Available via license: CC BY 3.0
Content may be subject to copyright.
Original Article
The Effects of Lemon balm on Menstrual Bleeding and the Systemic
Manifestation of Dysmenorrhea
Parvaneh Mirabia, S. Hanieh Alamolhodab, Mansooreh Yazdkhastic and Faraz Mojabd*
aInfertility and Reproductive Health Research Center, Health Research Institute, Babol
University of Medical Sciences, Babol, Iran. bMidwifery and reproductive health department,
Nursing and midwifery School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
cDepartment of Midwifery, Faculty of Midwifery, Alborz University of Medical Sciences, Karaj,
Iran. dPharmaceutical Sciences Research Center and School of Pharmacy, Shahid Beheshti
University of Medical Sciences, Tehran, Iran.
Abstract
We conducted a double-blind randomized placebo controlled trial to evaluate the impact
of Lemon balm (Melissa officinalis L.) on the bleeding and systemic manifestations of
menstruation. A total of 90 students were randomly assigned to treatment or placebo group.
Bleeding and systemic manifestations were evaluated with a menstrual pictogram and
multidimensional verbal scale before and during 2 consecutive menstrual cycles, respectively.
Statistical tests indicated that in both groups, the severity of the systemic symptoms associated
with dysmenorrhea significantly decreased (P = 0.001). Among the systemic symptoms, the
mean severity of fatigue, the lethargy, and nervous changes in the two groups decreased after
the treatment, which was statistically significant. There was no significant difference between
the two groups regarding fatigue in the three cycles, but there was a significant difference
between the two groups regarding lethargy in the first cycle (P = 0.05) and the second cycle (P
= 0.001) after the treatment. The present study demonstrated that Melissa officinalis decreases
the severity of the systemic signs associated with menstruation. It showed that the herb does
not increase the severity of bleeding and the duration of menstruation. However, it reduces the
mean total score of the severity of all the systemic symptoms associated with dysmenorrhea.
Keywords: Melissa officinalis; Bleeding; Menstrual cycles, Systemic manifestations of
dysmenorrhea.
Iranian Journal of Pharmaceutical Research (2018), 17 (Special Issue 2): 214-223
Received: July 2018
Accepted: December 2018
* Corresponding author:
E-mail: sfmojab@sbmu.ac.ir
Introduction
Medicinal plants have long been used as
healing substances in the treatment of conditions
like menstrual bleeding everywhere across the
world; Iran has been no exception. Dysmenorrhea,
or painful menstruation, is a pathological pelvic
complication and one of the most common
problems in women (1, 2). Dysmenorrhea is
one of the main factors that impair the quality
of life and the social activities of young women.
While it lasts, it decreases occupational and
educational efficiency, especially when it is
accompanied with symptoms such as headache,
fatigue, nausea, vomiting, diarrhea, shivering,
and muscular cramps. About 50% to 70% of
women experience dysmenorrhea (3, 4). These
uterine cramps are associated with one or more
systemic symptoms in more than 50% of the
cases, including nausea and vomiting (90%),
fatigue (85%), diarrhea (60%), lower back pain
(60%), and headache (45%). Dysmenorrhea is
clearly associated with lower abdominal cramps,
and even causes digestive problems and fatigue
(5, 6).
The cause of primary dysmenorrhea can
be attributed to the increased synthesis of
prostaglandins, which is secreted from the uterine
endometrium during menstruation. The causative
agents of the cramp and the systemic symptoms
include mental and psychological factors,
endocrine factors, cervical factors, abnormal
uterine activity, and also the overproduction and
excessive secretion of prostaglandins. Since the
endometrial concentrations of PGF2α and PGE2
are related to the severity of the gastrointestinal
symptoms associated with dysmenorrhea, the
theory of excess protein production and the
secretion of prostaglandins are confirmed, and
gain more credibility than the other causes (7,
8).
The prostaglandins work to contract the
smooth muscles of many tissues, including the
gastrointestinal system, the bronchi, and arteries;
therefore, one of the symptoms associated with
primary dysmenorrhea is digestive disorder,
including nausea, vomiting, and diarrhea,
which is suggested due to the spasm of the
gastrointestinal muscles at the initiation of
menstruation (3, 8, 9). The usual menstrual
bleeding period is 4–6 days, but in most women,
this period could be anywhere between two and
eight days. The normal volume of menstrual
bleeding is 30 milliliters. If it is more than 80
milliliters, it is unusual (10).
