We conducted a two-site clinical trial using a three-arm prospective, randomized, single-blind, sham-control design in peri- and postmenopausal women experiencing four or more hot flashes per day. Recruitment occurred between August and November 2004 at the University of North Carolina at Chapel Hill and between September 2005 and January 2006 at Massachusetts General Hospital. Participants were in the study for a total of 18 weeks, including a 2-week pretreatment diary collection period, 8 weeks of acupuncture treatment, and 8 weeks of follow-up after treatment was completed. The study was approved by the institutional review boards at both sites.
Participants eligible for the study were peri- or postmenopausal women ages 42 to 55 with at least four moderate to severe hot flashes per day. Perimenopause was defined as 3 or more months of self-defined amenorrhea and postmenopause was defined as amenorrhea for 12 or more months. Participants were excluded for the following reasons: had used HT, a selective estrogen-receptor modulator, an aromatase inhibitor, clonidine, Bellergal, antidepressant therapy, or gabapentin in the past 12 weeks; had received chemotherapy; had a significant psychiatric disorder; had used acupuncture treatment for any reason within the past 4 weeks; had any previous acupuncture treatment for hot flashes; had untreated thyroid disease; had been diagnosed with a bleeding or clotting problem other than heavy periods; or were currently taking any prescribed medications that increase the risk of bleeding (Coumadin, Enoxaparin, or Plavix).
Women were recruited through newspaper advertisements, radio announcements, and hospital postings. Initial eligibility was determined by a telephone screener. Eligible women were scheduled for an initial clinic visit where they completed a self-administered baseline questionnaire and received instructions on keeping a 2-week hot flash diary, which was then mailed back to the clinic and used to verify eligibility. Women who met the criteria of an average of at least four hot flashes per day were randomized to one of the three study groups. Those in the two treatment groups were scheduled for acupuncture visits. Those in the UC group were scheduled for a clinic visit in 4 weeks. Women who were not eligible were called, thanked, and informed that they were not eligible for the study. All study participants completed questionnaires 4 weeks after baseline and at the end of treatment.
Participants assigned to acupuncture (both TCM and sham) were seen twice a week for 8 weeks (a total of 16 treatment sessions) by a trained acupuncturist. Study staff who administered questionnaires were blinded to which form of acupuncture that the women received. All study participants were instructed not to take hormonal medications or initiate other treatments for their hot flashes during treatment. All study participants (including those in the UC group) were paid $10 for each clinic visit (baseline, mid-treatment, and end of treatment). Those who completed all three visits were paid an additional $20.
Eligible women were randomized to one of the three groups stratified by clinical center (Massachusetts General Hospital and University of North Carolina). Randomization sequences were prepared at Wake Forest University. Participants were considered to have been randomized when the group membership was made known, even if the woman did not actually attend any treatment sessions. We used a block randomization with block size unknown to the investigator and staff to ensure equal accrual to each arm of the study.
All treatments were performed by experienced acupuncturists trained in TCM. At the first treatment session, women received a TCM diagnosis and prescription based on standard acupuncture points. This prescription was maintained throughout the treatment period. Participants assigned to the TCM acupuncture group (TA) received needling at sites based on a standardized individual approach, a combined approach that maximized therapeutic benefits by customizing points based on a woman's presentation and use of standardized core points. Women assigned to the SA group received needling at sites thought to have minimal effects on hot flashes. The acupuncturists were blinded to the participant's treatment group until after making the TCM diagnosis.
TA Group. According to TCM theory, menopausal symptoms are mainly caused by a decline in kidney essence leading to a yin/yang imbalance. Women in the TA group received a standard acupuncture treatment designed to tonify or reinforce the kidney essence, balance yin/yang, and control hot flashes and night sweats. The standard treatment involved the following acupuncture points: CV-4, KI-3, SP-6, BL-23, HT-6, and KI-7. Except for CV-4, which is located in the midline, all standard treatment points were needled bilaterally, for a total of 11 acupuncture points (Figure 1). In addition to the standardized treatment that all participants received, additional points were needled based on a person's TCM diagnostic category or based on the acupuncturist's clinical judgment. No more than 16 acupuncture points were needled during any treatment. The diagnostic categories and the associated acupuncture points are summarized in Table 1 . We anticipated that most of the women's symptoms and clinical presentations would be consistent with one of four different TCM diagnostic categories: kidney yin deficiency; kidney yin deficiency and kidney yang deficiency; kidney yin and liver yin deficiency leading to liver yang rising, and kidney and heart not harmonized.
True and sham acupuncture points. True acupuncture points were located in specific acupuncture point locations thought to have an effect on hot flashes. Sham acupuncture points were located in sites away from the points and meridian pathways thought to have an effect on hot flashes.
