Menopause: The Journal of The North American Menopause Society

Vol. 16, No. 3, pp. 484/493

DOI: 10.1097/gme.0b013e31818c02ad
* 2009 by The North American Menopause Society

The Acupuncture on Hot Flushes Among Menopausal Women

(ACUFLASH) study, a randomized controlled trial
Einar Kristian Borud, MD, MPH,1 Terje Alraek, PhD,1 Adrian White, MD, PhD,2
Vinjar Fonnebo, MD, MSc, PhD,1 Anne Elise Eggen, PhD,3 Mats Hammar, MD, PhD,4
Lotta Lindh Åstrand, RN,4 Elvar Theodorsson, MD, PhD,4 and Sameline Grimsgaard, MD, MPH, PhD1,5

Abstract
Objective: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care
alone on hot flashes and health-related quality of life in postmenopausal women.
Methods: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms.
Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during
seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-
care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes
were registered in a diary. Urine excretion of calcitonin geneYrelated peptide was assessed at baseline and after
12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The
secondary endpoint was change in health-related quality of life measured by the Women’s Health Questionnaire.
Results: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per
24 hours in the control group (n = 133), a difference of 2.1 (P G 0.001). Hot flash intensity decreased by 3.2 units
in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P G 0.001). The acupuncture group
experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of
the Women’s Health Questionnaire compared with the control group. Urine calcitonin geneYrelated peptide ex-
cretion remained unchanged from baseline to week 12.
Conclusions: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and
increased health-related quality of life in postmenopausal women.
Key Words: Acupuncture Y Menopause Y Hot flash.

H
ot flash, a sudden feeling of heat in the face, neck, or
chest, is the most common complaint of postmeno-
pausal women. Hot flashes can occur at any time and
Received June 21, 2008; revised and accepted August 26, 2008.
From the 1The National Research Center in Alternative and Comple-
mentary Medicine, University of TromsL, TromsL, Norway; 2Depart-
ment of General Practice and Primary Care, Peninsula Medical School,
Universities of Exeter and Plymouth, UK; 3Institute of Community
Medicine, Faculty of Medicine, University of TromsL, TromsL, Nor-
way; 4Department of Clinical and Experimental Medicine, Faculty of
Health Sciences, Linköping University, Linköping, Sweden; and
5
Clinical Research Center, University Hospital of North Norway,
TromsL, Norway.
Funding/support : This project was funded by The Research Council of
Norway. The principal investigator was funded by the University
Hospital of North Norway.
Financial disclosure: None reported.
Role of the sponsor: The funding agencies had no role in the design and
conduct of the study; collection, management, analysis, and interpreta-
tion of the data; and preparation, review, or approval of this manuscript.
Address correspondence to: Einar Kristian Borud, MD, MPH, The Na-
tional Research Center in Complementary and Alternative Medicine,
University of TromsL, N-9037 TromsL, Norway. E-mail: einar.borud@
fagmed.uit.no
are often accompanied by sweating. A hot flash lasts, on
average, 4 minutes, ranging from a few seconds up to
10 minutes or more.1 Nocturnal hot flashes contribute to
sleep disturbances.2,3
Almost two thirds of postmenopausal women experience
hot flashes, and 10% to 20% of these find the flashes very
distressing. Almost a third report symptoms lasting up to
5 years after natural menopause, and flashes may persist for
up to 15 years in 20% or more of all women.1
Hormone therapy (HT) is considered the most efficacious
treatment of hot flashes. Estrogen plus progestogen therapy
relieves hot flash intensity by approximately 90%.4 Long-term
treatment, however, increases breast cancer risk,5,6 and recent
studies also show that HT initiated 10 to 15 years after meno-
pause increases the risk of coronary heart disease and stroke.7
Consequently, sales figures for systemic HT in Norway de-
creased by 60% from 2001 to 2007,8 and a similar reduction
in HT prescription rate was seen in the United States.9<11
Centrally acting nonhormonal agents such as selective se-
rotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine
reuptake inhibitors (SNRIs), clonidine, and gabapentin show
a statistically significant effect on hot flashes in randomized

