The Effect of Magnesium Sulfate on Pain Intensity and Menstrual Blood Loss in Students With Primary Dysmenorrhea: A Randomized Controlled Trial

Abstract

Background: No evidence exists for the lowest effective dose of magnesium on menstrual pain.
Objective: To determine and compare the effects of two different doses of magnesium on pain intensity and menstrual blood loss in students with primary dysmenorrhea.
Methods: Sixty dysmenorrhea patients were randomly assigned to one of two therapeutic groups and one placebo group (receiving one tablet a day of 300 or 150 mg magnesium sulphate or placebo from the 15th cycle day until no pain existed on the following cycle). Visual analogue scale (VAS) and Hjgham collected data for two cycles before and two cycles after the intervention. The data were analyzed using one-way ANOVA and ANCOVA tests.
Findings: No significant difference was observed between the groups in terms of baseline characteristics. Both intervention groups outperformed the placebo group in terms of pain intensity (adjusted differences of -2.9, 95% confidence intervals of -3.3 to -2.4 and -1.9, -2.4 to -1.5, respectively) and menstrual bleeding (-20.0, -26.0 to -14.0, and -13.0, -19.0 to -7.0, respectively), as well as the secondary outcome, i.e. rest duration and ibuprofen consumption. In terms of pain alleviation and menstrual bleeding, participants in the 300 mg magnesium group outperformed those in the 150 mg magnesium group. No significant difference was observed between intervention groups regarding secondary outcomes.
Conclusion: Both magnesium levels are useful in alleviating pain and reducing menstrual bleeding, although 300 mg of magnesium was more effective.

Full text

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Autumn 2022. Vol 26. Num 3
Salimeh Nezamivand-Chegini1 , Parvin Abedi2 , Azam Honarmandpour3 , Forough Namjouyan4 , Masoumeh Yaralizadeh5* , Saeed
Ghanbari6
1. Department of Midwifery, Faculty of Nursing & Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran.
2. Department of Midwifery, Menopause Andropause Research Center, Ahvaz Jundishapur University of Medical Sciences, Iran.
3. Department of Midwifery, Faculty of Nursing & Midwifery, Shoushtar University of Medical Sciences, Shoushtar, Iran.
4. Department of Pharmacology, Faculty of Pharmacy, JondiShapour University of Medical Sciences, Ahvaz, Iran.
5. Reproductive Health Promotion Research Center, Ahvaz Jundishapur University of Medical Sciences, Iran.
6. Department of Biostatistics and Epidemiology, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
* Corresponding Author:
Maoumeh Yaralizadeh, MSc.
Address: Menopause Andropause Research Center, Ahvaz Jundishapur University of Medical Sciences, Iran.
Phone:
+98 (937) 7501228
E-mail: m.yaralizade@gmail.com
Research Paper
The Eect of Magnesium Sulfate on Pain Intensity
and Menrual Blood Loss in Students With Primary
Dysmenorrhea: A Randomized Controlled Trial
Background: No evidence exists for the lowest effective dose of magnesium on menstrual pain.
Objective: To determine and compare the effects of two different doses of magnesium on pain
intensity and menstrual blood loss in students with primary dysmenorrhea.
Methods: Sixty dysmenorrhea patients were randomly assigned to one of two therapeutic
groups and one placebo group (receiving one tablet a day of 300 or 150 mg magnesium sulphate
or placebo from the 15th cycle day until no pain existed on the following cycle). Visual analogue
scale (VAS) and Hjgham collected data for two cycles before and two cycles after the intervention.
The data were analyzed using one-way ANOVA and ANCOVA tests.
Findings: No significant difference was observed between the groups in terms of baseline
characteristics. Both intervention groups outperformed the placebo group in terms of pain
intensity (adjusted differences of -2.9, 95% confidence intervals of -3.3 to -2.4 and -1.9, -2.4
to -1.5, respectively) and menstrual bleeding (-20.0, -26.0 to -14.0, and -13.0, -19.0 to -7.0,
respectively), as well as the secondary outcome, i.e. rest duration and ibuprofen consumption. In
terms of pain alleviation and menstrual bleeding, participants in the 300 mg magnesium group
outperformed those in the 150 mg magnesium group. No significant difference was observed
between intervention groups regarding secondary outcomes.
Conclusion: Both magnesium levels are useful in alleviating pain and reducing menstrual
bleeding, although 300 mg of magnesium was more effective.
