Summary of Vitex agnus castus
Primary Information, Benefits, Effects, and Important Facts
Vitex agnus-castus is a supplement derived from berries. It is also called Vitex, Chaste Tree, or Chasteberry.
It is primarily used today to alleviate the symptoms of premenstrual syndrome. Vitex agnus-castus has outperformed placebo in numerous trials, and has been shown to be effective at reducing hot flashes, bloating, irritability, sleep disturbances, depressions, various mood disorders and even cramping associated with premenstrual syndrome.
Though animal evidence suggests that taking Vitex agnus-castus may increase estrogen and progesterone levels, further research is needed to confirm this effect. Vitex agnus-castus has limited use outside of its effects on premenstrual syndrome.
Vitex agnus-castus acts similarly to dopamine, by reducing prolactin levels, which are elevated during premenstrual syndrome. It may also act on the opioid system by releasing beta-endorphins, something the human body lacks during premenstrual syndrome.
Though Vitex agnus-castus has been used for a long time, by people that also use birth control, further research is needed to confirm its safety. It does not appear to interact with any pharmaceuticals, but because of the lack of evidence, pregnant or lactating women should not take Vitex agnus-castus.
Tired of misinformation? Get unbiased info on supplements.
At Examine.com, our incentives line up with yours — getting unbiased information. It’s why we don’t sell any advertising or supplements.
If you’re tired of wasting time and money on supplements that don’t work, our free Supplement Mini-Course will teach you about what works, what's a waste, and what to look out for when buying supplements.
Join the over 200,000 people who have gone through this course (saving themselves time, money, and stress).
Things To Know & Note
May interact with drug-metabolizing enzymes, but this has not yet been linked to any interactions with pharmaceuticals
Usage during pregnancy and lactation currently unexplored
How to Take Vitex agnus castus
Recommended dosage, active amounts, other details
Vitex agnus-castus supplements are based on the dry weight of the plant’s fruit. The standard dose is between 150-250mg. There are also two extractions of Vitex agnus-castus:
BNO 1095 is a 10:1 extraction and provides benefits at doses as low as 4 mg.
Ze 110 is a 6-12:1 extraction and provides benefits at doses of 20mg.
Get access to the latest nutrition research
By becoming an Examine Plus member, you'll have access to all of the latest nutrition research on over 300 supplements across over 500 different health goals, outcomes, conditions, and more.
Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects vitex agnus castus has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
|Strong||Very High See all 11 studies|
|Notable||Very High See all 5 studies|
|Notable||- See study|
|Minor||- See study|
|Minor||- See study|
|Minor||Very High See all 3 studies|
|Minor||- See study|
|Minor||Very High See 2 studies|
|-||- See study|
|-||- See study|
Studies Excluded from Consideration
Get unbiased information on what works
At Examine.com, we pride ourselves on basing all our recommendations on evidence. It’s why we don’t sell any advertising or supplements — so that you know that our analysis is unbiased.
If you’re tired of wasting time and money on supplements that don’t work, our 17 Supplement Guides will help you figure out precisely what to take — and what to skip — based on your health goals and the latest scientific evidence.
Join over 50,000 people who rely on Examine.com's unbiased and science-based analysis.
I want unbiased recommendations »
Research Breakdown on Vitex agnus castus
Click on any below to expand the corresponding section. Click on to collapse it.
Vitex agnus-castus belongs to the Verbenaceae family of plants. The most well-known effect of this herb is the usage of its ripe berries for treatment of various various obstetric and gynecological disorders; there appears to be a history of usage in Greece for menstrual problems, pain, swelling, inflammation, headaches, rheumatism, and sexual dysfunction.
Traditional usage of Vitex Agnus in Turkish medicine includes its usage as a diuretic, digestive, antifungal, anti-anxiety, early birth and stomachache medication. It has been used in Greece, where it derived the name of Chastetree (and the berries Chasteberries), as it was believed consumption of the berries promoted Chastity. It was popular among clergymen wishing to be celibate.