484 Menopause, Vol. 16, No. 3, 2009

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 ACUPUNCTURE FOR POSTMENOPAUSAL HOT FLASHES
controlled trials. Antidepressants and gabapentin are the most
active and best tolerated.12 However, relatively few trials
have been published, and some have methodological defi-
ciencies; hence, generalizability of these results may be
limited. Effects of medications are smaller than those for
estrogen, and adverse effects and cost may be unacceptable.
These medications may be most useful for women with
severe symptoms, who wish to avoid HT.13
Many women seek nonprescription alternatives to HT to
relieve their climacteric complaints. These alternatives
include isoflavone extracts from red clover and soy and
herbal remedies such as black cohosh or vitamin E. There is a
lack of definitive documentation of their efficacy and
effectiveness and a lack of knowledge of interactions and
long-term safety.13,14 Commonly recommended lifestyle
changes include stress reduction, increased fruit and vegeta-
ble intake, reduced caffeine and alcohol intake, smoking
cessation, and increased physical exercise. The evidence for
these is anecdotal, supported in some cases by epidemio-
logical studies but not by intervention trials.15
Acupuncture is one of the most frequently used comple-
mentary therapies in Norway. In two recent surveys, 28%
reported lifetime use and 10.8% reported use within the
previous year.16,17 In the United States, 4.1% reported
lifetime use and 1.1% reported use of acupuncture within
the previous year.18 Acupuncture is considered safe in the
hands of competent practitioners.19
The theoretical framework, understanding, and practice of
acupuncture vary considerably. Traditional Chinese medicine
(TCM) acupuncture is based on the traditional Chinese
medical theories,20 whereas BWestern medical[ acupuncture
is based on theories from established medical physiology.21
TCM acupuncture includes a thorough medical history and
examination of the pulse and tongue, leading to a specific
TCM diagnosis. Based on this diagnosis, the treatment is
individually tailored and comprises both lifestyle advice and
needling in selected acupuncture points.22
Previous studies on the efficacy or effectiveness of
acupuncture on menopausal hot flashes are generally small
and report mixed results.23<27 Current data are insufficient to
draw any conclusions on the effect of acupuncture treatment
on hot flashes but sufficient to justify further research.
Calcitonin geneYrelated peptide (CGRP) is a potent vaso-
dilator and stimulator of cholinergic sweat glands and has
been suggested as a mediator of hot flashes and sweating in
postmenopausal women.28 In a study of acupuncture therapy
in women with hot flashes, the concentration of CGRP
decreased in 24-hour urine after acupuncture treatment.27
The effects of acupuncture treatment are those of a
treatment package including the therapeutic relationship and
expectation, and acupuncture is available for women seek-
ing an alternative to pharmacological treatment of vaso-
motor complaints. We wanted to estimate the effectiveness of
acupuncture in practice. Thus, the objective of this study was
to assess the effectiveness of a policy of use of acupuncture
plus self-care on hot flash frequency and intensity in post-
Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
menopausal women compared with a policy of use of self-
care alone. The effects on sleep and health-related quality of
life (HR-QOL) were also assessed, as were the changes in
urine excretion of CGRP.
METHODS
The study was a multicenter (TromsL, Bergen, and Oslo),
pragmatic, randomized, controlled trial with two parallel
arms, conducted in 2006 to 2007.29 It was performed ac-
cording to Good Clinical Practice30 and reported according to
the criteria of Standards for Reporting Interventions in
Controlled Trials of Acupuncture.31 The study was approved
by the Norwegian Data Inspectorate, the Norwegian Bio-
bank Registry, and the Regional Committee for Medical
Research Ethics.
Participants
Study participants were recruited by newspaper advertise-
ments and media coverage. Women who wanted to partic-
ipate phoned the study coordinator, received information
about the study, and were briefly screened by telephone for
eligibility. Potential participants received a diary by mail
and recorded frequency and severity of hot flashes and dura-
tion of sleep at night for a period of 14 days. Altogether,
535 women were assessed for eligibility by telephone, 428
women received the baseline diary, and 399 women
completed and returned it. Women who returned the diary
and fulfilled the inclusion criteria received an informed con-
sent form and the baseline questionnaires by mail. Baseline
assessment included sociodemographic data, medical his-
tory, previous experience with acupuncture, previous use of
other interventions to relieve climacteric complaints, current
use of medication and dietary supplements, level of phys-
ical activity, smoking status, and alcohol consumption. The
women completed the questionnaires at home and brought
them to the enrollment visit with the local study coordinator.
The coordinator double-checked the eligibility criteria and
obtained written informed consent.
Postmenopausal status was defined as at least 1 year since
last menstrual bleeding. Serum follicle-stimulating hormone
and serum estradiol measured in a subsample of women (n =
82) confirmed postmenopausal status. Postmenopausal
women were eligible if they documented, on average, seven
or more hot flashes per 24 hours during 7 consecutive days
within the 2-week qualifying period. Exclusion criteria were
surgical menopause, history of cancer within the past 5 years
(including use of tamoxifen), use of anticoagulant medica-
tion, heart valve disease, poorly controlled hypertension,
poorly controlled hypothyroidism, hyperthyroidism, poorly
controlled diabetes mellitus, organ transplant, mental disease,
overt drug or alcohol dependency, and inability to complete
study forms. Use of systemic HT and SSRIs/SNRIs required
an 8-week washout period, and use of local prescription HT
required a 4-week washout period. Participants were directly