A B S T R A C T
Keywords:
Primary dysmenorrhea,
Magnesium sulfate,
Clinical trial, Menstrual
bleeding, Pain Intensity
Citation
Nezamivand-Chegini S, Abedi P, Honarmandpour A, Namjouyan F, Yaralizadeh M, & Ghanbari S. The Effect of
Magnesium Sulfate on Pain Intensity and Menstrual Blood Loss in Students With Primary Dysmenorrhea: A Randomized Con-
trolled Trial. Journal of Inflammatory Diseases. 2022; 26(3):115-122. http://dx.doi.org/10.32598/JID.26.3.3
:
http://dx.doi.org/10.32598/JID.26.3.3
Use your device to scan
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Article info:
Received: 13 Jun 2022
Accepted: 23 Sep 2022
Publish: 01 Oct 2022

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Autumn 2022. Vol 26. Num 3
1. Introduction
rimary dysmenorrhea is painful menstrua-
tion that affects around half of the adult
women and 90% of teens [1]. It affects
women’s quality of life and interferes with
their regular tasks [2]. The overproduction
of uterine prostaglandins is thought to be
the cause of menstrual pain [3, 4]. Al-
though prostaglandin inhibitors can help with menstrual
discomfort, long-term use can have some side effects
[5]. As a result, most women nowadays seek alternative
pain medications that have few or no adverse effects [6].
Evidence shows that various dietary supplements, such
as Omega-3 fatty acids, such as fish oil, vitamin B1,
vitamin B6, vitamin D, and vitamin E, can help reduce
menstrual pain. Magnesium may also aid with menstrual
discomfort, but the research is mixed [6]. Several dif-
ferent mechanisms exist through which magnesium can
influence dysmenorrhea.It affects serotonin and other
neurotransmitters, as well as vascular contraction, neu-
romuscular function, and cell membrane stability [7].
Some research suggests that magnesium can help re-
duce premenstrual syndrome symptoms and menstrual
discomfort [8-11]. Based on the result of a study, the
amount of prostaglandin F2ɑ in the menstrual blood of
women with primary dysmenorrhea who were treated
with magnesium reduced compared to before treatment
[12]. The researchers demonstrated that lower levels of
prostaglandins, a hormone-like molecule, are associated
with reduced pain and inflammation [13]. So, magne-
sium may also influence pain by lowering prostaglan-
dins [14-16]. It may also reduce pain by activating B
vitamins, particularly vitamin B6, and influencing mus-
cular relaxation by reducing calcium’s effect on muscle
contraction [17].
According to our knowledge, this is the first study to
examine the effects of 300 and 150 mg magnesium sul-
fate on menstrual pain severity and blood loss (primary
outcome), as well as the number of analgesics used and
rest duration due to dysmenorrhea (secondary outcome).
2. Materials and Methods
This double-blind, randomized, placebo-controlled tri-
al with three parallel arms (two intervention groups and
one placebo group) was conducted on dysmenorrheal
college students living in dorms at Ahvaz Jundishapur
University of Medical Sciences, from April to June 2016
(Ahvaz, Iran).
Participants were required to have regular menstrual
periods, suffer from moderate or severe primary dysmen-
orrhea (pain scores of 5 to 9 on the visual analogue scale
in previous cycles), and be single. Students with chronic
conditions (such as epilepsy, gastrointestinal, cardiovas-
cular, or renal diseases), as well as those using oral con-
traceptives or vitamin supplements, were eliminated.
We used data from a previous similar study (Mean±SD:
6.8±1.4 of primary dysmenorrhea) to compute sample
size, α=0.05, β=0.10, and a dropout probability of 15%,
a sample size of 20 was determined for each group [6].
The degree of monthly pain and the amount of men-
strual bleeding was assessed using a visual analogue
scale (VAS) and a Higham chart, respectively. VAS is a
validated 10-cm scale with a 0 on the left end (no pain)
and a 10 on the right end (the greatest imagined suffer-
ing) [18]. A table was created to record the number of an-
algesics (ibuprofen) used and the amount of time (hours)
spent in discomfort during the two days before and three
days after menstruation began.
