Menopause, menstrual, and fertility disorders in women. Premenstrual syndrome (PMS), mastalgia, gynecomastia in men, adolescent acne, amenorrhea, ovarian cysts, hot flashes, menstrual bleeding irregularities.1,2,3
Mechanism of Action
Vitex agnus castus fruits contain flavonoid glycosides such as casticin, vitexin, penduletin, orientin, and apigenin; the iridoid compounds aucubin,4 agnuside,5,6 agnucastosides A, B, and C, mussaenosidic acid, and hydroxybenzoylmussaenosidic acid7; and labdane diterpene alkaloids such as vitexlactams A, B, and C8 and clerodadienol.9
Endometrial cell culture studies show that agnuside and rotundifuran (another compound found in Vitex) have estrogenic effects that are mediated via up-regulation of estrogen-inducible genes.10 Radioligand studies show Vitex extract competitively binds α- and β-estradiol receptors,11 with one study reporting that apigenin, vitexin, and penduletin act as selective estrogen receptor agonists.12
Vitex is also believed to be an estrogen receptor agonist and to induce certain estrogen-related genes via its linoleic acid content.11 In vitro studies have also shown Vitex stimulates progesterone expression in endometrial cells.13
To date, there have been few clinical trials of Vitex for menopausal symptoms, but an increasing number of experimental studies are providing evidence of its hormonal and neurotransmitter effects and thus scientific rationale for its use in menopause.14
Vitex influences dopaminergic transmission. It also regulates prolactin, follicle-stimulating hormone, and luteinizing hormone, which may regulate testosterone levels as well as levels of other reproductive hormones. Vitex has also been shown to bind opiate receptors,15,16,17 which in turn promotes dopamine activity.
According to subjective reports, essential oils from Vitex alleviated menopausal symptoms.18,19 In a double-blind, placebo controlled trial, Vitex was more effective than placebo in reducing both the intensity and duration of mastalgia.20
Safety in Pregnancy and Breastfeeding
Vitex is presumed to be contr aindicated in pregnancy and lactation, although evidence for its impact on lactation is contradictory.21 Given that Vitex affects numerous hormones, it is advisable to avoid it during pregnancy until more evidence is available.
Vitex is generally well tolerated, with the main side effects being nausea and gastrointestinal irritation, dizziness, dry mouth, headache, menstrual disorders, acne, pruritus, and erythematous rash, all of which reversed upon cessation of the medication.22,23,24
No herb–drug interactions have been reported, but it is possible that Vitex may have additive effects if combined with dopaminergic drugs, or it may interfere with the action of dopamine antagonists.
Traditionally, 20–1800 mg/day of the crude herb powder in divided doses is used.
Doses from 4 to 40 mg of the extract have been used in clinical trials.
Vitex agnus castus has been used for centuries to treat menstrual, menopausal, and fertility disorders in women and is a valuable medicine to consider in a broad treatment protocol for PCOS. Vitex is also known as monk’s pepper, a name that stems from the use of its peppercorn-like fruits to help maintain chastity in men’s religious orders. Vitex has a long history of use in formulas to treat PMS, mastalgia, male gynecomastia, adolescent acne, amenorrhea, ovarian cysts, hot flashes, bleeding irregularities, and menopausal complaints.
Akush Ginekol (Sofiia). 2011;50(6):18–20. Our experience with management of inherited thrombophilia during pregnancy. [Preliminary report]. Marinov B, Pramatarova T, Andreeva A, Larukova N, Slavov A.
2 Phytomedicine. 2012;19(14):1325–31. Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome. Schellenberg R, Zimmermann C, Drewe J, Hoexter G, Zahner C.
3 Arzneimittelforschung. 1993;43(7):752–6. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Milewicz A, Gejdel E, Sworen H, Sienkiewicz K, Jedrzejak J, Teucher T, Schmitz H.
