Efficacy of transcutaneous electrical acupoint stimulation (TEAS) for menopausal insomnia and its effect on serum hormone levels

Wang Min-chao(王敏超),Lin Li-hong (林丽红)

LishuiSecond People’sHospital, Zhejiang 323000,China

Abstract

Keywords: Acupoint Therapy; Transcutaneous Electric Nerve Stimulation; Insomnia;Climacteric; Perimenopause; Hormones;Women

Menopausal insomnia is caused by the decrease of ovarianfunctionandestradiol(E2)level,andthe increaseof folliclestimulatinghormone(FSH)level.Insomnia is a main clinical manifestation and a common psychiatricsymptominmenopausalwomen[1].The maincharacteristicsof the diseasearepoor sleep quality,difficulty falling asleep,shallow sleepand dreaminess,andalow spirit during theday,often accompaniedby anxiety, irritability,depressionand other adverseemotions[2].Theincidencerateof menopausalinsomniaishigh.Epidemiologicalsurvey shows that more than 50% of menopausal women have different degreesof sleepdisorders[3].Menopausal insomnia is difficult to cure, and will hinder the quality of lifeandseriously affect thephysicalandmental health of patients[4]. At present, conventional sedative and hypnotic drugs and hormone replacement are the maintreatment for thisdisease.However,sedative/ hypnotic drugs may cause adversereactions such as dizziness,drowsiness and fatigue, andlong-termuse will cause drug dependence and withdrawal reactions.Hormone replacement therapy can increase the risk of gynecologicaltumor andtheincidenceof vascular embolism disease[5]. Therefore, it is of vital importance to find a safe and effective treatment. In this study, the clinicalefficacy of transcutaneouselectricalacupoint stimulation(TEAS)for menopausalinsomniawas observed and its mechanism was explored.

1 Clinical Materials

1.1 Diagnostic criteria

1.1.1 Diagnostic criteria of Western medicine

According to the diagnostic criteria for insomnia in theChinese Classificationand Diagnosis of Mental Diseases-3rdEdition (CCMD-3)[6]: the main symptoms were difficulty falling asleep,light sleep,dreaminess,early wake-up, or not easy to sleep again after wake-up,discomfort after wake-up, or sleepiness during the day;sleep disorders caused obvious distress or impairment of social function; the disease duration ≥1 month.

1.1.2Patterndifferentiationcriteriaof traditional Chinese medicine (TCM)

The pattern differentiation criteria of TCM referred to the standard of disharmony between heart and kidney described in theGuiding Principles for Clinical Study of New Chinese Medicines[7].Themainsymptoms:vexation,sleeplessness,palpitations andanxiety. The minor symptoms:dizziness, tinnitus, soreness of low back,vexing heat inthechest,palmsandsoles,a reddish tongue with less or no coating, and fine and rapid pulses.

1.2 Inclusion criteria

Those whomet thediagnostic criteriaof both Western medicine and pattern differentiation criteria of TCM; female patients aged between 40 and 60 years old;signedtheinformedconsent andvoluntarily participated in the trial.

1.3 Exclusion criteria

Those who sufferedfromsecondary insomnia;serious heart, brain, liver and kidney diseases; local skin damage at the acupoints to be treated by TEAS; those who suffered from consciousness disorder or mental illnessandwereunabletocooperatewiththe completion of the trial; allergic to drugs used in this study.

1.4 Statistical methods

The SPSS version 20.0 statistical software was used for data analysis. Rank-sum test was used for counting data; the measurement data were expressed as mean ±standard deviation (±s).Pairedt-test wasused for intra-group comparison and groupt-test was used for inter-group comparison. TheP-value of less than 0.05 meant a statistically significant difference.

1.5 General data

Eighty insomniaoutpatients visiting LishuiSecond People's Hospital were selected between January 2018 and March 2019. According to the method of random number table, they were divided into a control group and an observation group, with 40 cases in each group.In the observation group, the youngest patient was 40 years old, and the oldest was 60 years old; the shortest disease duration was 5 months, and the longest was 24 months. In the control group, the age of patients was between 41 and 60 years old, and the duration was between 3 and 25 months. There were no significant differencesinthe ageandthedisease duration between the two groups (bothP＞0.05), indicating that the two groups were comparable (Table 1).