Historical usage for a myriad of female-related symptoms and complications associated with PMS and Menopause, with some other usage related to fighting inflammation-related conditions
The berries of Vitex Agnus appear to contain:
Rotundifuran (1.04-2.23% dry weight) and 6β,7β-diacetoxy-13-hydroxy-labda-8,14-diene (B110, 0.17-0.8% dry weight), which may be bioactive and belong to a labdane class of diterpenoid structures with 3 others including vitexilactone (0.33-1% dry weight) and vitexin (0.06% content); these four are commonly referred to as the active components (Labdane-type Diterpenoids)
Vitexlactam A, another Labdane diterpenoid
Penduletin (0.1% of BN1095 extract)
8,13-dihydroxy-14-labden (B111; 2mg/g dry weight), X-hydroxy-Y-keto-15,16-epoxy-13(16),14-labdadien (B115; 0.8mg/g), and X-Acetonxy-13-hydroxylabda-y-14-dien (B116; 0.7mg/g)
Cleroda-x,14-dien-13-ols (up to 5) and Cleroda-x,y,14-trien-13-ol, the Clerodadienol series of structures
When looking at non-fruit parts:
The Leaves appear to have much higher polyphenolic content than the roots, reaching 3.15% dry weight (caffeic acid equivalents) and a higher o-diphenol content (1.24% dry weight caffeine acid equivalents); higher in the methanolic extract compared to ethanolic (2.05% and 0.74%, respectively) Most of these phenolic compounds were flavonoids (55.2–69.1%)
The roots appeared to be slightly better sources of anthocyanins than the leaves, both outperforming seeds
A particular extract known as BNO-1095 is sometimes used due to standardization; it is a 70:30 ethanolic:water extract of the herb Vitex Agnus Castus and is the extract used for the brand name Agnucaston. 4mg of this extract appears to be bioequivalent to 40mg of the plants dry weight, and it is thus referred to as a 10:1 concentrated extract (pdf in German).
BNO 1095 is a 10:1 concentrated extract of Vitex, and is mostly an ethanolic extract which is under the brand name of Agnucaston
Ze 110 is another standardized extract that tends to be dosed around 10-20mg, with 20mg being derived from 120-240mg of the Vitex Agnus fruits, and has a drug:extract ratio of 6-12:1 while being standardized for casticin content. Ze 110 is a 60% ethanolic extract.
Ze 110 is an alternative extraction which has a more variable, but overall comparable, drug to plant ratio as BNO 1095 does
There appears to be dopaminergic agonists (D2 receptor assays) in the ethanolic:water extract BNO-1095. When testing isolated molecules, B115 was the most potent at 1uM having similar binding affinity to 218nM dopamine but the two clerodadienol structures appeared to be more practically relevant due to a higher concentrations; with their aspect of the extract exerting 5.7-fold more dopaminergic action than B115 and accounting for over 50% of dopaminergic action of Vitex Agnus. The water, butanol, and chloroform extract do not actually appear to possess any significant dopaminergic activity as all activity is concentrated in hexane or ethanolic extracts.
Beyond the clerodadeinol compounds, others that may contribute to dopaminergic effects are linoleic acid (IC50 of 40+/-12ug/mL), Rotundifuran (45+/-7ug/mL), and 6β,7β-diacetoxy-13-hydroxy-labda-8,14-diene (IC50 of 79+/-12ug/mL).
A basic 90% methanolic extract of Vitex Agnus Castus (VAC) has an IC50 of 88.4+/-8.47µg/mL on the Gamma-Opioid receptor, and the potency of the chloroform subset appeared to be enhanced with an IC50 of 23.8+/-2.81µg/mL and the EtOAc with an IC50 of 62.2+/-18.5µg/mL; no affinity was found in the water extract for either Gamma or Delta receptors. IC50 of the methanolic, chloroform, and EtOAc extracts against the Delta-Opioid receptor were 43.0+/-7.78µg/mL, 21.4+/-3.84µg/mL, and 20.7+/-16.9µg/mL; respectively. Interaction with the Opioid receptors appears to be noncompetitive.
The flavonoids of apigenin, luteolin, 3-methylkaempferol, and casticin have been reported to have dose-dependent agonistic properties on Gamma and Delta opioid receptors with isokaempferide having no effect and the effects on the Delta opioid receptor possibly only coming from Casticin; the opioid activating ingredients appear to be present in chloroform or ethanolic extracts for the most part.
