Effect of myrtle fruit syrup on abnormal uterine bleeding: a randomized double-blind, placebo-controlled pilot study
© Qaraaty et al.; licensee BioMed Central Ltd. 2014
Received: 22 December 2013
Accepted: 9 May 2014
Published: 2 June 2014
Myrtle (Myrtus communis L.) has been used in the Iranian Traditional Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal uterine bleeding-menometrorrhagia.
A randomized, double-blind, placebo-controlled pilot study was conducted on 30 women suffering from abnormal uterine bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup daily (5 ml three times a day) for 7 days starting from the onset of bleeding. The myrtle syrup along with placebo was repeated for 3 consecutive menstrual periods. Menstrual duration and number of used pads were recorded by the Pictorial Blood loss Assessment Chart at the end of each menstrual period. The quality of life was also evaluated using the menorrhagia questionnaire.
The mean number of bleeding days significantly declined from 10.6 ± 2.7 days to 8.2 ± 1.9 days after 3 months treatment with the syrup (p = 0.01) and consequently the participants in the intervention group used fewer pads after 3 months (16.4 ± 10.7) compared with the number of pads used at the beginning of the treatment (22.7 ± 12.0, p = 0.01). Bleeding days and number of pads used by the participants in the placebo group did not change significantly. Also significant changes of quality of life scores were observed in the intervention group after 3 months compared to the baseline.
Myrtle syrup is introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia.
KeywordsAbnormal uterine bleeding-menometrorrhagia Effrat-e-tams Iranian traditional medicine Myrtus communis L Myrtle Myrtaceae
Abnormal uterine bleeding (AUB) is one of the main reasons of visiting gynecologists . AUB affects up to one-third of sexually active women  and the overall prevalence of this abnormality is 11%-13%, reaching 24% at the age of 36–40 . AUB has a considerable high morbidity rate among women of childbearing age and imposes major medical, social and financial burdens on women, their families and health services . Different types of AUB include a range of dysfunctional conditions affecting regularity, frequency, duration or volume of menstrual flow [5, 6]. Menorrhagia or hypermenorrhea is defined as menstrual blood loss of more than 80 ml per cycle or longer than 7 days or both of them , while polymenorrhea is defined as having menstruations about every 21 days and occasionally at even shorter intervals causing irregular ovulation. Metrorrhagia is uterine bleeding at irregular intervals, particularly between the expected menstrual periods . Abnormal uterine bleeding-Menometrorrhagia (AUB-MM) is defined as prolonged and excessive uterine bleeding in irregular intervals . The most common causes of AUB may be pregnancy, genital tract diseases, certain medical conditions such as thyroid dysfunctions and hypothalamic suppressions including stress, weight loss, excessive exercise, and even coagulopathies [1, 10]. AUB treatment includes administration of non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics such as tranexamic acid, cyclic oral progestins, oral contraceptives and levonorgestrel-releasing intra-uterine system [1, 5, 11]. Hormone therapies have many side effects  and the common complication of tranexamic acid is gastrointestinal disturbances . AUB involves two-thirds of all hysterectomies leading to several complications [14, 15].
Iranian Traditional Medicine (ITM) practitioners such as Ibn Sina (Avicenna, 980–1037 A.D) believed that the normal menstruation is a good sign of healthy status of a woman which results in chastity and modesty [16–18]. In ITM literature, AUB is described under the title of “Effrat-e-Tams” or “Kasrat-e-Tams” [7, 18]. Menometrorrhagia is more compatible with Effrat-e-Tams in ITM [17–20].
Based on ITM literature, particularly Avicenna’s book (Al-Qanun fit-teb or Canon of medicine, 1025 A.D), myrtle is known as “mourd” or “aass” and its fruit that called Habbol- aass, is one of the effective medicinal herbs for decreasing the menstrual bleeding . Myrtle is a fragrant evergreen shrub belonging to myrtaceae family, growing wild in Iran [21, 22] and the Mediterranean area. The fruits have sweet-spicy tastes that are very astringent . Myrtle has been used as antiviral, antifungal, antiseptic and antioxidant agent [24, 25]. Myrtle berries extract has ulcer-protective properties  and anti-inflammatory effects . The essential oils obtained from leaves, flowers and fruits have been used in flavor and fragrance industries . Its biological effect in menstrual disturbances has been described in ITM which may be novel in modern medicine .
There is a lack of detailed trials on the effects of myrtle syrup on menstruation. The main objective of the present study was to investigate the effects of myrtle syrup on reducing AUB-MM in a pilot placebo-controlled clinical trial.