Table 1.Comparison of general data between the twogroups

2 Therapeutic Methods

2.1 Control group

Patients inthecontrolgrouptook eszopiclone(NationalMedicineStandard:H2007069,Jiangsu TianshiliDiyiPharmaceuticalCo.,Ltd.,China)orally,2 mg /time, once a day, for 4 weeks.

2.2 Observation group

Patients in the observation group received TEAS plus eszopiclone (the dosage and treatment course were the same as those in the control group).

Acupoints: Bilateral Shenmen (HT 7), Neiguan (PC 6),Taixi (KI 3) and Zhaohai (KI 6).

Methods:HwatoSDZ-V electroacupuncture(EA)instrument was used for TEAS treatment. The patient took a prone position to expose the local skin of the acupoints. The physician sterilized the local skin with 75% ethanol cotton ball and then applied the electrode platestothelocalskinof theselectedacupoints.Shenmen (HT 7) and Neiguan (PC 6) on the same side were as a pair, and Taixi (KI 3) and Zhaohai (KI 6) on the sameside as apair, 4 pairsin total. Turnedon the power switch, with continuous wave, 20 Hz in frequency,and20 mA inintensity.Eachtreatment lastedfor 30 min, and the treatment was conducted once every other day, for 4 weeks in total.

3 Observation of Therapeutic Efficacy

3.1 Observed items

3.1.1 PSQI score

Beforeandafter treatment,PSQIscoresinboth groups were observed. Because of the limited use of hypnotic drugs in both groups, the component of use of sleeping medication in the PSQI scale was not included in the analysis.

Thescores of 6 factors,including subjectivesleep quality,sleeplatency,sleepduration,habitualsleep efficiency, sleep disturbances and daytime dysfunction were recorded, as well as the total score of PSQI[8]. The score of each factor is 0-3 points, and the total score of PSQIis 0-18points. Thehigher the score, the more serious the insomnia symptoms.

3.1.2 Score of modified Kupperman scale

Beforeandafter treatment,thepatients inboth groups received modified Kupperman scale evaluation.ThemodifiedKupperman scale was composed of 13 menopausal symptoms such as hot flush and sweating,insomnia,paresthesia,depression,dizziness,fatigue,anxiety, and muscle and joint pain. The total score of the modifiedKuppermanscaleis 0-63points.The higher the score,themore seriousthemenopausal symptoms[9].

3.1.3 Levels of serum E2and FSH

Fasting venous blood of the patients was drawn in the early morning before and after treatment. Serum E2andFSHlevels of thepatientsinboth groupswere measured by radioimmunoassay.

3.2 Therapeutic efficacy criteria

The therapeutic efficacy was evaluated according to theGuiding Principles for Clinical Study of New Chinese Medicines[7].

Recovery: Sleep at night for more than 6 h and felt energetic after waking up.

Markedly effective: Symptoms improved significantly,sleep time increased by more than 3 h, and sleep depth increased.

Effective:Symptoms improvedandsleeptime increased by less than 3 h.

Failure: The symptoms of insomnia did not improve or even worsened after treatment.

3.3 Results

3.3.1 Comparison of clinical efficacy

After treatment,thetotaleffectiverateinthe observation group was 95.0%, which was significantly higher than77.5% inthecontrolgroup(χ2=5.16,P=0.02), (Table 2).

3.3.2 Comparison of the PSQI score

Beforetreatment,therewerenobetween-group statistical differences in the PSQI component scores and totalscore(allP＞0.05).After treatment,the PSQI component scores and total score in the observation group were significantly decreased (allP＜0.05). In the control group, only the score of sleep disturbances and totalscoreweresignificantly different fromthose before treatment (allP＜0.05). The scores of subjective sleepquality,sleeplatency,sleepduration,habitual sleepefficiency,andtotalscore of PSQIinthe observation group were significantly lower than those in the control group (allP＜0.05). Please see Table 3 for details.

