Chasteberry (Vitex agnus-castus) and PMS / premenstrual syndrome: evidence and sources

Background: Cyclic mastalgia (CM) is premenstrual bilateral and diffuse breast pain that presents cyclically and affects women in their reproductive years. It may associate with latent hyperprolactinemia due to the insufficient inhibitory effect of dopamine on the pituitary gland. Vitex agnus-castus (VAC) is known for its dopaminergic activity and its possible actions on CM and latent hyperprolactinemia. However, the treatment effect of VAC on CM remains unclear. Materials and Methods: To perform a systematic review and meta-analysis of clinical trials that report on the efficacy of VAC treatment in CM patients, literature search was performed in major research databases. Results: This review includes 25 studies (17 randomized control trials plus eight nonrandomized trials). VAC was effective in relieving breast pain intensity and lowering the increased serum prolactin level in reproductive age CM patients (18-45 years) with or without premenstrual syndromes. Typical dosage was 20-40 mg/day with a treatment duration of 3 months. A conservative meta-analysis included only six studies ( n = 718, VAC = 356, placebo = 362) and revealed a moderate effect size (SMD: 0.67, 95% CI: 0.5-0.85) favoring VAC over a placebo. Seven trials demonstrated VAC to be a noninferior alternative to pharmaceutical therapies for CM, including dopamine agonists, nonsteroidal anti-inflammatory drugs, serotonin reuptake inhibitors, and hormonal contraceptives. VAC was safe and associated with only mild and reversible adverse events. However, the risk of bias in most studies was unclear due to insufficient information. Conclusions: VAC is a safe and effective treatment option for CM. More high-quality clinical trials are needed to strengthen the evidence base.

Although chasteberry (Vitex agnus-castus, VAC) has been studied in several clinical trials and available as medicine for the alleviation of premenstrual syndrome (PMS) symptoms, the efficacy of properly characterised preparations has not been assessed in meta-analyses. The aim of our work was to evaluate the efficacy of VAC in PMS. The meta-analysis was performed following the PRISMA guidelines using the PICOS format, taking into account the CONSORT recommendations. PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched for studies on VAC. The analysis assessed the efficacy of properly characterised products VAC compared to a placebo for the alleviation of PMS symptoms in terms of responder rate, considering the decrease of Total Symptom Score or PMS Diary score. The random effects model was used to calculate summary relative risk (RR) and 95% confidence interval (CI). Only those randomised, double-blind, placebo-controlled trials were included that fulfilled the criteria of the CONSORT recommendations aiming at the proper characterization of herbal products. Out of the 21 clinical trials, three studies (520 females) fulfilled the inclusion criteria, comparing the efficacy of special extracts Ze 440 and BNO 1095 to a placebo for the treatment of PMS. VAC preparations were confirmed to be effective in the reduction of PMS symptoms: women taking VAC were 2.57 (95% CI 1.52-4.35) times more likely to experience a remission in their symptoms compared to those taking the placebo. Although several clinical trials have been carried out with VAC, the majority of the studies cannot be used as evidence for efficacy due to incomplete reporting, especially concerning the description of the used medication. More trials following the CONSORT recommendations are needed to assess the efficacy of VAC extracts.

Background Premenstrual syndrome is characterized by the cyclic occurrence of physical, behavioral and psychological symptoms during the luteal phase of the menstrual cycle disappearing within a few days of the onset of menstruation. Generally symptoms are mild, but 5-8% of women suffer from severe PMS. Apart from conventional drugs, like serotonin reuptake inhibitors and oral contraceptives, complementary and alternative medicines such as Vitex agnus castus are used by many women experiencing PMS. Objective Our objective was to determine the efficacy, tolerability, and acceptability of Vitex agnus castus preparations for treatment of premenstrual syndrome. Study design All journals in the Ovid software from inception through January 2016 were searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and PsycINFO. Gray literature was searched by Google Scholar and manufacturers of Vitex agnus castus preparations were contacted for information about unpublished trials. We included randomized controlled trials with Vitex agnus castus in women with premenstrual syndrome and/or premenstrual dysphoric disorder with a minimal duration of 2 menstrual cycles. The eligibility of the manuscripts was assessed by 2 reviewers independently. The data abstracted included characteristics of the study design, characteristics of the patient population, intervention details, type of comparator, method of diagnosis, and outcome measures. We adhered to the PRISMA guidelines. Results We found 17 randomized controlled trials of Vitex agnus castus in the treatment of premenstrual syndrome. Fourteen of these could be included in the quantitative analysis. Thirteen of 14 studies with placebo, dietary supplements, or herbal preparations as controls reported positive effects of Vitex agnus castus on total premenstrual syndrome symptoms. Unfortunately most of the trials are associated with a high risk of bias. The pooled effect of Vitex agnus castus in placebo-controlled trials was large (Hedges g, -1.21; 95% confidence interval, -1.53 to -0.88), but heterogeneity was extremely high (I 2 , 91%). We were unable to single out factors that could explain this heterogeneity satisfactorily. The funnel plot and Egger tests suggest the presence of publication bias. Conclusion Although meta-analysis shows a large pooled effect of Vitex agnus castus in placebo-controlled trials, the high risk of bias, high heterogeneity, and risk of publication bias of the included studies preclude a definitive conclusion. The pooled treatment effects should be viewed as merely explorative and, at best, overestimating the real treatment effect of Vitex agnus castus for premenstrual syndrome symptoms. There is a clear need for high-quality trials of appropriate size examining the effect of standardized extracts of Vitex agnus castus in comparison to placebo, selective serotonin reuptake inhibitors, and oral contraceptives to establish relative efficacy.