Casticin appears to be the most prominent player here (as defatted extracts do not have affinity, suggesting fatty acids play no role), binding to both receptors with IC50 values on Gamma-Opioid and Delta-Opioid being 2.84+/-0.707uM and 2.05+/-0.631uM while other flavonoids ranged in the 20-40uM range. It is unable to activate the Gamma-Opioid receptor, but activates the Delta-Opioid receptor with an EC50 value of 15.3+/-6.32uM and Emax of 74.6+/-18.2%.
Fat soluble compounds in Vitex Agnus appear to have efficacy in interacting with opioid receptors, and Casticin has been demonstrated to activate the opioid receptors
Opioid activity may play a role in Hot Flash symptoms due to a decrease of opioid activity preceding adrenergic instability (assessed by withdrawal from Opioid acting drugs) with is hypothesized to be normalized with opioid activity. Lower levels of B-endorphin (opioid peptide) has also been noted in menopause, and activation of Opioid receptor expressing neurons tends to release B-endorphin compounds.
Activation of Opioid receptors may release B-endorphin, which is inversely correlated with symptoms of menopause
In evaluating a variety of bioactives including flavonoids, no molecule appeared to have significant activity through serotonin receptors up to 40µg/mL.
One study has noted that binding directly to serotonin receptors failed to occur with Vitex in vitro, yet at least one study suggests a possible increase in anxiety at higher doses (100-300mg/kg rats) of Vitex Agnus via acting as an modulator of 5-HT1A receptors, increasing the anxiogenic effects of 5-HT1A antagonists while attenuating the anxiolytic effects of agonists.
May interact with serotonergic mechanisms, but no evidence supports direct agonist roles. Unknown significance for supplementation
When incubated in vitro with Prolactin cells, extracts from Vitex Agnus appear to suppress Prolactin secretion with the potency of one extract at 0.5mg/mL being as effective as 1uM Dopamine (reducing to 10% of control) and the other two at 5mg/mL reducing prolactin secretion to 60% of control. Diterpenoid structures present in these extracts appear to be rotundifuran and clerodadienols, with the latter outperfoming dopamine (1nM) when itself was at a slightly higher concentration of 86uM (underperforming at 43uM).
Histamine, which may influence prolactin, does not have its receptor (H1) affected with incubated Vitex Agnus. This release of prolactin appears to be a downstream effect of activation of Dopamine D2 receptors.
In vitro, reductions of prolactin appear to be apparent which may be mediated via D2 (dopamine) activation
The inhibition of prolactin release from isolated Casticin has been noted in vivo, where injections of 10, 20, and 40mg/kg for a week reduced prolactin levels by 33.9%, 54.3%, and 64.7%; 1mg/kg Bromocriptine used as a reference was approximately as effective as 15mg/kg (measuring at a 44.9% reduction). Another study in rats (800,1600mg/kg ethanolic extract) only noted this decrease of prolactin in rats undergoing experimental menopause (-30.44% and -37.83% at respective doses) and failed to find influence on otherwise normal female rats.
This reduction of prolactin may be mediated via the flavonoid Casticin, although due to other compounds exerting dopaminergic actions (Clerodane Diterpenoids) it may not be the only active ingredient
In otherwise healthy males an extract (BP1095E1) at 120, 240, and 480mg daily for 14 days was associated with an increase in prolactin (24 hour AUC and also in response to a TRH-stimulation test) was noted with 120mg but reductions were noted with 480mg.
Mastalgia is a common symptom of pre-mentrual syndrome (PMS) that affects anywhere between 50-80% of women, while being benign in most cases (only 1% of cases are associated with breast cancer). It is a tenderness of breast tissue that, in most cases, associated with menstration and is highly associated with an increase in serum prolactin and sensitive to stressful situations. The current hypothesis regarding Vitex Agnus and breast tenderness is secondary to acting as a prolactin antagonist (secondary to activating dopaminergic receptors) and suppressing prolaction secretion which subsequently reduces the tenderness associated with higher serum prolactin. Either the suppression of prolactin or the reduction of prolactin is also associated with reduced hot flash symptoms, as evidenced by administration of Bromocriptine (a D2 agonist).
