Systematic Review of Premenstrual, Postmenstrual and Infertility Disorders of Vitex Agnus Castus.

INTRODUCTION: Vitex agnus-castus, also called vitex is aboriginal to the Mediterranean region, with long leaves, tender stem, flowers and ripening seeds. The aim of this study was to overview premenstrual, postmenstrual and infertility disorder of Vitex agnus-castus.
METHODS: This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified about 87 references. In this study, 43 studies were accepted for further screening, and met all our inclusion criteria (in English, full text, therapeutic effects of Vitex agnus-castus and dated mainly from the year 2009 to 2016). The search terms were Vitex agnus-castus, premenstrual, postmenstrual, infertility disorder properties and pharmacological effects. RESULT: Vitex agnus-castus was shown to contribute to the treatment of premenstrual syndrome (PMS). Moreover, the result of the present study showed that this valuable plant is helpful in alleviation of pain resulting from postmenstrual disease. Furthermore, it was found that Vitex agnus-castus is beneficial in infertility disorder.
CONCLUSION: Vitex agnus-castus (AC) is a phytopharmaceutical compound and is shown to be widely used to treat PMS and PMDD. In addition, it was shown to be beneficial in post-menstrual cases and it can also contribute to treatment of infertility cases in both men and women. Dopaminergic compounds available in this plant help to treat premenstrual mastodynia as well as other symptoms of the premenstrual syndrome.

1. Introduction

1.1. Background

Botanical medicine has been traditionally used for medicinal purposes to cure many kinds of morbidity (1–13). Vitex agnus-castus, also called vitex is aboriginal to the Mediterranean region with long leaves and tender stem, along with flowers and ripening seeds. The main Chemical compound of this plant contain vitexin, casticin, agnuside, p-hydroxybenzoic acid, alkaloids, diterpenoids. Its fruit contain flavonoids, terpenoids, neolignans, and phenolic compounds, as well as one glyceride. The plant contributes to improve many morbidities including premenstrual syndrome, mastalgia, inflammation and sexual dysfunction, and also helps to relieve pain, and possesses antinociceptive effects (14). Vitex agnus-castus is effective in reducing symptoms of many gynecological problems. It is clinically used in abnormal uterine bleeding disorders and mastodynia. This plant is useful in mild hyperprolactinemia and luteal phase defect. It is also helpful in alleviating menstruation, bleeding management uterine fibroids, polycystic ovarian syndrome, prostate disorders, migrainous women with premenstrual syndrome.

1.2. Statement of problem

Herbalism, the use of plants for medical treatment, is still widely practiced today. The evidence from clinical trial studies show that herbalism could fulfill the prerequisite of humankind to cure their diseases. Organic, cost effective, compatible with the body and having less adverse effects, causes people to be more willing to partake of herbs for medicinal purposes, but there is still perplexity about their effectiveness, dosage, toxicity as well as standardization. Thus, a lot of research has been conducted to explore botanical plants generating useful chemical and pharmacological structure.

1.3. Objective of research

This review article is aimed to overview premenstrual, postmenstrual and infertility disorders of Vitex agnus-castus.

2. Material and Methods

2.1. Searching databases

This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified about 87 references. In this study, 43 studies were accepted for further screening and met all our inclusion criteria (in English, full text, therapeutic effects of Vitex agnus-castus L and dated mainly from the year 1997 to 2016). The search terms were: Vitex agnus-castus, premenstrual, postmenstrual, infertility disorder properties, and pharmacological effects.

2.2. Inclusion and exclusion criteria

Inclusion criteria were the following key words which were used to search for the relevant articles published from 1997 to 2016 whose full text should be available in English. Articles included consisted of clinical trials, in vitro, in vivo, review, or meta-analysis studies. Exclusion criteria were relating to other properties of this herb than its anti-premenstrual, anti-postmenstrual and anti-infertility activities, only abstract was available, not in the time line of study. Those articles that did not match our inclusion criteria (in languages other than English, between the time lines of study) were excluded from the study.

2.3. Quality assessment

The inclusion and exclusion criteria were checked. Based on our search strategy, 54 articles were included; meanwhile, 11 studies were excluded from the study; 43 articles were left for more study.

