European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Efcacy of the device combining high-frequency transcutaneous

electrical nerve stimulation and thermotherapy for relieving primary
dysmenorrhea: a randomized, single-blind, placebo-controlled trial
Banghyun Lee a, Seung Hwa Hong b, Kidong Kim a,*, Wee Chang Kang c, Jae Hong No a,
Jung Ryeol Lee a, Byung Chul Jee a, Eun Joo Yang d, Eun-Jong Cha e, Yong Beom Kim a
a
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-Do, Republic of Korea
b
Department of Obstetrics and Gynecology, Chungbuk National University, College of Medicine, Cheongju-Si, Chungcheongbuk-Do, Republic of Korea
c
Department of Business Information and Statistics, DaeJeon University, Daejeon-Si, Chungcheongnam-Do, Republic of Korea
d
Rehabilitation Medicine Department, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-Do, Republic of Korea
e
Department of Biomedical Engineering, School of Medicine, Chungbuk National University, Cheongju, Republic of Korea

A R T I C L E I N F O A B S T R A C T

Article history: Objective: To investigate the efcacy and safety of the combined therapy with high-frequency
Received 2 July 2015 transcutaneous electrical nerve stimulation (hf-TENS) and thermotherapy in relieving primary
Received in revised form 10 August 2015 dysmenorrheal pain.
Accepted 13 August 2015
Study design: In this randomized, single-blind, placebo-controlled study, 115 women with moderate or
severe primary dysmenorrhea were assigned to the study or control group at a ratio of 1:1. Subjects in
Keywords: the study group used an integrated hf-TENS/thermotherapy device, whereas control subjects used a
Dysmenorrhea
sham device. A visual analog scale was used to measure pain intensity. Variables related to pain relief,
Transcutaneous electrical nerve stimulation
Thermotherapy
including reduction rate of dysmenorrheal score, were compared between the groups.
Results: The dysmenorrheal score was signicantly reduced in the study group compared to the control
group following the use of the devices. The duration of pain relief was signicantly increased in the study
group compared to the control group. There were no differences between the groups in the brief pain
inventory scores, numbers of ibuprofen tablets taken orally, and World Health Organization quality of
life-BREF scores. No adverse events were observed related to the use of the study device.
Conclusions: The combination of hf-TENS and thermotherapy was effective in relieving acute pain in
women with moderate or severe primary dysmenorrhea.
2015 Elsevier Ireland Ltd. All rights reserved.

Introduction effectiveness in controlling pain is not enough [2,3]. Therefore,

Primary dysmenorrhea develops without pelvic pathology. The
pain of primary dysmenorrhea usually lasts 872 h during the
menstrual cycle [1] and is commonly managed with nonsteroidal
anti-inammatory drugs (NSAIDs) and oral contraceptive pills
[1,2]. However, these pain treatments are associated with various
adverse effects such as nausea, intermenstrual bleeding, and
breast tenderness [1,3]. Moreover, the evidence supporting their
Clinical trial registration: ClinicalTrials.gov, www.clinicaltrials.gov,
NCT01662934.
* Corresponding author at: Department of Obstetrics and Gynecology, Seoul
National University Bundang Hospital, 82, Gumi-ro 173 beon-gil, Bundang-gu,
Seongnam-Si, Gyeonggi-Do, Republic of Korea. Tel.: +82 31 787 7262;
fax: +82 31 787 4054.
E-mail address: kidong.kim.md@gmail.com (K. Kim).
there has been the need for non-pharmacologic management of
dysmenorrhea [2,3].
High-frequency transcutaneous electrical nerve stimulation (hf-
TENS, conventional TENS) commonly delivers low-intensity electri-
cal impulses at a frequency of 50120 Hz [4]. Several randomized
trials and a meta-analysis have reported that hf-TENS signicantly
reduced the intensity of primary dysmenorrheal pain compared to
placebo TENS [47]. Furthermore, two randomized studies have
demonstrated that low-intensity topical heat therapy delivered via a
abdominal patch or a heat wrap signicantly reduced the intensity of
primary dysmenorrheal pain [8,9]. It is not certain how TENS or
thermotherapy relieve pain. However, analgesic effect of these may
be explained by the gate control theory of pain in which stimuli from
TENS or thermotherapy are delivered to the A-beta nerve ber. Then,
the signals from the A-beta bers are transmitted to the spinal cord
where they temporarily block the transportation of pain sensations