4 Nat Prod Res. 2008;22(6):537–46. Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt. Ibrahim NA, Shalaby AS, Farag RS, Elbaroty GS, Nofal SM, Hassan EM.
5 Nat Prod Res. 2009;23(13):1201–9. A new iridoid glycoside from Vitex negundo Linn (Verbenacea). Sharma RL, Prabhakar A, Dhar KL, Sachar A.
6 Int Immunopharmacol. 2013;17(3):593–600. Synthesis of novel lipidated iridoid glycosides as vaccine adjuvants: 6-O-palmitoyl Agnuside elicit strong Th1 and Th2 response to ovalbumin in mice. Singh PP, Bhunia D, Verma YK, Sidiq T, Khajuria A, Guptha A, Pallavi MP, Vamshi SS, Qazi GN, Kumar HM.
7 Phytochemistry. 2003;63(8):959–64. Glucosides from Vitex agnus-castus. Kuruüzüm-Uz A, Ströch K, Demirezer LO, Zeeck A.
8 Evid Based Complement Alternat Med. 2013;2013:432829. Compounds from the fruits of the popular European medicinal plant Vitex agnus-castus in chemoprevention via NADP(H): Quinone oxidoreductase type 1 induction. Li S, Qiu S, Yao P, Sun H, Fong HH, Zhang H.
9 Phytomedicine. 2003;10(4):348–57. Chaste tree (Vitex agnus-castus)–pharmacology and clinical indications. Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlová-Wuttke D.
10 J Pharm Pharmacol. 2007;59(9):1307–12. Evaluation of the estrogenic activity of the constituents in the fruits of Vitex rotundifolia L. for the potential treatment of premenstrual syndrome. Hu Y, Hou TT, Zhang QY, Xin HL, Zheng HC, Rahman K, Qin LP.
11 Phytomedicine. 2004;11(1):18–23. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Liu J, Burdette JE, Sun Y, Deng S, Schlecht SM, Zheng W, Nikolic D, Mahady G, van Breemen RB, Fong HH, Pezzuto JM, Bolton JL, Farnsworth NR.
12 Planta Med. 2003;69(10):945–7. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Jarry H, Spengler B, Porzel A, Schmidt J, Wuttke W, Christoffel V.
13 J Agric Food Chem. 2001;49(5):2472–9. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL.
14 J Altern Complement Med. 2009;15(8):853–62. Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. van Die MD, Burger HG, Teede HJ, Bone KM.
15 Biochem Pharmacol. 2011;81(1):170–7. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Webster DE, He Y, Chen SN, Pauli GF, Farnsworth NR, Wang ZJ.
16 Phytomedicine. 2000;7(5):373–81. Pharmacological activities of Vitex agnus-castus extracts in vitro. Meier B, Berger D, Hoberg E, Sticher O, Schaffner W.
17 J Ethnopharmacol. 2006;106(2):216–21. Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ.
18 Complement Ther Nurs Midwifery. 2003;9(3):157–60. Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154]. Chopin Lucks B.
19 Complement Ther Nurs Midwifery. 2002;8(3):148–54. Vitexagnus-castus essential oil and menopausal balance: a self-care survey. Lucks BC, Sørensen J, Veal L.
20 Ceska Gynekol. 1998;63(5):388–92. Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo. Halaska M, Raus K, Bĕles P, Martan A, Paithner KG.
21 Can J Clin Pharmacol. 2008;15(1):e74–9. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Dugoua JJ, Seely D, Perri D, Koren G, Mills E.
22 Am Fam Physician. 2005;72(5):821–4. Chasteberry. Roemheld-Hamm B.
23 Planta Med. 2013;79(7):562–75. Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials. van Die MD, Burger HG, Teede HJ, Bone KM.
24 Drug Saf. 2005;28(4):319–32.Vitex agnus castus: a systematic review of adverse events. Daniele C, Thompson Coon J, Pittler MH, Ernst E.