Breast tenderness during PMS is associated with high prolactin levels, which are reduced secondary to dopamine activation
One systemic review notes that the anti-estrogenic effects of Vitex Agnus may play a role in Mastalgia etiology, as anti-estrogenic compounds have shown efficacy in Mastalgia elsewhere. The review noted that although the possibility of diterpenoids acting as an selective estrogen receptor modulator (SERM) may exist, which would attenuate the levels of excess estrogen while inducing weak estrogenic effects, that this possibility was not fully elucidated.
Anti-estrogenic effects may also play a role, but evidence for this is currently subpar
20mg of a Ze110 extract daily (seen as the lowest optimal dose) for three months spanning three menstrual cycles is associated with reduced general symptoms of PMS by 42.5% (as assessed by MMDQ) or 47.2% (VAS rating scale) which was reduced to 20-21.7% but not abolished after 3 months of cessation. Of this, 46.5% of persons were deemed 'responders' to treatment by having more than a 50% reduction of symptoms, and overall the average amount of days suffering from PMS was reduced from 7.5 to 6. Improvements on VAS have been noted elsewhere, and one blinded intervention (n=128) using the VAS rating scale used a liquid delivery systom (40 drops, 4.5mg; one morning dose in juice) noted that placebo was indeed effective in improving VAS Scores (to undermine the aforementioned unblinded study) but that Vitex Agnus was still associated with improvements on all parameters; headache (31%), nervousness (55%), restlessness (60%), depression (67.5%), breast swelling/pain (97.8%), and bloating/tympani (103%). Percentages are degree of improvement over placebo, which improved universally as well. These parameters as well as mood change were significantly reduced in another blinded study with a 52% response rate (greater than 50% reduction of symptoms), and the potency of Vitex Agnus appears to be similar to or slightly less (depending on paramater measured) than that of the SSRI drug Fluoxetine, and one trial noting similar efficacy to Vitamin B6.
The BNO 1095 (4mg of a 10:1 ethanolic extract, correlating to 40mg of the herb ethanolic extract once daily) extract also appears to be effective in women with moderate to severe PMS symptoms as assessed by Premenstrual Syndrome Diary (PMSD), although this particular study failed to find a benefit to lower abdominal cramping (with most benefit due to other pain symptoms and emotional instability). This particular study (duplicated in Medline) noted larger reductions in symptoms in both placebo and Vitex Agnus (due to worse symptoms at baseline), with placebo resulting in a reduction of 48.95-73.7% of symptom intensity and Vitex Agnus reduced symptom intensity by 80.1-92.46% yet a similar study design (cohort of Chinese women with moderate to severe PMS) noted 63% reductions in overall symptoms accompanied by a 46% reduction associated with placebo.
Null studies include one (cannot be found online, sourced in this study) noting that 600mg of basic Vitex Agnus extract daily (n=217) thrice a day had benefits to neurological symptoms of PMS but failed to influence bloating and edema.
Symptoms in general, assessed by total scores of self-reported rating scales (MMDQ or VAS) note global improvements of menopausal symptoms. Many studies are not blinded (which is important as placebo is active on PMS), but the blinded studies appear to show similar benefits that are both statistically significant and clinically relevant (with over half of users reporting over a 50% reduction in symptoms)
In regards to headaches specifically, one study assessing women who are prone to Migraines during menstrural cycles noted that 40mg/day of Vitex Agnus extract daily for 3 months was associated with a 66% response rate for 'dramatic' reductions in headaches (with 44% and 57% reporting over a 50% reduction in headaches per month and days each month suffering a headache; respectively) and an 8% nonresponse rate. This study was not blinded.