questioned about these conditions; no standardized instru-
ments were used.
Menopause, Vol. 16, No. 3, 2009 485
 BORUD ET AL
After enrollment, the local coordinator telephoned the
central randomization unit at the University Hospital of
North Norway (UNN) to obtain group allocation. Random-
ization lists were computer generated (block randomization,
random block size) and stratified by center.
Women randomized to receive acupuncture were referred
to a local study acupuncturist, who was instructed to see her
within a week. All participants met with the study coordina-
tors again at the end of the study period of 12 weeks.
Participants received NOK 400 (US $70) at the end of the
study to cover their personal expenses associated with the
trial participation.
Intervention
All participants in both groups were given a one-page
information leaflet on available self-provided care for meno-
pausal symptoms (eg, soy, herbs, physical activity, and relax-
ation techniques), and they were free to use any of these. The
information leaflet was prepared by the project team and was
based on an authoritative book and best current advice.15,32
Treatment group
The study acupuncturists met the current membership
criteria of the Norwegian Acupuncture Society, NAFO
(2,500 hours of training), and had at least 3 years’ experience
from practice. There were four acupuncturists in Oslo, three
in Bergen, and three in TromsL, all practicing TCM acu-
puncture in private clinics with from one to four acupunc-
turists. Before the study started, the acupuncturists met and
discussed the expected TCM diagnoses and the recom-
mended acupuncture point selection. The acupuncturists
were free to diagnose, select acupuncture points, and indi-
vidualize the acupuncture treatment for each participant.
Moxibustion (heated needles) could be added if indicated,
but no other treatments, as for instance herbs, were given.
De Qi (a characteristic dull and numb sensation) was ob-
tained if possible, and needle manipulation with even, re-
ducing, or reenforcing methods was used. Point location was
not standardized in the study but was left to the acupunc-
turists to decide. Details of the acupuncture treatment given
in each acupuncture session were recorded. The treatment
consisted of up to 10 acupuncture sessions over 12 weeks.
This period could be extended by 2 weeks, if needed. The
minimum number of sessions accepted as Bper protocol[ was
six. Details of the TCM theory and acupuncture treatment
given will be reported separately.
Control group
The participants in the control group were not prescribed
any medical treatment for menopausal symptoms within the
study. They were free to use any over-the-counter medication
and self-provided nonpharmaceutical interventions, guided
by the self-care information leaflet.
Outcomes
The primary endpoint was change in mean hot flash
frequency per 24 hours from the qualifying period to the
486 Menopause, Vol. 16, No. 3, 2009
Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
12th week after randomization. The participants recorded
the numbers of hot flashes in a daily diary.33 They scored the
mean daily hot flash intensity on a visual analog scale of 0 to
10, where 0 represents Bno bother at all[ and 10 represents
Bthe worst possible intensity of flashes.[ They also recorded
hours of sleep per night. The diaries were administered for
2 weeks during the qualifying period and for 1 week at weeks
4, 8, and 12 of the intervention period. Baseline values were
calculated using data from the last 7 days of the 2-week
qualifying period.
Secondary endpoint was HR-QOL, measured by the
Women’s Health Questionnaire (WHQ).34 The WHQ is a
self-administered questionnaire measuring the physical and
emotional health of women aged 40 to 65 years. The
questionnaire consists of 36 items covering the following
domains: depressed mood, somatic symptoms, anxiety/fears,
vasomotor symptoms, sleep problems, sexual behavior,
menstrual symptoms, memory/concentration, and attractive-
ness. Sexual behavior and menstrual symptoms were not
scored in the present study. When scoring the WHQ, the
four-point scales (yes definitely, yes sometimes, no not
much, and no not at all) are reduced to binary options (0/1).
Within each domain, an average score between 0 and 1 is
calculated, where 0 is an indicator of Bgood health status[
and 1 is an indicator of Bpoor health status.[ A clinically
significant change within each domain of the WHQ is a
difference of approximately 0.10 to 0.20.35
At weeks 8 and 12, the women in the acupuncture group
were asked if they had experienced any of the following
treatment reactions: temporary worsening of hot flashes,
dizziness, tiredness, increased energy, more relaxed, and
hungrier. At each acupuncture session, the acupuncturists
recorded any adverse effects that had occurred during or after
the previous session.
At weeks 4, 8, and 12, all participants were asked about
their use of healthcare providers, medication, and dietary
supplements during the last 4 weeks, and at weeks 4 and 8,
they were asked whether they had changed their living habits
(rest and sleep, physical activity, coffee drinking, alcohol
intake, and tobacco smoking) over the last 4 weeks. At week
12, they were asked about changes in their living habits over
the last 3 months and a global question addressing any
changes experienced regarding menopausal symptoms (inten-
sity and frequency of hot flashes, quality of sleep, and well-
being) during the study period.
Urine CGRP (u-CGRP) and urine creatinine (u-creatinine)
were measured in the morning and evening urine samples
obtained from the participants in the TromsL arm of the
study. Samples were collected at baseline and before the visit
at week 12. They were stored at j20-C until analysis.
Samples were then extracted and concentrated five times
(coefficient of variation, 4%) with the use of a reverse-phase
C18 cartridge (SepPak; Waters Corp, Milford, MA) and
analyzed in one batch for CGRP-like immunoreactivity with
the use of a competitive radioimmunoassay. CGRP-LI was
analyzed using antiserum CGRPR8 raised in a rabbit
* 2009 The North American Menopause Society
 ACUPUNCTURE FOR POSTMENOPAUSAL HOT FLASHES