The Higham chart’s validity has been demonstrated
in numerous studies and is widely recognized as one of
the most effective and reliable indicators of menstrual
bleeding. It is a table used to calculate menstrual blood
loss. Blood-stained pads are graded as light, moderate, or
severe, as well as the excretion of blood clots. A lightly
soiled pad receives a score of 1, a highly stained pad a
score of 5, and a blood-saturated pad a score of 20. Score
1 is assigned to each little clot and score 5 is assigned
to each large clot. Participants make a mark on the chart
each time they change the pad. At the end of the menstrua-
tion, each sign was multiplied by its score, and the figures
were calculated. At the end of the cycle, each sign was
multiplied by its score, the resulting numbers were added
together, and the overall score was calculated [19, 20].
We distributed the package to each participant in the
order decided at the enrollment visit. They were also giv-
en 20 ibuprofen tablets (400 mg) and the second diary.
The questionnaire had the same pre-intervention entries
as well as one extra item concerning the intervention
medication history. We asked the participants to take the
intervention pills daily, one pill per day, from day 15 of
their cycle until the day with no menstrual pain the next
cycle, and we kept a record of their pill intake. We then
instructed them to take the ibuprofen pills as needed and
to complete the remainder of the diary in the same man-
ner as before the intervention for two consecutive under-
intervention cycles (both the pills given as intervention
and the ibuprofen).
P
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Each tablet contains 300 mg or 150 mg of magnesium
sulfate, as well as lactose and microcrystalline cellulose
as excipients. Except for magnesium, all of the compo-
nents in the placebo were the same. The tablets were all
the same color, shape, and size. They were created in
the industrial pharmacy laboratory of Ahvaz Jundisha-
pur University of Medical Sciences Faculty of Pharmacy
under the direct supervision of a pharmacist from our re-
search team.
In this study, the dormitories were randomly selected,
while the subjects were recruited using convenience
sampling. The researcher visited the students’ rooms in
the designated dormitories to choose the subjects. She
introduced the study’s objectives to the students in each
room and requested those who were willing to partici-
pate and said yes to the question “Are you suffering
from painful menstruation?” To fill out a questionnaire
designed to determine who was qualified. A total of 99
suitable students were included in the study after sign-
ing a written informed consent form. Due to the danger
of pill pooling, we did not recruit more than one person
from each dormitory room. We gave the subjects 20 ibu-
profen (400 mg) tablets and a diary to fill up during the
next two menstrual cycles. We told them to only take the
medications for menstrual pain and not to take any other
pain medicines. Furthermore, they documented every
drug consumed in the diary. A list of potential adverse
effects was also given in the diary.
Sixty out of 99 cooperative students completed the pre-
intervention diaries completely and accurately and were
willing to continue participating in the study. They were
randomly assigned to one of three groups with a one-
to-one allocation ratio to receive two different doses of
magnesium or placebo tablets (Figure 1).
The allocation sequence was determined using automat-
ed randomized software and block randomization with
block sizes ranging from 6 to 9. The individual also made
sequentially numbered identical packets containing the 40
intervention pills based on the allocation order (for use
across two cycles). The skey outcomes of this study were
pain intensity and blood loss. The number of analgesics
(Ibuprofen) consumed during two menstrual cycles and
the period of rest due to dysmenorrhea was then measured
as secondary outcomes. As secondary outcomes, the in-
tensity of premenstrual symptoms was also recorded, and
the results are published in the other publication.
The menstrual pain intensity score was calculated
twice for each cycle, on the two days (2 days before and
3 days after the start of menstruation) with the highest
pain intensity; and on the five days overall. The reported
rest due to pain over five days was added to establish the
duration of rest at each cycle. The average of the out-
comes was used as the baseline value during the two pre-
intervention cycles, and the average of those recorded
was used as the under-intervention value during the two
post-intervention cycles.
Statistical analysis
The baseline values of the groups were compared using
one-way ANOVA. The ANCOVA test was performed to
compare the groups in terms of under-intervention pain se-
verity, quantity, and menstrual bleeding adjusted for baseline
values after correcting for model assumptions. Sidak was
utilized to perform multiple group comparisons. All analyses
were performed with SPSS software, version 16.0, and a sta-
tistically significant difference was defined as P<0.05.
3. Results
Nobody was excluded from the analysis of the 60 stu-
dents who were randomly assigned to groups. None of
the subjects in the groups reported any adverse effects.