Table 2.Comparison of clinical efficacy between the two groups (case)

Table 3.PSQI score comparison between the twogroups (±s, point)

Table 3.PSQI score comparison between the twogroups (±s, point)

Note:BT=Before treatment;AT=After treatment;compared with thesame groupbefore treatment,1)P＜0.05;compared with the control groupafter treatment,2) P＜0.05

GroupnTime Subjective sleepquality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbances daytime dysfunction Total score Observation 40 BT 1.98±0.89 1.88±0.791.95±0.901.85±0.771.93±0.86 1.78±0.8311.35±1.85 AT 1.25±0.741)2) 1.03±0.771)2) 1.08±0.801)2) 0.98±0.891)2)1.00±0.851) 1.25±0.811) 6.38±1.711)2)Control 40 BT 1.88±0.882.00±0.781.73±0.82 1.85±0.801.73±0.751.93±0.86 11.10±2.19 AT 1.74±1.17 1.49±1.211.69±1.16 1.54±1.121.28±1.051) 1.48±1.199.23±2.491)

3.3.3 Comparison of the modified Kupperman score

There was no significant between-group difference in themodifiedKuppermanscorebeforetreatment(P＞0.05),indicating that thetwo groupswere comparable. After treatment, the modified Kupperman scoreintheobservationgroupwassignificantly decreased(P＜0.05),andtherewas asignificant difference between the two groups (P＜0.05). Please see Table 4 for details.

3.3.4 Comparison of the serum E2and FSH levels

There were no significant between-group differences in the serum E2and FSH levels before treatment (bothP＞0.05),indicating that the twogroupswere comparable.After treatment,thelevelof E2inthe observation group increased (P＜0.05), and the level of FSH decreased (P＜0.05). The between-group differences intheserumE2andFSHlevels werestatistically significant after treatment (bothP＜0.05), (Table 5).

Table 4.Comparison of the modified Kupperman score between the two groups (±s, point)

Table 4.Comparison of the modified Kupperman score between the two groups (±s, point)

Note:Compared with thesame groupbeforetreatment,1)P＜0.05;compared with the control groupafter treatment,2)P＜0.05

Groupn Before treatment After treatment Observation 4024.70±4.4512.08±1.651)2) Control 4024.98±4.3023.58±3.46

Table 5. Comparison of the serum E2 and FSH levels between the two groups (±s)

Note:BT=Before treatment;AT=After treatment;compared with the samegroupbefore treatment,1)P＜0.05;compared with thecontrol groupafter treatment,2) P＜0.05

Groupn Time E2 (pmol/L)FSH (U/L)Observation 40 BT 32.16±4.20 64.71±5.62 AT43.06±4.591)2) 42.96±6.681)2)Control 40 BT 32.46±4.2164.75±5.88 AT32.20±4.1963.30±4.08

3.4 Adverse reactions

During the treatment,twopatientsin thecontrol groupdevelopedabitter tasteinmouthandtwo patients experienced symptom of dizziness. One patient in the observation group had a bitter taste in mouth.The adverse reactions of the patients were not serious,and they were relieved within days without any special treatment.

4 Discussion

Insomnia falls under the category of ‘sleeplessness’and ‘inability to sleep’ in TCM. The pathogenesis of the diseaseisyang excess andyindeficiency,and disharmony betweenyinandyang.Thedisease is located in the heart and is closely related to the liver,spleenandkidney.Menopausalwomenare often diagnosed as kidney essence deficiency, exhaustion of Tiangui (congenital kidney essence) and dysfunctions of Zang-fu organs. Abnormal function of ‘kidney-Tiangui(congenitalkidney essence)-Thoroughfareand ConceptionVessels-uterus’axisleadstodisharmony betweenheart andkidney,anddisturbedheart and spirit. It can also cause insomnia, often accompanied by restlessness, irritability, palpitations, sweating and other symptoms[10]. Disharmony between heart and kidney is a common syndrome type of menopausal insomnia[11].Therefore, this study focused on menopausal insomnia patients with syndrome of disharmony between heart andkidney to observetheclinicaleffect of TEAS treatment and explore its mechanism.