The objective of this study was to evaluate whether Vitex agnus castus is a safe and effective treatment for PMS and premenstrual dysphoric disorder (PMDD) and to discuss the implications of these findings for clinical practice. A systematic review of literature was conducted using PubMed and Scielo databases. The inclusion criteria were randomized controlled trials (RCT) using V. agnus castus in individuals with PMS or PMDD that compared this intervention with placebo or an active comparator and included a description of blinding and dropouts/withdrawals. The search was conducted by two independent investigators who reached consensus on the included trials. A total of eight RCTs were included in this study. Most studies focused on PMS, and the diagnostic criteria of PMS and PMDD changed over the years. Three different preparations of V. agnus castus (VAC) were tested, and there was significant variability in the measurement of treatment outcomes between the studies. Nevertheless, all eight studies were positive for VAC in the treatment of PMS or PMDD and VAC was overall well tolerated. Main limitations were differences in definition of diagnostic criteria, the instruments used as main outcome measures, and different preparations of VAC extracts limit the comparison of results between studies. In conclusion, the RCTs using VAC for treatment of PMS/PMDD suggested that the VAC extract is a safe and efficacious alternative to be considered for the treatment of PMS/PMDD symptoms.

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials.

Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.

Background Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

In this randomized, placebo-controlled, double-blind study, 128 women suffering from premenstrual syndrome were evaluated (active 62, placebo 66). All patients answered a self-assessment questionnaire about headache, anger, irritability, depression, breast fullness and bloating during the premenstrual period. Forty drops of Vitex agnus extract or matching placebo were administered for 6 days before menses for 6 consecutive cycles. Rank of variables differed significantly in active and placebo groups before and after the study (P<0.0001), and there were significant differences for Vitex agnus in comparison with placebo (P<0.0001). Vitex agnus can be considered an effective and well tolerated treatment for the relief of symptoms of mild and moderate PMS.

The aim of the present study was to compare the efficacy of fluoxetine, a selective serotonin reuptake inhibitor, with that of the Vitex agnus castus (AC) extract in premenstrual dysphoric disorder (PMDD). After a period of 2 screening months, 41 patients with PMDD according to DSM-IV were recruited. The patients were randomized to fluoxetine or AC for 2 months of single-blind, rater-blinded and prospective treatment. At endpoint, using the clinical criterion for improvement, a similar percentage of patients responded to fluoxetine (68.4%, n = 13) and AC (57.9%, n = 11). There was no statistically significant difference between the groups with respect to the rate of responders. However, fluoxetine was more effective for psychological symptoms while the extract diminished the physical symptoms.

Purpose To evaluate clinical characteristics, quality of life (QoL) and effectiveness in patients with menstrual cycle disorders (MCDs) including abnormal uterine bleeding, dysmenorrhea and mastodynia/mastalgia related to premenstrual syndrome taking the Vitex agnus-castus (VAC) products Cyclodynon® or Mastodynon® in a real-world setting. Methods A single-center retrospective longitudinal cohort study (3 ± 1 months), using data obtained from healthcare data archive and telephone interviews. The main study variables were changes in bleeding, menstrual pain, breast tenderness and patients' QoL. Results Data from 1700 women with a mean age of 30.2 years (± 6.3) were analyzed. The most common MCDs were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%). Three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). Improvement in bleeding intensity, frequency and menstrual pain was experienced by 83.4%, 79.2%, and 85.2% of the patients, respectively. When analyzed by disease category, these parameters improved in almost all dysmenorrhea patients, while they improved to a lesser extent in mastodynia/mastalgia patients. QoL improved in all aspects, but was reported by a higher proportion of dysmenorrhea patients compared to mastodynia/mastalgia patients. Treatment was overall well tolerated with a favorable safety profile. Conclusion These real-world data demonstrate the effectiveness of the VAC-containing products Cyclodynon® and Mastodynon® in the three-month treatment of MCDs, with a pronounced improvement in key disease symptoms and QoL. Intriguingly, while QoL was generally greatly improved, the response to VAC therapy varied depending on the type of underlying MCD.

The review includes 161 references on the genus Vitex, and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies, and toxicology of the prominent species of Vitex. Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these, leaves and fruits of V. agnus-castus Linn. (Verbenaceae) has been traditionally used in treatment of women complaints. V. agnus-castus has also been included in herbal remedies, which are in clinical use to regulate the menstrual cycle, reduce premenstrual symptom tension and anxiety, treat some menopausal symptoms as well as to treat hormonally induced acne. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Vitex species has been emphasized with a view to establish their multifarious biological activities and mode of action.