In terms of baseline characteristics, no discernible differ-
ence was observed between the groups. Their Mean±SD
age was 21.0±1.5, and their Body Mass Index (BMI)
was 24.6±2.5. Regular exercise was mentioned by one-
third (33.3%) of participants. Three-quarters (75%) had
a family history of dysmenorrhea, and around three-
quarters (70%) said their menstrual pain interfered with
their activities (Table 1).
The characteristics of the groups did not significantly
differ from one another. Participants in both interven-
tion groups (300 and 150 mg magnesium) outperformed
the placebo group in terms of both primary outcomes,
namely menstrual pain intensity (adjusted difference:
-2.8 [95% confidence interval: -3.4 to -2.2], and [-2.4 to
-1.2], respectively); as well as menstrual blood loss (ad-
justed difference: -20.- [95% confidence interval:-26.0
to -14.0], and -13.0 [-19.0 to -7.0]), as well as in the sec-
ondary outcome, i.e. the rest duration (-0.7 [-0.9 to -0.5]
and -0.6 [-0.9 to -0.5], respectively]), and the different
number of ibuprofen taken (mean difference [95%CI],
-1.7 [-2.4 to -1.1] and -1.8 [-2.4 to -1.1], respectively). In
terms of pain reduction, participants in the 300 mg mag-
nesium group did better than the 150 mg magnesium
group (-0.9 [-1.4 to -0.5]) and blood loss during men-
struation (-7.0 [-13.0 to -1.05]) (Table 2). No significant
difference was observed between intervention groups
regarding secondary outcomes, resting time (-0.0 [-0.2
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to 0.2]), and no significant difference was observed in
the number of ibuprofen taken (0. [-0.6 to 0.6]) (Table 3).
4. Discussion
The severity of primary dysmenorrhea and menstrual
blood loss were examined, and the effects of two differ-
ent dosages of magnesium sulphate were compared for
the first time. The current study showed that both thera-
pies can reduce the severity of primary dysmenorrhea,
monthly blood loss, rest length owing to menstrual pain,
and the number of analgesics used. The participants re-
ported no side effects. The effect of 300 mg of magne-
sium sulfate in reducing pain and the amount of men-
strual bleeding was greater than 150 mg of magnesium
sulfate and placebo.
Menstrual pain is the most prevalent symptom among
women with regular periods
[21]
, and the most common
treatment for it is nonsteroidal anti-inflammatory drugs,
which have a failure rate of about 25% and can produce
negative effects in some circumstances
[22]
; As a result,
many researchers are trying to uncover other treatments,
such as complementary and alternative therapies, and sev-
eral studies are being conducted in this area. The genesis
and treatment of menstruation problems may be influ-
enced by nutritional and metabolic factors. Dietary treat-
ments are numerous, but more research is needed
[23]
.
Magnesium supplementation has been shown in clini-
cal trials to lessen menstrual discomfort, which is con-
sistent with the results of the current study [8, 11]. In
a study conducted by Benassi et al., every woman re-
Table 1. Baseline characteristics of the subjects by the study groups (n=20)
Characteriscs
Mean±SD/No. (%)
Magnesium 300 mg Magnesium 150 mg Placebo P
Age (y) 21.3±0.9 21.0±1.6 20.9±1.9 0.67
BMI (kg/m2)24.5±2.3 25.2±2.4 24.2±2.7 0.47
Educational level
Bachelor of science 13(35) 13(35) 17(85)
0.27
Higher 7(65) 7(65) 3(15)
Regular exercise 9(45) 6(30) 5(24) 0.39
Age at Menarche (y)
Mean±SD 12.2±0.4 12.4±0.5 12.2±0.7
0.51
Min-max 12-13 12-13 11-14
Family history of dysmenorrhea 15(75) 17(85) 13(65) 0.35
Interference with daily activities 16(80) 12(60) 14(70) 0.39
Duration of men-
strual bleeding (day)
6, <6 12(60) 8(40) 10(50)
0.27>6 8(40) 12(60) 10(50)
Min-max 4-7 5-7 5-7
Amount of menstrual
bleeding (CC)
Less than 50 8(40) 2(10) 7(35)
0.51
50-59 2(10) 9(45) 5(25)
60-69 6(30) 4(20) 7(35)
70 and more than 70 4(20) 5(25) 1(5)
Min-max 37-83.5 36-74 40.5-72.5
P for qualitative variables was calculated using chi-square test and in quantitative variables using one-way ANOVA.