against conjugated rat CGRP. High-performance liquid
chromatography-purified 125I-histidyl rat CGRP was used as
the radioligand; and human CGRP>, as the standard. The
detection limit of the assay for human CGRP is 7 pmol/L and
the crossreactivity of the assay to substance P, neurokinin A,
neurokinin B, neuropeptide K, gastrin, neurotensin, bomb-
esin, neuropeptide Y, and calcitonin was less than 0.01%.
Crossreactivity toward human CGRP> and A was 93% and
24%, respectively; and toward rat CGRP> and A, 100% and
120%, respectively. Intra-assay and interassay coefficients of
variation were 9% and 14%, respectively. The variation of
the u-CGRP excretion was evaluated by comparing the mean
u-CGRP/u-creatinine ratio values at baseline and at week 12
in the morning and evening urine samples separately and the
morning and evening sample values added and divided by 2.
Blinding
All study researchers remained blinded throughout the
study. A person blinded to group allocation entered data on
hot flashes and sleep into the database. The randomization
code was broken only after the analyses of the primary
outcomes were completed.
Statistical analysis
SPSS software, version 14.0 (SPSS Inc, Chicago, IL), was
used for all statistical analyses. The primary analysis was

FIG. 1. Trial flow diagram in the ACUFLASH study. HT, hormone therapy; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin-
norepinephrine reuptake inhibitor.

Menopause, Vol. 16, No. 3, 2009 487

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 BORUD ET AL

TABLE 1. Baseline characteristics of the study participants studies reduce hot flash activity by 20% to 30%.33 In a study
in the ACUFLASH studya of the effect of hormonal therapy of hot flashes, women were
Acupuncture group Self-care group defined as responders if they gained a 50% or greater re-
Characteristics (n = 134) (n = 133) duction in hot flash frequency.38 In a small study (N = 17),
Age at randomization, y 53.5 T 4.4 54.1 T 3.7 women reported that a clinically relevant hot flash reduc-
Age at menopause, y 49.3 T 4.0 48.6 T 4.9 tion was approximately 50%.39 On this basis, it has been
Self-reported weight, kg 71 T 12 70 T 12
Self-reported height, cm 167 T 6 168 T 6 advocated that clinically relevant interventions should re-
Years of education duce hot flash frequency by 50% or more. We aimed to
e10 60 (44.8) 64 (48.1) detect a 50% reduction in hot flash rate in the acupuncture
11-13 12 (9.0) 13 (9.8)
14-17 31 (23.1) 18 (13.5) group and a 20% difference between groups. The sample size
917 31 (23.1) 36 (27.1) was calculated using data from previous trials of HT, herbs,
Missing 0 2 (1.5) and acupuncture. Assuming a baseline hot flash rate of 7.0
Hypertension 23 (17.3) 23 (17.3)
Hypothyroidism 17 (12.7) 13 (9.8) (SD, 3.5) for change in flash rate, and using a two-sample
Previous use of HT 71 (53.0) 61 (45.9) t test, 100 women in each group were needed to obtain 80%
Previous use of acupuncture 86 (64.2) 85 (63.9) power with a two-sided > value of 0.05. Assuming 30%
Expect acupuncture relieves hot flashes?
Yes 80 (59.7) 68 (51.1) withdrawal and dropout rate, we estimated that 286 women
No 0 (0) 0 (0) were required.
Do not know 53 (39.6) 61 (45.9)
Missing 1 (0.7) 4 (3.0) RESULTS
Self-reported health
Very bad 2 (1.5) 3 (2.3) Between February 2006 and March 2007, 535 women
Bad 31 (23.1) 37 (27.8) contacted the study coordinators, and 267 were included
Good 78 (58.2) 74 (55.6) (Fig. 1)V82 in TromsL, 105 in Bergen, and 80 in Oslo.
Excellent 22 (16.4) 16 (12.3)
Missing 1 (0.7) 3 (2.3) Altogether, 19 women (7%) dropped outV16 in the control
Sleep problems group and 3 in the acupuncture group. No participants
Never 32 (23.9) 33 (24.9) withdrew because of adverse effects. Two women withdrew
One to three nights per month 22 (16.4) 19 (14.3)
Once a week 14 (10.4) 12 (9.0) from the acupuncture group before week 4 and another one
9Once a week 66 (49.3) 66 (49.6) before week 8. Two participants withdrew immediately after
Missing 0 3 (2.3) being allocated to the control group. Another 14 withdrew
Sleep problems affecting work last year
Yes 63 (47.0) 63 (48.8) from the control group before week 4. A total of 131
No 70 (52.2) 66 (49.6) participants in the acupuncture group and 117 in the control
Missing 1 (0.7) 4 (3.0) group were included in the final analyses. The dropouts were
Tobacco smoking
Present 34 (25.4) 39 (29.3) asked but were not willing to provide hot flash data after the
Past 67 (50) 53 (39.8) termination of their study participation. The mean number of
Never 33 (24.6) 39 (29.3) acupuncture sessions per participant was 9.8.
Missing 0 2 (1.5)
Teetotaller 6 (4.5) 6 (4.5) The study groups were well balanced with respect to
HT, hormone therapy. background characteristics at baseline (Table 1). Missing data
a
Data are presented as either mean T SD or n (%), where appropriate.
TABLE 2. Primary outcomes in the ACUFLASH studya
intention to treat. Change was calculated as mean hot flash Acupuncture
frequency at 12 weeks minus mean hot flash frequency group (n = Control group
during the last 7 days of the qualifying period. Differences 134) (n = 133) Pb
in change between groups were evaluated with two-sample Hot flash frequency per 24 h n = 131 n = 117
t tests, and Wf tests were used for categorical variables. Two- Baseline 12.0 (4.3) 13.1 (4.9)
Difference from baseline at
sided P G 0.05 was considered statistically significant. 4 wk j3.3 (3.7) j2.4 (3.2)
Missing data were handled by single imputation of missing 8 wk j5.1 (4.6) j3.1 (3.7)
values. Missing data on hot flash frequency and intensity or 12 wk j5.8 (4.6) j3.7 (3.7) G0.001
Hot flash intensity (0-10) n = 111 n = 107
sleep at 12 weeks were substituted with the mean value of the Baseline 6.7 (2.0) 7.1 (1.7)
entries in the diary if at least 3 days’ data had been recorded. Difference from baseline at
If less than 3 days’ data were recorded, the data were 4 wk j1.8 (2.1) j1.1 (1.9)
8 wk j2.7 (2.4) j1.4 (2.0)
considered missing. Single imputation is considered fairly 12 wk j3.2 (2.5) j1.8 (2.2) G0.001
accurate if the proportion of missing values is small (G5%),36 Hours of sleep/night n = 131 n = 115
and replacing the missing values by the mean value is Baseline 6.2 (1,1) 6.1 (1.0)
Difference from baseline at
considered a valid strategy.37 4 wk 0.19 (0.78) 0.13 (0.69)
8 wk 0.34 (0.81) 0.14 (0.74)
Power and sample size calculations 12 wk 0.42 (0.96) 0.14 (0.79) 0.015
Hormone therapy reduces hot flash activity (frequency and a
Data are presented as mean (SD).
severity) by 90%,4 whereas placebo interventions in hot flash b
Results from t tests, acupuncture group versus control group.

