Reference: Schellenberg R. Treatment of the premenstrual syndrome with agnus castus fruit extract: prospective, randomized, placebo controlled study. BMJ 2001;322:134–7.

Summary: In this study 170 women (mean age 36 years) with a diagnosis of premenstrual syndrome (PMS) entered a prospective, randomized, placebo-controlled clinical trial of the efficacy of chasteberry extract, from chaste tree (Vitex agnus-castus L., Verbenaceae). Study participants were randomized to receive either 20 mg of the chasteberry extract ZE 440 (Zeller AG, Romanshorn, Switzerland) or placebo once daily for three menstrual cycles. The ZE 440 chasteberry product used in the trial is an ethanolic extract (6–12:1 extract ratio) and standardized for casticin. The casticin content in the dry extract was at least 0.3%, in the native extract 0.6%. The primary efficacy variable was the change from baseline to the end of the study (end of the third cycle) on the total score of a subjective questionnaire measuring irritability, headache, breast fullness, and other PMS symptoms. Secondary efficacy variables included change in the clinical global impressions (CGI) and responder rate (50% reduction in symptoms). Twenty-three women took oral contraceptives (11 in the chasteberry group and 12 in the placebo group).

At the end of the treatment period, women taking the chasteberry extract had a significantly greater reduction in overall PMS symptom score compared to those taking placebo (p<0.001). Five of the six self-assessment items indicated a significantly greater reduction for the chasteberry group with the exception of the item listed "others and bloating" which was measured as unaffected by treatment with chasteberry. The CGI also showed a significantly greater reduction of PMS symptoms compared to placebo (p<0.001). The overall responder rate was 52% for the chasteberry group compared to 24% for the placebo group. Adverse events were few in both groups and included acne, intermenstrual bleeding, and skin rash in the chasteberry group.

Comments/Opinions: Surprisingly, this is the first placebo-controlled clinical trial designed to measure the efficacy of chasteberry for the treatment of PMS. A previous 3-month double-blind trial found comparable efficacy for chasteberry and vitamin B6 (200 mg/day) for treating PMS,¹ but did not include a placebo group. Other trials of chasteberry to treat PMS were primarily uncontrolled, clinical monitoring studies.^2-4

Coordinated by researchers at the Institute for Health Care and Science in Hüttenberg, Germany, this new trial provides an important step toward the acceptance of chasteberry extract as a safe and efficacious treatment for PMS. The product, sold in tablet form, is not currently available in North America.

Native to valleys and riverbanks of the Mediterranean and central Asia, chaste tree produces dark brown to black fruit the size of a peppercorn. Preparations of the fruit have been approved by German health authorities (Commission E) for the treatment of menstrual irregularities such as PMS and cyclical breast pain (mastalgia).⁵ Clinical trials supporting the use of chasteberry for mastalgia have primarily been completed with a product that combines 32.4 mg of a chasteberry extract with various homeopathic ingredients (Mastodynon®, Bionorica Arzneimittel, Neumarkt, Germany).⁶

While earlier research suggested that chasteberry may increase the release of luteinizing hormone (LH), the pituitary hormone responsible for the development of the corpus luteum and subsequent release of progesterone during the luteal phase of a woman’s menstrual cycle,⁷ more recent research has focused on the ability of chasteberry to reduce elevated levels of prolactin late in a woman’s menstrual cycle.⁸ Apparently due to a dopaminergic action of chasteberry leading to a reduction in prolactin,⁹ this action may directly relate to the lengthening of the luteal phase and reduction in breast tenderness seen with chasteberry treatment. It may also partially explain the preliminary success found in clinical trials using chasteberry in the treatment of infertility and secondary amenorrhea.^10,11

Clinical trials have reported that adverse events are rare, but include urticaria (skin rash with itching), mild gastrointestinal upset, and intermenstrual bleeding. Chasteberry is not recommended for use during pregnancy¹² and use during lactation is questioned due to the possible dopaminergic actions mentioned above, leading to a suppression of lactation. Due to theoretical interactions, some authors suggest that chasteberry be avoided by women taking oral contraceptives or on hormone therapy.¹³ However, 20 patients in the current study used oral contraceptives concurrently with no reported adverse interactions. The lack of interaction between the two medicines was also noted in another recent trial.¹⁴ The potential dopaminergic action of chasteberry also suggests that it should not be used concomitantly with dopamine antagonist drugs such as haloperidol or metoclopramide.

Practice Implications: These new results support the safety and efficacy of chasteberry extract as a viable tool to manage PMS symptoms. Chasteberry is typically taken once in the morning before breakfast and should be taken for at least three menstrual cycles to determine efficacy. Further clinical trials are needed to determine the optimal dosage and amount of time that chasteberry should be used to treat PMS.

1. Lauritzen C, Reuter HD, Repges R, et al. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4:183–9.

2. Peteres-Welt C, Albrecht M. Menstrual abnormalities and PMS: Vitex agnus-castus. Ther Gynäkol 1994;7:49–52.

3. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Women Health Gender-Based Med 2000;9:315–20.

4. Dittmar FW, Böhnert KJ, Peeters M, et al. Premenstrual syndrome: Treatment with a phytopharmaceutical. Therapiwoche Gynäkol 1992;5:60–8.

5. Blumenthal M, Goldberg A, Brinkmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications, 2000, 62–4.

6. Halaska M, Beles P, Gorkow C, Sieder C. Treatment of cyclical mastalgia with a solution containing Vitex agnus extract: results of a placebo-controlled double-blind study. The Breast 1999;8:175–81.

7. Amnon W. Removing an obstipation using Agnolyt®. Ther Gegenw 1965;104:1263–5.

8. Milewicz A, Gejdel E, Sworen H, et al. Vitex agnus castus extract for the treatment of menstrual irregularities due to latent hyperprolactinemia. Arzneimittlforschung 1993;43:752–6.

9. Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin release in inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994;102:448–54.

10. Gerhard I, Patek A, Monga B, et al. Mastodynon® for female infertility. Randomized, placebo-controlled, clinical double-blind study. Forsch Komplementärmed 1998;5:272–8.

11. Propping D, Katzorke T. Treatment of corpus luteum insufficiency. Zeitschr Allgemeinmedizin. 1987;63:932–3.

12. Blumenthal M, Goldberg A, Brinkmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications, 2000,62–4.

13. Böhnert KJ. The use of Vitex agnus castus for hyperprolactinemia. Quart Rev Natural Med 1997;Spring:19–21.

14. Berger D, Schaffner W, Schrader E, Meier B, Brattström A. Efficacy of Vitex agnus-castus L. extract Ze440 in patients with pre-menstrual syndrome. Arch Gynecol Obstet 2000;264:150–3.