Cochrane Database of Systematic Reviews

by
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Vitamin or mineral supplements
t u t for premenstrual syndrome
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(Protocol) Ins nizo
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Kaewrudee S, Kietpeerakool C, PattanittumsP,
i c LumbiganongP
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Kaewrudee S, Kietpeerakool C, Pattanittum P, Lumbiganon P.

Vitamin or mineral supplements for premenstrual syndrome.
Cochrane Database of Systematic Reviews 2018, Issue 1. Art. No.: CD012933.
DOI: 10.1002/14651858.CD012933.

www.cochranelibrary.com

Vitamin or mineral supplements for premenstrual syndrome (Protocol)

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . .
b . y
. . . . . . . . . . 6
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . .
j o l
. . . . . . . . . . . . 8
CONTRIBUTIONS OF AUTHORS
DECLARATIONS OF INTEREST .
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SOURCES OF SUPPORT . . . . . . . . . . . . . .
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Vitamin or mineral supplements for premenstrual syndrome (Protocol) i

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Vitamin or mineral supplements for premenstrual syndrome

Srinaree Kaewrudee1 , Chumnan Kietpeerakool1 , Porjai Pattanittum2 , Pisake Lumbiganon1

1 Department
b y
of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 2 Department of
j o l
Epidemiology and Biostatistics, Public Health Faculty, Khon Kaen University, Khon Kaen, Thailand

P u
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Contact address: Srinaree Kaewrudee, Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon
Kaen, Thailand. ksrina@kku.ac.th. u
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Editorial group: Cochrane Gynaecology and Fertility Group.
n a
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Publication status and date: New, published in Issue 1, 2018.
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Citation: Kaewrudee S, Kietpeerakool C, Pattanittum P, Lumbiganon P. Vitamin or mineral supplements for premenstrual syndrome.

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Cochrane Database of Systematic Reviews 2018, Issue 1. Art. No.: CD012933. DOI: 10.1002/14651858.CD012933.
I n i
i & Sons, Ltd.il. co
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Copyright © 2018 The Cochrane Collaboration. D
Published by John Wiley
a
d e i l a m
d a r i sc @
g
p rie a P A B S T RbAaC T
ro for a Cochrane
This is a protocol
f t p a r Thelobjectives
Review (Intervention). i ad are as follows:
P o and safety sc supplementation for alleviating symptoms in women with a diagnosis
oof vitamin andrimineral
i s
To evaluate the effectiveness d
of premenstrual n ia dysphoric i.p disorder.
O syndrome nor cpremenstrual t r
c e n u
L i il:
a
B A C K G R O U N -Dm physical symptoms include breast tenderness, headaches, muscu-
E loskeletal pain, abdominal swelling, swelling of extremities, and
weight gain (O’Brien 2011). Common psychological and be-
Description of the condition havioural symptoms include depression, changes in appetite, fa-
tigue or lethargy, mood swings, irritability, sleep disturbances, ten-
Premenstrual syndrome (PMS) is a common health problem for
sion, social withdrawal, and poor concentration (O’Brien 2011).
women. Previous studies have shown that up to 90% of women
Diagnosis of PMS stipulates (1) the presence of at least one of a
have experienced some form of PMS during their reproductive
number of affective symptoms (depression, angry outbursts, irri-
years (Jarvis 2008). Furthermore, in approximately 5% to 8% of
tability, anxiety, confusion, social withdrawal) and at least one so-
these women, affective symptoms are severe and cause substan-
matic symptom (breast tenderness, abdominal bloating, headache,
tial impairment of normal daily functioning (Jarvis 2008). An in-
swelling of extremities) during the five days before menses in each
teraction of gonadal steroid hormone and central nervous sys-
of the three prior menstrual cycles; and (2) spontaneous regression
tem neurotransmitters appears to contribute to development of
of these symptoms within four days of the onset of menses, with-
PMS (Yonkers 2008; Rapkin 2009). In line with this notion, oral
out recurrence until at least cycle day 13, excluding cases involving
contraceptives and selective serotonin reuptake inhibitors (SSRIs)
pharmacological treatment, hormone intake, alcohol consump-
have been shown to reduce the symptoms of PMS (Lopez 2012;
tion, or socioeconomic performance disability (ACOG 2015).
Marjoribanks 2013).
This information should be obtained by prospective collection
PMS occurs during the luteal phase of the menstrual cycle and
rather than by retrospective recall (ACOG 2015).
spontaneously diminishes within a few days after onset of menstru-
Premenstrual dysphoric disorder (PMDD) is a subtype of PMS.
ation. Characteristic symptoms of PMS include physical symp-
Therefore all women given a diagnosis of PMDD meet the diag-
toms and psychological and behavioural symptoms. Common
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 1
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
nostic criteria for PMS as well, but their symptoms are more severe How the intervention might work
(Steiner 2000). Appendix 1 presents the standard diagnostic cri-
Deficiencies of certain vitamins and minerals including vita-
teria for PMDD as proposed by the American Psychiatric Associa-
min B, vitamin D, calcium, and magnesium may play a role
tion (Freeman 2003). Predominant symptoms of PMDD include
in PMS. This hypothesis is based primarily on the high inci-
anger, irritability, and internal tension (Steiner 2000). Through-
dence of PMS in populations with low levels of these micronu-
out this review, we use the term PMS to include PMDD.
trients (Posaci 1994; Rosenstein 1994; Bertone-Johnson 2005;
The diagnosis of PMS can be established only after exclusion of
Thys-Jacobs 2007; Chocano-Bedoya 2011).
other possible causes of symptoms, including affective disorders
b y
Magnesium is essential for the brain’s dopaminergic synthesis.
(e.g. depression, anxiety, dysthymia, panic); anorexia or bulimia;
j o l
Dopamine imbalance can affect mood and can lead to overwhelm-
and chronic medical conditions such as anaemia, diabetes mellitus,
hypothyroidism, or substance abuse (O’Brien 2011).
u
ing anxiety (Li 2001). Previous studies have reported decreased cir-
P
u l a
culating magnesium concentrations during the luteal phase among
women with PMS, suggesting that magnesium deficiency may be

P a
a key factor in the aetiology of PMS (Posaci 1994; Rosenstein

n a 1994).
Bertone-Johnson 2005 conducted a substudy of a prospective
A
Description of the intervention
t u to Nurses’ Health Study, which found that women with high intake
of vitamin D and calcium carried lower risk of developing PMS
Because the aetiology of PMS is not clear, symptom
s ti relief is the compared with those in the group with low intake, with a risk
m
goal of treatment. Cochrane Reviews evaluatingI n the efficacy of an iniz o
ratio of 0.59 (95% confidence interval (CI) 0.40 to 0.86) and
c
SSRI and an oral contraceptive containing
d o(Lopezdrospirenone for man-
2012; Marjoribanks a
D a il.
0.70 (95% CI 0.50 to 0.97), respectively. A previous study noted

il
that a calcium deficiency during the luteal phase among women
agement of PMS have shown benefit
2013). Women presenting d
e c g m
with PMS was secondary to the disturbance of calcium-regulating
are prescribed SSRIs, d a with severe PMS symptoms usually
i s
non-steroidalranti-in-
a@
hormones that follows the rise in ovarian steroid hormone con-
flammatory drugs e oral contraceptives,
ir (NSAIDs), P
diuretics, or gonadotropin-releas-
b
centrations and vitamin D deficiency (Thys-Jacobs 2007).