SD: Standard deviation; BMI: Body mass index
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ceived 4.5 mg of oral magnesium pidolate three times
a day from the seventh day before menstruation until
the third day of menstruation [8]. Dysmenorrhea was
reduced in magnesium-treated cycles, with a significant
difference compared to the control group. Fontana et al.
studied the therapeutic benefits of magnesium on men-
strual pain in another investigation. According to the re-
searchers, magnesium had a therapeutic impact on both
back pain and lower abdomen discomfort on the second
and third days of the cycle [11]. No other study exists
that can be directly compared with the current study’s
findings. Therefore, in the following, other related stud-
ies will be discussed.
It has been reported that plasma levels of magnesium
in the premenstrual period are lower in people suffering
from premenstrual syndrome [24]. This finding can con-
firm the result of our study. According to Mohammad-
Alizadeh et al. (2013), combining 300 mg magnesium
stearate with 600 mg calcium carbonate is more benefi-
cial than calcium carbonate alone in lowering menstrua-
tion discomfort [25]. According to one study, increasing
dietary magnesium intake in women with primary dys-
menorrhea can reduce the degree of menstrual discomfort
[26]. However, another study found that a daily intake of
500 mg of magnesium did not affect pain reduction when
compared to the placebo and vitamin B6 groups [17].
Table 2. Comparison of the magnesium groups and placebo group with regard to the primary outcomes of study
Primary
Outcomes
Mean±SD
(n=20 in Each Group)
Comparison
Three
Groups
Magnesium 300
mg With Placebo
Magnesium 150 mg
With Placebo
Magnesium 300 mg
With 150 mg
Magnesium
Placebo P
Dier-
ence
(95% CI)
PDierence
(95% CI) PDierence
(95% CI) P
300 mg 150 mg
Pain intensity
(VAS, 0-10)
*
Baseline
†
6.3±0.6 6.2±0.6 6.3±1.2 0.863
Under-
intervention
‡
2.8±0.7 3.7±0.5 5.7±0.7 <0.001
-3.0
(-2.3 to
-3.3)
<0.001 -2.0
(-2.4 to -1.5) <0.001 -1.0
(-1.4 to -0.5) <0.001
Amount of menstrual
bleeding (Higham chart, CC)
Baseline 58.2±13.2 59.1±2.7 55.1±9.9 0.510
Under-
intervention 34.4±7.0 41.4±9.2 54.4±11.8 <0.001
-20.0
(-26.0 to
-14.0)
<0.001
-13.0
(-19.0 to
-7.0)
<0.001 -7.0
(-13.1 to -1.0) 0.023
Duration of menstrual
bleeding (day)
Baseline 6.0 ±0.7 6.3±0.6 6.1±0.6 0.278
Under-
intervention 4.9±0.5 5.6±1.3 6.0±0.8 0.002
-1.1
(-1.7 to
-0.5)
<0.001 -0.4
(-1.0 to -0.1) 0.130 -0.6
(-1.2 to -0.1) 0.031
* Each person reported average of pain intensity during 2 days before and 3 days after starting menstruation during two cycles
before and two cycles under intervention, in each cycle, mean pain intensity during 5 days was considered as pain intensity
at each cycle and mean of pain intensity during the two pre-intervention cycle considered as baseline pain intensity and mean
intensity during two months after starting the intervention was considered as under-intervention pain intensity.
† One-way ANOVA was used for the baseline comparisons.
‡ ANCOVA test was used for the under-intervention pain intensity, amount and duration of menstrual bleeding comparisons
adjusted for the baseline values using Sidak for the multiple comparisons between the groups.
Abbreviations: CI: condence interval; VAS: Visual Analogue Scale
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Table 3. Comparison of the magnesium groups and placebo group with regard to the secondary outcomes of study
Secondary
Outcomes
Mean±SD
(n=20 in Each Group)
Comparison
Three
Groups
Magnesium 300
mg With Placebo
Magnesium 150 mg
With Placebo
Magnesium 300
mg With 150 mg
Magnesium
Placebo PDierence
(95% CI) PDierence
(95% CI) PDierence
(95% CI) P
300 mg 150 mg
Rest length due to
dysmenorrhea at each
cycle (h)
Baseline†
0.8±1.1 0.7±0.5 0.9±0.6 0.486
Under-
intervention‡
0.2±0.2 0.3±0.2 1.0±0.5 <0.001
-0.7
(-0.9 to
-0.5)
<0.001
-0.6
(-0.9 to
-0.4)
<0.001
-0.0
(-0.2 to
0.2)
0.890
Number of Ibuprofen
taken at each cycle ∫
Baseline
3.3±2.2 2.7±1.5 3.1±1.7 0.652
Under-
intervention
0.6±1.1 0.6±0.9 2.4±1.1 <0.001
-1.7
(-2.4 to
-1.1)
<0.001
-1.8
(-2.4 to
-1.1)
<0.001
-0.0
(-0.6 to
0.6)
0.939
† One-way ANOVA was used for the baseline comparisons.
