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Chaste Tree

Scientific Name(s): Vitex agnus-castus L.
Common Name(s): Agnus castus, Chaste tree, Chasteberry, Gattilier, Indian spice, Lilac chaste tree, Monk's pepper, Sage tree hemp, Vitex, Wild pepper

Clinical Overview

Use

Chaste tree extract has been used to manage symptoms related to premenstrual syndrome (PMS) and cyclic mastalgia and may be a suitable alternative to standard pharmacological management. Although the Complete German Commission E Monographs supports its use for PMS and cyclic mastalgia, there are limited clinical trials to support these uses. Limited evidence exists for its use in amenorrhea, hyperprolactinemia, and menopause.

Dosing

Daily doses of chaste tree fruit extract are typically 20 to 40 mg.

Contraindications

Patients who have an allergy to or are hypersensitive to V. agnus-castus or patients who are pregnant or breast-feeding should avoid use. Safe use in children has not been established.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. However, chaste tree may have estrogenic, progesterogenic, and/or uterine stimulant activity and should be avoided in pregnancy and while breast-feeding.

Interactions

None well documented.

Adverse Reactions

Generally regarded as safe; mild and reversible adverse effects include GI reactions, itching, rash, headache, fatigue, acne, and menstrual disturbances.

Toxicology

Information is limited and safety has not been determined in children.

Botany

The chaste tree is a small (6 to 7 m) tree or shrub native to river banks in southern Europe and the Mediterranean region. The plant is cultivated in China. It blooms in summer, developing light purple flowers and palm-shaped leaves. The dark brown to black fruits are the size of peppercorns. These fruits have a pepperish aroma and flavor and are collected in autumn.Chevallier 1996, PLANTS 2011

History

The dried, ripe fruit is used in traditional medicine. The plant has been recognized since antiquity and has been described in works by Hippocrates (AD 460), Dioscorides (AD 40), and Theophrastus (AD 372). In Homer's epic The Iliad, the plant was featured as a symbol of chastity, capable of warding off evil. Early physicians recognized its effect on the female reproductive system, suggesting its use in controlling hemorrhages and expelling the placenta after birth. Monks have chewed it to decrease sexual desire.Chevallier 1996, Christie 1998, Hobbs 1991

Chemistry

V. agnus-castus contains iridoids, flavonoids, diterpenoids, progestins, essential oils, and ketosteroids. Iridoid glycosides have been isolated from the leaves and fruit of the plant and include agnuside and aucubin. Flavonoid content (including kaempferol, quercetagetin, and casticin) has been identified in chaste tree leaves, flowers, and fruits. Flavonoids were isolated from the root bark.

The alkaloid vitricine is present in the plant. Vitexlactam A, a labdane diterpene, has been isolated from the fruit of V. agnus-castus. In vitro studies show that labdane diterpenes have dopamine receptor affinity.

Clerodadienols are potent inhibitors of prolactin release. Although present in only trace amounts, progesterone, hydroxyprogesterone, testosterone, and androstenedione have been isolated from the leaves and flowers of V. agnus-castus. Numerous fatty acids also have been found.Ahmad 2010, Chen 2011, Choudhary 2009, Hirobe 1997, Hoberg 1999, Ibrahim 2008, Kuruüzüm-Uz 2003, Liu 2004, Marongiu 2010, Mesaik 2009, Ono 2011, Sarikurkcu 2009

Uses and Pharmacology

Amenorrhea/Infertility

There have been case reports for the reinstatement of regular cycles in amenorrhea; however, information from controlled clinical trials is limited.Gallagher, 2008, Gerhard 1998, Roemheld-Hamm 2005, van Die 2009 A 2017 systematic review of V. agnus-castus for use in premenstrual, postmenstrual, and infertility disorders identified a clinical trial that confirmed antifertility effects. Linoleic acid and phytoestrogens (ie, apigenin flavonoid) found in the fruits were identified in other studies as possessing estrogen receptor-specific activity.Rafieian-Kopaei 2017

Cancer

Ethanol extracts from the fruit of V. agnus-castus have shown in vitro cytotoxic activity against various human cancer cell lines, including cervical, ovarian, breast, and gastric cancer, and small cell lung carcinoma. Numerous mechanisms of action may be involved in inducing apoptosis.Carmichael 2008, Imai 2009, Ohyama 2005

Galactorrhea

Two case reports provide equivocal results regarding the effectiveness of V. agnus-castus for galactorrhea and prolactinoma. Three-months consumption of 15 drops of the commercial product Agnolyt reduced prolactin levels (masking prolactinoma) and returned normal menstruation to an 18-year-old amenorrheic female.Gallagher 2008 However, 20 drops twice daily of a V. agnus-castus compound for 3 months failed to control hyperprolactinemia and related symptoms in a 31-year-old woman with amenorrhea.Tamagno 2007

Immune system

Experimental studies suggest immunomodulatory effects of chaste tree flavonoids, diterpenes, and other chemical constituents.Ahmad 2010, Chen 2011, Choudhary 2009, Mesaik 2009

Mastalgia/Cyclic breast pain

Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. The plant has been approved for this condition by the Complete German Commission E Monographs.Blumenthal 2000

