Menopause
Conditions
Keywords
electro-acupuncture, menopause, menopausal transition symptoms, efficacy, RCT, placebo control
Brief summary
This trial aimed at exploring the efficacy as well as safety of electro-acupuncture for MT symptoms.
Detailed description
This was a RCT pilot study to assess the efficacy of Electro-acupuncture for menopausal transition participants.90 patients were randomly assigned to electro-acupuncture or sham electro-acupuncture group with a ratio of 1:1.During the whole process,all participants, evaluators and statisticians apart from acupuncturists remained strictly blinded.The changes of average 24 h hot flash scores of week8 from baseline was set as primary outcome. With statistical power of 90%, and a two-sided α at 0.05, as well as a drop-out rate less than 20%, sample size was estimated at 90 participants. Data analysis was based on ITT principles, and 89 participants were included in data analysis(1 participant didn't want to participate).According to methods of LOCF, missing data were imputed to fill any gaps according to the last visit. For comparison between baseline and treatment (average 24h hot flash scores, MRS, hormone levels), data was tested by the t test or nonparametric test; for comparison between two independent samples, data were tested with t test, nonparametric test or X2 test. P\<0.05 was regarded as statistically significance.
Interventions
DEVICEEelectro-acupuncture
The bilateral acupoints of EX-CA1, ST25, SP6 and RN4 were selected for the treatment program.After regular disinfection,adhesive pads were placed on surface of all these acupoints. For RN4, EX-CA1, ST25, needles (0.30\*75mm) were inserted into the points vertically throughout the pads, skin, fat tissue, and abdominal muscles until the participant had feeling of pricking. For SP6, needles were inserted into the acupoint to a depth of 1 cun,accompanied by manipulation of lifting, thrusting, and twisting 3 times. Electronic stimulator was connected to EX-CA1 and ST25 with dilatational wave, 10/50HZ, 0.1 to 1.0mA. The current intensity was adjusted to abdomen shivering without pain. Treatment lasted for 30 minutes and acupuncture manipulation for RN4 and SP6 were performed every 10 minutes.
DEVICESham Eelectro-acupuncture
Non-acupoints approximate to RN4, ST25, EX-CA1 and SP6 were selected bilaterally, and adhesive pads were placed on the surface of selected non-acupoints' location. Blunt needles were inserted into the pads and to touch, rather than penetrate the surface of skin. Meanwhile, like EA group, manipulations of lifting, thrusting and twisting on non-acupoint approximate to RN4 and SP6 were performed 3 times. Sham Electronic stimulator was applied to the non-acupoint approximate to EX-CA1 and ST25, providing the outward appearance of the procedure in EA group but with no current intensity actually applied. Any other interventions were rigorously maintained the same as in the EA group.
Sponsors
Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Participants meeting the following criteria were included in study: 1. Had a diagnosis of MT (cycle length irregularity: 7 days earlier or later than usual, the last menstruation was no longer than 11 month earliar over the previous year; Specific symptoms of MT: hot flashes, night sweating, insomnia, sexual problems, anxiety, depression etc.); 2. Aged from 40 to 55 years old; 3. Pregnancy test was negative; 4. Participants were informed about the study and signed a consent form voluntarily.
Exclusion criteria
* Participants with any of the following criteria were omitted from the study: 1. 3 month regular cycle length before enrollment; 2. Took drugs for treatment in past month like estrogen, soybeans isoflavone, SSRIs, progestin, black sesame or vitamin E; 3. Ovarian and uterine disease: ovarian cyst, uterine myoma more than 4cm in diameter, history of ovariectomy or hysterectomy; 4. Willing or plan to become pregnant or to breast-feed; 5. Regular took sedatives or anxiolytics; 6. Habitual smoker or heavy alcoholic; 7. Severe disease: history of radio-chemotherapy, coagulation disorders, severe dysfunction of liver or kidney, application of cardiac pacemaker or artificial joints, insufficiency controlled hypertension, diabetes, thyroid diseases, malignant tumor and psychiatric problems).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Average 24 h Hot Flash Score From Baseline | week8;wee4,20,32 | Every day during the 4th, 8th, 20th, and 32nd weeks, symptoms and specific times of hot flashes were recorded in hot flash diaries by the participants.Data from weeks 4, 20 and 32 were recorded as the second time frame.According to the severity categories suggested by Food and Drug Administration (FDA), hot flashes were assessed as mild, moderate, or severe. Hot flash scores are calculated as (hot flash frequency x severity)/7, with severity scores ranging from 1=mild 2=moderate to 3=severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of MRS (Menopause Rating Scale) From Baseline | week8;wee4,20,32 | MRS(Menopause Rating Scale) was designed to measure MT symptoms and to explore the influences on life qualities in a standardized way. In MRS, symptoms such as impaired memory, depression, insomnia, sweating, hot flashes, nervousness, joints complaints, lack of concentration were evaluated and calculated in numbers to describe the situation of patient. Scores on MRS range from 0 to 44, with higher scores indicating more severe symptoms. |
| Change of FSH From Baseline | week8,week20 | Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th. |
| Change of LH From Baseline | week8,week20 | Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th. |
| Change of FSH/LH From Baseline | week8,week20 | Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th. |
| Change of E2 From Baseline | week8,week20 | Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th. |
Countries
China
Participant flow
Recruitment details
This prospective RCT was conducted at Guang'anmen Hospital, China Academy of Chinese Medical Sciences (Beijing, China), from April 2013 to December 2014. Participants with MT were recruited via hospital posters.