The Lemon balm (Melissa officinalis) herb,
from Labiatae family, is a stable, slightly fluffy
plant with a height of 30 to 80 cm, which usually
grows beside the hedges on the edges of forests
and on shady lands. They often grow in the wild.
Animal models have been studied to ascertain
the analgesic and sedative effects of this plant
(11, 12). Some compounds were reported in
lemon balm, such as volatile oil (0.02- 0.8%)
(Chief components are citral and citronellal),
glycosides, caffeic acid derivatives, flavonoids,
terpene acids, etc (13).
In traditional medicine, M. officinalis has
been described as a potent, sedative, anti-
bacterial, antiviral, and intestinal antispasmodic,
and is an effective medicine for treating
migraine headaches, calming the intestinal
muscles, improving fatigue due to menstrual
disorders, calming the stomach contractions
that cause vomiting, and calming nerve-induced
stomachache, unilateral headaches, vertigo,
vomiting during pregnancy, and bad temper in
women (2, 14). Its hydroalcoholic extract has
a sedative effect and antinociceptive effect in
mice and stimulates and enhances sleep in the
animals (12). The anti-inflammatory activity of
this plant is achieved by rosemary acid and
prevents the activity of C3 convertase (2, 15).
In addition to the softening and protection
from spasms, the essential oil of this plant
has antimicrobial and antifungal effects. Severe
diarrhea and fever, sometimes accompanied by
vomiting, are common symptoms of rotavirus in
children. The use of this plant has been proposed
to prevent the spread of the virus as an effective
drug for the treatment of rotavirus gastroenteritis
infections (15, 16). In spasms associated with
diarrhea and colic, even in irritable bowel
syndrome, lemon balm is used (17, 18).
According to Reiter et al., M. officinalis
inhibited contractions in guinea pig ileum, rat
duodenum and vas deferens, and rabbit jejunum.
The essential oil also exhibited smooth muscle
relaxant activity in tracheal muscle of guinea
pig (19). In clinical trials with the extract of
this plant, no adverse effects, unwanted effects,
or allergies have been reported and its use is
approved by the Food and Drug Administration
(20, 21).
Apparently, due to its biochemical properties,
M. officinalis can affect the systemic symptoms
associated with dysmenorrhea. Regarding the
prevalence and the mechanism of dysmenorrhea,
and the significant digestive and neurological
disorders, this study aimed at to study the effects
of M. officinalis on menstrual bleeding and
systemic symptoms of primary dysmenorrhea.
The goal of this study is to address the need for
an efficient, easy to use and inexpensive drug.
Experimental
This study was a double-blind controlled
trial. After approval from the Shahid Beheshti
The Effects of Lemon balm on Menstrual Bleeding and the Systemic Manifestation of Dysmenorrhea
215
Mirabi P et al. / IJPR (2018), 17 (Special Issue 2): 214-223
216
University of Medical Science Ethics Committee,
this study was registered in IRCT with the code:
IRCT201107096826N2.
All single female resident students in university,
who had moderate to severe dysmenorrhea as
deduced by a verbal multidimensional scoring
system, were evaluated. The inclusion criteria
were the following: single status, age between
18 and 26 years, having moderate to severe
dysmenorrhea according to the McGill system,
having symptoms associated with dysmenorrhea
according to the verbal multidimensional
scoring system, having no severe hemorrhage,
having no known chronic disease, having
no symptoms such as irritation, itching, and
abnormal discharge, having regular menstrual
cycles at intervals of 21–35 days, and having no
history of pelvic inflammatory disease, myoma,
and tumor.
The sample size was estimated to be 45 in
group, based on similar studies8) ), considering
95% confidence, 5% error, and 0.6 effect size,
considering 10% loss from an initial sample
size of 55 in each group in the follow-up phase.
Initially, the research objectives and the protocol
were explained to the students living in the
dormitories. In case of willingness to participate
in the study, written consent was obtained from
them. The research tool used in this research for
collecting data was a questionnaire, which was
designed in two sections:
The first section was completed in the
first stage of the study and before the start
of the treatment. The second section of the
questionnaire, information forms 2 and 3,
was related to the severity of bleeding and
systemic symptoms, completed twice in two
successive cycles by the research units. In order
to determine the validity of the questionnaire
and the information form, content validity was
used and the reliability of the test was evaluated
by the re-test method which resulted in (r = 0.8).
For the eligible participants, the demographics,
including age, body mass index (BMI), exercise,
the presence of stressor in the last six months,
and the table of systemic symptoms and severity
of bleeding were completed.
