pms is defined as the periodical recurrence of a set of annoying physical , psychological , and social symptoms in the luteal phase of menstrual cycle .
millions of females worldwide experience this disorder in their reproductive ages ( 3 ) . the relative prevalence rate of pms and premenstrual dysphoric disorder is reported to be between 98.5% and 2.8% , respectively ( 4 ) .
the prevalence of this syndrome varies from 60% to 80% in the asian countries ; 66.6% in turkey ( 5 ) , 76% in china ( 6 ) , and 63.1% in malaysia ( 7 ) .
american college of obstetrics and gynecology ( acog ) reported the prevalence of this syndrome 65.5% , with 8.75% of the patients requiring specialized treatments ( 8) . in iran , it is estimated that 98.2% of university female students experience at least one of the pms symptoms at age of 18 - 27 years old ( 9 ) . sometimes the physical and mental symptoms of pms are so severe that need to be treated ( 10 , 11 ) .
the etiology of pms and dysphoric disorder are unknown , but they are considered multi - factorial resulting from internal and external factors ( 12 ) .
biological , physiological , environmental , and social factors are also reported to be involved in the disorder ( 13 ) .
although the causes of this disorder are still unknown , research demonstrated that supportive strategies , such as writing the symptoms down , might be beneficial in diagnosis and management of the disorder .
moreover , changing lifestyle ( healthy diet , vitamins , mineral supplements , primrose oil , restricting use of sodium and caffeine , reduction of stress , and doing sports ) ( 2 ) , hormone therapy ( estrogen , oral contraceptive pills , gnrh analogues , danazol and progesterone ) , diuretics , anti - depressants , bromocriptine , surgery , psychotherapy , and serotonin reuptake inhibitors ( sris ) are proposed as the first line treatments in this regard ( 14 ) . besides , fluoxetine , paroxetine , and sertralin
however , side effects of pharmacological treatments are mentioned in some studies ( 15 - 19 ) . in the past decades ,
complementary and alternative methods such as homeopathy and herbal medicine were frequently used in alleviation of the pms ( 11 , 20 - 23 ) symptoms .
a study performed in iran , investigated the effects of aquatic extract and essence of m. officinalis and reported that this plant has anti - depression and sedative effects ( 24 ) .
although more than 100 chemical compounds have been identified in m. officinalis , its main components include citral , linalool , geraniol , -caryophyllene oxide , phenolic acid , tannins , rosmarinic acid and caffeic acid .
melissa officinalis can be effective to improve cognitive function and its effect is similar to that of triazolam ( 25 , 26 ) .
several studies are conducted on pms in iran . however , most of them focused on the prevalence of premenstrual symptoms and dysphonic ( 27 ) , types of symptoms ( 28 ) , efficacy of stress management or counseling to reduce symptoms ( 29 ) .
however , less attention is paid to treatment and a few herbal surveys exist on the treatment of pms in iran .
nonetheless , due to the sedative effects of m. officinalis , this question comes to mind that  can melissa officinalis be used to treat pms symptoms ?
the current study aimed to investigate the effect of m. officinalis capsule , as a substitute for chemical medicines , on the intensity of menstrual cycles in high - school girl students in shiraz , iran .
the current double - blind randomized clinical trial was conducted on 100 high school girls during 2013 - 2014 .
sample size was calculated based on the results of a study that used crocus sativus l. ( saffron ) to treat pms ( 20 ) .
considering the effect size of 2 ( reflecting the difference between the two groups ) , standard deviation ( sd ) of 1.3 , type i error probability of 5% , power of 0.9 , it was estimated that 42 subjects were needed in each group . yet , considering a possible attrition rate of 20% , 50 subjects were recruited in each group .
the study subjects were selected through random cluster sampling . at first , under the supervision of the department of education ,
four girl high schools ( including 800 students ) were selected from the four educational districts of shiraz , iran .
then , in each high school , the students with symptoms of pms were invited to take part in the study among which , considering the inclusion criteria , 100 subjects were selected and then randomly allocated into the intervention ( n = 50 ) and the placebo groups ( n = 50 ) .
the inclusion criteria were willing to participate in the study , being a high school student , obtaining a score < 23 from the general health questionnaire ( ghq ) , gaining a score > 20 from the premenstrual syndrome screening tool ( psst ) , not using vitamin supplements during the study , not having used hormonal drugs such as oral contraceptive pills at least two months prior to the study , length of menstrual cycle between 24 and 35 days , not suffering from other diseases such as thyroid , diabetes and mental disorders .