Materials and methods
Study design and target group
Women were excluded from the study if they had a history of significant medical problems (coagulopathies, diabetes mellitus, chronic inflammatory disease, thyroid dysfunctions); had a history of endometrial abnormalities (such as hyperplasia), cervical carcinoma, uterine or ovary malignancy; sub-mucosal or intramural fibroids more than 5 cm; needed surgery and emergency procedure because of increasing bleeding during the study. All of the subjects were free to withdraw at any time during the course of study.
Participants were not permitted to use mefenamic acid, tranexamic acid, any hormonal therapy, herbal medicine and medicinal herb during the study. Use of acetaminophen, oral iron therapy and analgesic opioids was permitted throughout the study.
All participants signed a written informed consent before recruiting in the study. The Ethics Committee of Shahed University approved the protocol (approval number: 41/138342). In addition, the trial was registered in the Iranian Registry of Clinical Trials under the number IRCT 201109077511 N1.
Myrtle dried berries were collected from Manjil on road to Gilan (North of Iran) in 2011 and its identity was authenticated by Professor Gholamreza Amin. A voucher specimen of the plant has been deposited in Herbarium Tehran University of Medical Sciences, Faculty of Pharmacy under the voucher No 6632-TEH.
Preparation of syrup and placebo
Traditional decoction was prepared as described in “Qarabadin” (Ghayeni, Qarabadin-e-Salehi, 1765 AD; Aghili, Qarabadin-e-Kabir, 1781 AD) [29, 30] texts belonging to ITM pharmaceutical discipline. 63 g of the pulverized samples of myrtle fruits were macerated for 24 hours with 200 ml of distilled water, filtered and boiled for 15 min. 108 g sucrose was added to the extract in order to prepare the syrup. The medication was supplied in bottles of 120 ml, containing either drug or placebo.
Placebo was prepared based on pharmacopoeia simple syrup formula including approved color additives and looked the same as the myrtle syrup.
Myrtle syrup is standardized based on total phenols (Folin-Ciocalteau method) and gallic acid (Rhodanine assay) content. Each 5 ml of syrup contains 0.05 ± 0.03 g dry residue and 41 mg total phenols as gallic acid equivalents.
The participants were given either 5 ml of prepared syrup or placebo three times a day, 30 minute after each meal for seven days starting from the onset of bleeding. This treatment was repeated for three consecutive menstruation cycle.
The myrtle syrup and placebo were identical in the same physical form, packaging and labeling and divided to groups 1 and 2. Physician prescribed syrups to the patients according to the label numbers. Physician and presenter of the myrtle syrup or placebo were blind for the contents. The pharmacist was the only person who was aware of the numbers assigned to the myrtle syrup or placebo.
All the participants were evaluated based on a complete medical history and gynecological examination. Menstrual blood loss was assessed with Pictorial Blood loss Assessment Chart (PBAC). The quality of life was evaluated with menorrhagia questionnaire (MQ-Iranian Version) [31, 32] before treatment and at the end of the study. Certain blood test including complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) were done before the study. PT and PTT were done to exclude bleeding disorders. TSH, FSH and LH were done to exclude thyroid dysfunction and hypothalamic pituitary dysfunction, respectively. CBC was performed to determine hemoglobin (Hb) and hematocrit (Hct). Trans-vaginal ultra sonography was also performed to find out if the subject had any pelvic pathological disorders and to determine the endometrial thickness. Cervical cytology (Pap smear) was done to rule out other abnormalities.
Menstrual blood loss and menstrual duration were measured using PBAC chart during three consecutive treatment cycles and was compared with the ones at the beginning of the treatment (baseline). The participants were requested to report the details of their menstrual cycle i.e., the start date, duration of menstruation, the number of sanitary pads used (considered as the intensity of bleeding) and any adverse effects. The information was recorded at the beginning of the treatment and at the end of each menstrual cycle. The PBAC chart had a sensitivity of 80% and specificity of 88% in diagnosing menorrhagia (as defined in the alkaline hematin method) .
The primary outcome measures included the duration of menstrual period, number of pads used during menstruation. The MQ score and the side effects were the secondary outcome measures.
Normal probability plot was used to test for normality of data in GraphPad Prism version 5. The data points appeared linear on the plot and the data were considered as normal distribution. Repeated-measures ANOVA function in the program GraphPad Prism version 5 was used to test for differences of primary outcomes within the groups. Repeated-measures ANOVA compares the means of more than two matched groups in a longitudinal study in which change over time is assessed. Student’s t-test was used to compare the MQ scores before and after the treatment.
