Health Care Professional Information

Scientific Name
Vitex agnus castus
Common Name

Chasteberry, Vitex, Chaste tree fruit, monk’s pepper

Clinical Summary

The fruit of chasteberry is widely used to relieve symptoms associated with premenstrual syndrome and to treat infertility. It is said to have a normalizing action on the menstrual cycle and contains non-steroidal progestins that can interact with and activate hormone receptors in the body (1).

Chasteberry has opioidergic (2), dopaminergic (3), hepatoprotective(4), and antiproliferative (5) properties in vitro. Clinical studies in women suggest its efficacy in reducing symptoms associated with PMS (6) (7) (8), and for the treatment of mastalgia (9). However, in combination with St. John’s wort, chasteberry was not found to be effective for treating menopausal symptoms (10).

Chasteberry influences hormonal activities (11) (12) (13) and should be avoided by patients with hormone-sensitive diseases.

Purported Uses
  • Dysmenorrhea
  • Mastalgia
  • Menopausal symptoms
Constituents
  • Flavonoids: Casticin, penduletin, chrysophanol D, vitexin, apigenin
  • Iridoid alkaloids: Viticin, agnuside, aucubin
  • Progestins: Progesterone
  • Volatile oils
  • Diterpenes: clerodadienols, rotundifuran b, 7b-diacetoxy-13-hydroxy-labda-8,14-diene
  • Vitetrifolin D, vitexlactams
    (1) (2) (3) (11) (14) (15) (13) (16)
Mechanism of Action

In vitro studies have identified several flavonoids in chasteberry, especially casticin, that exert opioidergic effects through the activation of mu- and delta-opioid receptor subtypes (MOR and DOR respectively) (2). Dopaminergic compounds, particularly clerodadienols, dose-dependently inhibit pituitary prolactin release, which could explain its effect during the premenstrual cycle when serum prolactin levels can be chronically elevated (3). Other diterpenes including rotundifuran also modulate dopamine (d2) receptors (14). Linoleic acid from chasteberry binds to estrogen receptors (ER) and can induce certain estrogen genes (12). The flavonoid apigenin was identified as the most active ER isoform-selective phytoestrogen (11), and can also induce progestogenic activity (13).

In human studies, chasteberry restores progesterone concentrations, prolongs the hyperthermic phase in the basal temperature curve, and restores the luteinizing hormone (LH)-releasing hormone (LHRH) test to normal. It is thought to act on the pituitary-hypothalamic axis rather than directly on the ovaries (11).

Contraindications
  • Chasteberry may have estrogenic (11) (12) and progestogenic (13) activity and should be avoided or used cautiously by patients with hormone-sensitive disease.
  • Chasteberry should also be avoided during pregnancy and lactation (17) (18).
Adverse Reactions

Reported: The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash (9) (19).

Herb-Drug Interactions

Antipsychotics (Phenothiazines, Dopamine D2-Antagonists): Chasteberry may interfere with the action of these drugs or enhance their side effects (17) (20).
Antiparkinson agents (Dopamine agonists): Chasteberry may interfere with the action of these drugs or enhance their side effects (17) (20).
Cytochrome P450 substrates: Chasteberry inhibits CYP2C19 and CYP3A4 and may affect drugs metabolized by these enzymes (21).
Hormonal therapies: Chasteberry may decrease the effects of hormone therapies (11) (12) (18).
Oral contraceptives: Chasteberry may decrease the effects of contraceptives (18).

Literature Summary and Critique

In this study, 128 women were randomized to receive 40 drops of Vitex extract or matching placebo administered for 6 days before their menstrual cycle for 6 consecutive cycles. The mean ages were 30.77 years in the active group and 30.89 (SD=4.02) years in the placebo group. Participants answered a self-assessment questionnaire about headache, anger, irritability, depression, breast fullness and bloating, and tympani before and after 6 menstrual cycles. Each item was rated using a visual analogue scale (VAS). There was a significant difference in the variables in both groups before and after the study (P<0.0001), as well as between groups (P<0.0001). Researchers concluded that Vitex agnus may be an effective treatment for controlling symptoms associated with mild and moderate PMS, and that larger studies are warranted.