o p agonists, depending onatheir

ing hormone (GnRH)
r ra predominant ad
In addition, the risk of developing PMS is lower in women with
f t p may be effectiveilfor
P
symptoms (O’Brien 2011). These therapies
sc ad-
o but they aredolinked with substantial
i
high dietary intake of vitamin B than in those with low intake
many women with PMS,
i s
n with long-term r (Chocano-Bedoya 2011). Vitamin B is thought to be involved in
verse effects (particularly
adherence toO
ia use),trwhich
treatment (Wangc1995; Sundstrom-Poromaa
i .p may reduce various steps of serotonin metabolism including converting tryp-

e n u
tophan amino acid to serotonin and generating the active sub-
2000;

icas any of a group : nof natural organic sub-

Martin 2014).
Vitamins are defined L i l
stances that are necessary in smallaamounts and act as coenzymes
and precursors of coenzymes
E -min regulating various metabolic pro-
cesses (Ward 2014). Minerals are defined as chemical elements
required as essential nutrients to maintain body functions (Ward
2014). Several vitamins and minerals including vitamin B, vita-
min D, calcium, and magnesium are essential for neurotransmitter
synthesis and hormonal balance, both of which are potentially in-
volved in the underlying pathogenesis of PMS. Vitamin and min-
eral supplements may be effective in alleviating PMS symptoms;
it has been noted that the incidence of PMS is low among women
with diets rich in vitamins or minerals (Rosenstein 1994; Bertone-
Johnson 2005; Chocano-Bedoya 2011). Reported adverse effects
of vitamin and mineral supplements for PMS include nausea, con-
stipation, abdominal discomfort, dizziness, and headache (Whelan
2009). Cochrane systematic reviews of vitamin and mineral sup-
plements used for indications such as subfertility (Showell 2014;
Showell 2017), diabetic kidney disease (Raval 2015), and preg-
nancy (Haider 2015) have not provided evidence of serious ad-
verse effects. However, uncertainty remains regarding the safety
of vitamin and mineral supplements owing to poor reporting of
adverse events in the included studies.
stances required for metabolism of serotonin. Vitamin B deficiency
can thus hinder serotonin production, which can result in mood
disorders (Hvas 2004; Lewis 2013).
Why it is important to do this review
PMS may have a negative impact on social relationships, pro-
fessional activities, and healthcare resource utilisation (O’Brien
2011). Thus it is necessary to gather reliable scientific evidence
regarding effective interventions for ameliorating PMS symp-
toms. Research has suggested that PMS is associated with low
dietary intake of some select vitamins or minerals (Rosenstein
1994; Bertone-Johnson 2005; Chocano-Bedoya 2011); therefore
a promising treatment option may consist of supplementation of
these vitamins or minerals to achieve optimal status, although
available evidence regarding the benefits and harms of vitamin and
mineral supplements for PMS is largely inconclusive. It is impera-
tive to establish whether vitamin or mineral supplements are effec-
tive and safe for alleviating PMS symptoms - a task that would be
best accomplished through a systematic review and meta-analysis
of findings of randomised controlled trials. Accordingly, we will
conduct this Cochrane systematic review with the goal of evaluat-

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 2

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ing the effectiveness and safety of vitamin or mineral supplements • Vitamins or minerals or both in any dose and through any
in alleviating PMS symptoms. route of administration versus other vitamins or minerals or both
in any dose and through any route of administration.

Types of outcome measures

OBJECTIVES
To evaluate the effectiveness and safety of vitamin and mineral
supplementation for alleviating symptoms in women with a diag- Primary outcomes
l by
nosis of premenstrual syndrome or premenstrual dysphoric disor-
u
• End scores and jochange scores for all symptoms of PMS,
der. measured via Pa validated prospective symptom rating tool. Our
preferredla
tools (in order of preference) include Calendar of
a u Experience (COPE); Daily Record of Severity of
Premenstrual

aP
METHODS Problems (DRSP); Moos’ Menstrual Distress Questionnaire

An
(MDQ); and Premenstrual Tension Syndrome Self-Rating Scale
(PMTS-SR). We will include end scores or change scores from
t o each study, if feasible. We prefer to use end scores and to report
Criteria for considering studies for this review
it tu change scores as a separate outcome.

I ns ini
z m
• Adverse effects, categorised as:
co
il.
◦ all adverse events per participant;
Types of studies d o D a
◦ specific adverse effects, which may include digestive
a
d e cil
We will include randomised controlled trials (RCTs) irrespective of
a is g m
symptoms (e.g. diarrhoea, constipation, nausea, abdominal
discomfort, gastric upset, dry mouth); neurological symptoms
d r
language of publication, publication status, year of publication, or
a@
rie P
sample size. We will exclude quasi-randomised trials (e.g. studies (e.g. headache, insomnia, dizziness); and skin symptoms (e.g.

ra b
op ft d
with evidence of inadequate sequence generation such as use of rash, acne); or
r p a
alternate days or patient numbers) and non-randomised studies
P ila ◦ withdrawals due to adverse effects.

i s o o i sc
as they tend to have high risk of bias. We will include cross-over
d r
On ncia i.p
trials and cluster-randomised trials (if any are available), as these
t r
designs are valid in this context. However, we will use only first-
u
Secondary outcomes

e n
phase data of cross-over trials in our analyses to avoid a carryover
i c
effect.
L a il:
m
E-
Types of participants
We will include studies of women of reproductive age who met
medically defined diagnostic criteria for PMS (including PMDD,
which is a severe form of PMS). Diagnosis of PMS requires that
symptoms are confirmed by prospective recording for at least two
menstrual cycles. Diagnosis must have been made by healthcare
professionals before inclusion of women in the study. We will
exclude studies that were based solely on self-diagnosis.
Types of interventions
We will include trials comparing the following interventions.
• Vitamins or minerals or both in any dose and through any
route of administration versus placebo or no treatment.
• Vitamins or minerals or both in any dose and through any
route of administration versus other treatment.
• Vitamins or minerals or both in any dose and through any
route of administration combined with other treatment versus
that other treatment alone or that other treatment plus placebo.
• End scores and change scores for specific PMS symptoms:
psychological, physical, and functional symptoms; irritability
measured on a single-item visual analogue scale (VAS).
• Response rate: assessed as the number of participants with
improved PMS symptoms from baseline (i.e. complete reduction
or improvement vs slightly better or no difference from baseline).
• Rate of use of additional medications (e.g. SSRIs, oral
contraceptives, NSAIDs), depending on the participant’s
predominant symptoms.
• Cost-effectiveness.
• Quality of life (QoL): end scores and change scores for QoL,
provided this information has been recorded in a reproducible
and validated format. Our preferred tools (in order of preference)
include Pre-Menstrual Symptoms Impact Survey (PMSIS); 36-
item Short Form (SF 36); and 12-item Short Form (SF 12).
If data permit, we will analyse outcomes at the following time
points: three months (our preferred follow-up time), six months,
and one year from the start of treatment, and at the end of the
trial.
We will present a ’Summary of findings’ (SoF) table to report
primary outcomes listed in order of priority.
• End scores for all PMS symptoms.
• All adverse effects.