TEAS combines the transcutaneous electrical nerve stimulation(TENS) therapy of modernmedicine with the theory of meridians andacupoints of TCM, and stimulates specific acupointsonthehumanbody through low-frequency electric pulse, so as to achieve similar therapeutic effect as EA[12], which can maintain the characteristicsof ‘EA-like’stimulation,butalso overcome the disadvantages of acupuncture pain. It is non-invasive,basically painless,easy-to-operateand convenient to promote acupoint stimulation[13-14]. The action principle of TEAS is similar to that of acupuncture,whichis to stimulate specific acupoints, arouselocal meridianqi,dredgemeridiansandcollaterals,and regulate Zang-fuorganstoprevent andtreat diseases[15].

Shenmen(HT 7),Neiguan(PC 6), Taixi(KI3)and Zhaohai(KI 6) were selectedin this study. Shenmen(HT 7), the experiential acupoint in treating insomnia, is theYuan-Primary pointof theHeart Meridian,functioning to tranquilize heart and mind, and regulate qi. Neiguan (PC 6) is the Luo-Connecting point of the Pericardium Meridian, one of the Confluent Points of the Eight Extraordinary Meridians, and connects the Yin Link Vessel. It has the effect of tranquilizing the heart and mind, and regulating qi and harmonizing stomach,and thus is often used for cardiovascular, mental and digestive diseases. Taixi (KI 3) is the Yuan-Primary point of theKidney Meridianandhas thefunctionof nourishing kidney yin.Zhaohai(KI6)isoneof the Confluent Points of the Eight Extraordinary Meridians.As the crossing point of the Kidney Meridian and Yin HeelVessel,it wasselectedtonourishkidney and inducesleepbecausetheHeel Vesselsgovernthe opening and closing of the eyes[16-17]. The combination of these four acupoints can connect and harmonize the heart and kidney, and tranquilize the heart and mind[18].

The occurrence of menopausal insomnia is related to the changes of serumE2andFSHlevels.Thesex hormonelevelcanbe regulatedby TEAS.Withthe decline of ovarian function in menopausal women, the function of hypothalamus-pituitary-ovary axis is out of order,andthesecretionof sex hormoneappearsa series of changes: thelevels of progesterone andE2decrease significantly while the level of androgen and FSHincrease,whichwillleadto thedisorder of autonomic nerve function and the occurrence of sleep disorder[19].Regulating serumE2andFSHlevelscan improve thesleep condition of menopausalwomen.Clinicalresearchshowedthat after theestrogen replacement therapy was adopted for postmenopausal womenwithinsomnia,the recovery of sleep electroencephalogram(EEG)of thepatientswas significantly better than that in the control group[20].Jiang SR,et al[21]investigated perimenopausal women with PSQI and detected their serum E2and FSH levels.The results showed that the lower the E2level and the higher the FSH level, the worse the sleep quality. TEAS has a goodregulatory effect on sex hormonelevels.Clinical research showed that the therapeutic effect of TEAS on asthenospermia of renal spermatogenesis was reliable[22],andit cansignificantly increasethe percentage of motile sperm, the total sperm activity,and reduce the serum FSH level. Guo ZP,et al[23]applied TEAS to the patients with functional uterine bleeding,and found that TEAS can establish normalmenstrual cycle by regulating their E2level.

The results of this study showed that the effective rate in the observation group was significantly higher than that in the control group (P＜0.05); the PSQI and modifiedKuppermanscoresof the patientsinthe observationgroupweresignificantly improved(bothP＜0.05)after treatment;theserumE2levelof the patients in the observation group increased significantly (P＜0.05), while the FSH level decreased (P＜0.05) after treatment. These results indicated that TEAS should be effective in the treatment of menopausal insomnia, and cansignificantly improvethesymptomsof insomnia and menopause, which may be related to the regulation of serumE2andFSHlevels.However, there are still some deficiencies in this study, such as small sample size, lack of objective indicators to evaluate the severity of insomnia, and lack of follow-up. Further researches are needed in these areas.

C onflict of Interest Thereis noconflict of interest in this article.Acknowledgments Thiswork wassupported by Scienceand Technology Planning Project of LishuiCity,Zhejiang Province(浙江省丽水市科技计划项目, No.2017GYX28).Statement of Informed Consent Informed consent wasobtained from all individual participants.

Received:24July 2019/Accepted:30 August 2019