van Die MD, et al. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause. 2009;16:156-163.  
Chasteberry in combination with St. John’s wort was evaluated for effects on menopausal symptoms in a double-blind, randomized, controlled trial (RCT). A total of 100 women who were either late-perimenopausal or postmenopausal and experiencing hot flushes and other related symptoms received either chasteberry 500 mg twice daily and St. John’s wort 300 mg 3 tablets daily, or placebo. The combination regimen was determined by referring to previous RCTs and current popular usage of these herbs. Frequency and severity of hot flush episodes was used as the primary endpoint, with secondary endpoints including Greene Climacteric Scale scores, Hamilton Depression Inventory scores, and Utian Quality of Life Scale scores. Among 93 women who completed the study, there were no significant between-group differences for any endpoint over the 16 week period, and no significant differences at interim weeks 4, 8, or 12 for daily weighted flushes or secondary endpoint scores. However, across the treatment phase, both placebo and active treatment groups did experience significant improvements for these endpoints, leading investigators to conclude that this herbal combination was not superior to placebo in treating menopausal symptoms. The active treatment regimen was also well tolerated among participants.

Dosage (Inside MSKCC Only)
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References
  1. Toh MF, Sohn J, Chen SN, et al. Biological characterization of non-steroidal progestins from botanicals used for women's health. Steroids. Jun 2012;77(7):765-773. doi: 10.1016/j.steroids.2012.03.013
  2. Webster DE, He Y, Chen SN, et al. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Biochem Pharmacol. Jan 1 2011;81(1):170-177. doi: 10.1016/j.bcp.2010.09.013
  3. Wuttke W, Jarry H, Christoffel V, et al. Chaste tree (Vitex agnus-castus)—pharmacology and clinical indications. Phytomedicine. May 2003;10(4):348-357. doi: 10.1078/094471103322004866
  4. Tandon VR, Khajuria V, Kapoor B, et al. Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatotoxicity. Fitoterapia. Dec 2008;79(7-8):533-538. doi: 10.1016/j.fitote.2008.05.005
  5. Weisskopf M, Schaffner W, Jundt G, et al. A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines. Planta Med. Oct 2005;71(10):910-916. doi: 10.1055/s-2005-871235
  6. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. Jan 20 2001;322(7279):134-137.
  7. He Z, Chen R, Zhou Y, et al. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas. May 20 2009;63(1):99-103. doi: 10.1016/j.maturitas.2009.01.006
  8. Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Med Iran. 2012;50(2):101-106.
  9. Carmichael AR. Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence? Evid Based Complement Alternat Med. Sep 2008;5(3):247-250. doi: 10.1093/ecam/nem074
  10. van Die MD, Burger HG, Bone KM, et al. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause. Jan-Feb 2009;16(1):156-163. doi: 10.1097/gme.0b013e31817fa9e0
  11. Jarry H, Spengler B, Porzel A, et al. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Planta Med. Oct 2003;69(10):945-947. doi: 10.1055/s-2003-45105
  12. Liu J, Burdette JE, Sun Y, et al. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. Jan 2004;11(1):18-23. doi: 10.1078/0944-7113-00331
  13. Hajirahimkhan A, Dietz BM, Bolton JL. Botanical modulation of menopausal symptoms: mechanisms of action? Planta Med. May 2013;79(7):538-553. doi: 10.1055/s-0032-1328187
  14. Meier B, Berger D, Hoberg E, et al. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. Oct 2000;7(5):373-381. doi: 10.1016/S0944-7113(00)80058-6
  15. Li S, Qiu S, Yao P, et al. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction. Evid Based Complement Alternat Med. 2013;2013:432829. doi: 10.1155/2013/432829
  16. Hajimehdipoor H, Shekarchi M, Piralihamedani M, et al. A Validated HPTLC-Densitometric Method for Assay of Aucubin in Vitexagnus-castusL. Iran J Pharm Res. Fall 2011;10(4):705-710.
  17. Roemheld-Hamm B. Chasteberry. Am Fam Physician. Sep 1 2005;72(5):821-824.
  18. Dugoua JJ, Seely D, Perri D, et al. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Can J Clin Pharmacol. Winter 2008;15(1):e74-79.
  19. Daniele C, Thompson Coon J, Pittler MH, et al. Vitex agnus castus: a systematic review of adverse events. Drug Saf. 2005;28(4):319-332.
  20. Jarry H, Leonhardt S, Gorkow C, 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;102(6):448-454. doi: 10.1055/s-0029-1211317
  21. Ho SH, Singh M, Holloway AC, 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. Jul 2011;25(7):983-989. doi: 10.1002/ptr.3371