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 3

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 • Specific adverse effects. • Latin American Caribbean Health Sciences Literature
• Withdrawals due to adverse effects. (LILACS) database, at http://regional.bvsalud.org/php/
index.php?lang=en (for trials from the Portuguese and Spanish
speaking world).
Search methods for identification of studies • PubMed and Google Scholar (for recent trials not yet
indexed in the major databases).
We will search for all published and unpublished RCTs in consulta-
tion with the Cochrane Gynaecology and Fertility Group (CGFG)
Information Specialist, with no restrictions regarding language,
l
Searching other resources by
We will handsearchjo
publication status, year of publication, or sample size.
by the search.P
u reference lists of reviews and articles retrieved
We will also handsearch relevant journals and con-
Electronic searches la that are not included in the CGFG Register, in
ference abstracts
liaisonuwith the CGFG Information Specialist.
Pa
We will search the following electronic databases, trial registers,
and websites from their inception to the present.
• Cochrane Gynaecology and Fertility Group (CGFG) n a
Specialised Register of Controlled Trials (Procite platform)
o A Data collection and analysis
t
it tu
(Appendix 2).
• Cochrane Central Register of Studies Online (CRSO) (web
platform) (Appendix 3).
I ns i z
Selection of studies
n c o m
i downloadilall. titles and abstracts retrieved through the
d o
• MEDLINE (Ovid platform) (Appendix 4).
D
We will
searcha
• Embase (Ovid platform) (Appendix 5).
d e i l a After removing
electronic
m to a reference management database (EndNote).
• PsycINFO (Ovid platform) (Appendix 6).
a i s c (Covidence). g Two review authors
duplicates, we will transfer these data to Covidence

ir ed
• Allied and Complementary Medicine Database (AMED)
(Ovid platform) (Appendix 7). P r a @the remaining references.(SKWeandwillCK)exclude
will independently

p r a
• Cumulative Index to Nursing and Allied Health Literature
d bclearly do not meet the inclusion criteria. We will obtain
examine studies that

ro f t
(CINAHL) (Ebsco platform) (Appendix 8).
p a i l a of full texts of potentially relevant references. Two review authorscopies
P
We will combine thes o search owith the Cochrane
i scHighly (SK and CK) will independently assess the eligibility of retrieved
Sensitive Search n
i MEDLINE
d r
ptrials, which reports/publications. We will resolve disagreements through dis-
OCochrane c iafor Systematic
Strategy for identifying
i
randomised
r .
appears in the
e n 6, 6.4.11).uWet will combine
Handbook Reviews of Inter- cussion, or, if required, we will consult a third review author (PL).

i c
ventions (Version 5.0.2, Chapter
l : nusing trial filters devel-
Em- We will identify and exclude duplicates and will collate multiple
base, PsycINFO, andL CINAHL
a iGuidelines Network (SIGN) reports
searches
oped by the Scottish Intercollegiate
of the same study, so that each study rather than each report

-m
- http://www.sign.ac.uk/methodology/filters.html#random.
E
Other electronic sources of trials will include the following.
• Trial registries for ongoing and registered trials -
ClinicalTrials.gov, a service of the US National Institutes of
Health, at http://www.clinicaltrials.gov; and the World Health
Organization International Trials Registry platform search
portal, at http://www.who.int/trialsearch/Default.aspx.
• Database of Abstracts of Reviews of Effects (DARE), in the
Cochrane Library, at http://onlinelibrary.wiley.com/o/cochrane/
Cochrane cldare articles fs.html (for reference lists from relevant
non-Cochrane reviews).
• ProQuest Dissertations & Theses (PQDT), at http://
www.proquest.com/libraries/academic/dissertations-theses/ (for
unpublished dissertations and theses).
• Conference abstracts and other trials on the Web of
Science, at http://wokinfo.com/.
• Web of Knowledge, at http://wokinfo.com/ (another source
of trials and conference abstracts).
• OpenGrey, at http://www.opengrey.eu/ (for unpublished
literature from Europe).
is the unit of interest in the review. We will use details regarding
the selection process to complete a PRISMA flow diagram and
’Characteristics of excluded studies’ tables (Liberati 2009).
Data extraction and management
Two review authors (SK and CK) will independently extract study
characteristics and outcome data from included studies using Cov-
idence. We will note any outcome data not reported in a usable
way in the ’Characteristics of included studies’ tables. We will re-
solve disagreements by reaching consensus or by involving a third
review author (PL). We will correspond with study investigators
to request further data on methods and/or results, as required. We
will estimate data values from graphs when necessary.
Assessment of risk of bias in included studies
Two review authors (SK and CK) will independently assess risk
of bias in included studies by using the criteria available in the
Cochrane Handbook for Systematic Reviews of Interventions (Higgins
2011); we will resolve differences by discussion or by appeal to a

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 4

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
third review author (PL). We will assess each study on the basis of
six categories: selection bias (sequence generation and allocation
concealment); performance bias (blinding of participants and per-
sonnel); detection bias (blinding of outcome assessment); attrition
bias (incomplete outcome data); reporting bias (selective outcome
reporting); and other biases (any ’other issues’ also considered for
assessment). We will judge each item as being at high, low, or un-
clear risk of bias, as set out in the criteria displayed in Appendix 9
(Higgins 2011). However, we anticipate that the studies included
in this review will be highly susceptible to detection and attrition
bias owing to the combination of self-reported outcome measures
and the likelihood that dropout might be associated with the in-
dividual’s condition. We will acknowledge studies without effec-
tive blinding of participants, personnel, and outcome assessors as
n a
having high risk of performance and detection bias, respectively. If
The unit of analysis is per woman randomised. In a study with
multiple groups, we will combine all relevant experimental inter-
vention groups into a single group to create a single pair-wise com-
parison (Higgins 2011). We will include only data from the first
phase in cases of cross-over trials to minimise a carryover effect.
Dealing with missing data
b y
o l
In so far as it is possible, we will carry out analyses on an intention-
j
P u
to-treat basis for all outcomes. This means that we will attempt
to include in analyses all participants randomised to each group,
l a
and we will analyse all participants in the group to which they
u
P a
were allocated, regardless of whether or not they received the al-
located intervention. We will attempt to contact study authors to
obtain missing data. We anticipate finding data missing from trial

o A
at least 80% of randomised women were included in the analysis, reports because of loss to follow-up; we will attempt to impute
t
we will rated the study as having low risk of attrition bias.
it tu
missing data for primary outcomes using the ’informative miss-
We will provide in the ’Risk of bias’ table a quote from the study ingness (IM)’ approach suggested by Higgins 2008. For continu-
ns
report and/or a statement as justification for judgement for each
I ini
z o m
ous outcomes, we will apply the informative missing difference of
c
il.
item. We will summarise results in both a ’Risk of bias graph’ and
d o
a ’Risk of bias summary’, if feasible. When interpreting treatment
means (IMDOM), and for dichotomous outcomes, we will calcu-
D a
late the informative missing odds ratio (IMOR) using ’metamiss’
a
a d e
effects and meta-analyses, we will take into account the risk of
is
bias of included studies that contribute to that outcome. When cil m
or ’metamiss2’ in STATA 14 (StataCorp 2015). For secondary
g
d r a@
outcomes, if we are unable to obtain missing data, we will include

rie P
information on risk of bias relates to unpublished data or corre- only available data.
ra b
op ft d
spondence with a trial author, we will note this in the ’Risk of bias’
table.
P r p a ila
i s o d o r i sc Assessment of heterogeneity