488 Menopause, Vol. 16, No. 3, 2009 * 2009 The North American Menopause Society

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 ACUPUNCTURE FOR POSTMENOPAUSAL HOT FLASHES

FIG. 2. Primary outcomes in the ACUFLASH study.

on hot flash frequency and intensity or sleep were found in a
total of 16 hot flash diaries at week 12. The rate of missing
information was 1.5%. Missing values for 1 day were
substituted with the mean of the reported data in 10 diaries,
for 2 days in two diaries, for 3 days in two diaries, and 4 days
in two diaries. Analysis of the data excluding the hot flash
diaries with missing data did not change any of the results.
No serious adverse effects were reported. At week 12, 27
participants reported that they had experienced temporary
worsening of hot flashes after acupuncture treatment, 13
reported dizziness, 53 reported tiredness, 76 reported
increased energy, 86 had been more relaxed, and 24 had
been hungrier.
Primary outcomes are shown in Table 2 and Fig. 2. Mean
frequency of hot flashes per 24 hours among all partici-
pants was 12.6 (range, 4.7-31.0) at baseline. At 12 weeks, the
mean reduction in hot flash frequency per 24 hours was 5.8
in the acupuncture group and 3.7 in the control group, a
difference of 2.1 (95% CI, 1.0-3.2; P G 0.001). Mean hot
flash intensity at baseline was 6.9 (range, 2.1-10 on the 0-10
scale) among all participants. At 12 weeks, mean reduction in
hot flash intensity was 3.2 units in the acupuncture group
and 1.8 units in the control group, a difference of 1.4 (95%
CI, 0.7-2.0; P G 0.001).
Baseline mean hours of sleep per night were 6.1 (range,
2.9-8.3) among all participants. At 12 weeks, mean hours of
sleep increased by 0.42 hours in the acupuncture group and
0.14 hours in the control group, a difference of 0.28 (95% CI,
0.05-0.50; P = 0.015).
There were no statistically significant differences between
the study centers regarding changes in hot flash frequency
and intensity and duration of sleep at 12 weeks.
Fifty percent of the participants in the acupuncture group
experienced 50% or greater reduction in hot flash frequency
from baseline to 12 weeks (responders) compared with 16%
in the control group (P G 0.001; Table 3). Responders did
not differ from nonresponders with respect to baseline hot
flash frequency and intensity, hours of sleep at night, age at
menopause, previous use of HT, hypertension, and previous
use of acupuncture or expectation of the acupuncture treat-
ment effect.
The baseline scores and the changes in scores for the seven
domains of the WHQ are shown in Table 4. At baseline, the
participants reported slightly better mental health and
attractiveness and poorer somatic health, memory/concen-
tration, and sleep compared with a European reference
population.40 Mean vasomotor domain score was 0.98 (1.0
is worst possible), compared with 0.47 in the reference

TABLE 3. Hot flash reduction at 12 weeks in the ACUFLASH study

Acupuncture group (n = 134) Control group (n = 133)

Hot flash reduction, as % of baseline No. of participants % Cumulative % No. of participants % Cumulative %
100 3 2.2 2.2 0 0 0
75-99 23 17.2 19.4 5 3.8 3.8
50-74 41 30.6 50.0 16 12.0 15.8
26-49 33 24.7 74.7 41 30.8 46.6
0-25 24 17.9 92.6 38 28.6 75.2
G0 7 5.2 97.8 17 12.8 88.0
Missing 3 2.2 100.0 16 12.0 100.0