May reduce headaches associated with PMS
One review assessing studies on menopause (with variable stages of menopause, from 3-12 months after amenorrhea) notes that studies on Vitex Agnus Castus and menopause tend to be confounded with the inclusion of other herbs and botanicals (such as Black Cohosh or Soy Isoflavones or just St.John's Wort), although one study using the essential oils of Vitex Agnus (both leaves and fruit), where 2.5mL of a 1.5% cream, applied daily most days for 3 months, was associated with a 33% persons reporting significant reduction of symptoms (mostly mood and hot flushes) and 36% reporting mild reduction in symptoms (7.5% reporting no effects and 23.5% reporting worsened symptoms).|published=2003 Aug|authors=Chopin Lucks B|journal=Complement Ther Nurs Midwifery] This study is limited due to its lack of placebo, which limits conclusions on Menopausal symptoms (due to high placebo influence).
Interventions with Vitex Agnus Castus do not currently support its usage for menopausal symptoms despite its theoretical benefit
It appears one study (cited vicariously through a review) found benefits to symptoms of menorrhagia (heavy bleeding) in women given 15 drops of a tincture thrice daily (the product, Agnolyt®, appears to have a variable 20-240mg dry fruit equivalent). The aforementioned review also cites numerous studies using this brand name product finding benefits to oligomenorrhoea, polymenorrhoea, and secondary amenorrhoea although the primary studies (conducted throughout 1954-1982) are not located online.
While there appear to be some early evidence for benefits to menstrual disorders, these studies do not appear to be indexed online and they appear to be all using the same brand name product; more evidence is required
One study (n=43) noted that 16 persons were concurrently using contraceptive medication, but failed to state the specific drugs used; there did not appear to be any interference.
It has been noted that there are no current case studies of clinically relevant or letahl herb-drug interactions with Vitex Agnus supplementation. One review hypothesized that it may interfere with hormonal therapy or contraceptives acting via hormonal means (due to dopaminergic interactions) and these same dopaminergic actions are also a reason Vitex is currently contraindicted in persons undergoing medical therapy for Parkinson's disease (treated with dopaminergic drugs).
No known medication interactions exist, although there isn't a sufficient body of evidence to declare that there aren't any interactions
Casticin, a bioactive flavonoid in Vitex and standardized in the extracts, in concentrations of 0.78-25µg/mL shows efficacy in suppressing monocytic oxidative burst patterns ranged from 20-50%.
In regards to T-cells, Casticin was able to abolish (100% prevention) PHA-induced T-cell activation (as assessed by thymidine incorporation) at concentrations of 7.5µg/mL and above; outperforming Prednisolone on average (but not statistically significant due to high variability seen with Prednisolone). No toxicity was seen acutely up to 50µg/mL, but some was noted in an MDBK cell line after 5 days incubation with an IC50 of 0.7µg/mL.
Casticin may have immunosuppressive properties, relevance to oral consumption unknown
Cytotoxic effects have been observed with Casticin in three Leukemia cell lines with IC50 values varying from 5.95-15.56uM.
Casticin (as well as artemetin, a related flavonoid) can suppress lipoxygenase with IC50 values of 26+/-0.5uM and 54.6+/-3.3uM respectively.
Several compounds (Casticin, Artemetin, and benzoic acid derivatives) show some anti-inflammatory effects in activated neutrophils, but no compound surpassed the efficacy of Aspirin at the same concentrations.
May possess anti-inflammatory properties, significance unknown
In vivo studies measuring serum levels of estrogen in female rats note increases in circulating estrogen (and progesterone), with 600mg/kg and 1200mg/kg of the ethanolic fruit extracts increasing estrogen by 332 and 432% as assessed by vaginal smears; estradiol (positive control) increased this number 625%. When measuring plasma estrogen in this same study, the increase was 24.3% and 115.5% (and progesterone changes being 32.14% and 76.79%, respectively). These increases in serum were attenuated to 11.99% and 23.62% in rats undergoing experimental menopause.
At least one study has noted increased serum estrogen (and progesterone) in female rats as a result of supplementation with Vitex Agnus
Vitex Agnus extract appears to have affinity for the estrogen receptor (ER; cytosolic prepared from human endometrium) and appears to have affinity for the beta-subunit of the ER with no affinity for the alpha subunit, which has been noted elsewhere. The binding affinity of BN1095 extract appears to have an EC50 value of 10µg/mL, and this may be mediated by penduletin (EC50 of 0.25µg/mL), vitexin (10µg/mL), or Apigenin (EC50 0.08µg/mL).