O n
Measures of treatment
c ia
effect
r i.p
We will consider whether clinical and methodological character-

For dichotomous data (e.g. n t

u events),
e occurrence ofnadverse we will
istics of included studies are sufficiently similar for meta-analysis
to provide a clinically meaningful summary. We will assess statis-
L
use numbers of events i c
in control and :intervention
l ratios (ORs). For contin-
iodds groups of each tical heterogeneity using the I² measurement. We will consider I²
study to calculate Mantel-Haenszel
uous data (i.e. end scores andm
a greater than 50% to indicate substantial heterogeneity (Higgins

E-the same outcomes, we will calculate

change scores for PMS symptoms),
if all studies report exactly
mean differences (MDs) between treatment groups. If similar out-
comes are reported on different scales, we will calculate standard-
ised mean differences (SMDs). We will reverse the direction of ef-
fects of individual studies, if required, to ensure consistency across
trials. We will treat ordinal data (i.e. scores obtained from visual
analogue scales (VASs) and quality of life scores) as continuous
data. We will extract end scores in preference to change scores,
when available, and will include them in the ’Summary of find-
ings’ table. We will present 95% confidence intervals (CIs) for all
outcomes. When data needed to calculate ORs or MDs are not
available, we will utilise the most detailed numerical data available
that may facilitate similar analyses of included studies (e.g. test
statistics, P values). We will compare the magnitude and direction
of effects reported by studies with how they are presented in the
review, while taking account of legitimate differences.
Unit of analysis issues
2003).
Assessment of reporting biases
In view of the difficulty of detecting and correcting for publication
bias and other reporting biases, review authors will aim to minimise
the potential impact of biases by ensuring a comprehensive search
for eligible studies, and by staying alert for duplication of data.
If we include 10 or more studies in an analysis, we will use a
funnel plot to explore the possibility of small-study effects (i.e. the
tendency for smaller studies to estimate the intervention effect as
more beneficial than reported by larger studies).
Data synthesis
We will carry out statistical analyses with Review Manager 5
software (RevMan 2014), using the Mantel-Haenszel fixed-effect
model for combining data when included trials examine the same
intervention, and when trial populations and methods are ac-
knowledged as sufficiently similar (DerSimonian 1986). We will

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 5

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
convert continuous data/standardised mean differences to an in- • Repeating the analysis while excluding unpublished studies
terpretable scale/natural units. We will analyse end scores and (if any).
change scores separately and will not pool these data. We will re- • Repeating the analysis while excluding studies judged to be
port separately the results of each comparison listed under Types at ’high’ or ’unclear’ risk of bias for allocation concealment.
of interventions. If we identify substantial heterogeneity between • Repeating the analysis using a random-effects model.
included studies, we will summarise findings narratively. • As a consequence of the imputation method (informative
• Vitamins and/or minerals versus placebo or no treatment missingness (IM)) for missing outcome data, we will perform a
(stratified by type of comparator and pooled). y
series of sensitivity analyses to examine the impact of attrition on
b
• Vitamins and/or minerals versus other treatment (separate l
treatment effect estimates by using a different assumption
j o
comparisons for different comparators).
• Vitamins and/or minerals plus other treatment versus other P u
regarding missing data, an available case analysis (ACA), and
imputed case analyses (ICAs), as suggested by Higgins 2008.
treatment (± placebo) (separate comparisons for different
u l a
comparators).
• Vitamins and/or minerals versus other vitamins and/or
a
POverall quality of the body of evidence: ’Summary of
minerals (separate comparisons for different comparators).
n a findings’ table
o A We will prepare a ’Summary of findings’ table using GRADEpro
t GDT 2014 software. This table will present the overall quality
it tu
Subgroup analysis and investigation of heterogeneity of the body of evidence according to GRADE criteria for our

I ns
When data are available, we will perform subgroup analyses using
ini
z m
main comparison (vitamins or minerals or both vs placebo or
co
il.
no treatment) for the primary outcomes including end scores for
d o
the RevMan 2014 test for subgroup differences to assess the influ-
D a
all symptoms at three months’ follow-up (or closest follow-up
a
e cil
ence of the following issues on effect size.
d
• Subgroups by severity of PMS symptoms (with reference to
g m
to three months reported), rates of all adverse effects, rates of

d a r is specific adverse effects, and rates of withdrawal due to adverse

a@
the trial inclusion criteria): mild to moderate PMS versus severe
rie P effects. These criteria include study limitations (i.e. risk of bias),
PMS. Severity of PMS will depend on self-rated scores from
ra b
op ft d consistency of effect, imprecision, indirectness, and publication

ila
rating tools, and PMDD will be defined as severe PMS.
P r p a
• Subgroups by dosage of vitamins or minerals or both.
c
bias. Two review authors (SK and CK) will work independently to

i s o d o r i spossible determine judgements about evidence quality (high, moderate, or

low) and will resolve disagreements by discussion. We will justify,
explanationsO
n
If we detect substantial heterogeneity,
c
by performing subgroup
we will
i.p sensitivity
ia analysestrand/orexplore
document, and incorporate judgements into reporting of results
n u into account
e statistical heterogeneity for each outcome (Schünemann 2011).
analyses. We will take any
i c n
L
when interpreting trial
il: we note any variation
results, especially
in the direction of effect. a
if

m
E- ACKNOWLEDGEMENTS
Sensitivity analysis We thank Helen Nagels, Jane Marjoribanks, and Cindy Farquhar
We will perform sensitivity analysis to determine the effects of the for clinical and editorial advice. We thank Marian Showell for
following factors. designing the search strategy, and Dylan Southard for assisting
with English language presentation.