The severity and the duration of bleeding
were evaluated based on the Campbell and
Munga menstrual pictogram (22) and the verbal
multidimensional scoring system—scored from
zero to 3—was used to evaluate the systemic
symptoms.
The participants with a history of a specific
disease, who needed to use a drug, had symptoms
such as burning, itching, discharge, the presence
of stressors in the last six months, irregular
menstrual cycles, and mild dysmenorrhea were
excluded from the study. The eligible individuals
were divided equally into separate blocks
(moderate and severe symptoms). In the next
stage, the participants were matched in terms
of the severity of the symptoms and randomly
divided into two groups of drug and placebo.
Randomization
Computer-generated random numbers were
used to allocate the participants to receive either
M. officinalis or the placebo. Allocation sequence
will be password-protected and only accessible
to the one midwife not involved in the study.
Capsules were prepared for both the groups in
similar packages with the codes A and B and
the questioner and participants were unaware
of the drugs since only the codes A and B were
detectable. The capsules were administered with
the codes and the findings were documented in
a separate form. The subjects and the researchers
were uninformed of the groups.
The method of drug preparation: The M.
officinalis samples were taken from the farms
around Karaj (Alborz Province, Center of Iran)
and after the identification and verification, in the
School of Pharmacy, Shahid Beheshti University
of Medical Sciences, they were ground by the
electrical grinder. The resultant powder was
extracted with ethanol 96% (maceration ×3), the
extract was mixed with corn starch and then, the
powdered extract was put into capsules (size 0)
with a handy machine.
The placebo capsules containing cornstarch
were made under the same conditions. For the
M. officinalis group, the capsules containing
330 mg extract of the herb were given to the
participants for three days from the beginning of
menstruation, thrice daily over two cycles. The
placebo group was given capsules containing
corn starch with the same protocol.
Each herbal capsule was standardized and
contains 1.3 total flavonoids (rutin).
The Effects of Lemon balm on Menstrual Bleeding and the Systemic Manifestation of Dysmenorrhea
217
Masking
To achieve the purpose of blinding, the
characteristics of the real drug and placebo
should be identical in color, appearance and
smell, so the capsules were similar in shape
and package and we put capsules (lemon balm
and placebo capsules) next to the each other for
more contamination.
In addition, envelopes containing the forms
2 and 3 were given to the participants, in
order to determine the severity of the systemic
symptoms, menstruation, severity, and the
duration of bleeding. The forms were filled up
over two cycles. The data regarding menstruation
(menstrual blood loss, number of pads) and the
systemic manifestation of dysmenorrhea were
collected through these forms. The primary
endpoints were the severity of the systemic
symptoms and secondary endpoint was the
severity of bleeding.
Statistical analysis. Standard statistical
procedures were carried out with the Statistical
Package for Social Sciences (SPSS) version
21.0. The normality of the quantitative variables
was revealed by the Kolmogorov-Smirnov test
and the Student’s t-test was used to compare
the quantitative variables. The outcomes were
assessed in the ITT analyses.
The descriptive analysis was conducted for
each variable including the frequencies, means,
and standard deviations, and the percentage
of the variables in samples. The Friedman
statistical test was used to compare the bleeding
and the systemic manifestation of dysmenorrhea
between three cycles and the Mann Whitney test
compared the findings between the two groups.
Insignificant results of the Friedman test, the
therapeutic cycles were compared in pairs by
modification of α and the Wilcoxon test.
Results
Of the 620 single female dormitory residents,
304 reported primary dysmenorrhea and of
these, 119 students met the study’s eligibility
criteria. Out of them, 110 agreed to participate.
The final analysis included 100 students, 50
of whom received the M. officinalis and 50
received placebo (Figure 1, consort).
In Table 1 the demographic characteristics,
body mass index, and the menstruation
characteristics of the samples were presented,
indicating that there was no significant
difference between the two groups in terms
of these variables and the two groups were
homogeneous.
In both groups, the mean changes in
the systemic symptoms associated with
dysmenorrhea before and after the intervention
were evaluated. The severity of the systemic
symptoms associated with dysmenorrhea
decreased significantly (P = 0.001).
Among the systemic symptoms, the mean
severity of fatigue, the lack of energy and nervous
changes in the two groups decreased after the
treatment, which was statistically significant
(Table 2). Then, the difference between the
two groups of M. officinalis and placebo was
evaluated before and after the first and second
treatment cycles, by the Mann–Whitney test.
There was no significant difference between
the two groups regarding fatigue in the three
cycles, but there was a significant difference
between the two groups regarding lethargy in
the first cycle (P = 0.05) and the second cycle
(P = 0.001) after the treatment. The changes in
the neurological variability were significantly
different between the two groups only in the
second cycle of the intervention (P = 0.01).