the exclusion criteria were a decision to withdraw from the study , parents request for exclusion of their child from the study , experiencing a stressful event such as death , marriage , or surgery during the study , experiencing a change in the intervals of menstrual cycles for less than 24 and more than 35 days , and experiencing changes in the length of menstrual cycles for less than three and more than seven days .
melissa officinalis capsules were made in the pharmacology department in the shiraz medical school under the supervision of a professional counselor .
moreover , the placebo was prepared from starch in capsules similar to m. officinalis . to keep the study blind ,
the drug and placebo were marked with codes 1 and 2 and only the specialized consultant knew about the drugs .
a self - report questionnaire was designed consisting of demographic characteristics , the ghq-28 questionnaire , and the premenstrual syndrome screening tool ( psst ) .
the ghq-28 consists of four subscales including somatic symptoms ( items 1 - 7 ) , anxiety / insomnia ( items 8 - 14 ) , social dysfunction ( items 15 - 21 ) and severe depression ( items 22 - 28 ) .
all items are responded on a 4-point likert scale of none , mild , moderate , and severe which are scored from zero to three .
the score 23 or above was the cut - off point for probability of having a mental health disorder ( 30 ) .
the farsi version of ghq-28 questionnaire was validated by yaghoubi , as cited in ozgoli et al . and its sensitivity and specificity
the first and second sections includes 14 items on physical , and psychological symptoms , and the third section contains five items that assesse the effects of symptoms on subject s life ( social symptoms ) ( 32 ) .
all items are responded on a four options likert scale namely none , mild , average , and severe , receiving a score from zero to three , respectively .
scores ranging from 0 - 19 , 20 - 38 , and 39 - 57 represented mild , average , and severe conditions , respectively .
the content validity ratio and content validity index of this scale were obtained as 0.7 , and 0.8 , respectively . moreover ,
the reliability of the scale was confirmed by a cronbach s alpha of 0.9 ( 8) .
subjects in the intervention group were required to consume 1200 mg m. officinalis essence daily ( two 600 mg capsules ) from the first to the last day of their menstrual cycle for three cycles . in the control group ,
the first researcher called the subjects in both groups at least 3 - 4 times to guide them and explain about consumption of the medication .
all subjects in the two groups were required to complete the psst questionnaire at the beginning of the study and then in three consecutive months ( three menstrual cycle ) .
the protocol of the study was approved by the ethics committee of shiraz university of medical sciences .
they were all assured of the confidentiality of their personal information . in order to prevent any probable error ,
moreover , subjects in the intervention group were allowed to withdraw from the study at any time .
paired t - test was used to compare the changes of pms scores in each group before and after the intervention .
moreover , the repeated measures anova was used to compare the severity of symptoms in the two groups during the four subsequent measurements .
subjects in the intervention group were required to consume 1200 mg m. officinalis essence daily ( two 600 mg capsules ) from the first to the last day of their menstrual cycle for three cycles . in the control group ,
the first researcher called the subjects in both groups at least 3 - 4 times to guide them and explain about consumption of the medication .
all subjects in the two groups were required to complete the psst questionnaire at the beginning of the study and then in three consecutive months ( three menstrual cycle ) .
the protocol of the study was approved by the ethics committee of shiraz university of medical sciences .
they were all assured of the confidentiality of their personal information . in order to prevent any probable error ,
moreover , subjects in the intervention group were allowed to withdraw from the study at any time .
paired t - test was used to compare the changes of pms scores in each group before and after the intervention .
moreover , the repeated measures anova was used to compare the severity of symptoms in the two groups during the four subsequent measurements .
the mean age of the participants was 16.2  1.06 years in the intervention group and 16.3  0.66 years in the placebo group .
the two groups were homogeneous with respect to age ( p = 0.32 ) , education level ( p = 0.83 ) , and body mass index ( bmi ) ( p = 0.42 ) . the results of repeater measures anova showed that the mean ( sd ) of symptoms in the intervention group was 42.56  15.73 before , 30.72  13.24 one month after , 30.2  12.08 two months after , and 13.90  10.22 three months after the intervention , and the differences were statistically significant ( table 1 ) .  
data are presented as mean  sd . the results of paired t - test showed that the intensity of physical symptoms significantly decreased in the subjects who consumed the capsules of m. officinalis ( p < 0.001 ) , but no significant difference was observed in the placebo group in this regard .
the results of the paired t - test also indicated a significant decrease in psychological and social symptoms of the subjects in the intervention group .
however , no significant difference was found in the control group in this respect ( p < 0.001 ) ( table 2 ) .  
the study results revealed a significant difference between the two groups regarding the total intensity mean of physical , psychological and social symptoms of pms in the first , second and third months after the intervention .
of course , in the control group there was also a decrease in the severity of symptoms .
