amenorrhea, and 4%-18% in the patients with secondary amenorrhea[5]. At present, hormone replacement therapy is commonly adopted in western medicine. Estradiol valerate, included in Climen, is a precursor of natural human 17 β-estradiol; another component cyproterone acetate is a kind of synthesized derivative of hydroxyprogesterone with the characteristics of progestational hormone and antigonadotropic hormone, thus achieving the purpose of treatment of premature ovarian failure. In spite of the good effect, the recurrence rate is higher after discontinuation, and it is not suitable for the patients with hysteromyoma and diabetes. It is believed in traditional Chinese medicine that premature ovarian failure is usually caused by kidney qi deficiency and kidney essence depletion, and related with liver, spleen, heart, thoroughfare vessel and conception vessel[6]. “The menstruation is from the kidney”. The kidney stores the essence, and governs reproduction, which is the foundation of congenital constitution, and the root of the five
viscera and six bowels. It has been verified in modern medicine that the kidney plays a leading role in the process of menstruation. Acupuncture-moxibustion for supplementing kidney can regulate the endocrine mechanism, and improve the ovarian response to FSH. The liver governs the free flow of qi, and stores the blood, which can be equivalent to all the neuroendocrine functions. The flow of qi of liver can maintain the amassment and regurgitation of SP 10, playing an important role in the maintaining of menstruation[7]. According to this, EX-CA1, SP 10, CV 4, SP 6 and LR 3 were selected as the main acupoints, and BL 18, BL 23, BL 20 were selected as the combined acupoints for jointly enriching and nourishing liver and kidney, balancing yin yang, soothing the liver qi, and regulating thoroughfare vessel and conception vessel. EX-CA1 and SP 10 can nourish the uterus, nourish blood and invigorate blood, jointly supplementing kidney and fortifying the spleen, as well as soothing the liver and invigorating blood; CV 4 and BL 23 can supplement kidney qi and enrich kidney yin; SP 6 can supplement kidney, fortify the spleen and soothe the liver; ST 36 and BL 18 can fortify the spleen and soothe the liver. Electroacupuncture stimulation at the acupoints can effectively activate the functions of related organs, make the menstruation pass and the symptoms disappear, improving the clinical efficacy to a great extent[8]. Under the disease state, the related acupoints of human body are heat-sensitive, and a series of strange moxibustion sensation phenomenons may be seen, such as heat penetration, heat expansion, heat transfer, and non (micro) local heat but distant heat. When the moxibustion sensations transfer to a lesion, the symptoms will be released accordingly. Heat-sensitive moxibustion is a new moxibustion therapy firstly researched and developed in Jiangxi University of Traditional Chinese Medicine [9], the hormonoid function of heat-sensitive moxibustion can significantly redeploy the whole functions, improve the ovarian response to gonadotropin, thus restoring and improving ovarian function, delaying senescence and regulating immunity, which is a safe and effective method for treatment of premature ovarian failure. When hormone replacement therapy is still used
·14· in most regions of the country, electroacupuncture combined with heat-sensitive moxibustion for treatment of premature ovarian failure has already broken through the conventional method, it is a new treatment idea, and an emerging technology in current China. This method is the inheritance of traditional medicine with satisfactory effect and no toxic neither side effect, which is safe and reliable, and easily accepted by patients. Heat-sensitive moxibustion is worthy of clinical popularization and application.
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Kalantaridou SN, Davis SR, Nelson LM. Premature ovarian failure.Endocrinol Metab Clin North Am 1998; 27(4): 989 1006. He SL, Wang J, Wang JJ. TCM Research Design & Statistics (Chin). Changsha: Hunan Science & Technology Press; 2003: 252 253. State Administration of Traditional Chinese Medicine of the People’s Republic of China. Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in
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Traditional Chinese Medicine (Chin). Nanjing: Nanjing University Press; 1994: 234-235. Cao ZY. Chinese obstetrics and gynecology. Version 2. Beijing: People’s Medical Publishing House; 2004: 2568. Goswami D, Conway G S. Premature ovarian failure. Hormone Research 2015;68(4):196 202. Yu B, Wang JL, Zhao ZS, Chen J, Zhang YP, Wei Bo. Research progress of acupuncture-moxibustion treatment for premature ovarian failure. J Shandong Univ Tradit Chin Med (Chin) 2015; 39(2) 32 38. Yang XH, Lai XM, Huang ZB. Clinical observation of acupuncture-moxibustion treatment for 60 cases of premature ovarian failure. J Sichuan Tradit Chin Med (Chin) 2008; 26(5): 106 107. Luo X, Jin WT, Yang XM, Zhang B, Wang WZ, Shang LJ. Research progress of acupuncture-moxibustion treatment for premature ovarian failure. Chin Foreign Med Res (Chin) 2015; 13(35) 55 60. Chen RX, Kang MF. Practical Guidance of Heatsensitive Moxibustion (Chin). Beijing: People’s Medical Publishing House; 2009: 4.
ABSTRACT IN CHINESE
[摘 要] 目的：比较电针合热敏灸法与常规口服西药治疗卵巢早衰的临床疗效差异。方法：采用随机对 照的方法，将80例患者分为电针合热敏灸组（40例）和西药组（40例）。电针合热敏灸组给予子宫、血 海、肝俞、肾俞等穴位针刺配合热敏灸法治疗，西药组口服克龄蒙。比较治疗两个疗程前后两组患者月 经周期评分、潮热汗出评分、情绪激动评分、腰膝酸软评分、头晕耳鸣评分变化及愈显率。结果：电针 合热敏灸组的愈显率为72.5%（29/40），优于西药组的37.5%（15/40，P＜0.05）。两组治疗后各症状评 分较治疗前均明显改善（均P＜0.05），且电针合热敏灸组优于西药组（均P＜0.05）。结论：电针合热敏 灸法治疗卵巢早衰疗效优于常规西医疗法。 [关键词] 卵巢早衰（肾虚肝郁型） 电针 热敏灸 随机对照试验