Pre-assignment details
A total of 192 participants were assessed for eligibility; 102 participants were excluded from the trial(53 didn't meet inclusion criteria, 26 declined to participate the trial, 23 for other reasons). 90 participants were randomly allocated to the EA group or the sham EA group.
Participants by arm
| Arm | Count |
|---|---|
| Electro-acupuncture Group Eelectro-acupuncture: The bilateral acupoints of EX-CA1, ST25, SP6 and RN4 were selected for the treatment program.After regular disinfection,adhesive pads were placed on surface of all these acupoints. For RN4, EX-CA1, ST25, needles (0.30\*75mm) were inserted into the points vertically throughout the pads, skin, fat tissue, and abdominal muscles until the participant had feeling of pricking. For SP6, needles were inserted into the acupoint to a depth of 1 cun,accompanied by manipulation of lifting, thrusting, and twisting 3 times. Electronic stimulator was connected to EX-CA1 and ST25 with dilatational wave, 10/50HZ, 0.1 to 1.0mA. The current intensity was adjusted to abdomen shivering without pain. Treatment lasted for 30 minutes and acupuncture manipulation for RN4 and SP6 were performed every 10 minutes. | 44 |
| Sham Electro-acupuncture Group Sham Eelectro-acupuncture: Non-acupoints approximate to RN4, ST25, EX-CA1 and SP6 were selected bilaterally, and adhesive pads were placed on the surface of selected non-acupoints' location. Blunt needles were inserted into the pads and to touch, rather than penetrate the surface of skin. Meanwhile, like EA group, manipulations of lifting, thrusting and twisting on non-acupoint approximate to RN4 and SP6 were performed 3 times. Sham Electronic stimulator was applied to the non-acupoint approximate to EX-CA1 and ST25, providing the outward appearance of the procedure in EA group but with no current intensity actually applied. Any other interventions were rigorously maintained the same as in the EA group. | 45 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Electro-acupuncture Group | Sham Electro-acupuncture Group |
|---|---|---|---|
| 24 h Hot Flash Score | 7.71 Scores on a scale | 8.07 Scores on a scale | 7.26 Scores on a scale |
| Age, Continuous | 50.84 years STANDARD_DEVIATION 4.1 | 51.05 years STANDARD_DEVIATION 4.41 | 50.69 years STANDARD_DEVIATION 3.79 |
| E2 | 65.77 pmol/l | 73.73 pmol/l | 51.38 pmol/l |
| Educational Level Preliminary education | 1 participants | 0 participants | 1 participants |
| Educational Level Secondary education | 58 participants | 33 participants | 25 participants |
| Educational Level Tertiary education | 30 participants | 11 participants | 19 participants |
| Ever Received Drug Therapy No | 83 participants | 39 participants | 44 participants |
| Ever Received Drug Therapy Yes | 6 participants | 5 participants | 1 participants |
| FSH | 44.12 mIU/ml | 42.85 mIU/ml | 44.47 mIU/ml |
| FSH/LH | 1.42 ratio | 1.38 ratio | 1.44 ratio |
| Height | 159.44 cm STANDARD_DEVIATION 3.85 | 159.39 cm STANDARD_DEVIATION 3.87 | 159.49 cm STANDARD_DEVIATION 3.88 |
| LH | 32.89 mIU/ml | 33.08 mIU/ml | 32.89 mIU/ml |
| Menopausal Course | 16.00 month | 16.00 month | 16.00 month |
| Menopausal Stage Early stage | 41 participants | 17 participants | 24 participants |
| Menopausal Stage Late stage | 48 participants | 27 participants | 21 participants |
| Menopause Rating Scale | 16.00 Scores on a scale | 17.50 Scores on a scale | 15.00 Scores on a scale |
| Sex: Female, Male Female | 89 Participants | 44 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 57.84 Kg STANDARD_DEVIATION 6.87 | 58.02 Kg STANDARD_DEVIATION 5.66 | 57.66 Kg STANDARD_DEVIATION 7.95 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 44 | 2 / 45 |
| serious Total, serious adverse events | 0 / 44 | 0 / 45 |
Outcome results
Primary
Change of Average 24 h Hot Flash Score From Baseline
Every day during the 4th, 8th, 20th, and 32nd weeks, symptoms and specific times of hot flashes were recorded in hot flash diaries by the participants.Data from weeks 4, 20 and 32 were recorded as the second time frame.According to the severity categories suggested by Food and Drug Administration (FDA), hot flashes were assessed as mild, moderate, or severe. Hot flash scores are calculated as (hot flash frequency x severity)/7, with severity scores ranging from 1=mild 2=moderate to 3=severe.