‡ ANCOVA test was used for the under-intervention comparisons adjusted for the baseline values using Sidak for the multiple
comparisons between the groups.
∫ Mean number of Ibuprofen 400 mg taken at each cycle due to dysmenorrhea at the two pre-intervention cycle (baseline) and
at two months after starting the intervention (under-intervention).
CI: Condence interval
Figure 1. Flow diagram of study
Pre-intervention follow up
Allocation
Post-intervention
Follow up
Fig 1: Flow diagram of study
Assessed for eligibility (n = 150)
Excluded (n = 51)
Not meeting eligibility criteria (n =
47)
Refused to participate (n=4)
Follow up for 2 cycles (n = 99)
Allocated to magnesium 300 mg (n = 20)
Received allocated intervention (n = 20)
Allocated to magnesium 150 mg (n = 20)
Received allocated intervention (n = 20)
Allocated to placebo (n = 20)
Received allocated intervention (n = 20)
Did not complete and deliver the
questionnaires (n = 0)
Followed up for two months (n = 20)
Did not complete and deliver the
questionnaires (n = 0)
Followed up for two months (n = 20)
Did not complete and deliver the
questionnaires (n= 0)
Followed up for two months (n = 20)
Analyzed (n = 20)
Analyzed (n = 20)
Analyzed (n = 20)
Excluded (n=39)
No good cooperation (n = 11)
Regret to participate (n = 28)
Randomized (n = 60)
Enrollment
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Some reports
indicate that college students’ dietary sta-
tus is inadequate. Fiber, vitamin D, vitamin E, calcium,
magnesium, potassium, and iron are the most commonly
reported nutrients to be deficient in the normal college
student’s diet
[27]
. Dietary deficiencies in minerals and
vitamins have been reported among Iranian students
[28].
5. Conclusion
It has been demonstrated that taking 150 to 300 mg of
magnesium per day from the 15th day of the menstrual
cycle until the onset of dysmenorrhea of the following
cycle significantly reduced menstrual pain severity and
flow. Compared to 150 mg of magnesium and a placebo,
the effect of 300 mg of magnesium was stronger. Nev-
ertheless, for widespread application of the findings,
further study on the efficacy and safety of the results in
different contexts with a bigger sample size is recom-
mended.
Limitations of the study
The requirement to take the medications daily can be
annoying and lead to a lack of follow-up. We did not
measure the participants’ magnesium intake in this study.
The strong benefits of the therapies on pain alleviation
found in this study could be attributed to magnesium in-
sufficiency in the dormitory students, and the findings
may not apply to other girls with good diets.
Another limitation of this study is the short period of
the investigation and the absence of follow-up following
supplementation withdrawal. Based on the outcomes of
this study, we cannot estimate the long-term influence of
these supplements on menstrual discomfort.
Ethical Considerations
Compliance with ethical guidelines
This trial is registered in the Iranian registry system
with a code of IRCT2015080319743N2 and approved
by the ethics committee of Ahvaz Jundishapur Univer-
sity of Medical Sciences with a code of ethics AJUMS.
REC.1394.347 dated October 4, 2015.
Funding
Ahvaz Jundishapur University of Medical Sciences fi-
nancially supported this project.
Authors' contributions
Conceptualization and supervision: Parvin Abedi,
Masoumeh Yaralizadeh and Salimeh Nezamivand
chegini; Methodology, investigation, writing-original
draft, and writing-review and editing: All authors; Data
collection: Azam Honarmandpour and Masoumeh
Yaralizadeh; Data analysis: Saeed Ghanbari and Salimeh
Nezamivand chegini; Funding acquisition and resourc-
es: Parvin Abedi, Masoumeh Yaralizadeh and Salimeh
Nezamivand chegini.
Conict of interest
The authors declared no conflict of interest.
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