Chasteberry

• How It Works

  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 chasteberry has phytoestrogenic properties, patients with hormone-sensitive cancers should consult their physicians before using it.

• Purported Uses
  • To ease difficult and painful menstruation
    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
    One study that evaluated chasteberry in combination with St. John’s wort did not find it effective for menopausal symptoms.
• Do Not Take If
  • 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

• Scientific Name

  Vitex agnus castus

• 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 suggest its efficacy in reducing symptoms associated with PMS ^{(6) (7) (8) (22)}, but a systematic review highlighted the need for well-designed studies for definitive conclusions ⁽²³⁾. Chasteberry was also reported useful for the treatment of mastalgia ^(9) (24). However, in combination with St. John’s wort, it was shown to be ineffective for treating menopausal symptoms ⁽¹⁰⁾.

  Because chasteberry has phytoestrogenic properties ^{(11) (12) (13)}, patients with hormone-sensitive cancers should consult their physicians before using it.

• Purported Uses
  • Dysmenorrhea
  • Mastalgia
  • Menopausal symptoms
• Mechanism of Action

  In vitro studies have identified several flavonoids in chasteberry, especially casticin, which exert opioidergic effects through the activation of mu- and delta-opioid receptor subtypes (MOR and DOR respectively) ⁽²⁾. Casticin was also shown to reduce lung inflammation induced by cigarette smoke in a murine model ⁽²⁵⁾ by inhibiting the numbers of neutrophils, macrophages, and lymphocytes, and by reducing the levels of proinflammatory cytokines and chemokines.

  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
  • Because chasteberry has phytoestrogenic properties ^{(11) (12) (13)}, patients with hormone-sensitive cancers should consult their physicians before using it.
  • Chasteberry should 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⁾.

• 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

  22. Cerqueira RO, Frey BN, Leclerc E, Brietzke E. Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review. Arch Womens Ment Health. 2017 Dec;20(6):713-719.

  23. Verkaik S, Kamperman AM, van Westrhenen R, Schulte PFJ. The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017 Aug;217(2):150-166.

  24. Mirghafourvand M, Mohammad-Alizadeh-Charandabi S, Ahmadpour P, Javadzadeh Y. Effects of Vitex agnus and Flaxseed on cyclic mastalgia: A randomized controlled trial. Complement Ther Med. 2016 Feb;24:90-5.

  25. Lee H, Jung KH, Lee H, Park S, Choi W, Bae H. Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model. Int Immunopharmacol. 2015 Oct;28(2):1097-101.