http://dx.doi.org/10.1016/j.ejogrb.2015.08.020
0301-2115/ 2015 Elsevier Ireland Ltd. All rights reserved.
 B. Lee et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863 59

to the brain [1012]. Therefore, both treatments may be effective for
primary dysmenorrhea [13,14].
In this study, we used a pain-relieving device that integrates hf-
TENS and thermotherapy. A treatment combining TENS and
neuromuscular electrical stimulation was reported to be more
effective in reducing chronic back pain than each method alone
[15]. Similarly, both TENS and thermotherapy may provide
analgesia through altering pain sensation following peripheral
stimulation. Therefore, we hypothesized that a similar effect could
be achieved by applying this combinatory approach to dysmenor-
rhea.
The effectiveness of non-pharmacologic therapies such as TENS,
topical heat therapy, and acupuncture for relieving dysmenorrhea
have been demonstrated through randomized studies although
they have been limited to small-scale trials (39). However, the
effectiveness of combination therapies have not been evaluated.
Therefore, this study aimed to test the efcacy and safety of the
combined therapy comprising hf-TENS and thermotherapy in
relieving dysmenorrheal pain.
Methods
Our prospective, randomized, single-blind, placebo-controlled
study included women who enrolled for clinical trial in two
University Hospitals from May 24, 2012 to November 23, 2012. This
study was approved by the Institutional Review Board of Seoul
National University Bundang Hospital (no. E-1112/069-001) on
July 23, 2012 and Chungbuk National University (no. 2009-03-019)
on March 26, 2009.
Inclusion criteria were as follows: premenopausal women who
were over 20 years old, had moderate or severe lower abdominal
dysmenorrhea [visual analog scale (VAS) score  5/10] that required
analgesics to control pain for a minimum of 6 months, and provided
voluntary consent to the present clinical trial. Exclusion criteria
were as follows: pregnant women; women with history of surgery in
the lower abdomen; women who had been diagnosed with cancer in
the last 5 years or had suspected cancer; those who could not use
TENS, for example, because of a permanent pacemaker or skin
disease; and those with contraindications for ibuprofen, such as
peptic ulcer.
Fig. 1 shows the ow diagram of this randomized trial. At the
rst visit, participants were asked for informed consent. Assess-
ment of eligibility, urinary human chorionic gonadotropin test,
gynecological examination, transvaginal ultrasound, and random-
ization were performed.
Gynecological examination and transvaginal ultrasound, which
is commonly used in our country, were performed to determine
the type of dysmenorrhea. The ndings of gynecological examina-
tion indicating secondary dysmenorrhea were as follows: uterine
hypertrophy, uterine mass, adnexal mass, and chronic pelvic
inammatory disease. The ndings of transvaginal ultrasound
indicating secondary dysmenorrhea were as follows: uterine
myoma (largest diameter >5 cm), adenomyosis (globular uterine
enlargement with an obscure endometrial/myometrial border or
asymmetrical uterine wall thickening [16]), and endometrioma
(unilocular cyst with homogeneous ground glass echogenicity of
cyst uid [17]). The diagnosis of secondary dysmenorrhea could be
established based on other ndings at the discretion of the
investigators. Subjects were diagnosed with primary dysmenor-
rhea if secondary dysmenorrhea was excluded.
Stratied randomization was performed according to the
clinical trial hospital and the type of dysmenorrhea by a statistician
who had no direct contacts with the participants. Subjects were
randomly assigned to the study and control groups at a 1 to 1 ratio,

Moderate or severe dysmenorrhea

(n = 118)

Gynecologic examination
Transvaginal ultrasound

Dropout (n = 3)
Prior to randomization
Randomization (n = 115)
Stratification: Clinical trial hospitals
Primary or secondary dysmenorrhea

Study group (n = 57) Control group (n = 58)

Study device (hf-TENS and thermotherapy) Sham device
Intake ibuprofen (if needed) Intake ibuprofen (if needed)

Change of dysmenorrheal pain score

Duration of dysmenorrheal pain relief
BPI score
Number of ibuprofen tablets taken orally
WHOQOL-BREF score