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 BORUD ET AL

TABLE 4. WHQ scores at baseline and mean change in scores in the ACUFLASH studya
WHQ dimensions Acupuncture, mean (SD) Control, mean (SD) Pb Reference values,c mean (SD)
Depressed mood
Baseline (n = 265) 0.19 (0.21) 0.23 (0.22) 0.30 (0.26), n = 4,484
Mean change from baseline to 12 wk (n = 247) j0.09 (0.18) j0.04 (0.24) 0.083
Somatic symptoms
Baseline (n = 265) 0.48 (0.26) 0.55 (0.24) 0.38 (0.28), n = 4,468
Mean change from baseline to 12 wk (n = 247) j0.12 (0.24) j0.05 (0.21) 0.011
Memory/concentration
Baseline (n = 265) 0.49 (0.38) 0.54 (0.38) 0.37 (0.37), n = 4,461
Mean change from baseline to 12 wk (n = 247) j0.09 (0.29) j0.03 (0.30) 0.108
Vasomotor symptoms
Baseline (n = 263) 0.98 (0.09) 0.98 (0.10) 0.47 (0.45), n = 4,429
Mean change from baseline to 12 wk (n = 243) j0.28 (0.39) j0.04 (0.20) G 0.001
Anxiety/fears
Baseline (n = 264) 0.22 (0.26) 0.29 (0.26) 0.30 (0.32), n = 4,502
Mean change from baseline to 12 wk (n = 246) j0.09 (0.20) j0.05 (0.27) 0.101
Sleep problems
Baseline (n = 265) 0.57 (0.33) 0.61 (0.32) 0.46 (0.37), n = 4,549
Mean change from baseline to 12 wk (n = 247) j0.17 (0.36) j0.04 (0.27) 0.002
Attractiveness
Baseline (n = 263) 0.35 (0.39) 0.31 (0.39) 0.58 (0.38), n = 4,193
Mean change from baseline to 12 wk (n = 240) j0.14 (0.35) j0.09 (0.34) 0.194
WHQ, Womens Health Questionnaire; IQOL, International Health Related Quality of Life Outcomes Database.
a
The values of the scores vary between 0 and 1, where 0 is an indicator of Bgood health status[ and 1 is an indicator of Bpoor health status.[
b
Results from t tests, acupuncture group versus control group.
c
Reference values are taken from the IQOL WHQ Database, postmenopausal women.

population. At week 12, the acupuncture group experienced a
mean reduction of 0.28 in the vasomotor symptoms domain
score, 0.17 in the sleep domain score, and 0.12 in the somatic
symptoms domain score, compared with 0.04, 0.04, and 0.05,
respectively, in the control group (P G 0.001, P = 0.002, and
P = 0.011, respectively).
Thirty-eight (28%) of the participants in the acupuncture
group had changed one or more of their living habits at week
12, compared with 49 (37%) of the participants in the control
group (P = 0.02). In the acupuncture group, 121 (90%) of
the participants reported that their climacteric complaints had
changed during the study period, compared with 52 (39%) in
the control group (P G 0.001).
There was no statistically significant difference between
the acupuncture group and the control group regarding the
number of participants using allowed medication and dietary
supplements for menopausal complaints at baseline. At week
12, however, 16 participants in the acupuncture group and 32
in the control group used dietary supplements for menopausal
symptoms, a statistically significant difference (P G 0.05).
There were no statistically significant changes in the
u-CGRP/u-creatinine ratio in the morning and evening urine
samples in the two groups from baseline to week 12 or
between responders and nonresponders at week 12 in a
substudy. Median u-CGRP/u-creatinine ratios at baseline in
morning urine samples were 5.5 in the acupuncture group
(n = 33) and 5.9 in the control group (n = 33), whereas
the corresponding values at week 12 were 6.6 and 6.3,
respectively. In evening urine samples, the median u-CGRP/
u-creatinine ratio at baseline in the acupuncture group (n =
33) was 5.9, and in the control group (n = 28), it was 6.8.
At week 12, the corresponding values were 6.1 and 5.6. To
evaluate the CGRP excretion among responders and non-
responders, the morning and evening u-CGRP/u-creatinine
sample values were summated and divided by 2. No sta-
tistically significant differences were observed; the median
value at 12 weeks was 8.0 among responders and 7.2
among nonresponders.
DISCUSSION
The overall reduction in hot flash frequency was 48%
among women who received acupuncture, compared with
28% reduction in the control group. These results suggest
that a policy of use of acupuncture plus self-care can reduce
hot flash frequency by 50% or more in half of the post-
menopausal women experiencing frequent hot flashes.
Strengths of the study are the randomized design, large
sample size, and high follow-up rate. The study showed
consistent results across hot flash diary data and quality of
life outcomes, and this consistency supports the validity of
the results.
We aimed to compare two treatment policies available to
postmenopausal women with vasomotor complaints, namely,
acupuncture plus self-care and self-care alone. Whether the
addition of acupuncture treatment to self-care contributes to
a clinically relevant reduction in symptoms is highly
important for symptomatic women looking for alternatives
to HT. This study tested acupuncture as a complete treatment
package on a generic level. It was pragmatic, not explan-
atory; hence, no placebo treatment was given in the control
group. The study does not allow us to estimate what pro-
portion of the clinical benefit was due to the effects of the
needling itself and what was due to other factors, such as the
patient-provider interaction. Altogether, 10 acupuncture prac-
titioners participated in the study, ensuring that the study