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Lewis JE, Tiozzo E, Melillo AB, Leonard S, Chen L, Mendez
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Vitamin B and its derivatives for diabetic kidney disease.
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Showell 2014
Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A,
Stankiewicz MT, Hart RJ. Antioxidants for male subfertility.
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[DOI: 10.1002/14651858.CD007411
Thys-Jacobs 2007
Thys-Jacobs S, McMahon D, Bilezikian JP. Cyclical changes
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Showell 2017 Wang 1995

Showell MG, Brown J, Clarke J, Hart RJ. Antioxidants for Wang M, Hammarback S, Lindhe BA, Backstrom T.
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Ward E. Addressing nutritional gaps with multivitamin and
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Whelan 2009

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Steiner M, Born L. Diagnosis and treatment of premenstrual Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins
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o A and minerals in the treatment of premenstrual syndrome:
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ti tut Pharmacology 2009;16(3):e407–29.

s
Sundstrom-Poromaa I, Bixo M, Bjorn I, Nordh O.
z
Yonkers 2008
m
o In
Compliance to antidepressant drug therapy for treatment of
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Yonkers KA, O’Brien PM, Eriksson E. Premenstrual
syndrome. Lancet 2008;371(961):1200–10.
& Gynecology 2000;21:205–11. d a ∗
a
Indicates the major publication for the study

ad
e
iscil g m
d r a@
rie ra
P b
rop ft p a ila
d
P o o i sc
APPENDIC
i s ES
d r
On ncia t r i.p
c e diagnostic
Appendix 1. Standard n ucriteria for premenstrual dysphoric disorder (PMDD)
L i il:
m a
E-
Symptoms required to diagnoses

Depressed mood Mood swings

Fatigue Irritability

Anxiety/tension Feeling out of control

Appetite changes/food cravings Decreased interest

Insomnia/hypersomnia Concentration difficulties

Physical symptoms

Standard diagnostic criteria for PMDD

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 8

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

1. Symptoms are present for most of the time in the week before menses, diminish with the onset of menses and are absent in the
week following menses. At least 5 symptoms occur in most menstrual cycles for at least one year

by
2. The symptoms markedly interfere with relationships with others, work or school, or usual social activities

3. The disturbance is not merely an exacerbation of another physical or mental disorderjo l

P u
u la
4. All criteria must be confirmed by prospective daily ratings for at least two consecutive menstrual cycles

P a
Appendix 2. Cochrane Gynaecology and Fertility n aGroup Specialised Register search strategy
From inception to present (PROCITE platform)
Keywords CONTAINS “premenstrual aggravation”u
oA
ort“premenstrual dysphoria” or “premenstrual dysphoric disorder” or “Premenstrual
Syndrome-Symptoms” or “premenstrual syndrome”
s tit or “Premenstrual TensionzScale” or “premenstrual m symptoms” or “premenstrual
symptom scores” or “premenstrual scores”nor “premenstrual pain” or “premenstrual”
I i n i oor “Premenstrual Syndrome-Symptoms”
or “PMDD”
c or “PMS” or Title CONTAINS

d o
“premenstrual aggravation” or “premenstrual dysphoria” or “premenstrual
D dysphoric .
il or “premenstrual symptom scores” or
disorder”
Tension Scale” ora“premenstrual symptoms”
e pain” or “premenstrual”
or “premenstrual syndrome” or “Premenstrual
ilor “PMDD” gor m a
a d
“premenstrual scores” or “premenstrual
i s c “PMS”

ied“antioxidants” or “antioxidant” r @
AND
P or “antioxidanta
Keywords CONTAINS
r ra“sodium” b levels” or “vitamin” or “vitamin A” or “vitamin B” or “Vitamin-

ropor “*Calcium”
B-12” or “Vitamin-B-12-Therapeutic-Use”
t
or “vitamin
a
f or “zinc”oorp“fatty acids” sorc“oil” i l a d C” or “Vitamin D” or “vitamin E” or “vitamins” or “selenium”
B6” or “vitamin
P
or “folic acid”
o
or “potassium” or
i
or “Copper” or “Manganese” or “Magnesium” or “iron” or “minerals” or

i
“Mineral” or“ ascorbics acid”
d r or “fish oils” or “plant extracts” or “tocopherol” or “multivitamins”

On primrose ia . p
or “alpha tocopherol” or “melatonin” or “dietary supplement” or “nutritional supplement” or “nutritional supplements” or “Myo-
inositol” or “evening
n coil” or “chromium r i
t B6” or “vitamin C” or “Vitamin D”ororTitle“vitamin
supplementation” or “Pyridoxine” CONTAINS “antioxidants” or “vitamin”

c e
or “vitamin B” or “Vitamin-B-12”or“vitamin u
n”Manganese“ or ”Magnesium“ or ”iron“ or ”minerals“ orE””Mineral“ or “vitamins” or“*Calcium” or
L i
”potassium“ or ”sodium“ or
i
”Copper“ l : or or ”Pyridoxine“
a
E -m
Appendix 3. CENTRAL Register of Studies Online (CRSO) search strategy
From inception to present (Web platform)
#1 MESH DESCRIPTOR Premenstrual Syndrome EXPLODE ALL TREES
#2 (premenstrual syndrome):TI,AB,KY
#3 (pmt or pms):TI,AB,KY
#4 #1 OR #2 OR #3
#5 MESH DESCRIPTOR Vitamin B Complex EXPLODE ALL TREES
#6 MESH DESCRIPTOR Vitamins EXPLODE ALL TREES
#7 MESH DESCRIPTOR Minerals EXPLODE ALL TREES
#8 mineral*:TI,AB,KY
#9 vitamin*:TI,AB,KY
#10 MESH DESCRIPTOR Antioxidants EXPLODE ALL TREES
#11 antioxidant*:TI,AB,KY
#12 MESH DESCRIPTOR Calcium Carbonate EXPLODE ALL TREES
#13 (calcium or manganese):TI,AB,KY
#14 MESH DESCRIPTOR Manganese EXPLODE ALL TREES
#15 (iron or copper):TI,AB,KY
#16 MESH DESCRIPTOR Copper EXPLODE ALL TREES
#17 MESH DESCRIPTOR Sodium, Dietary EXPLODE ALL TREES
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 9
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
#18 MESH DESCRIPTOR Sodium EXPLODE ALL TREES
#19 sodium:TI,AB,KY
#20 zinc:TI,AB,KY
#21 (dietary supplement*):TI,AB,KY
#22 MESH DESCRIPTOR Dietary Supplements EXPLODE ALL TREES
#23 Nutriceutical*:TI,AB,KY
#24 MESH DESCRIPTOR Melatonin EXPLODE ALL TREES
#25 melatonin:TI,AB,KY 1371
b y
#26 MESH DESCRIPTOR Ascorbic Acid EXPLODE ALL TREES
j o l
#27 MESH DESCRIPTOR Magnesium EXPLODE ALL TREES
#28 magnesium:TI,AB,KY P u
#29 multivitamin*:TI,AB,KY
u l a
#30 MESH DESCRIPTOR Fatty Acids EXPLODE ALL TREES
#31 (fatty acid*):TI,AB,KY P a
#32 omega:TI,AB,KY
n a
#33 selenium:TI,AB,KY
o A
#34 (ascorbic acid):TI,AB,KY t
#35 (evening primrose):TI,AB,KY it tu
#36 chromium:TI,AB,KY
I ns ini
z
co m
il.
#37 #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #
d o D a
20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #
a
35 OR #36
#38 #4 AND #37 a d e
is cil g m
d r a@
p rie ra
P
d b
r o t p a
f searcho strategy ila
P 4. MEDLINE
Appendix
o i sc
i s d r
On Syndrome/ i.p
From 1946 to present (OVID platform)
1 exp Premenstrual
n cia t r
2 PMS.tw.
c e n u
i
3 luteal phase disorder$.tw.
L disorder$.tw.il:
4 premenstrual dysphoric
a
5 PMDD.tw.
E -m
6 premenstrual aggravation.tw.
7 premenstrual tension$.tw.
8 Premenstrual Syndrome$.tw.
9 PMT.tw.
10 or/1-9
11 exp antioxidants/ or free radical scavengers/
12 (antioxidant$ or radical scavengers).tw.
13 exp vitamins/ or exp ascorbic acid/ or exp dehydroascorbic acid/ or exp vitamin a/ or exp vitamin e/ or exp vitamin u/ or exp alpha-
tocopherol/ or exp beta carotene/ or exp beta-tocopherol/ or exp gamma-tocopherol/
14 vitamin$.tw.
15 exp Minerals/ or mineral$.tw.
16 exp Zinc/
17 Potassium.tw.
18 exp potassium/
19 (zinc or selenium).tw.
20 exp Selenium/
21 sodium.tw.
22 exp sodium/
23 copper.tw.
24 exp copper/
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 10
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
25 manganese.tw.
26 exp manganese/
27 iron.tw.
28 exp Iron/
29 exp Glutathione Peroxidase/ or exp folic acid/
30 (Glutathione$ or folate).tw.
31 exp Ubiquinone/
32 (ubiquin$ or folic acid).tw.
b y
33 coenzyme q10.tw.
j o l
34 exp Carnitine/
35 (carnitine$ or carotenoid$).tw. P u
36 (astaxanthin$ or lycopene$).tw.
u l a
37 multivitamin$.tw.
38 (betacarotene$ or beta carotene$).tw. P a
39 ascorbic acid.tw.
n a
40 n-acetylcysteine.tw.
o A
41 exp Acetylcysteine/ t
42 alpha-tocopherol$.tw. it tu
43 (fish adj2 oil$).tw.
I ns ini
z
co m
il.
44 omega$.tw.
d o D a
45 exp fatty acids/ or exp fish oils/ or exp cod liver oil/ or exp fatty acids, omega-3/ or exp plant oils/
a
46 fatty acid$.tw.
47 (plant adj4 oil$).tw. a d e
is cil g m
d r a@
rie P
48 primrose oil$.tw.

