Chaste Tree Berry for Premenstrual Syndrome

June 1999; Volume 2: 64-67

By Teresa Klepser, PharmD and Nicole Nisly, MD

Between 20-50% of women suffer from premenstrual tension at some time during their lives.1 Many women experience premenstrual symptoms such as nervousness, irritability, depression, bloating, breast tenderness, weight gain, skin problems, and digestive problems. Various therapies have been studied for the management of premenstrual symptoms including hormones, vitamins, dopamine agonists, non-steroidal anti-inflammatory drugs, diuretics, magnesium, calcium, lithium, exercise, and lifestyle modification.

One herb that may be useful in treating premenstrual syndrome is chaste tree berry, also commonly called chasteberry and monk’s pepper.2 Chaste tree berry is from the fruit of Vitex agnus-castus that grows along the Mediterranean coastal region and in central Asia. The berries have a pepper-like taste and smell and are used as an inexpensive substitute for the black pepper spice.3

The chaste tree berry gets its name from the belief that the plant would inspire chastity. To help with chastity, monks would eat the berries or seeds as a spice to decrease sexual desire.2,3 It is also believed that chaste tree berry is useful in passing afterbirth and increasing milk secretion.4 Chaste tree berry has been used in Europe for many years to treat female reproductive tract disorders such as menstrual abnormalities, premenstrual syndrome, menopausal complaints, and infertility.5,6

Indications

Vitex agnus-castus is approved in Germany for use in disorders of the menstrual cycle, premenstrual syndrome and mastodynia.2,7

Constituents

Vitex agnus-castus contains a wide variety of bioactive compounds, including iridoid glycosides, flavonoids, progestins, and volatile oils.2 (See Table 1 for progestin components of Vitex agnus-castus.) Although many compounds have been identified in Vitex agnus-castus, few are known to be active, including aucubin, luteolin 7-O-(6’-p-benzoylglucoside), casticin, testosterone, a-pinene, sabinene, b-pinene, b-myrcene, r-cymene, terpinene-4-ol, a-terpineol, and caryophyllene epoxide.8

    Table 1 
    Progestins found in Vitex agnus-castus leaves and flowers 
    progesterone (leaf) 
    hydroxyprogesterone (leaf) 
    testosterone* (leaf) 
    epitestosterone (leaf) 
    androstenedione (flower) 

    Source: Chaste Tree. In: The Review of Natural Products. St. Louis, MO: Facts and Comparisons: 1998.
    ____________________________________________________

Mechanism of Action

Some of the active ingredients in vitex—including a-pinene, b-pinene, caryophyllene-oxide, chrysosplenol, luteolin-7-glucoside, and orientin—are believed to possess anti-inflammatory effects.8 Ascaridole, myrcene, and r-cymene are believed to have analgesic properties; 1,8-cineole, a-pinene, a-terpineol, ascaridole, bornyl-acetate, citronellol, and limonene are thought to have sedative properties; and terpinen-4-ol is believed to be a diuretic.8 Testosterone may be the only active hormone.9 Studies show that vitex may have dopaminergic properties.10 However, it is unknown which active ingredients possess the dopaminergic properties and how these properties affect premenstrual syndrome symptoms.

Laboratory and Animal Studies

In vitro studies show that vitex binds to dopamine receptors and inhibits the secretion of prolactin from the rat pituitary gland.2,5,11 Vitex does not appear to inhibit the pituitary’s production of luteinizing hormone or follicle stimulating hormone.11 Animal studies have also shown an increase in lactation and mammary enlargement.2 No in vivo human studies to support this finding and no published studies that analyze the pharmaco-kinetics of vitex could be found.7

Clinical Studies for Premenstrual Syndrome

A 1992 study evaluated the efficacy of vitex liquid extract in 1,542 women, aged 13-62 years, with a diagnosis of premenstrual syndrome. These women received 40 drops of vitex liquid extract every morning for an average of 25.3 days. Questionnaires were given to the patients and their gynecologists to rate each patient’s symptomatic response to vitex. Physicians rated vitex as "very good" or "good" 92% of the time. In contrast, 57% of the patients reported improvement in symptoms and 33% noted complete relief of their symptoms.12

A randomized, placebo-controlled, intention-to-treat trial compared the safety and efficacy of Agnolyt® (a vitex capsule formulation) with pyridoxine (vitamin B6).1 The study included 175 women, aged 18-45 years, with premenstrual tension.