490 Menopause, Vol. 16, No. 3, 2009 * 2009 The North American Menopause Society

Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
 ACUPUNCTURE FOR POSTMENOPAUSAL HOT FLASHES
tested the effects of acupuncture in general, not the individual
practitioner.
Study participants were recruited through media coverage
and advertisements and had a positive attitude toward acu-
puncture. This may have affected the participants in the
acupuncture group positively and the participants in the con-
trol group, who probably hoped to receive acupuncture,
negatively. Patient expectations can have a sizeable impact
on clinical outcomes,41 and this may lead to an over-
estimation of the acupuncture treatment effect. However,
the positive expectation provided by the therapeutic context
is understood to be an integral component of the neurological
effects of acupuncture and may even be essential for the
central nervous system effects to occur.42
The primary endpoint was frequency of hot flashes re-
corded in participant diaries. This is a subjective measure of
vasomotor episodes. The use of hot flash diaries is considered
a valid and reliable method of measuring vasomotor epi-
sodes, and it has been used in several studies of pharmaco-
logical treatment of menopausal complaints.33 The use of
self-report diaries for data collection is further established
as a valid approach to obtain data on subjective phenomena
such as patient-reported symptoms and perceptions.33,43<45
However, in a comparison of subjective hot flash reports and
continuous sternal skin conductance monitoring, the positive
predictive value of the hot flash diary was low (34%-52%)
and the negative predictive value was high (94%-97%).
Hence, the use of hot flash diaries may seriously underesti-
mate hot flash frequency.46 A possible reason for the discre-
pancy between the hot flash diary and the sternal monitoring
may be that only bothersome hot flashes were registered. For
future studies of hot flash interventions, the use of a single
daily rating of hot flash intensity in addition to a sternal
monitoring device was proposed.46 In our study, the assess-
ment of hot flash intensity and bother was a single rating per
24 hours, and the results corresponded closely with the hot
flash frequency results.
Quality-of-life instruments are widely used in research. In
the medical field, the term health-related quality of life is
frequently used. It is claimed that this approach takes into
account qualitative aspects, such as the effect of subjective
symptoms on a day-to-day functioning and well-being.47 The
secondary endpoint was HR-QOL, measured by the WHQ.
This questionnaire has been used as a quality-of-life measure
in several trials of hormonal preparations for perimenopausal
and postmenopausal women.34,35 A psychometric evaluation
of the Norwegian translation of the WHQ has been per-
formed and will be reported elsewhere. Participants in the
acupuncture group experienced statistically and clinically
significant improvements in the vasomotor, sleep, and so-
matic symptoms dimensions of the WHQ.
Menopausal women experience more sleep problems than
nonmenopausal women do,48,49 partly due to vasomotor symp-
toms.2,3 At baseline, 48% of our study participants reported
sleep problems affecting work last year. Mean hours of sleep
per night increased significantly in the acupuncture group
Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
compared with the control group, and the sleep domain in the
WHQ showed a statistically and clinically significant improve-
ment. It has been observed that acupuncture treatment may
improve sleep in patients with fibromyalgia,50 but a Cochrane
review concluded that recent evidence does not support the
use of acupuncture for insomnia,51 mainly because of a small
number of studies and poor methodological quality. Some of
the improvement in sleep seen in our study may be due to the
reduction in hot flashes during the night.
Increased somatic symptoms are inconsistently associated
with menopause.52 Current evidence suggests that acupunc-
ture is a useful treatment for musculoskeletal pain.53 This
finding supports our finding of a statistically and clinically
significant improvement in the somatic symptoms dimension
of the WHQ in the acupuncture group.
We observed that more participants in the control group
than in the acupuncture group had changed their living habits
(rest and sleep, physical activity, coffee drinking, alcohol
intake, and tobacco smoking) during the study, and twice
as many participants in the control group as in the acu-
puncture group used dietary supplements for menopausal
symptoms at week 12. The differences were statistically
significant and may lead to an underestimation of the acu-
puncture effect.
The mechanisms behind hot flashes are not known in de-
tail. One theory is that the concentrations of endorphins in the
hypothalamus decrease with decreasing estrogen concentra-
tions. The reduced endorphin levels increase the release of
serotonin and norepinephrine, and this may in turn cause a
drop in the set point in the thermoregulatory center in the
hypothalamus and elicit inappropriate heat loss.54<56 The heat
loss is achieved by vasodilatation and sweating, and these
reactions may be mediated by the potent vasodilator CGRP.27
Endogenous opioids modulate the release of CGRP at the
spinal cord level,57 and postmenopausal women with vaso-
motor symptoms had increased urinary excretion of CGRP.58
Acupuncture probably affects serotonin and A-endorphin
activity in the central nervous system59,60 and may thus in-
fluence the thermoregulatory center and make it more
stable.27 A change in the A-endorphin concentration may
also affect the CGRP excretion. A study showed that CGRP
decreased in 24-hour urine after acupuncture therapy in wo-