Fig. 1. Flow diagram of this randomized, single-blind, placebo-controlled study. Three subjects were excluded from the analyses before randomization based on the exclusion
criteria.
60 B. Lee et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863
and block randomization was performed. The size of the block unit
was not disclosed to prevent investigators from predicting
subjects assignments. The participants and investigators did not
know whether a participant was assigned to the study or control
group. However, women could realize that they were assigned to
the control group because the sham device did not perform TENS
and thermotherapy. Therefore, this study was considered a single-
blind trial.
During the rst menstrual cycle, participants completed
dysmenorrhea diaries, and assessments of efcacy and adverse
events (AEs) were performed. World Health Organization quality
of life (WHOQOL)-BREF [18] assessment was carried out once, and
AEs were evaluated during the visit after the rst menstrual cycle.
Participants recorded the beginning of menstruation in the
dysmenorrhea diary. The clinical trial device was used whenever
dysmenorrheal pain was felt, and the starting time of its
application and degree of dysmenorrheal pain immediately before
the application were recorded. If dysmenorrheal pain was
sufciently relieved or the clinical trial device was used for
30 min, it was removed, and the ending time and degree of
remaining dysmenorrheal pain were recorded. The diary was
recorded at the end of every day until the end of the menstruation
as determined based on disappearance of bleeding, but not longer
than 8 days. AEs were monitored until the end of the menstruation
even if it lasted for more than 8 days. VAS was used to measure pain
intensity.
To use the hf-TENS/thermotherapy or sham device, a gel pad
was attached to a silicon patch, the controller was connected to the
patch, the patch was attached in the lower abdomen where there
was pain, the power was turned on, and the sequential mode was
selected. The frequency of electrical signal (range: 100110 Hz)
and temperature (40  1 8C or 37  1 8C) were then adjusted
depending on personal preferences, and nerve stimulation was
performed for 10 min, immediately followed by 20 min of thermo-
therapy.
If the pain was not adequately relieved after 30 min of device
application, oral ibuprofen was immediately taken. The initial
ibuprofen dose of 200 mg was increased by 200 mg after a
minimum of 4 h if the pain did not subside until the maximum
daily dose of 1200 mg (6 tablets). Devices were not applied if they
would interfere with work or other duties. The doses, timing, and
reasons for taking the medication were recorded. The trial device
was not used within 1 h after taking ibuprofen [19].
Efcacy assessment occurred in all randomized participants.
The primary endpoint was reduction of dysmenorrheal pain score
(VAS score). Secondary endpoints were duration of dysmenorrheal
pain relief, brief pain inventory (BPI) score, number of ibuprofen
tablets taken, and WHOQOL-BREF score. For all variables, the
averages of values measured after applying the clinical device in
each episode by each participant were used for calculations.
Absolute reduction of dysmenorrheal pain score was calculated
as follows: reduction = pain score immediately before wearing the
clinical trial device  pain score immediately after removing the
clinical trial device. Duration (h) of dysmenorrheal pain relief was
dened as the time interval between removing the clinical trial
device and its next application or taking ibuprofen. If analgesics
were taken because dysmenorrheal pain was not adequately
relieved with the clinical trial device, duration time of pain relief
was considered 0.
Participants recorded BPI scores in the evening of the following
day on which the rst menstruation began after the enrollment in
the clinical trial. Ibuprofen tablets taken orally were counted.
Quality of life (QOL) during the clinical trial was assessed.
The expected AEs were electrical shock, low-temperature burn,
pruritus, and dermatitis. Participants were asked whether they
experienced the specic expected AEs. Other AEs reported by
participants were also recorded and assessed according to the
National Cancer Institute Common Terminology Criteria for
Adverse Events, version 4.0. The study device was considered
safe if no participants suffered from AEs of grade 3 that had
possible/probable/denite association with the use of the study
device during the clinical trial. If there were participants who
experienced the above AEs, frequency, type, and severity of AE, as
well as associations between the use of the clinical trial device and
AE, were assessed.
I-Rune, a battery-powered portable pain reliever (model name:
I-200L, Medirune Co., Ltd., Seoul, Republic of Korea) was used in the
study group. This device provides pain relief by applying hf-TENS
and thermotherapy. The sham device used in the control group
looked like the study device. The participants of the study group
used the clinical trial device without payment during the study.
Since no previous data obtained under the same conditions
were available, the results of two trials that utilized similar setups
[20,21] were used for estimating the expected magnitude of
changes. In particular, the difference in mean rate of change in
dysmenorrheal pain score between the groups (d) and standard
deviation (s) were set at 20% and 32%, respectively. Independent
two-sample t-test with 80% power at the 0.05 level of signicance
was performed based on estimated compliance (w) and dropout
rates (r) of 10% and 15%, respectively. Sample size was calculated as
follows:
2s 2 Z a=2 Z b 2 2  322 1:96 0:8422
n 2
 59
2
d 1  w 1  r 202 1  0:12 1  0:15
Fifty-seven and fty-eight women were assigned to the study
and control groups, respectively.
SAS 9.2 software (SAS Institute, Cary, NC, USA) was used for all
analyses. Efcacy assessments were based on intention-to-treat
(ITT) analyses and used reference per-protocol (pp) analyses. ITT
analyses were performed in participants from the study groups
who took clinical trial devices. PP analyses were performed in
participants who completed the clinical trial according to the
initial plan without violations and for whom efcacy assessments
were performed. All subjects completed the study without dropout
or violations after randomization. Therefore, both ITT and PP
analyses yielded identical results for primary and secondary
endpoints. Continuous variables were analyzed using the inde-
pendent t-test or MannWhitney rank sum test. Categorical
variables were analyzed using the Pearsons chi-square test or
Fishers exact test. Differences in primary and secondary endpoints
between the groups were analyzed using a multivariate linear
regression model with adjustments for the clinical trial hospital
and type of dysmenorrhea. If confounding factors did not yield
signicant differences in the multivariate linear regression model,
they were removed from the model. Signicant variables were
selected using stepwise selection, and the signicance criterion for
inclusion or exclusion was the P-value of 0.1. The efcacy of the
clinical trial device was assessed after removing these confounding
factors. A P-value of <0.05 was considered to indicate statistical
signicance.
Results
The study and control groups included 57 and 58 subjects with
primary dysmenorrhea, respectively. Age, height, body weight, and
mean VAS scores of dysmenorrheal pain intensity at baseline were
not signicantly different between the study and control groups.
The distribution of subjects in the study and control groups
between the clinical trial hospitals also did not differ signicantly
(P > 0.05; Table 1). The current trial was completed including the
subjects with primary and secondary dysmenorrhea. However,
 B. Lee et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863 61