The mean severity of bleeding before
and after the treatment was evaluated by the
Friedman test, which revealed no significant
differences (P = 0.52).
To study the mean difference in menstrual
periods between the two groups of drugs and
placebo, before and after the first and second
cycle after the treatment, the repeated measures
test was used, which did not show a significant
difference between the two groups in the three
cycles (P = 0.27). Also, in order to determine and
compare the duration of menstruation between
the two groups, a t-test was used that showed no
significant difference.
Discussion
This experiment did not detect any evidence
after the treatment on the severity of bleeding
and the duration of menstruation; however the
severity of the systemic symptoms associated
Mirabi P et al. / IJPR (2018), 17 (Special Issue 2): 214-223
218
with dysmenorrhea decreased significantly.
Most women have a mean normal volume of
menstrual bleeding, but if it is more than 80
milliliters, they could develop anemia. Given the
prevalence of iron deficiency, anemia in Iranian
girls and women is not so uncommon. People
are very willing to receive herbal medicines
and therefore, the physicians and midwives
need to be fully aware of the side effects of
herbal medicines in obstetrics and gynecology
(23). Several papers have been published in this
regard (24-26).
Figure 1. Flow of participants through the study
Assessed for eligibility (n=304)
Excluded (n=194)
Not meeting inclusion criteria (n =
133)
Declined to participate (n = 32)
Other reasons (n = 29)
Marriage,Ovarian cyst and other
disease needed to use OCP, Family
opposition,Changing student
di
Analysed (n=50)
Excluded from analysis (n=0)
Lost to follow-up(n=3)(non – adherence because of
perceived lack of effect and Changing student dormitory.
Discontinued intervention (n=2) Drowsiness, Nausea
Allocated to intervention (n = 55) Mellisa group
Received allocated intervention (n= 55)
Did not receive Mellisa (n = 0)
Lost to follow-up (n=2) (non – adherence
because of perceived lack of effect.
Discontinued intervention (n=3)Nausea
and cramping
Allocated to intervention (n=55) placebo
group
Received allocated intervention
(n = 55)
Analysed (n=50)
Excluded from analysis (n=0)
Allocation
Anal
y
sis
Follow‐U
p
Randomize
d
(
n=110
)
Enrollment
Figure 1. Flow of participants through the study.
The Effects of Lemon balm on Menstrual Bleeding and the Systemic Manifestation of Dysmenorrhea
219
Given the traditional use of M. officinalis as a
prescriptive drug and the fact that M. officinalis
is a phytoestrogen, the essence of which can
inhibit smooth muscle contractions (20), it is
expected that M. officinalis increases the severity
of menstrual bleeding, but the present study did
not approve this theory.
These results are in agreement with Mir
Ghafour et al., (2016), who showed that a
treatment with M. officinalis did not decrease
menstrual bleeding in students with premenstrual
syndrome (27).
Based on our search, we did not find another
study on this subject. But other medicinal plants
such as valerian, cinnamon, and fennel, which
are antispasmodic and have effects similar to
M. officinalis—that has positive effects on
dysmenorrhea and the systemic symptoms—did
not affect the duration and severity of bleeding
(8, 28, 29). Other important findings include
the systematic signs. Herbal medicines reduce
the level of prostaglandins, have a modulating
effect on nitric oxide, increase the levels of beta-
endorphin, block calcium channels, and improve
circulation; thus, they are effective in the
treatment of menstrual pain and the systematic
manifestation of dysmenorrhea (4, 30).
M. officinalis is one of the oldest and most
traditional herbal medicines. It is deemed to
be antispasmodic, sedative/hypnotic, and it is
used for strengthening the memory and for the
relief of stress-induced headache (31, 32). The
oil extracted from M. officinalis has an anti-
inflammatory effect and issued for dysmenorrhea
and its systematic sign (2, 33). In this study, with
regard to the systemic symptoms associated
with dysmenorrhea, the subjects in both groups
had a similar severity of symptoms before the
treatment and the severity of these symptoms
changed after the treatment in both groups.
The administration of M. officinalis reduced the
severity of the systemic symptoms associated
with primary dysmenorrhea, including fatigue,
neurological changes, and lethargy. However,
the severity of nausea and vomiting, diarrhea,
headache, and fainting was not significantly
different between the placebo and the treatment
groups, although there was a decrease after the
treatment.