In vitro experimental studies suggest dopaminergic activity of the plant's diterpenes, similar to bromocriptine, may result in decreases in serum prolactin. Additionally, estrogen receptor binding by phytoestrogens or linoleic acid from the fruits has been postulated as a possible mechanism for effect.Carmichael 2008, Roemheld-Hamm 2005, Tamagno 2009

Clinical data

A limited number of controlled clinical trials have been conducted, and reviews of these trials are concordant in finding a benefit for treatment with V. agnus-castus. Decreased pain and shorter durations of pain have been demonstrated when chaste tree preparations are used for at least 2 cycles.Carmichael 2008, Mirghafourvand 2016, Roemheld-Hamm 2005, van Die 2009

Menopause

Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. With regard to menopausal symptoms, effects of chemical constituents of chaste tree on dopamine receptors, opioid receptors, and melatonin were described in animal experiments and in vitro studies.Chopin Lucks 2003, Jarry 1994, van Die 2009, Webster 2011, Wuttke 2003

Clinical data

Few controlled clinical trials have evaluated the efficacy of V. agnus-castus as a single agent in the management of menopausal symptoms.van Die 2009 Chaste tree was evaluated in combination with other natural products in the Herbal Alternatives for Menopause Trial. Other observational studies and pharmacological experiments suggest V. agnus-castus may be a suitable alternative to standard management, such as hormone replacement therapy, but quality clinical trials are required to support a definitive role in therapy.van Die 2009

Orchiectomy

Inhibition of testosterone in rats and bone-sparing effects in castrated rats have been demonstrated by extracts of chaste tree.Nasri 2007, Sehmisch 2009

Premenstrual syndrome

Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. The plant has been approved for this condition by the Complete German Commission E Monographs.Blumenthal 2000

Clinical data

A limited number of high-quality, controlled clinical trials have evaluated the efficacy of V. agnus-castus preparations in treating symptoms associated with PMS (moderate to severe)Atmaca 2003, Berger 2000, He 2009, Ma 2010, Ma 2010, Schellenberg 2001 with most conducted in Germany and China.Freeman 2010 Despite a large placebo response observed in these trials (approximately 50%) and heterogeneity in trial conditions, a 2011 systematic review found that chaste tree extract demonstrated an overall benefit in reducing adverse physical symptoms and poor mood.Dante 2010, Roemheld-Hamm 2005 Several other systematic reviews published between 2014 and 2017 reported similar results usually with administration of 20 to 80 mg/day over 2 to 6 cycles.Izzo, 2016, Jang, 2014, Rafieian-Kopaei 2017, Verkaik 2017 The number needed to treat for improvement in global symptoms score in 1 person was determined to be "4" in a quality controlled trial involving 104 women followed for at least 3 menstrual cycles.Roemheld-Hamm 2005, Schellenberg 2001 Chaste tree has also been favorably compared with fluoxetine in the management of depression associated with PMS.Atmaca 2003 The clinical studies have found the preparations to be well tolerated with few adverse effects, although data from larger controlled trials are still needed.Dante 2010, Freeman 2010, Roemheld-Hamm 2005

Dosing

The effect of chaste tree extract on hormones in women may be dose-dependent. Some studies suggest lower doses result in increases in prolactin and estrogen as well as decreases in progesterone, while higher doses decrease prolactin levels.Roemheld-Hamm 2005

Daily doses of chaste tree fruit extract are typically 20 to 40 mg, although dosages of up to 1,800 mg/day have been used.Roemheld-Hamm 2005 Chaste tree fruit is available in several different extracts standardized to casticin or agnuside content.Christie 1998, Huddleston 2001, Loch 2000

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. However, chaste tree may have estrogenic, progesterogenic, and/or uterine stimulant activity and should be avoided in pregnancy.Brinker 1998, Dugoua 2008, Ernst 2002, Roemheld-Hamm 2005

No consensus exists regarding the efficacy of extracts in increasing milk production.Brown 1994, Roemheld-Hamm 2005 When analyzed chemically, human breast milk revealed no compositional changes after chaste tree use.Taylor 2001 Despite low toxicity and a lack of evidence that chemical constituents pass into the milk, chaste tree products should be avoided during breast-feeding because safety has not been established.Dugoua 2008, Roemheld-Hamm 2005

Interactions

Case reports are lacking; however, chaste tree has dopamine agonist activity. An interaction with dopamine agonists (eg, bromocriptine, levodopa), dopamine receptor antagonists, and fertility and contraceptive drugs may be theoretically possible.Taylor 2001, Sliutz 1993, Russell 2002, Daniele 2005

Adverse Reactions

Chaste tree administration is generally regarded as safe for use because it has not been associated with any major adverse reactions. Minor and reversible adverse effects reported in clinical trials and surveillance include GI reactions, pruritus, rash, headache, fatigue, acne, and menstrual disturbances.Roemheld-Hamm 2005, Daniele 2005

Toxicology

Information is limited. The safety of the plant's use in children has not been determined.Leung 1996

References

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Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol. 2003;18(3):191-195.12672170
Berger D, Schaffner W, Schrader E, Meier B, Brattström A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. 2000;264(3):150-153.11129515
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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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