Baseline characteristics of study subjects
41.33 ± 7.228
41.13 ± 6.978
28.86 ± 4.68
31.99 ± 6.29
47.8 ± 15.7
41.2 ± 15.3
Duration of abnormality (month)
53.93 ± 61.46
72.33 ± 69.92
Effects of myrtle fruit syrup on duration and intensity of bleeding
The effect of myrtle fruit syrup in bleeding at baseline and post treatment
Mean difference (±SE) compared with baseline
Menstrual duration (day)
Intervention (n = 15)
After 1st cycle
After 2nd cycle
After 3rd cycle
Placebo (n = 15)
After 1st cycle
After 2nd cycle
After 3rd cycle
Number of pads used
Intervention (n = 15)
After 1st cycle
After 2nd cycle
After 3rd cycle
Placebo (n = 15)
After 1st cycle
After 2nd cycle
After 3rd cycle
Intervention (n = 15)
After 3 months
Placebo (n = 15)
After 3 months
The number of bleeding days and consequently number of pads used by the participants significantly decreased in the intervention group after 3 months (P = 0.01), while changes of these variables were not significant in the placebo group.
Significant changes of MQ score was observed in the intervention group after 3 months compared to the baseline (P = 0.02).
To the best of our knowledge, the present study is the first randomized placebo-controlled trial on the effects of myrtle fruit in women with AUB-MM. The results of this study showed that myrtle syrup had notable advantages over placebo in women with AUB-MM. Also, the quality of life was significantly improved in the intervention group with minor side effects.
During luteal phase in menstrual cycle, some inflammatory processes lead to tissue edema in endometrium and continue with excessive menstrual bleeding (EMB). Unusual secretion of local pro-inflammatory cytokines responsible in the vascular tone has been observed [2, 4]. In these women, endometrium synthesizes much more prostaglandin E2 (PGE2) than it does with vasoconstrictor PGF2α. A noticeable increased PGE2/PGF2α ratio happens during luteal phase in women with menstrual blood loss (>90 ml). Endometrial synthesis of PGs and signaling in women with profuse menstruation is greater than women with normal menstrual bleeding . These inflammatory molecules can be targeted to treat the disturbances in women suffering from AUB.
Myrtle berries aqueous extract contains phenolic-like tannins (galllic acid derivatives), anthocyanins and flavonoids . Tannin-containing medications have been used traditionally as styptics . Anti-inflammatory activities of anthocyanins have been proven in some studies . Some studies have demonstrated that flavonoids can inhibit inflammatory mediators . According to a preliminary study, micronized flavonoids suppressed endometrial prostaglandins and were safe and effective in AUB . Another phytochemical compound in myrtle that suppresses prostaglandin E2 formation efficiently is myrtucommulon . Therefore, the presence of the effective anti-inflammatory components in the myrtle extract can render the myrtle syrup a potential source to reduce prostaglandin secretion and to cure AUB subsequently. Further mechanistic studies are suggested to prove the anti-inflammatory effects of the components in the myrtle extract.
This study had some potential limitations which are usually part of the nature of human studies. Firstly, ITM has two groups of principal variables: one is part of human nature, mezaj (temperament), racial/ethnic, sex, age, season, zone, profession , and the second factor is the composition of the herbal preparations which may vary based on the geographical habitat of the plant, the climate, and the time of reaping . These factors have not been considered in our study.
In the present study, the subjects received syrup only for three cycles; therefore we cannot comment on any long-term efficacy of myrtle syrup. Also, the subjects were not followed up after finishing the study and the long-lasting effects are not clear to us.
The outcomes of this study showed that myrtle syrup is an effective drug as a short-term treatment of AUB-MM. Women in the test group experienced significant reductions of bleeding duration, as well as a significant decline of the intensity of bleeding while placebo did not affect the variables significantly. The quality of life improved among the subjects in the syrup-treated group. Based on the current novel results, a therapeutic role of myrtle syrup is suggested for women with AUB-MM, which is accessible and cost-effective therapy. Larger and longer randomized trials are being planned in our research group to confirm the long-term effects of myrtle on bleeding reduction in AUB-MM.
Abnormal uterine bleeding-menometrorrhagia
Complete blood count
Excessive menstrual bleeding
Follicle- stimulating hormone
Heavy menstrual bleeding
Iranian traditional medicine
Partial thomboplastin time
Thyroid stimulating hormone.
The authors thank all the study participants for their participation. The authors gratefully acknowledge the help of the following individuals: Dr Jale aliasl Mamaghani for editing the data and revising; Dr Zahra Ghorbanifar for editing and Dr. Maliheh Tabarrai for revising. This was supported by a research grant provided by Shahed University.
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