One of the symptoms was neurological
changes. The treatment with M. officinalis
and placebo both decreased the severity of the
neurological changes, compared to before the
treatment. But the decrease in the neurological
changes was higher in the treatment group
than in the placebo group, and in the second
cycle after the treatment, there was a significant
difference between the two groups. Therefore,
according to these results, M. officinalis appears
to mitigate the severity of neurological changes
associated with dysmenorrhea.
Today, M. officinalis products are mainly
used for mild forms of neurologic weakness,
anxiety and stress, menstrual agitation, and
other neurological changes, and most studies
found to be one of its most important effects
(12, 231). Several reports have shown that M.
officinalis can reduce the neurological symptom
Table 1. Demographic characteristics of the participants .a
Characteristics Melissa Placebo P value b
Age (year) 21.08±1.34 21.14±1.61 0.60
Menarche 13.30±1.35 13.46±1.05 0.50
Age of dysmenorrhea 15.62±2.23 15.66±1.84 0.92
Body mass index (kg/m2)c21.73±3.07 22.59±3.82 0.24
Length of bleeding (day) 6.12±1.35 6±1.21 0.64
Length of Menstrual Cycle (day) 26.78±2.7 27.48±2.9 0.22
a Values are given as mean±SD unless otherwise indicated.
b t- test.
c Calculated as weight in kilograms divided by the square of height in meters.
Mirabi P et al. / IJPR (2018), 17 (Special Issue 2): 214-223
220
of premenstrual syndrome (PMS) through
the GABA neurotransmitters. The GABA
neurotransmitters have great inhibitory effects on
the central nervous system and are essential for
creating a balance between nervous stimulation
and suppression of the brain’s normal function.
It is reported that the brain’s GABA levels are
highly associated with anxiety in such a way that
benzodiazepines used as sedatives in the past
decades imitate the GABA neurotransmitters.
These medications result in sedative and
anxiolytic effects by binding to the GABAergic
receptors and changing other neurotransmitters
of the brain, such as norepinephrine and serotonin
(34-36). One study examined the effects of M.
officinalis in the treatment of anxiety disorders.
In this study, 20 men and women took 600 mg
of a proprietary M. officinalis extract twice daily
for 15 days. At the end of the study, 14 out of
the 20 patients reported full remission of their
anxiety (12).
In another study in 2009, the anti-depressant
effects of M. officinalis were compared with
imipramine and fluoxetine and in the end, the
researchers concluded that M. officinalis has an
antidepressant-like effect similar to imipramine
and this may have a potential clinical value
for the treatment of depression (37). In a study
by Adefunmilayo et al., a significant decrease
was observed in the severity of anxiety and
Table 2. Severity of systemic signs associated with dysmenorrhea, as measured on a multidimensional verbal scale (score range 0–3) a.
P-value c
nd Cycle 2st Cycle 1Base lineSystemic sign
0.02
1.58±0.91.48±0.91.44±0.1Melissa
Fatigue 0.611.80±0.81.46±1.031.50±1.07Placebo
-
0.770.970.33P -value b
0.820.50±0.760.50±0.810.62±1.01Melissa
Nausea and
vomiting 0.51 0.44±0.60.49±0.760.48±0.82Placebo
-0.560.81
0.05P -value
>0.001
1.08±0.81.34±0.872.30±0.8Melissa
Lack of energy 0.006
1.60±0.841.66±0.72.14±0.9Placebo
-0.0010.05
0.35
P -value
0.690.72±1.010.64±10.66±1.02Melissa
Headache 0.10.66±0.80.42±0.60.48±0.6Placebo
-0.360.610.96
P -value
0.310.30±0.60.34±0.60.36±0.6Melissa
Diarrhea 0.540.44±0.70.40±0.70.42±0.5Placebo
-0.340.890.30
P -value
>0.001
1.65±1.091.97±1.12.38±1.05Melissa
Mood swings >0.001
1.92±1.71.74±1.12.34±1.02Placebo
-0.01
094.0.64
P -value
0.360.20±0.40.24±0.40.32±0.62Melissa
Faint 0.01
0.30±0.60.34±0.60.38±0.7Placebo
-0.03
0.140.89
P -value
a Values are given as mean±SD unless otherwise indicated
b Mann–Whitney U test
c Friedman test
The Effects of Lemon balm on Menstrual Bleeding and the Systemic Manifestation of Dysmenorrhea
221
neurological symptoms with the administration
of M. officinalis (12).
Fatigue and lethargy are the other symptoms
on which M. officinalis has an effect. In traditional
books and some studies, the beneficial effects of
this plant on fatigue and lack of energy have
been expressed. The result of this study is,
therefore, in line with the previous studies (36).