men with hot flashes.27
We found no statistically significant changes in u-CGRP
concentration in morning and evening urine samples from
baseline to week 12 or between responders and nonrespond-
ers in a substudy. Urine CGRP concentration analyses should
ideally have been performed in 24-hour urine samples. This
was not feasible in the present study; thus, morning and
evening samples were analyzed and we used the u-CGRP/
u-creatinine ratio to evaluate possible changes in CGRP
excretion. The analysis may therefore suffer from poor pre-
cision and must be interpreted with care.
The effect of the acupuncture treatment is comparable to
the effect of SSRIs/SNRIs on hot flashes.13 Ten acupuncture
treatment sessions cost NOK 3,000 to 3,500 (US $550-640),
Menopause, Vol. 16, No. 3, 2009 491
 BORUD ET AL
compared with NOK 500 to 1,000 (US $90-180) for
3 months of SSRI or SNRI use. The acupuncture treatment
is more expensive, but the rate of adverse effects with acu-
puncture treatment is low19 and may be lower than that seen
with SSRI/SNRI treatment. The duration of the acupuncture
effect is unclear and will need further exploration.
Previous studies of the effect of acupuncture treatment on
menopausal complaints were smaller, used sham acupunc-
ture, and showed mixed results. A randomized trial with 24
participants found that hot flashes decreased by 50% among
women who received standardized electro-acupuncture.27 A
further study (N = 30) found a trend in favor of electro-
acupuncture compared with sham acupuncture for climacteric
symptoms.25 A small randomized controlled trial (N = 18)
found TCM acupuncture to be more effective than sham
acupuncture, with a 76% reduction in hot flashes.23 A study
of 103 participants found no effect on daily flash frequen-
cy,26 but a second study of 29 participants found a reduction
in severity, although not in frequency, of nocturnal flashes.24
A recent randomized study (N = 56) with three arms (TCM
acupuncture, sham acupuncture, and usual care) showed no
significant difference in reduction in daily flash frequency
between the three groups but a significantly greater decrease
in flashes in the two acupuncture groups compared with the
usual care group.61 All these studies used various types of
standardized acupuncture treatment. In actual practice, the
treatment is individualized, as in our study, and this may
improve the treatment results.
The present study provides a good basis for further studies
of the efficacy of acupuncture treatment for hot flashes. Such
studies will, however, face many challenges. Neither super-
ficial nor minimal acupuncture, needling of Bnonacupuncture[
points, nor Bstage-dagger[ needles that do not penetrate the
skin (Streitberger needles), can be considered physiologically
inert placebo controls.62 In addition, sham needles that do not
penetrate the skin are technically difficult to use in practice.
A great variety of sham interventions has been used in acu-
puncture trials, but these are hardly true Bplacebo controls.[63
Needling in acupuncture points usually elicits de Qi, con-
sidered by many as essential for the effect of acupuncture.64
Thus, to obtain single blinding, we may have to recruit
acupuncture-naive study participants. In the present study,
more than 60% of the participants had tried acupuncture pre-
viously, suggesting that acupuncture-naive individuals may
be difficult to recruit. Blinding of the practitioners in addition
to the participants, that is, double blinding, seems very
difficult. Hence, designing double-blind, sham-controlled
studies of acupuncture treatment seems challenging.
The use of acupuncture is more prevalent in Norway than
in the United States. Almost two thirds of the participants in
the study had used acupuncture previously, and the partic-
ipants in the study were self-selected. These facts may limit
the generalizability of the findings. However, the acupunc-
ture treatment given represents actual practice, and the study
results seem relevant to women seeking nonpharmacological
relief of postmenopausal vasomotor symptoms. The results
492 Menopause, Vol. 16, No. 3, 2009
Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
may be of interest also for healthcare providers, acupunc-
turists, and researchers.
CONCLUSIONS
In conclusion, use of acupuncture in addition to self-care
can contribute to a clinically relevant reduction in hot flashes
and increased HR-QOL among postmenopausal women.
Acknowledgments: We thank the staff at The Clinical Research
Center, UNN, for their participation in the study planning and data
collection. Participating acupuncturists: Morten SLrli, Mette
Neslein, Live Storruste, Olav Kise, Mette Trolie, Tove Hjellegjerde,
Anne-Grete Meyer, Torun Svendsen, Hege Gjerdrum, and Håkon
MjLen. Study coordinators: Sissel Andersen, Heidi Hveem Holtes-
taul, Merete Allertsen, and Anne-Sofie Sand. Acupuncture case
report forms: Kate J. Thomas, School of Health and Related
Research, University of Sheffield, UK. E.K.B. is research fellow
and main author of this article. He had full access to all the data in
the study and takes responsibility for the integrity of the data and
the accuracy of the data analysis. S.G. conceived the study and is the
principal investigator. T.A. is responsible for the design of the acu-
puncture intervention, a member of the steering group, and parti-
cipated in the design of the study. A.W. is a member of the steering
group and gave substantial input to the study design. V.F. parti-
cipated in the design of the study and is a member of the steering
group. A.E.E., L.L.Å., and M.H. participated in the design of the
study. E.T. performed the u-CGRP and u-creatinine analyses. The
whole group gave comments on the drafts for this article.
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