Due to this, administration of the Vitex Agnus extract for up to 3 months failed to significantly modify uterine weight in rats (no observable estrogenic effect) and has been noted in vitro that despite activation of the ERb and an induction of ERb mRNA that no increase of Estrogen-dependent Alkaline Phosphatase (indicative of estrogenicity via ERa) was noted.
Other studies note that a methanolic extract of Vitex Agnus can displace 50% of estrogen from the ERa and ERb receptors with IC50 values of 46+/-3µg/mL and 64+/-4µg/mL, respectively. Linoleic acid in isolation (found in the extract) was able to bind to both receptors with an IC50 of 27+/-2uM and 30+/-2uM (respectively) but this may be too high a concentration to be practically relevant for oral Vitex. Additionally, this studies that actually noted binding to ERa appear to stand alone against other studies that fail to find any binding to ERa at all concentrations tested, and even in one study noting ERa binding there was a failure to induce estrogenic effects as measured by Alkaline Phosphatase Induction (Ishikawa cells); one other study actually notes a decrease of ERa mRNA trancription levels that coexist with an increase in ERb mRNA content.
Vitex Agnus has the classification of containing phytoestrogens, but due to potent binding to the beta subunit of the Estrogen Receptors (ERb) and not the alpha subunit typically associated with 'estrogen-like effects', the overall actions of Vitex Agnus may be practically anti-estrogenic
One study conducted in male rats with injections of Vitex Agnus (fruit hydroalcoholic extract 80:20) at 65-465mg/kg daily for 30 days was associated with a reduction in testosterone and LH hormone levels at concentrations ranging from 165-365mg/kg, but with no significant effect at either extreme (65mg/kg or 465mg/kg). This effect was attenuated slightly with administration of a dopamine antagonist (Haloperidol) and the same research group has previously noted reductions in testosterone following the same injected doses.
The only human study in males investigating the effects of Vitex Agnus noted that 120-480mg of a BP1095E1 extract failed to influence testosterone levels after 20 days of supplementation, despite influencing prolactin.
Injections of Vitex Agnus appear to have anti-androgenic effects, but the dosage range showing reductions in testosterone (165-365mg/kg) equate to a human dose of 1.8-4g of an 80:20 hydroalcoholic extract (150lb male, significantly higher than that commonly supplemented)
One study that noted a large increase in estrogens in menopausal mice suggested that this was indicative of increased androgen synthesis being converted to estrogens (via aromatase); androgens were not measured in this study.
Drops in Luteinizing hormone have been noted in a rat model of menopause following ingestion of 600-1200mg/kg ethanolic extract of the fruits and with relatively large dosed injections of hydroalcoholic Vitex Agnus in otherwise normal male mice; concurrent with drops in testosterone. In normal female mice, no abnormalities are noted with Luteinizing Hormone.
St.John's Wort and Vitex Agnus are commonly associated with each other due to being herbs with dopaminergic (acting on dopamine) actions.
The combination has been assessed in women going through menopause with PMS-like symptoms, and over 16 weeks in this double-blind trial with the daily dose of St.Johns Wort (5.4g dry plant extract conferring 990µg Hypericin and 9mg Hyperforin) and Vitex Agnus (1000mg dry herb equivalent) noted that while both placebo and treatment had significant reductions in overall symptoms at week 4 that placebo had partial attenuation of this improvement while treatment proceeded to exert slightly more benefit over 16 weeks, with significant differences at the time points of 8, 12, and 16 weeks between groups. When looking at subscales, it appeared to have more benefit for cravings and depression associated with PMS-like symptoms and less significant effects on hydration and anxiety (although a positive trend was noted, with hydration failing to be statistically significant).
The combination is used and both appear effective, but interventions do not currently support additive or synergistic effects of the two
One review assessing the evidence for the safety of Vitex Agnus in persons noted that despite a lack of case studies associated with Vitex consumption, that there is insufficient evidence to conclude whether or not Vitex is safe for consumption by pregnant or lactating women and it is uncertain if Vitex crosses into breast milk from the mother.