Table 1 signicant [reduction of 1.44  0.22 (24.47%), P < 0.000; Table 3].
Baseline characteristics of the study population.
Furthermore, the dysmenorrheal pain score decreased progressively
Study group Control group P-value with the repeated use of the study device, with later applications
(n = 57) (n = 58) providing signicantly stronger relief (P < 0.001, data not shown),
Age (years), mean  SE 28.14  6.17 27.02  5.94 0.322 which reected the more frequent use of the study device than the
Height (cm), mean  SE 161.22  5.20 160.91  5.48 0.750 placebo device. The duration of relief from dysmenorrheal pain was
Body weight (kg), 52.28  5.88 52.58  5.81 0.786 4.08  4.8 h in the study group and 0.72  1.92 h in the control group.
mean  SE
This value was signicantly higher in the study group (increase of
VAS scores for 6.90  1.14 7.21  1.35 0.196
dysmenorrheal 3.12  0.72 h, P < 0.000; Table 3).
pain, mean  SE The BPI scores, numbers of ibuprofen tablets taken orally, and
Number of subjects WHOQOL-BREF scores did not differ between the groups (Table 3).
Hospital 1 (n = 59), n 30 29
Neither expected nor unexpected AEs occurred in the study and
Hospital 2 (n = 56), n 27 29 0.778
control groups.
SE standard error: VAS visual analog scale.