One of the systemic symptoms was a headache.
In various studies and sources, M. officinalis
has been introduced as an effective medication
for headache and migraine (12, 31, 38). Fritz
and Speroff also state that menstrual headaches
are most often due to muscle contraction or
psychological stress. Given that M. officinalis an
anti-contraction and anti-stress herbal medicine
and has been found to be effective in treating
headache and migraine, it was expected that the
herb would have a better effect in this regard.
But the results of the present study were different
from the previous findings (39). The mean
severity of headache was lower in both groups
after the treatment and although this decrease
was not the same in the groups of M. officinalis
and placebo, the difference was not statistically
significant. It seems that M. officinalis, with this
dose and three-day interval administration, does
not improve the severity of headache associated
with dysmenorrhea, but a higher dose or a
greater number of administration days may have
significant effect.
During menstruation, prostaglandin that
contracts the smooth muscle of the uterus can
cause symptoms of smooth muscle contraction
else where in the body, including dyspnea due
to bronchial constriction and diarrhea due to
increased intestinal movements (39). Considering
the effect of M. officinalis on calming the
intestinal muscle (19), the digestive symptoms
associated with dysmenorrhea including
diarrhea,were expected to reduce. But in this
study, the severity of diarrhea after the treatment
did not change dramatically in both groups. In
traditional medicine, this herb is effective in the
treatment of diarrhea. According to our review,
no study has been done in this regard. But studies
have been conducted on plants similar to M.
officinalis that have antispasmodic and sedative
effects. One of the studies conducted on valerian
did not have any effect on the gastrointestinal
symptoms associated with dysmenorrhea (4). In
the study by Jafari et al., the effects of valerian
were studied on the reserpine rats and valerian
was not effective in reucing diarrhea, nausea,
and vomiting (40)
The main strength of this study is that it
Figure 2. Comparison of the mean severity of menstrual bleeding previous and after
intervention in two groups.
Figure 2. Comparison of the mean severity of menstrual bleeding previous and after intervention in two groups.
Mirabi P et al. / IJPR (2018), 17 (Special Issue 2): 214-223
222
is the first time that M. officinalis has been
assessed for its effectiveness on bleeding and
the systemic manifestation of dysmenorrhea.
Therefore, our results are innovative.
This study is subject to several limitations,
including the fact that the information was self-
reported by the participants and the responses
of the people were reassured in this regard.
The uncontrollable factors such as culture,
genetic profile, and lifestyle, which influence
the symptoms of dysmenorrhea, were the
weak points of this study. Also, considering
that this research was only conducted on the
dormitory students with almost similar weather
and nutritional conditions, it cannot indicate the
state of all women of reproductive ages. The
generalizability is compromised.
Conclusion
The present study demonstrated that M.
officinalis decreases the severity of the systemic
signs associated with menstruation, given that
no adverse effects have been reported for M.
officinalis. The present study also demonstrated
that M. officinalis does not increase the severity
of bleeding and the duration of menstruation.
However, M. officinalis, without any special
side effects, reduces the mean total score of the
severity of all the systemic symptoms associated
with dysmenorrhea. In the present study, the
severity of the neurological symptoms, fatigue,
and lethargy showed a significant decrease.
Therefore, the herb can be administered safely for
the management of the systemic manifestations
of dysmenorrhea.
Acknowledgment
This paper is the result of a research
project by Pharmaceutical Sciences Research
Center (PSRC), Shahid Beheshti University of
Medical Sciences. Hereby, the Chancellor, Vice
Chancellor and the Research Affairs Department
are warmly appreciated.
References
memory. Afr. J. Tradit. Complem. (2016) 13:199-209.
Bounihi A, Hajjaj G, Alnamer R, Cherrah Y and
Zellou A. In-vivo potential anti-inflammatory activity
of Melissa officinalis L. essential oil. Adv. Pharmacol.
Sci. (2013) 2013: 101759.
Bernstein MT, Graff LA, Avery L, Palatnick C,
Parnerowski K and Targownik LE. Gastrointestinal
symptoms before and during menses in healthy
women. BMC Womens Health (2014) 14.
Mirabi P, Dolatian M, Mojab F and Alavi Majd
H. Effects of valerian on the severity and systemic
manifestations of dysmenorrhea. Int. J. Gynaecol.
Obstet. (2011) 115: 285-8.