3. Results

3.1. Pre-menstrual stress syndrome (PMS)

The effect of Vitex agnus-castus extract in women with premenstrual syndrome (PMS) was investigated. The plant showed to be effective, safe and well tolerated (15). The VAC extract was shown to be efficient in the treatment of hyperprolactinemia, menstrual disorders, PMS and mastalgia. The VAC benefits are its high tolerability, with no side-effects and no drug interactions (16). In a study in Germany, the cases of PMS/PMDD were investigated in which the plant extract Vitex agnus-castus was used as a complementary method to heal PMS/PMDD (17). In another study, patients with PMDD were treated with fluoxetine and Vitex agnus-castus. The fluoxetine helped to treat psychological symptoms while the VAC extract reduced the physical symptoms (18). Efficacy of Vitex agnus-castus extract in premenstrual syndrome was assessed in China. Results showed that the plant is very beneficial in moderate-to-severe PMS treatment (19). The plant extract BNO 1095 shows powerful effects in treating moderate to serious PMS, particularly in manifestations of negative effect and water maintenance (20). Additionally, Vitex agnus can relieve mild and moderate PMS symptoms (21). In another study, it was found that Vitex agnus-castus extract Ze 440 is helpful in PMS improvement in the case of gradual return after cessation (22). The VAC extract Ze 440 can relieve PMS symptoms in a dose of 20mg (23). In comparison with pyridoxine, VAC markedly alleviates PMTS complaints, including bosom delicacy, edema, inward pressure, cerebral pain, obstruction, and depression. Thus, Agnolyt® capsules were shown to be helpful in the treatment of PMTS (24). The new Vitex preparation showed high efficiency, and is safe for all aspects of PMS, compared to other Vitex preparations (25). In a Japanese population, VAC extract improved PMS symptoms with no marked side effects (26). The use of VAC in migrainous women with PMS proved to be safe and well tolerated, and decreased migraine attack frequency and duration (27). Vitex agnus-castus fruit extract decreases pathophysiological increased prolactin serum levels and could be an effective treatment for women suffering from premenstrual syndrome (28). These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR (29). VAC acted as an agonist at the mu-opiate receptor (30). Combination of Hypericum perforatum and Vitex agnus-castus are useful in PMS treatment among premenopausal women. However, further research is required to warrant its effect (31). In a clinical trial study, intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory, and VACS was found to be useful in the treatment of cyclical breast pain in women (32).

3.2. Postmenopausal period

The crude extract and butanolic fraction of VAC from Vitex agnus-castus demonstrated to be effective in prohibiting frequent causes of abnormal liver functions in the postmenopausal period (33). Vitex agnus-castus alleviates menopausal symptoms suggesting that more research may be appropriate (34). It protects the cortical and additionally the trabecular bone and may be a sheltered option for HRT. Testosterone supplementation affects trabecular bone, which are all the while balanced by the loss of cortical bone (35).

3.3. Anti-Fertility disorders

The result of a clinical trial study confirmed anti-fertility effects of Vitex agnus-castus L. (36). Linoleic acid present in the fruits of the plant possess the ability to bind to estrogen receptors and cause some estrogen genes induction (37). Estrogenic activities are intervened by means of estrogen receptors (ER). The flavonoid apigenin was disconnected and distinguished as the most dynamic ERss-particularly phytoestrogen in VAC. Other disconnected mixes were vitexin and penduletin. The outcome shows that the phytoestrogens in VAC are ERss-specific (38). In a male study, it was demonstrated that dopamine controls the gonadotroph-leydig cells hub. It creates the impression that VAC applies impacts through dopaminergic framework and different pathways. The result of this research demonstrates that VAC concentrate can be utilized for obsessive instances of expanding LH and testosterone (39).

4. Discussion and conclusions

PMS and its derivative PMDD are medical disorders (40). PMS possesses a variety of symptoms including anxiety moodiness, melancholia, breasts sensitivity and food desire (15). The premenstrual syndrome is associated with hormonal and neuronal dysbalance, diet and lifestyle. Hyperprolactinaemia is an important cause considered to be part of the endocrine disorder. PMDD is one of the major complications of the premenstrual phase (41). Vitex agnus-castus is shown to be widely used to treat PMS and PMDD. In addition, it was shown to be beneficial in post-menstrual cases and it also contributes in anti-infertility treatment. Dopaminergic compounds available in Vitex agnus-castus contribute to improve premenstrual mastodynia as well as other symptoms of the premenstrual syndrome. Some of the chemical compounds present in the plant influence the pituitary gland explaining its effects on hormonal levels. A decrease of prolactin will affect the levels of follicle-stimulating hormones (FSH) and estrogen in women and testosterone in men. In conclusion, Vitex agnus-castus (AC) is a phytopharmaceutical compound shown to be widely used to treat PMS and PMDD. Furthermore, it was shown to be beneficial in post-menstrual cases. In addition, it contributes to treatment of infertility cases in both men and women. Dopaminergic compounds found in the plant are helpful in improving premenstrual mastodynia as well as other symptoms of the premenstrual syndrome.