only 4 women with secondary dysmenorrhea were enrolled. And
the low number of subjects included did not allow drawing a
conclusion regarding the efciency of the study device in relieving
secondary dysmenorrhea pain. Therefore, women with secondary
dysmenorrhea were excluded from the analyses.
The mean dysmenorrheal pain score after the rst use of the
device as well as the average of mean pain score after all device
applications every episode by each patient were signicantly
reduced in the study group compared with the control group
(rst use, 4.53  1.71 vs. 5.72  1.74, P < 0.001; all applications,
4.53  1.71 vs. 5.64  1.58, P < 0.001), whereas the corresponding
values obtained before applying the device did not differ (P > 0.05).
The number of times the device was used was lower and declined
more quickly in the control group. The proportion of instances where
the device was removed before the end of the 30 min session and the
time interval before the removal did not differ between the groups
(P > 0.05; Table 2).
The dysmenorrheal pain intensity score after using the clinical
trial devices decreased by 1.78  1.35 (30.34%) in the study group
and 0.34  0.93 (5.87%) in the control group. The averages of mean
reduction values of dysmenorrheal pain score measured after
applying the clinical device at every episode by each participant
were calculated. The difference between the groups was statistically
Discussion
Unlike the previous studies, which investigated individual
effects of hf-TENS or thermotherapy on primary dysmenorrheal
pain, we evaluated the efciency of the approach combining the
two therapies. We hypothesized that the combined device would
be more efcient in relieving primary dysmenorrheal pain than
devices implementing hf-TENS or thermotherapy alone. However,
although we did not compare the efciencies directly, an estimate
based on published data suggested similar extents of reduction of
the dysmenorrheal pain score for the combined, hf-TENS, and
thermotherapy devices when compared to a placebo device (study
device, 1.44; hf-TENS, 1.26; thermotherapy, 1.32) [6,8].
The initial menstrual pain intensity score in our study was
similar to those reported previously (4.447.94) [6,8,22]. However,
even though the dysmenorrheal pain intensity score decreased
signicantly after using the clinical trial device, the averages of
mean VAS scores measured after removing the device at every
episode in each participant were still high in both groups. The
participants in both groups of this study took only 1.4 ibuprofen
tablets on average. Therefore, we believe that a tendency to take
less analgesics in our country may explain this nding [23,24]. To
take this tendency into account, we used a low dose of ibuprofen
initially and progressively increased it.

Table 2
Visual analog scale pain scores and details of the study devices application.

Study group (n = 57) Control group (n = 58) P-value

VAS score, mean  SE Before wearing device (rst use) 6.06  1.28 6.05  1.57 0.899
After removing device (rst use) 4.53  1.71 5.72  1.74 <0.001
Before wearing device (all uses) 6.01  1.03 5.98  1.36 0.563
After removing device (all uses) 4.23  1.50 5.64  1.58 <0.001a

Number of device 205 151

applications

Times used n n

Distribution of numbers 1 57 58
of times the device was used 2 49 32
3 39 21
4 21 11
5 11 5
6 8 3
7 7 2
8 5 1
9 3
10 3
11 1
12 1

Cases where the device was n (%) 12 (5.85%) 25 (16.56%) 1.000

removed before 30 min Time before removing the 20.00  4.55 18.04  4.19 0.255
device (min), mean  SE

VAS visual analog scale: SE standard error.

a
P-value was determined using the independent t-test. The remaining P-values were determined using the MannWhitney rank sum test or Fishers exact test.
62 B. Lee et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863

Table 3
The effect of the application of the study devices on various characteristics of dysmenorrhea.

Study group (n = 57) Control group (n = 58) Multivariate analysis

Estimate (SE) P-valuea

Absolute reduction of 1.78  1.35 (30.34) 0.34  0.93 (5.87) 1.44 (0.22) <0.000
VAS score, mean  SE (%)

Duration of dysmenorrheal 4.08  4.8 0.72  1.92 3.12  0.72 <0.000

pain relief (h), mean  SE

BPI scores, mean  SE Highest 6.68  1.49 6.78  1.56 0.09 (0.28) 0.758
Lowest 2.22  1.56 2.74  1.77 0.52 (0.31) 0.098
Average 4.89  1.42 5.12  1.61 0.22 (0.29) 0.434
Life interference 34.58  15.26 38.97  13.89 4.37 (2.76) 0.116

Number of ibuprofen tablets 1.42  2.09 1.43  2.20 0.01 (0.40) 0.980
taken orally, mean  SE