Consumer Information

How It Works

Bottom Line: There is evidence to suggest that chasteberry helps improve symptoms associated with premenstrual syndrome.
Chasteberry is used widely to treat infertility and for relief of premenstrual syndrome (PMS) symptoms. Laboratory analysis has shown that chasteberry contains hormonal precursors that can prompt hormone changes within the body by activating those receptors. Various studies have found chasteberry to be effective in reducing breast pain and other PMS symptoms, but not for symptoms of menopause.

Because of its ability to influence hormone levels in the body, chasteberry should be avoided by patients with hormone-sensitive diseases including certain types of cancers.

Purported Uses
  • To ease difficult and painful menstruation
    A handful of clinical trials support this use in women aged 20–40 whose ovarian function was not greatly impaired and who had no other hormone imbalances.
  • To prevent premenstrual symptoms
    A few studies support this use in women aged 20–40 whose ovarian function was not greatly impaired and who had no other hormone imbalances.
  • To treat breast pain
    A few clinical trials support this use for breast pain associated with menstruation.
  • To prevent menopausal symptoms
    There is no evidence to support this claim. One study that evaluated chasteberry in combination with St. John’s wort did not find it effective for menopausal symptoms. Because chasteberry contains sex hormones like progesterone, it is not known whether it would be a safe alternative to hormone replacement therapy.
Research Evidence

Premenstrual Syndrome
In this study 128 women were randomized to receive 40 drops of Vitex agnus extract or matching placebo administered for 6 days before their menstrual cycle for 6 consecutive cycles. Participants answered a self-assessment questionnaire about headache, anger, irritability, depression, breast fullness and bloating and tympani before and after 6 menstrual cycles. There were significant differences in variables for both groups before and after the study as well as between the two groups. Researchers concluded that Vitex agnus may be an effective treatment for controlling symptoms associated with mild and moderate PMS.

Menopausal Symptoms
In this study, 100 women experiencing hot flashes and other menopausal symptoms were randomly divided into 2 groups: those who received a combination of chasteberry and St. John’s wort, and a second group who received a placebo. This combination was tested because it reflected current popular use of these herbs. Among 93 women who completed the study, there were no significant differences between the two groups. However, both placebo and active treatment groups had similar improvements throughout the study, meaning this herbal combination was comparable to placebo in treating menopausal symptoms.

Patient Warnings
  • Chasteberry should be avoided or used cautiously by patients with hormone-sensitive disease.

  • Chasteberry contains sex hormones such as progesterone, and it is unknown whether chasteberry is a safe alternative to hormone replacement therapy.

Do Not Take If
  • You have hormone-sensitive cancer: Chasteberry has hormonal activity and can stimulate cancer.
  • You are taking drugs that are substrates of Cytochrome P450 enzymes CYP2C19 and CYP3A4: Chasteberry may increase the risk of side effects of these drugs.
  • You are taking medicines used to treat serious mental and emotional disorders (chlorpromazine, haloperidol, prochlorperazine): Chasteberry may interfere with the action of these drugs or enhance their side effects.
  • You are taking medicines for Parkinson’s disease: Chasteberry may interfere with the action of these drugs or enhance their side effects.
  • You are taking any hormonal medications, such as oral contraceptives (birth control pills):  Chasteberry may interfere with their effects.
  • You are pregnant or nursing.
Side Effects

Reported:  Nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, itching, redness/rash

E-mail your questions and comments to aboutherbs@mskcc.org.