The LD50 of the ethanolic extract of vitex agnus castus in female rats appears to be 12.5g/kg, and while both a monograph and assessment report from European Medicines Agency (EMA) cite indications of liver damage associated with 26 weeks continued usage of unspecified doses of vitex agnus castus the claim was uncited (beyond "part of a national dossier").
Due to a current lack of evidence, the usage of vitex agnus castus during pregnancy is not advicsed and due to an influence on lactation (paired with a lack of safety data on this particular topic) it is not recommended during this period either; it is contraindicted during breast cancer therapy due to unknown effects on estrogen during this period.
There is a report in existence of a case where a woman with a microadenoma tumor (which increaes prolactin levels in serum which is used as diagnosis) was falsely masked by consumption of Vitex Agnus Castus. It has intentionally been used in another case study where a lowering of prolactin levels in a 31 year old women with an adenoma tumor reached 80% of baseline levels, but no reduction in symptoms associated with high prolactin levels appeared to exist.
There appears to be case reports of pruritic exanthema associated with vitex agnus castus with other skin symptoms such as erythema and worsening of preexisting acne being sporadically associated with the supplement. It is possible that this is due to an allergic reaction, as at least one study has noted dermatitis after a single dose leading to cessation of the study medication.
- Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women.
- Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.
- A pilot study to examine a combination botanical for the treatment of menopausal symptoms.
- Webster DE, et al. Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. J Ethnopharmacol. (2006)
- Extraction of phenolic compounds from Vitex agnus-castus L.
- Honda G, et al. Traditional medicine in Turkey. VI. Folk medicine in west Anatolia: Afyon, Kütahya, Denizli, Muğla, Aydin provinces. J Ethnopharmacol. (1996)
- Tesch BJ. Herbs commonly used by women: an evidence-based review. Am J Obstet Gynecol. (2003)
- Tamagno G, et al. Vitex agnus castus might enrich the pharmacological armamentarium for medical treatment of prolactinoma. Eur J Obstet Gynecol Reprod Biol. (2007)
- Meier B, et al. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. (2000)
- Wuttke W, et al. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Phytomedicine. (2003)
- Hoberg E, Meier B, Sticher O. Quantitative high performance liquid chromatographic analysis of diterpenoids in agni-casti fructus. Planta Med. (2000)
- Jarry H, et al. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Planta Med. (2003)
- Vitexlactam A, a novel labdane diterpene lactam from the fruits of Vitex agnus-castus.
- Ono M, et al. A new diterpenoid glucoside and two new diterpenoids from the fruit of Vitex agnus-castus. Chem Pharm Bull (Tokyo). (2011)
- Ono M, et al. Five new diterpenoids, viteagnusins A--E, from the fruit of Vitex agnus-castus. Chem Pharm Bull (Tokyo). (2008)
- Ono M, et al. Three new diterpenoids from the fruit of Vitex agnus-castus. Chem Pharm Bull (Tokyo). (2009)
- Chen SN, et al. Phytoconstituents from Vitex agnus-castus fruits. Fitoterapia. (2011)
- Sena Filho JG, et al. Ecdysteroids from Vitex species: distribution and compilation of their 13C-NMR spectral data. Chem Biodivers. (2008)
- Ahmad B, et al. Anti-inflammatory and enzyme inhibitory activities of a crude extract and a pterocarpan isolated from the aerial parts of Vitex agnus-castus. Biotechnol J. (2010)
- Mönchspfeffer bei prämenstruellem Syndrom.
- Berger D, et al. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. (2000)
- Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.