Armour M, Dahlen HG, Zhu X, Farquhar C and
Smith CA. The role of treatment timing and mode of
stimulation in the treatment of primary dysmenorrhea
with acupuncture: An exploratory randomised
controlled trial. PLoS One (2017) 12: e0180177.
Bernardi M, Lazzeri L, Perelli F, Reis FM and Petraglia
F. Dysmenorrhea and related disorders. F1000 Res.
(2017) 6: 1645.
Xu T, Hui L, Juan YL, Min SG and Hua WT. Effects of
moxibustion or acupoint therapy for the treatment of
primary dysmenorrhea: a meta-analysis. Altern. Ther.
Health Med. (2014) 20: 33-42.
Jaafarpour M, Hatefi M, Najafi F, Khajavikhan J and
Khani A. The effect of cinnamon on menstrual bleeding
and systemic symptoms with primary dysmenorrhea.
Iran. Red Crescent Med. (2015) 17:
Dawood MY and Khan-Dawood FS. Clinical
efficacy and differential inhibition of menstrual fluid
prostaglandin F2alpha in a randomized, double-blind,
crossover treatment with placebo, acetaminophen, and
ibuprofen in primary dysmenorrhea. Am. J. Obstet.
Gynecol. (2007) 196: 35 e1-5.
Care CAH. Menstruation in girls and adolescents:
using the menstrual cycle as a vital sign. Obstet.
Gynecol. (2015) 126: e143-e6.
Martinelli M, Ummarino D, Giugliano FP, Sciorio E,
Tortora C, Bruzzese D, De Giovanni D, Rutigliano I,
Valenti S, Romano C and Campanozzi A. Efficacy of
a standardized extract of Matricariae chamomilla L.,
Melissa officinalis L. and tyndallized Lactobacillus
acidophilus (HA122) in infantile colic: An open
randomized controlled trial. Neurogastroenterol.
Motil. (2017) 29: e13145
Cases J, Ibarra A, Feuillere N, Roller M and Sukkar
SG. Pilot trial of Melissa officinalis L. leaf extract in
the treatment of volunteers suffering from mild-to-
moderate anxiety disorders and sleep disturbances.
Med. J. Nutrition Metab. (2011) 4: 211-8.
LaGow B. (ed.) PDR for Herbal Medicines. 3rd ed.,
Thomson, Montvalle (2004) 502-3.
Ammon HP, Kelber O and Okpanyi SN. Spasmolytic
and tonic effect of Iberogast (STW 5) in intestinal
smooth muscle. Phytomedicine (2006) 5: 67-74.
Allahverdiyev A, Duran N, Ozguven M and Koltas
S. Antiviral activity of the volatile oils of Melissa
officinalis L. against Herpes simplex virus type-2.
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
Shojaii A, Ghods R and Abdollahi Fard M. Medicinal
herbs in Iranian traditional medicine for learning and
(1)
The Effects of Lemon balm on Menstrual Bleeding and the Systemic Manifestation of Dysmenorrhea
223
This article is available online at http://www.ijpr.ir
Phytomedicine (2004)11: 657-61.
Knipping K, Garssen J and van›t Land B. An evaluation
of the inhibitory effects against rotavirus infection of
edible plant extracts. Virol. J. (2012) 9: 137.
Thompson A, Meah D, Ahmed N, Conniff-Jenkins R,
Chileshe E, Phillips CO, Claypole TC, Forman DW
and Row PE. Comparison of the antibacterial activity
of essential oils and extracts of medicinal and culinary
herbs to investigate potential new treatments for
irritable bowel syndrome. BMC Complement. Altern.
Med. (2013) 13: 338.
Srivastava JK, Shankar E and Gupta S. Chamomile:
A herbal medicine of the past with a bright future
(Review). Mol. Med. Rep. (2010) 3: 895-901.
Reiter M and Brandt W. Relaxant effects on
tracheal and ileal smooth muscles of the guinea pig.
Arzneimittelforschung (1985) 35: 408-14.
Ulbricht C, Brendler T, Gruenwald J, Kligler B, Keifer
D, Abrams TR, Woods J, Boon H, Kirkwood CD,
Hackman DA and Basch E. Lemon balm (Melissa
officinalis L.): an evidence-based systematic review
by the Natural Standard Research Collaboration. J.
Herb Pharmacother. (2005) 5: 71-114.
Ebadollahi A, Parchin RA and Farjaminezhad M.
Phytochemistry, toxicity and feeding inhibitory
activity of Melissa officinalis L. essential oil against a
cosmopolitan insect pest; Tribolium castaneum Herbst.
Toxin Rev. (2016) 35: 77-82.