ra b
op ft d
49 l-arginine$.tw.
r
50 flavonoid$.tw.
P p a ila
i s o
51 riboflavin$.tw.
d o r i sc
On ncia i.p
52 pycnogenol$.tw.
53 lutein$.tw.
u t r
54 lipoic acid$.tw.
i c e n
il:
55 n acetyl cysteine.tw.
L
56 melatonin.tw.
a
m
E-
57 dietary supplement$.tw.
58 nutritional supplement$.tw.
59 micronutrient$.tw.
60 Nutraceuticals$.tw.
61 (myoinositol or mesoinositol or Inositol).tw.
62 exp Inositol/
63 exp Calcium/ad, tu, th [Administration & Dosage, Therapeutic Use, Therapy]
64 calcium.tw.
65 exp Chromium/
66 chromium.tw.
67 magnesium.tw.
68 exp Magnesium/
69 or/11-68
70 10 and 69 (1313)
71 randomized controlled trial.pt.
72 controlled clinical trial.pt.
73 randomized.ab.
74 randomised.ab.
75 placebo.tw.
76 clinical trials as topic.sh.
77 randomly.ab.
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 11
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
78 trial.ti.
79 (crossover or cross-over or cross over).tw.
80 or/71-79
81 exp animals/ not humans.sh.
82 80 not 81
83 70 and 82

by
j o l
P u
Appendix 5. Embase search strategy
u l a
From 1980 to present (OVID platform)
1 exp Premenstrual Syndrome/ P a
2 PMS.tw.
n a
3 luteal phase disorder$.tw.
o A
4 premenstrual dysphoric disorder$.tw. t
5 PMDD.tw. it tu
6 premenstrual aggravation.tw.
I ns ini
z
co m
il.
7 premenstrual tension$.tw.
8 Premenstrual Syndrome$.tw. d o D a
a
9 PMT.tw.
10 or/1-9 a d e
is cil g m
d r a@
rie P
11 exp antioxidants/ or free radical scavengers/

ra b
op ft d
12 (antioxidant$ or radical scavengers).tw.
r
13 vitamin$.tw.
P p a ila
i s o d o r i sc
14 exp vitamin/ or exp ascorbic acid/ or exp carotenoid/ or exp tocopherol/

On ncia i.p
15 Potassium.tw. or exp potassium/
16 sodium.tw. or exp sodium/
u t r
i c e
17 copper.tw. or exp copper/
n
il:
18 manganese.tw. or exp manganese/
L a
19 iron.tw. or exp iron/
m
E-
20 exp Zinc/
21 (zinc or selenium).tw.
22 exp Selenium/
23 exp Glutathione Peroxidase/ or exp folic acid/
24 (Glutathione$ or folate).tw.
25 exp Ubiquinone/
26 (ubiquin$ or folic acid).tw.
27 coenzyme q10.tw.
28 exp Carnitine/
29 (carnitine$ or carotenoid$).tw.
30 (astaxanthin$ or lycopene$).tw.
31 multivitamin$.tw.
32 (betacarotene$ or beta carotene$).tw.
33 ascorbic acid.tw.
34 n-acetylcysteine.tw.
35 exp acetylcysteine/
36 n-acetyl-cysteine.tw.
37 alpha-tocopherol$.tw.
38 (fish adj2 oil$).tw.
39 omega$.tw.
40 fatty acid$.tw.
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 12
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
41 exp edible oil/ or exp castor oil/ or exp cod liver oil/ or exp fish oil/ or exp lyprinol/ or exp olive oil/ or exp safflower oil/ or exp fatty
acid/ or exp essential fatty acid/ or exp arachidonic acid/ or exp linoleic acid/ or exp linolenic acid/ or exp gamma linolenic acid/ or
exp unsaturated fatty acid/ or exp omega 3 fatty acid/ or exp omega 6 fatty acid/ or exp polyunsaturated fatty acid/
42 (plant adj4 oil$).tw.
43 l-arginine$.tw.
44 flavonoid$.tw.
45 riboflavin$.tw.
46 pycnogenol$.tw.
b y
47 lipoic acid$.tw.
j o l
48 melatonin.tw.
49 dietary supplement$.tw. P u
50 micronutrient$.tw.
u l a
51 nutritional supplement$.tw.
52 Nutraceutical$.tw. P a
53 exp inositol/
n a
54 (Inositol or mesoinositol or myoinositol).tw.
o A
55 exp Pentoxifylline/ or Pentoxifylline$.tw. t
56 primrose oil.tw. it tu
57 exp Mineral/ or mineral$.tw.
I ns ini
z
co m
il.
58 exp calcium/ or calcium.tw.
d
59 exp magnesium/ or magnesium.tw. o D a
a
d e
60 exp chromium/ or chromium.tw.
61 or/11-60 a is cil g m
d r a@
rie P
62 10 and 61

ra b
op ft d
63 Clinical Trial/
r
64 Randomized Controlled Trial/
P p a ila
i s o
65 exp randomization/
d o r i sc
On ncia i.p
66 Single Blind Procedure/
67 Double Blind Procedure/
u t r
i c e
68 Crossover Procedure/
n
il:
69 Placebo/
L a
70 Randomi?ed controlled trial$.tw.
m
E-
71 Rct.tw.
72 random allocation.tw.
73 randomly.tw.
74 randomly allocated.tw.
75 allocated randomly.tw.
76 (allocated adj2 random).tw.
77 Single blind$.tw.
78 Double blind$.tw.
79 ((treble or triple) adj blind$).tw.
80 placebo$.tw.
81 prospective study/
82 or/63-81
83 case study/
84 case report.tw.
85 abstract report/ or letter/
86 or/83-85
87 82 not 86
88 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
89 87 not 88
90 62 and 89