- Ho SH, et al. The effects of commercial preparations of herbal supplements commonly used by women on the biotransformation of fluorogenic substrates by human cytochromes P450. Phytother Res. (2011)
- Dericks-Tan JS, Schwinn P, Hildt C. Dose-dependent stimulation of melatonin secretion after administration of Agnus castus. Exp Clin Endocrinol Diabetes. (2003)
- Webster DE, et al. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Biochem Pharmacol. (2011)
- Tuchman E. Exploring the prevalence of menopause symptoms in midlife women in methadone maintenance treatment. Soc Work Health Care. (2007)
- Simpkins JW, Katovich MJ, Song IC. Similarities between morphine withdrawal in the rat and the menopausal hot flush. Life Sci. (1983)
- Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flush mechanism. Clin Endocrinol (Oxf). (1985)
- Giannini AJ, Price WA, Loiselle RH. beta-Endorphin withdrawal: a possible cause of premenstrual tension syndrome. Int J Psychophysiol. (1984)
- Giannini AJ, et al. Symptoms of premenstrual syndrome as a function of beta-endorphin: two subtypes. Prog Neuropsychopharmacol Biol Psychiatry. (1994)
- Barden N, et al. Changes in the beta-endorphin content of discrete hypothalamic nuclei during the estrous cycle of the rat. Brain Res. (1981)
- Genazzani AR, et al. Effect of steroid hormones and antihormones on hypothalamic beta-endorphin concentrations in intact and castrated female rats. J Endocrinol Invest. (1990)
- Possible Modulation of the Anexiogenic Effects of Vitex Agnus-castus by the Serotonergic System.
- Sliutz G, et al. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Horm Metab Res. (1993)
- Jarry H, et al. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol. (1994)
- YE Q, et al. Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro. Acta Pharmacol Sin. (2010)
- Ibrahim NA, et al. Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt. Nat Prod Res. (2008)
- Merz PG, et al. The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects. Exp Clin Endocrinol Diabetes. (1996)
- Carmichael AR. Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence. Evid Based Complement Alternat Med. (2008)
- van Die MD, et al. Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. J Altern Complement Med. (2009)
- Mühlenstedt D, et al. Short luteal phase and prolactin. Int J Fertil. (1978)
- Jeske W, et al. Serum prolactin in women with premenstrual syndrome. Mater Med Pol. (1980)
- Zichella L, et al. Effects of different dopamine agonists and antagonists on post-menopausal hot flushes. Maturitas. (1986)
- Oksa S, Luukkaala T, Mäenpää J. Toremifene for premenstrual mastalgia: a randomised, placebo-controlled crossover study. BJOG. (2006)
- Caleffi M, et al. Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain. J Endocrinol. (1988)
- Schellenberg R, et al. Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome. Phytomedicine. (2012)
- Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Med Iran. (2012)
- Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol. (2003)
- Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine.
- Ma L, et al. Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Aust N Z J Obstet Gynaecol. (2010)
- He Z, et al. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas. (2009)
- Ambrosini A, et al. Use of Vitex agnus-castus in migrainous women with premenstrual syndrome: an open-label clinical observation. Acta Neurol Belg. (2012)
- van Die MD, et al. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause. (2009)
- Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154.
- van Die MD, et al. Predictors of placebo response in a randomized, controlled trial of phytotherapy in menopause. Menopause. (2009)
- Assessment report on Vitex agnus-castus L., fructus.
- Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. (2001)
- Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med. (2000)
- Dugoua JJ, et al. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Can J Clin Pharmacol. (2008)
- Mesaik MA; Azizuddin, et al. Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus. Phytother Res. (2009)
- Shen JK, et al. Casticin induces leukemic cell death through apoptosis and mitotic catastrophe. Ann Hematol. (2009)
- Choudhary MI; Azizuddin, et al. Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus. Phytother Res. (2009)
- Liu J, et al. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. (2004)
- Liu J, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. (2001)
- Nasri S, et al. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Pak J Biol Sci. (2007)
- The Effects of Vitex agnus castus L. Extract on Gonadotrophines and Testosterone in Male Mice.
- van Die MD, et al. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. (2009)
- Community herbal monograph on Vitex agnus-castus L., fructus.
- Gallagher J, Lynch FW, Barragry J. A prolactinoma masked by a herbal remedy. Eur J Obstet Gynecol Reprod Biol. (2008)
- Momoeda M1, et al. Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in Japanese patients: a prospective, open-label study. Adv Ther. (2014)
- Lauritzen C, et al. Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine. (1997)
- Mirghafourvand M, et al. Effects of Vitex agnus and Flaxseed on cyclic mastalgia: A randomized controlled trial. Complement Ther Med. (2016)
- Verkaik S, et al. The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis. Am J Obstet Gynecol. (2017)