Magnay JL, Nevatte TM, O›Brien S, Gerlinger C
and Seitz C. Validation of a new menstrual pictogram
(superabsorbent polymer-c version) for use with
ultraslim towels that contain superabsorbent polymers.
Fertil Steril. (2014) 101: 515.
Akramipour R, Rezaei M and Rahimi Z. Prevalence of
iron deficiency anemia among adolescent schoolgirls
from Kermanshah, Western Iran. Hematology (2008)
13: 352-5.
Mirabi P, Alamolhoda H, Esmaeilzadeh S and Mojab F.
Effect of medicinal herbs on primary dysmenorrhoea-
a systematic review. Iran. J. Pharm. Res. (2014) 13:
757-767.
Khodakarami N and Moatar F. Efficacy of traditional
medicine for the treatment of primary dysmenorrhea.
Iran. J. Pharm. Res. (2004) 3 (Suppl. 2): 37-37.
Khorshidi N, Ostad NS, Mosaddegh M and Soodi
M. Clinical effects of fennel essential oil on primary
dysmenorrhea. Iran. J. Pharm. Res. (2003) 2: 89-93.
Mirghafour V, Malakouti J, Charandabi SMA,
Farshbaf-Khalili A and Ghanbari-Homayi S. The
effects of lemon balm (Melissa officinalis L.) alone
and in combination with Nepeta menthoides on the
menstrual bleeding in students with premenstrual
syndrome: a randomized controlled trial. Iran Red
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
Crescent Med. (2016) 18: e28941.
Bokaie M and Enjezab B. The effects of oral fennel
extract on the intensity of menstrualbleeding in
relieving dysmenorrhea: a randomized clinical trial.
Community Health (2014) 8: 55-62.
Mirabi P, Dolatian M, Mojab F and Namdari M. Effects
of valerian on bleeding and systemic manifestations of
menstruation. J. Med. Plants Res. (2012) 4: 155-64.
Jia W, Wang X, Xu D, Zhao A and Zhang Y. Common
traditional Chinese medicinal herbs for dysmenorrhea.
Phytother. Res. (2006) 20: 819-24.
Shakeri A, Sahebkar A and Javadi B. Melissa officinalis
L. - A review of its traditional uses, phytochemistry
and pharmacology. J. Ethnopharmacol. (2016) 188:
204-28.
Hosseini SR, Kaka G, Joghataei MT, Hooshmandi
M, Sadraie SH, Yaghoobi K and Mohammadi A.
Assessment of neuroprotective properties of Melissa
officinalis in combination with human umbilical cord
blood stem cells after spinal cord injury. ASN Neurol.
(2016) 8(6).
Mirabi P, Namdari M, Alamolhoda S and Mojab F. The
effect of Melissa officinalis extract on the severity of
primary dysmenorrhea. Iran. J. Pharm. Res. (2017)
16: 171-7.
Kennedy DO, Little W, Haskell CF and Scholey
AB. Anxiolytic effects of a combination of Melissa
officinalis and Valeriana officinalis during laboratory
induced stress. Phytother. Res. (2006) 20: 96-102.
Taiwo AE, Leite FB, Lucena GM, Barros M, Silveira
D, Silva MV and Ferreira VM. Anxiolytic and
antidepressant-like effects of Melissa officinalis (lemon
balm) extract in rats: Influence of administration and
gender. Indian J. Pharmacol. (2012) 44: 189-92.
Akbarzadeh M, Dehghani M, Moshfeghy Z,
Emamghoreishi M, Tavakoli P and Zare N. Effect
of Melissa officinalis capsule on the intensity of
premenstrual syndrome symptoms in high school girl
students. Nurs. Midwifery Stud. (2015) 4: e27001.
Emamghoreishi M and Talebianpour MS.
Antidepressant effect of Melissa officinalis in the
forced swimming test. Daru (2009) 17: 42-7.
Joukar S and Asadipour H. Evaluation of Melissa
officinalis (Lemon Balm) effects on heart electrical
system. Res. Cardiovasc. Med. (2015) 4: e27013.
Speroff L and Fritz MA. (Eds.) Clinical Gynecologic
Endocrinology and Infertility. 8th ed. Lippincott
Williams & Wilkins, (2010) 1488.
Jafari H RG. The effect of Valeriana officinalis and
amitriptyline on reserpinated rats. J. Gazvin Uni. Med.
Sci. (2001)16: 3-6.
(28)
(29)
(30)
(31)
(32)
(33)
(34)
(35)
(36)
(37)
(38)
(39)
(40)