Sterile, single-use, Vinco 34-gauge, 1-inch (0.22 x 25 mm) and 30-gauge, 1.5-inch (0.30 x 40 mm) needles were used. Needles were inserted through the skin to a depth of from 0.5 to 3 cm based on anatomical location. Acupuncturists attempted to achieve a de Qi sensation upon insertion of acupuncture needles (a sensation of soreness, numbness, heaviness, or distention around the needled acupuncture point), whenever possible. The duration of each treatment was approximately 30 minutes: 20 minutes for anterior points and 10 minutes for posterior points.
SA Group. This group was included to assess effects that may be related to attention, relaxation, anticipation of benefit, and the needling process itself, but which are not secondary to physiologic changes that may be induced by needling locations on the body that correspond to conventional acupuncture points. The sites in which the SA needles were placed are believed to have minimal possible effects on hot flashes. Each woman assigned to the SA group had six needles on the right side of the body and six on the left: nonacupuncture point sites needled shallowly, without attempting to elicit the de Qi sensation ( Table 1 and Figure 1).
The participants in this group did not receive any form of acupuncture needling. They were instructed not to initiate any new treatments for their hot flashes over the next 2 months, but could continue with any nonpharmacologic treatments that they were currently using.
The primary study outcomes were frequency and severity of hot flashes as measured by the Daily Diary of Hot Flashes. This diary records the frequency and severity of hot flashes and allows the investigator to calculate hot flash frequency and a hot flash index score (the sum of the number of hot flashes multiplied by severity). Women were asked to record the number and severity of hot flashes each day during the treatment phase of the trial. Women were provided counters to help them keep track of the number of hot flashes throughout the day. We modified the severity rating scale, using 1 to 3 (1 = mild, 2 = moderate, 3 = severe) in place of 1 to 4 as used in the studies of Loprinzi et al.[25,38,39] The simplified scale is easier to understand. Our modified scale also distinguishes between daytime and nighttime vasomotor symptoms.
Secondary study outcomes were hot flash interference, sleep, symptoms bothersomeness, mood, and general quality of life.
Hot Flash Interference. The 10-item Hot Flash Related Daily Interference Scale measures the degree that hot flashes interfere with daily life or overall quality of life and nine specific domains within the past week (work, social activities, leisure activities, sleep, mood, concentration, relation with others, sexuality, and enjoyment of life).
Sleep. The Women's Health Initiative Insomnia Rating Scale was used to measure sleep patterns and quality. This 6-item scale is designed to measure sleep initiation and maintenance in the past 4 weeks. The scale assesses sleep problems including, but not limited to, the ability to fall asleep, sleep quality, and fatigue.
Symptoms. In addition to assessing frequency and severity of vasomotor symptoms with the daily diaries, we administered the Menopause-specific Quality of Life Questionnaire to measure bothersomeness of vasomotor symptoms and other menopause-related symptoms. This questionnaire contains 30 symptoms categorized into four domains, vasomotor, physical, psychological, and sexual, and a global quality-of life-item.
Mood. The Psychological General Well-Being Index was used to assess the following moods: vitality, self-control, well-being, general health, depressed mood, and anxiety and a composite score that ranges from 0 (most negative affective experience) to 110 (most positive effective experience).[43,44]
Health-related Quality of Life. Two measures of quality of life were included: a single global 100-mm visual analogue scale with which women rated their overall quality of life along a line where 0 is the lowest possible quality of life and 100 is the highest, and the Medical Outcomes Study 36-Item Short Form Health Survey.
Study covariates included sociodemographics (age, education, marital status, employment status), medical information (body mass index, blood pressure, past HT use, other complementary alternative medicine use), and the Somatosensory Amplification Scale. This scale is a 10-item questionnaire that assesses sensitivity to a range of uncomfortable bodily sensations and physiologic states that are not typically symptoms of disease. The scale has been shown to prospectively predict the persistence of hypochondriacal symptomatology in transient hypochondriacal patients and frequency of hot flashes.
All analyses were conducted using the intent-to-treat approach. Descriptive and regression analyses were performed using SAS software (SAS Institute Inc., Cary, NC). Repeated-measures models were used to describe the relationship between hot flash frequency and the index score with treatment and time. The dependent variable was the log of the ratio of the follow-up measures divided by baseline (ie, loge [follow-up + 1/baseline + 1]). The independent variables included intervention group and week. Results were adjusted for baseline values and clinical center. The addition of the constant (1) to baseline and follow-up measures was necessary because some participants had hot flash frequency and index equal to zero for some weeks. In further analyses the two acupuncture groups were combined as they did not differ significantly.
Menopause. 2008;15(6):1070-1078. © 2008 The North American Menopause Society
Published by Lippincott Williams & Wilkins
Cite this: A Randomized, Controlled Pilot Study of Acupuncture Treatment for Menopausal Hot Flashes - Medscape - Dec 01, 2008.