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 13

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Appendix 6. PsycINFO search strategy
From 1806 to present (OVID platform)
1 exp Premenstrual Syndrome/
2 PMS.tw.
3 luteal phase disorder$.tw.
4 premenstrual dysphoric disorder$.tw.
5 PMDD.tw.
6 premenstrual aggravation.tw. by
7 premenstrual tension$.tw.
j o l
8 Premenstrual Syndrome$.tw.
P u
9 PMT.tw.
10 or/1-9
u l a
11 exp Antioxidants/
P a
12 (antioxidant$ or radical scavengers).tw.
13 exp Vitamins/ n a
14 vitamin$.tw.
o A
t
it tu
15 exp Zinc/

ns
16 (zinc or selenium).tw.
z m
I ini o
17 (Glutathione$ or folate).tw.
18 (ubiquin$ or folic acid).tw. o D il. c
d a a
cil
19 coenzyme q10.tw.
d e
20 (carnitine$ or carotenoid$).tw.
g m
d a r is
a@
21 multivitamin$.tw.
rie
22 (betacarotene$ or beta carotene$).tw.
ra
P b
rop ft
23 ascorbic acid.tw.
p a ila
d
P
24 n-acetylcysteine.tw.
o o i sc
i s
25 alpha-tocopherol$.tw.
d r
On ncia i.p
26 (fish adj2 oil$).tw.
27 omega$.tw.
u t r
c
28 exp Fatty Acids/
i e n
L
29 fatty acid$.tw.
30 l-arginine$.tw. a il:
m
31 melatonin.tw.
E-
32 dietary supplement$.tw.
33 nutritional supplement$.tw.
34 micronutrient$.tw.
35 Nutraceuticals$.tw.
36 (Pentoxifylline or myoinositol or inositol).tw.
37 mineral$.tw.
38 exp POTASSIUM/
39 potassium.tw.
40 exp SODIUM/
41 exp COPPER/
42 copper.tw.
43 sodium.tw.
44 manganese.tw.
45 exp IRON/
46 iron.tw.
47 exp Dietary Supplements/
48 exp CALCIUM/
49 calcium.tw.
50 primrose oil.tw.

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 14

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
51 chromium.tw.
52 magnesium.tw.
53 myo inositol.tw.
54 or/11-53
55 10 and 54
56 random.tw.
57 control.tw.
58 double-blind.tw.
by
59 clinical trials/
j o l
60 placebo/
61 exp Treatment/ P u
62 or/56-61
u l a
63 55 and 62
P a
n a
Appendix 7. AMED search strategy o A
t
From 1985 to present (OVID platform) it tu
1 exp Premenstrual syndrome/
I ns ini
z
co m
il.
2 premenstrual syndrome.tw.
3 PMS.tw. d o D a
a
d e
4 premenstrual dysphoric disorder.tw.
5 PMDD.tw. a is cil g m
d r a@
rie P
6 premenstrual tension.tw.

ra b
op ft d
7 PMT.tw.
r a
8 1 or 2 or 3 or 4 or 5 or 6 or 7
P p ila
i s o d o
9 exp Vitamins/ or exp Minerals/
r i sc
On ncia i.p
10 (vitamin$ or mineral$).tw.
11 antioxidant$.tw.
u t r
12 exp Calcium/
i c e n
il:
13 calcium.tw.
L
14 chromium.tw.
a
m
E-
15 copper.tw.
16 exp Copper/ or exp Iron/
17 exp Magnesium/ or exp Potassium/
18 magnesium.tw.
19 (iron or potassium).tw.
20 exp Sodium/
21 sodium.tw.
22 manganese.tw.
23 primrose oil.tw.
24 exp Antioxidants/ or exp Free radicals/
25 exp Ascorbic acid/
26 vitamin$.tw.
27 exp Zinc/
28 (zinc or selenium).tw.
29 (Glutathione$ or folate).tw.
30 exp Selenium/
31 (ubiquin$ or folic acid).tw.
32 coenzyme q10.tw.
33 exp Carnitine/
34 (carnitine$ or carotenoid$).tw.
35 multivitamin$.tw.
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 15
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
36 ascorbic acid.tw.
37 n-acetylcysteine.tw.
38 Acetylcysteine.tw.
39 alpha-tocopherol$.tw.
40 (fish adj2 oil$).tw.
41 omega$.tw.
42 exp Fatty acids/
43 exp Fish oils/
by
44 fatty acid$.tw.
j o l
45 (plant adj4 oil$).tw.
46 l-arginine$.tw. P u
47 flavonoid$.tw.
u l a
48 riboflavin$.tw.
49 pycnogenol$.tw. P a
50 micronutrient$.tw.
n a
51 nutriceutical$.tw.
o A
52 dietary supplement$.tw. t
53 Pentoxifylline$.tw. it tu
54 (myoinositol or inositol).tw.
I ns ini
z
co m
il.
55 melatonin.tw.
56 exp Dietary supplements/ d o D a
a
57 or/9-56
58 8 and 57 a d e
is cil g m
d r a@
rie P
59 randomized controlled trials/

ra b
op ft d
60 randomized controlled trial.pt.
r a
61 controlled clinical trial.pt.
P p ila
62 placebo.ab.
i s o d o r i sc
On ncia i.p
63 random*.ti,ab.
64 trial.ti,ab.
u t r
65 groups.ab.
i c e n
il:
66 or/59-65
67 58 and 66L a
m
E-
Appendix 8. CINAHL search strategy
From inception to present (EBSCO platform)

# Query

S62 S49 AND S61

S61 S50 OR S51 OR S52 OR S53 OR S54 OR S55 OR S56 OR S57 OR S58 OR S59 OR S60

S60 TX allocat* random*

S59 (MH ”Quantitative Studies“)

S58 (MH ”Placebos“)

S57 TX placebo*

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 16

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

S56 TX random* allocat*

S55 (MH ”Random Assignment“)