Time frame: week8;wee4,20,32
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week8 | -2.29 Scores on a scale |
| Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week4 | -0.78 Scores on a scale |
| Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week20 | -2.43 Scores on a scale |
| Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week32 | -3.79 Scores on a scale |
| Sham Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week32 | -0.87 Scores on a scale |
| Sham Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week8 | -0.71 Scores on a scale |
| Sham Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week20 | -1.14 Scores on a scale |
| Sham Electro-acupuncture Group | Change of Average 24 h Hot Flash Score From Baseline | week4 | -0.71 Scores on a scale |
Secondary
Change of E2 From Baseline
Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th.
Time frame: week8,week20
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of E2 From Baseline | week8 | 2.92 pmol/l |
| Electro-acupuncture Group | Change of E2 From Baseline | week20 | 13.75 pmol/l |
| Sham Electro-acupuncture Group | Change of E2 From Baseline | week8 | 0.40 pmol/l |
| Sham Electro-acupuncture Group | Change of E2 From Baseline | week20 | 2.43 pmol/l |
Secondary
Change of FSH From Baseline
Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th.
Time frame: week8,week20
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of FSH From Baseline | week8 | -1.90 mIU/ml |
| Electro-acupuncture Group | Change of FSH From Baseline | week20 | -1.69 mIU/ml |
| Sham Electro-acupuncture Group | Change of FSH From Baseline | week8 | 0.70 mIU/ml |
| Sham Electro-acupuncture Group | Change of FSH From Baseline | week20 | 1.93 mIU/ml |
Secondary
Change of FSH/LH From Baseline
Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th.
Time frame: week8,week20
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of FSH/LH From Baseline | week8 | 0.10 ratio |
| Electro-acupuncture Group | Change of FSH/LH From Baseline | week20 | 0.06 ratio |
| Sham Electro-acupuncture Group | Change of FSH/LH From Baseline | week8 | -0.01 ratio |
| Sham Electro-acupuncture Group | Change of FSH/LH From Baseline | week20 | -0.01 ratio |
Secondary
Change of LH From Baseline
Serum sample of participants was examined at the 2nd to 4th day of menstrual period; if the participant was not in menstrual period, Serum sample would be tested in coming cycle length; for participants in menopause period, Serum sample was examined at the end of the week of 8th and 20th.
Time frame: week8,week20
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of LH From Baseline | week8 | -2.58 mIU/ml |
| Electro-acupuncture Group | Change of LH From Baseline | week20 | -0.66 mIU/ml |
| Sham Electro-acupuncture Group | Change of LH From Baseline | week8 | 0.99 mIU/ml |
| Sham Electro-acupuncture Group | Change of LH From Baseline | week20 | 0.79 mIU/ml |
Secondary
Change of MRS (Menopause Rating Scale) From Baseline
MRS(Menopause Rating Scale) was designed to measure MT symptoms and to explore the influences on life qualities in a standardized way. In MRS, symptoms such as impaired memory, depression, insomnia, sweating, hot flashes, nervousness, joints complaints, lack of concentration were evaluated and calculated in numbers to describe the situation of patient. Scores on MRS range from 0 to 44, with higher scores indicating more severe symptoms.
Time frame: week8;wee4,20,32
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week8 | -4.00 Scores on a scale |
| Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week4 | -1.50 Scores on a scale |
| Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week32 | -7.00 Scores on a scale |
| Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week20 | -6.00 Scores on a scale |
| Sham Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week32 | -5.00 Scores on a scale |
| Sham Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week20 | -5.00 Scores on a scale |
| Sham Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week4 | -4.00 Scores on a scale |
| Sham Electro-acupuncture Group | Change of MRS (Menopause Rating Scale) From Baseline | week8 | -6.00 Scores on a scale |