WHOQOL-BREF scores, General 3.65  0.64 3.77  0.60 0.13 (0.12) 0.284
mean  SE Health 3.53  0.89 3.53  0.68 0.00 (0.15) 0.993
Physical 95.44  18.89 90.53  15.87 4.95 (3.28) 0.134
Psychological 79.58  14.61 80.35  12.34 0.80 (2.55) 0.754
Social 41.82  5.75 41.67  5.95 0.13 (1.12) 0.906
Environmental 100.84  22.40 100.00  18.30 0.82 (3.86) 0.832

VAS visual analog scale: SE standard error: BPI scores brief pain inventory scores: WHOQOLBREF scores World health organization quality of life (WHOQOL)BREF scores.
a
P-values were determined using multivariate linear regression analysis with adjustment for the clinical trial hospital and type of dysmenorrhea.

There is limited evidence regarding the duration of analgesia
induced by hf-TENS in the management of primary dysmenorrhea.
According to the results of randomized trials, the intensities of
primary dysmenorrheal pain continuously decreased at 8 h and
24 h from the beginning of TENS application, and the usage of TENS
for two cycles signicantly delayed the need for ibuprofen intake
by an average of 5.9 h compared to 0.7 h when ibuprofen was used
alone [7,22]. Supporting the previous studies, the duration of pain
relief by our combined therapy was signicantly longer compared
to that achieved with the placebo device.
In the current study, the women in the control group could realize
that they were using a placebo device based on the lack of sensations
typical of TENS/thermotherapy. This reduced the compliance in the
control group, as reected by fewer repeated uses of the device. To
minimize this bias, the study was completed in 1 menstrual cycle.
A recent study reported that hf-TENS relieved the autonomic
symptoms associated with primary dysmenorrhea when compared
with placebo TENS [6]. Topical heat therapies were also reported to
reduce the overall severity of menstrual symptoms, including
tension, headache, fatigue, and mood swings, when compared with
placebo or NSAIDs [8,9]. In contrast, other studies detected no
differences in the number of women needing additional analgesics,
number of additional analgesic tablets used, and absence from work
or school between hf-TENS and placebo TENS [4,5,7]. In support of
the latter negative results, we found that the use of the new
combined therapy for primary dysmenorrhea did not affect the BPI
and WHOQOL-BREF scores and the number of ibuprofen tablets
taken orally when compared with the use of the sham device.
Most studies of TENS found no AEs associated with the use of
this method [46,8,9,22]. However, a single trial reported that the
application of hf-TENS resulted in muscle vibrations, tightness, and
headaches, as well as slight skin redness or burning sensation [7].
Similarly, the use of heat therapy was linked to transient redness in
the area where the patch was attached [8]. In contrast, we detected
no AEs associated with the application of the combined therapy,
suggesting that the hf-TENS/thermotherapy treatment approach is
safe.
Conclusions
In this randomized study, we demonstrated that the combined
therapy comprising hf-TENS and thermotherapy effectively
relieved pain in women with moderate or severe primary
dysmenorrhea. In particular, the intensity and duration of dysme-
norrheal pain decreased signicantly after using the integrated hf-
TENS/thermotherapy device compared to the placebo device.
Importantly, no AEs occurred during the trial, demonstrating the
safety of the study device. Therefore, this new non-pharmacologic
therapeutic strategy may be an effective and safe approach for the
management of dysmenorrhea. Randomized, large-scale trials are
necessary to further clarify the efcacy and safety of using this study
device.
Competing interests
The authors declare that they have no conicts of interest.
Acknowledgements
We are grateful to nurse Kyung Hee Kim for her contributions,
including data collection. This study was nancially supported by
Medirune Co., Ltd. The sponsors were not involved in study design;
collection, analysis, and interpretation of data; writing of the
