INDEX

Chaste Tree Berry (Vitex agnus castus 2)

Indications

Polycystic Ovarian Syndrome (PCOS)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

Vitex influences dopaminergic transmission. It also regulates prolactin, follicle-stimulating hormone, and luteinizing hormone (LH), which may regulate testosterone levels, as well as levels of other reproductive hormones. Vitex has also been shown to bind opiate receptors,10,11,12 which in turn promotes dopamine activity.

Casticin and the diterpenes are believed to reduce elevated prolactin levels.9,13 Dopaminergic activity will also reliably reduce hyperprolactinemia,14 and radioligand studies of Vitex extracts confirm that diterpenes bind to type 2 dopamine receptors and to all subtypes of opiate receptors.11 Animal studies suggest that casticin at a dose of 1 µmol/L inhibits estradiol stimulation of prolactin secretion via suppression of pituitary α-estrogen receptor mRNA expression, while increasing β-estrogen receptor mRNA expression at the higher dose of 10 µmol/L.15 Vitex also blocks thyrotropin-releasing hormone-stimulated prolactin secretion in rat pituitary cells.13 The diterpene clerodadienol binds dopamine receptors and suppresses prolactin release as effectively as dopamine.9

Because dopamine suppresses pituitary secretion of both LH and prolactin, Vitex also reduces LH release and thereby reduces serum testosterone levels.16 This can be therapeutic in women with polycystic ovary syndrome (PCOS) and elevated androgens. This may also be one of the mechanisms contributing to its anticomedogenic effects in adolescent acne.

Evidence-Based Research

Vitex can increase progesterone levels4 and reduce elevated prolactin9,17 and testosterone16 levels, all of which contribute to the restoration of regular menstruation in women with amenorrhea. Stress,14 elevated estrogens, and thyrotropin-releasing hormone18 can promote prolactin release, which may suppress ovulation and lead to amenorrhea. Vitex reduces elevated prolactin,19,20 helping to restore menstrual regularity and improve fertility.

An ethanolic extract of Vitex dosed at 0.6 and 1.2 g/kg body weight significantly increased uterine weight in ovariectomized rats. This was associated with significant increases in plasma progesterone and total estrogen levels and a significant reduction in LH and plasma prolactin hormone at both dosages.4 Animal studies have also shown that Vitex normalizes elevated testosterone levels,16 which are often found in women with PCOS, and contributes to hirsutism and amenorrhea.

Vitex may exert a dopaminergic effect equal to the pharmaceutical agent bromocriptine.21 A randomized controlled trial conducted by Stanford University’s Department of Obstetrics and Gynecology compared the use of Vitex and other supportive nutrients to placebo in 93 women with infertility. After 3 months, progesterone levels in women on Vitex had increased compared with those receiving placebo. Furthermore, 13 of the 53 women receiving Vitex became pregnant compared with none in the placebo group.22

Another randomized controlled trial of women with luteal-phase defect menstrual cycle irregularities attributable to elevated prolactin found that 20 mg of Vitex lowered prolactin levels and normalized menstrual cycles after 3 months. Luteal-phase estradiol levels also increased with Vitex, with no effect on other hormonal parameters.3

Safety in Pregnancy and Breastfeeding

Vitex is presumed to be contraindicated in pregnancy and lactation, although evidence for its impact on lactation is contradictory.23 Given that Vitex affects numerous hormones, it is advisable to avoid it during pregnancy until more evidence is available.

General Safety

Vitex is generally well tolerated, 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.24,25,26

Vitex may reduce fertility in males. The flavonoid fraction of Vitex negundo, a species related to Vitex agnus castus, has been shown to diminish citric acid in the prostate, fructose in seminal vesicles, and epididymal α-glucosidase activity in male rats. These changes were also associated with a decrease in sperm count and motility.27 Vitex negundo has been shown to have antiandrogenic effects on dogs at a dose of 10 mg/kg parenterally, blocking the effects of testosterone propionate supplementation.28

No herb–drug interactions have been reported, but it is possible that Vitex may have additive effects if combined with dopaminergic drugs, or interfere with the action of dopamine antagonists.

Dosage

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.

Traditional Uses

Vitex agnus castus has been used for centuries to treat menstrual, menopausal, and fertility disorders in women, and it 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 premenstrual syndrome, mastalgia, male gynecomastia, adolescent acne, amenorrhea, ovarian cysts, hot flashes, bleeding irregularities, and menopausal complaints.

References

1

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 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.

11 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.

12 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.

13 Horm Metab Res. 1993;25(5):253–5. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Sliutz G, Speiser P, Schultz AM, Spona J, Zeillinger R.

14 Evid Based Complement Alternat Med. 2008;5(3):247–50. Can Vitex agnus castus be used for the treatment of mastalgia? What is the current evidence? Carmichael AR.

15 Acta Pharmacol Sin. 2010;31(12):1564–8. Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro. Ye Q, Zhang QY, Zheng CJ, Wang Y, Qin LP.

16 Pak J Biol Sci. 2007;10(14):2300–7. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Nasri S, Oryan S, Rohani AH, Amin GR.

17 Med Monatsschr Pharm. 2009;32(5):186–91. The premenstrual syndrome: effectiveness of Vitex agnus castus. Döll M.

18 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.

19 Maturitas. 2009;63(4):369. Are changes of prolactin levels the effectors of vitex agnus castus beneficial effects on the pre-menstrual syndrome? Tamagno G.

20 Phytomedicine. 2007;14(10):668–74. Anti-nociceptive and anti-hyperprolactinemia activities of Fructus viticis and its effective fractions and chemical constituents. Hu Y, Xin HL, Zhang QY, Zheng HC, Rahman K, Qin LP.

21 BMC Complement Altern Med. 2014;14(1):511. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. Arentz S, Abbott JA, Smith CA, Bensoussan A.

22 Clin Exp Obstet Gynecol. 2006;33(4):205–8. Double-blind, placebo-controlled study of Fertilityblend: a nutritional supplement for improving fertility in women. Westphal LM, Polan ML, Trant AS.

23 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.

24 Am Fam Physician. 2005;72(5):821–4. Chasteberry. Roemheld-Hamm B.

25 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.

26 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.

27 Phytother Res. 2004;18(1):8–13. Reproduction in male rats is vulnerable to treatment with the flavonoid-rich seed extracts of Vitex negundo. Das S, Parveen S, Kundra CP, Pereira BM.

28 J Ethnopharmacol. 1989;27(3):327–39. Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: a histological and biochemical study in dogs. Bhargava SK.