no previous studies were available on the effect of m. officinalis on the intensity of pms ; however , the effects of other herbal products were investigated on anxiety , depression , sleep disorder , stress and other symptoms of pms ( 21 , 22 , 31 , 33 ) .
moreover , taiwo et al . investigated the effect of m. officinalis on mice and showed the positive psychoactive potentials of this herb ( 34 ) .
another study indicated the effectiveness of m. officinalis in reduction of restlessness and insomnia in children ( 35 ) .
another study also reported m. officinalis as a mediator of mood and cognitive function with anxiolytic effects ( 36 ) .
melissa officinalis leaves have also been shown to have anxiolytic and spasmolytic properties ( 37 ) .
the results of the above studies are similar to those of the current study in reducing psychological symptoms and mood changes .
still no blood or biochemical test is available to diagnose this disorder ( 38 ) .
the main mechanism of pms is perhaps related to the level of serotonin ( 39 ) .
although there is no evidence in favor of hormonal disorders in this syndrome , since its symptoms can begin at the beginning , middle , or end of the luteal phase , it might be attributed to the progesterone produced by ovaries .
overall , gabaergic and serotonergic neurotransmitter systems and reduction of serotonin are involved in the occurrence of these symptoms ( 40 , 41 ) .
some studies investigated the effects of herbs such as crocus sativus ( 20 ) and hypericum perforatum ( 21 ) on the symptoms of pms and reported that these herbs probably affected the reduction of pms symptoms through increasing the level of circulating serotonin .
some studies also revealed that m. officinalis can reduce the symptoms of pms through gaba neurotransmitters ( gamma - aminobutyric acid , gabaergic system ) .
gaba neurotransmitters have great inhibitory effects on the central nervous system and are essential to create balance between nervous stimulation and suppression in 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 gaba .
these medications result in sedative and anxiolytic effects through binding to gabaergic receptors and changing other neurotransmitters of brain , such as norepinephrine and serotonin ( 42 , 43 ) .
review of the studies performed on treatment of pms demonstrated that some of the herbs could , to some extent , decrease the symptoms of this disorder .
however , which herb is more effective , efficient , and cost - effective , and which mechanisms are involved in the effects yet remains to be determined .
thus , further studies are recommended to compare other plants to m. officinalis to confirm the results of the present study and find an answer to the above - mentioned questions .
one of the limitations of the current study was its small sample size and its implementation in high school girls . moreover , the placebo group also experienced some reductions in their symptoms that might be attributed to the psychological effects of placebo .
a self- report questionnaire was used to assess the symptoms and this may affect the students responses . furthermore , the subjects of the present study were at different stages of puberty and , consequently , did not experience the changes related to this period similarly . also , individual differences in learning ability and interest might have affected the participation in the adoption of plans . therefore further studies with larger sample size , among older females from different levels of the community , and also studies without a placebo are suggested . in conclusion
, the results of the current study showed that m. officinalis capsules were effective to reduce the intensity of pms symptoms . yet
, this plant is recommended to be compared to other herbal medicines and its degree of effectiveness should be assessed up to several months after the intervention .
 background : several studies are conducted on premenstrual syndrome ( pms ) . 
 however , a few herbal surveys exist on the treatment of pms in iran . due to the sedative effects of melissa officinalis ( m. officinalis ) , this question comes to mind that  can it be used in the treatment of pms symptoms?objectives : the current study aimed to assess the effect of m. officinalis capsule on the intensity of pms in high - school girls.materials and methods : a double - blind randomized , placebo - controlled trial was performed on 100 high school girls from 2013 to 2014 . the intervention group ( n = 50 ) received 1200 mg of m. officinalis essence daily from the first to the last day of their menstrual cycle for three consecutive cycles . the second group ( n = 50 ) received the placebo . 
 the premenstrual symptoms screening tool was used to assess the intensity of pms symptoms in the two groups before and one , two , and three months after the intervention . 
 the data were analyzed using paired t - test and repeated measures analysis of variance.results:the results of repeated measures test revealed a significant reduction ( p < 0.001 ) in pms symptoms . 
 overall , the mean score of pms intensity in the intervention group was 42.56 + 15.73 before the intervention and changed to 32.72  13.24 , 30.02  12.08 , and 13.90  10.22 at the three consecutive months after the intervention , respectively ( p = 0.001).conclusions : m . 
 officinalis capsules were effective in reduction of the pms symptoms . yet , 
 application of this medication requires further investigations . 
1. Background
2. Objectives
3. Materials and Methods
3.1. The Procedure
3.2. Ethical Considerations
3.3. Data Analysis
4. Results
5. Discussion