report; and the decision to submit the report for publication. This
work was also supported through the Industrial Complex Cluster
Program of Korea Industrial Complex Corporation.
References
[1] Proctor M, Farquhar C. Diagnosis and management of dysmenorrhoea. BMJ
2006;332:11348.
[2] Osayande AS, Mehulic S. Diagnosis and initial management of dysmenorrhea.
Am Fam Phys 2014;89:3416.
[3] Kannan P, Claydon LS. Some physiotherapy treatments may relieve menstrual
pain in women with primary dysmenorrhea: a systematic review. J Physiother
2014;60:1321.
[4] Proctor ML, Smith CA, Farquhar CM, Stones RW. Transcutaneous electrical
nerve stimulation and acupuncture for primary dysmenorrhoea. Cochrane
Database Syst Rev 2002. CD002123.
[5] Thomas M, Lundeberg T, Bjork G, Lundstrom-Lindstedt V. Pain and discomfort
in primary dysmenorrhea is reduced by preemptive acupuncture or low
frequency TENS. Eur J Phys Med Rehabil 1995;5:716.
[6] Wang SF, Lee JP, Hwa HL. Effect of transcutaneous electrical nerve stimulation
on primary dysmenorrhea. Neuromodulation 2009;12:3029.
[7] Dawood MY, Ramos J. Transcutaneous electrical nerve stimulation (TENS)
for the treatment of primary dysmenorrhea: a randomized crossover
comparison with placebo TENS and ibuprofen. Obstet Gynecol 1990;75:
65660.
 B. Lee et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 194 (2015) 5863
[8] Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:
9719.
[9] Sluka KA, Walsh D. Transcutaneous electrical nerve stimulation: basic science
mechanisms and clinical effectiveness. J Pain 2003;4:10921.
[10] Akin MD, Weingand KW, Hengehold DA, Goodale MB, Hinkle RT, Smith RP.
Continuous low-level topical heat in the treatment of dysmenorrhea. Obstet
Gynecol 2001;97:3439.
[11] Akin M, Price W, Rodriguez Jr G, Erasala G, Hurley G, Smith RP. Continuous,
low-level, topical heat wrap therapy as compared to acetaminophen for
primary dysmenorrhea. J Reprod Med 2004;49:73945.
[12] Verrill P. Does the gate theory of pain supplant all others? Br J Hosp Med
1990;43:325.
[13] Smith RP, Heltzel JA. Interrelation of analgesia and uterine activity in women with
primary dysmenorrhea. A preliminary report. J Reprod Med 1991;36:2604.
[14] Rushton DN. Electrical stimulation in the treatment of pain. Disabil Rehabil
2002;24:40715.
[15] Moore SR, Shurman J. Combined neuromuscular electrical stimulation and
transcutaneous electrical nerve stimulation for treatment of chronic back
pain: a double-blind, repeated measures comparison. Arch Phys Med Rehabil
1997;78:5560.
[16] Sakhel K, Abuhamad A. Sonography of adenomyosis. J Ultrasound Med 2012;
31:8058.
63
[17] Van Holsbeke C, Van Calster B, Guerriero S, Savelli L, Paladini D, Lissoni AA,
et al. Endometriomas: their ultrasound characteristics. Ultrasound Obstet
Gynecol 2010;35:73040.
[18] WHO. Scoring of the WHOQOL-100 and the WHOQOL-BREF. In: World Health
Organization, editor. WHOQOL user manual (WHO/MNH/MHP/984Rev1). Ge-
neva: World Health Organization; 1998. p. 54.
[19] Sadaba B, Campanero MA, Munoz-Juarez MJ, Gil-Aldea I, Garcia-Quetglas E,
Esteras A, et al. A comparative study of the pharmacokinetics of ibuprofen
arginate versus dexibuprofen in healthy volunteers. Eur J Clin Pharmacol
2006;62:84954.
[20] Schiotz HA, Jettestad M, Al-Heeti D. Treatment of dysmenorrhoea with a new
TENS device (OVA). J Obstet Gynaecol 2007;27:7268.
[21] Mannheimer JS, Whalen EC. The efcacy of transcutaneous electrical nerve
stimulation in dysmenorrhea. Clin J Pain 1985;1:7583.
[22] Tugay N, Akbayrak T, Demirturk F, Karakaya II, Citak K, Ozge T, et al. Effec-
tiveness of transcutaneous electrical nerve stimulation and interferential
current in primary dysmenorrhea. Pain Med 2007;8:295300.
[23] Jung HS, Lee J. The effectiveness of an educational intervention on proper
analgesic use for dysmenorrhea. Eur J Obstet Gynecol Reprod Biol 2013;170:
4806.
[24] Han T. Opioids in cancer and non-cancer pain management in Korea: the past,
present and future. Eur J Pain 2001;5(Suppl. A):738.