S54 TX randomi* control* trial* b y

j o l
S53 u
TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or
P
(tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
u l a
S52 TX clinic* n1 trial*
P a
n a
S51 PT Clinical trial
o A
t
S50 (MH ”Clinical Trials+“)
it tu
S49 S8 AND S48
I ns ini
z
co m
d o D a il.
a
e cil
S48 S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR
d g m
S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR
d a r is
a@
S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47
rie ra
P b
S47
rop ft
(MM ”Inositol“)
p a ila
d
PTX primrose o o i sc
S46
n i s d r
S45 (MMO
n cia
”Evening Primrose“) t r i.p
c e n u
S44 i il:
L or TX magnesium
TX chromium

m a
S43 TX iron
E-
S42 TX copper or TX manganese

S41 (MM ”Chromium“) OR (MM ”Copper“) OR (MM ”Iron“) OR (MM ”Manganese“)

S40 TX sodium

S39 (MM ”Sodium“)

S38 TX potassium

S37 (MM ”Potassium“)

S36 (MM ”Calcium“)

S35 TX mineral*

S34 (MM ”Minerals+“)

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 17

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

S33 TX Nutraceutical*

S32 TX micronutrient*

S31 TX nutritional supplement*

by
j o l
S30 TX dietary supplement*
P u
S29 TX melatonin u l a
P a
S28 TX n acetyl cysteine
n a
o A
S27 TX l-arginine
t
it tu
ns z m
S26 TX (fish N2 oil*)

o I
D ini il. co
S25 (MH ”Acetylcysteine“)
e d l a a
d i m
S24
a
TX n-acetylcysteine
d r i sc @
g
p rieacid a P ba
ad
S23 TX ascorbic
ro t a r l
P f p i
S22 TX
i s o
multivitamin*
d o r i sc
S21
On ornlycopene*)
TX(astaxanthin*
cia t r i.p
corecarotenoid*) n
u
S20 i
TX (carnitine*
L il:
(MM ”Carnitine“) m
a
S19
E -
S18 TX coenzyme q10

S17 TX (ubiquin* or folic acid)

S16 TX (zinc or selenium)

S15 TX omega$

S14 TX fatty acid*

S13 (MH ”Fatty Acids, Omega 3“) OR (MH ”Fatty Acids, Unsaturated+“)

S12 TX vitamin*

S11 (MH ”Vitamins+“)

S10 TX antioxidant*

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 18

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

S9 (MM ”Antioxidants+“)

S8 S1 or S2 or S3 or S4 or S5 or S6 or S7

S7 TX PMDD b y
j o l
S6 TX PMS
P u
S5 TX premenstrual tension
u l a
P a
S4 TX premenstrual dysphoric disorder
n a
S3 TX luteal phase disorder*
o A
t
it tu
ns m
S2 TX Premenstrual Syndrome
I n i z o
o OR ”Premenstrual Syndrome“ D il. c
iOR (MH ”Premenstrual
S1 (MH ”Premenstrual Syndrome+“)
d a a Dysphoric Disorder“)

de c il g m
a i s
Appendix 9. Risk
ir edof bias assessment a Pr b a@
Assessment of p d
r 8 of Higginsla2011.
ro risk of bias will be based on Chapter
f t p a i
P
• Random sequence generation.
obias, e.g. participants c
o assigned rtoistreatments
◦ Low riskiof
n s d p
O c i a i . on the basis of a computer-generated random sequence or a table
of random numbers.
◦ High risk of bias,ne.g. participants
e u tr to treatments on the basis of date of birth, clinic ID-number or surname, or no
assigned
attempt to randomiseic participants. : n
◦ UnclearL a
risk of bias, e.g. inotl reported, information not available.
m
E-
• Allocation concealment.

◦ Low risk of bias, e.g. when the allocation sequence could not be foretold.
◦ High risk of bias, e.g. allocation sequence could be foretold by patients, investigators, or treatment providers.
◦ Unclear risk of bias, e.g. not reported.

• Blinding of participants and personnel.

◦ Low risk of bias if participants and personnel were adequately blinded.

◦ High risk of bias if participants were not blinded to the intervention that the participant received.
◦ Unclear risk of bias if this was not reported or was unclear.

• Blinding of outcomes assessors.

◦ Low risk of bias if outcome assessors were adequately blinded.

◦ High risk of bias if outcome assessors were not blinded to the intervention that the participant received.
◦ Unclear risk of bias if this was not reported or was unclear.

• Incomplete outcome data: We will record the proportion of participants whose outcomes were not reported at the end of the
study. We will code a satisfactory level of loss to follow-up for each outcome as follows.

◦ Low risk of bias, e.g. if fewer than 20% of participants were lost to follow-up and reasons for loss to follow-up were similar
in both treatment arms.
Vitamin or mineral supplements for premenstrual syndrome (Protocol) 19
Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 ◦ High risk of bias, e.g. if more than 20% of participants were lost to follow-up or reasons for loss to follow-up differed
between treatment arms.
◦ Unclear risk of bias, e.g. if loss to follow-up was not reported.
• Selective reporting of outcomes.
◦ Low risk of bias, e.g. review reports all outcomes specified in the protocol.
◦ High risk of bias, e.g. it is suspected that study outcomes have been selectively reported.
◦ Unclear risk of bias e.g. it is unclear whether outcomes have been selectively reported
b y
• Other bias.
j o l
P u
◦ Low risk of bias, e.g. review authors do not suspect any other source of bias and the trial appears to be methodologically
sound.
u l a
P a
◦ High risk of bias, e.g. review authors suspect that the trial was prone to an additional bias.
◦ Unclear risk of bias, e.g. review authors are uncertain whether an additional bias may have been present.
n a
A
CONTRIBUTIONS OF AUTHORS
t u to
s i and developed and completed the protocol.
tquestion
Srinaree Kaewrudee (SK) conceived the review
I n i z o m
Chumnan Kietpeerakool (CK) conceived o the review question and developed n
i and completed c
il. the protocol.
d D a
Porjai Pattanittum (PP) editede
d ila on a portion
a portion of the protocol and advised
c g mof the protocol.
Pisake Lumbiganon (PL)a edited the protocol and advised ionsthe protocol.@
e d r a
P before bsubmission.
All review authorsriapproved the final version of the protocol
o p r a ad
P r f t p a i l
D E C L A R Ais
o
TIONS d
o
O F I N T E rRi E S T
sc
On ncia
SK: none known. t r i.p
CK: none known. ic
e n u
L a il:
PP: none known.
m
PL: none known. E-
SOURCES OF SUPPORT

Internal sources
• Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Thailand.
• Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Thailand.
• Cochrane Thailand, Thailand.

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 20

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
External sources
• Thailand Research Fund (Distinguished Professor Award), Thailand.
• Long term institutional development HUBs (LID-HUBs), the Human Reproduction Programme (HRP) Alliance for Research
Capacity Strengthening, World Health Organization, Switzerland.

by
j o l
P u
u l a
P a
n a
o A
t
it tu
I ns ini
z
co m
d o D a il.
a
a d e
is cil g m
d r a@
rie ra
P b
rop ft p a ila
d
P o o i sc
i s d r
On ncia t r i.p
c e n u
L i il:
m a
E-

Vitamin or mineral supplements for premenstrual syndrome (Protocol) 21

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.