For three menses, women were given one capsule of vitex dried fruit extract (3.5-4.3 mg) plus one placebo capsule daily or one placebo capsule on days 1-15 of the menstrual cycle and 100 mg of vitamin B6 twice daily on days 16-35 of the menstrual cycle. End points assessed included the premenstrual tension syndrome scale, six typical premenstrual symptoms, and the clinical global impression scale. A sample size of 100 women in each group was calculated; however, 175 women were enrolled and only 127 women completed the trial and were included in the efficacy analysis. Twenty women terminated the study prematurely; 12 in the vitex group and eight in the B6 group; no explanation was given.13

Vitex and vitamin B6 produced similar reductions in the premenstrual tension syndrome scores (-47.7% vs. -48%, respectively). In the vitex group, 77.1% of the patients reported improvement in the clinical global impression scale compared to 60.6% of the vitamin B6 patients.12 Eighty percent of the women received "adequate" efficacy when assessed by the investigators. However, when efficacy was assessed by the patients, 36% of the vitex group reported having no complaints, compared to 21.1% of the vitamin B6 group. The absence of a placebo group, the inability to achieve calculated sample size, and the uneven baseline for the two groups make this study less than definitive.13

Of the 175 women enrolled, adverse events occurred in 17 patients; 12 women in the vitex group and five women in the vitamin B6 group. Side effects included gastrointestinal and lower abdominal complaints, allergic and acneiform skin reactions, and temporary headaches. No serious side effects occurred.6,14

Another randomized, double-blind, placebo-controlled trial evaluated the efficacy of vitex in 52 women with menstrual cycle disturbances secondary to latent hyperprolactinemia. Women were given 20 mg of Strotan®, an aqueous-alcoholic extract of vitex fruit, once daily for three months. Women who received vitex had a significant reduction of prolactin release and a significant reduction of their premenstrual syndrome symptoms compared to placebo.15

Adverse Effects

Side effects may include gastrointestinal and lower abdominal complaints, allergic reactions (i.e., itching and rash), headache, and increased menstrual flow.2 Early menstruation following delivery is noted as a rare side effect.4 Side effects have been reported in fewer than 2% of patients.4

Contraindications/Precautions

Vitex is contraindicated in pregnancy, lactation, and in women receiving hormone replacement therapy.2,7 Although vitex contains progestins, the long-term effects of such "natural hormones" (e.g., the development of various hormone-medicated neoplasms) is unknown.

Drug Interactions

No drug interactions have been reported in the literature. However, dopamine-receptor antagonists, such as haloperidol, may weaken or block the effects of vitex.7

Dosage/Formulations

There are a variety of recommended preparations and dosages. Vitex is available as aqueous-alcoholic extracts (50-70% V/V) from the crushed fruit, tinctures, tea, or capsules.4,7 Some preparations are formulated to give an average daily dose of 20-40 mg of berries. The daily dose of crushed fruit may then be divided and administered two or three times daily.4 Vitex extract containing 175-225 mg is recommended to be standardized to contain 0.5% agnuside;15 however, agnuside is thought to be an inactive ingredient. In Germany, the aqueous-alcoholic extracts are recommended. Results may be seen as early as four months or as late as 18 months.4

Herbalists recommend 1-2 ml of the tincture tid or 40 drops of a standardized tincture daily.4,16 However, no strength for the tincture is given. Tea should be ingested three times a day.16 The amount of vitex in tea is unknown. A cream preparation is also available that contains vitex and wild yam.

Many products containing vitex also contain other herbs such as black cohosh, dong quai, wild yam, Siberian ginseng, and licorice. Many of the combination products are not standardized. (See Table 2 for price comparison.)

    Table 2
    Sample Vitex agnus-castus prices                                                                                      
    Brand
    Formulation
    Recommended Dose
    Price/Count
    Enzymatic Therapy Inc. 225 mg chaste tree berry (Vitex agnus-castus) extract standardized to contain 0.5% agnuside (1,130 mcg/capsule) per capsule 1-2 capsules daily $16.95/60 capsules
    Nutritional Dynamics  150 mg chasteberry fruit standardized to contain 0.5% agnuside and 0.6% aucubin per capsule 1 capsule daily $15.95/60 capsules
    Nature’s Herbs 100 mg chasteberry fruit and seeds (Vitex agnus-castus) concentrate standardized for a minimum of preferred 0.9-1.1% glycosides (a unique active component of which a minimum is 0.5% agnuside) per capsule. Combined with a base of dong quai root and Siberian ginseng 4 capsules daily $11.99/60 capsules 
    Nature’s Answer Chasteberry 0% alcohol Chaste tree berry extracted using alcohol and water or other menstruums to capture active constituents; alcohol removed via cold extraction process 6-8 drops in water tid $9.90/1 oz
    Source: Online mail-order firms
    _____________________________________________________________________________________

Conclusion

Traditionally and historically, Vitex agnus-castus has been used in the treatment of female reproductive tract disorders. The clinical evidence is weak regarding the use of vitex in the treatment of premenstrual syndrome, but side effects appear to be rare and safety high.

Recommendation

Vitex may be an option for women who have tried vitamin B6 and calcium, and who do not wish to use prescription hormonal treatment. However, it may be difficult for patients to find a standardized product. Although the effective dose remains unknown, most information suggests using a product that contains 20-40 mg of the dried berry extract standardized to contain 0.5% agnuside. Patients should be aware that results may take up to 18 months. However, systemic side effects should be minimal.

Dr. Klepser is an Assistant Professor in the College of Pharmacy and Dr. Nisly is an Assistant Professor in the College of Medicine at the University of Iowa in Iowa City.

References

    1. Lauritzen C, et al. Treatment of premenstrual tension syndrome with Vitex agnus castus: Controlled, double-blind study versus pyridoxine. Phytomedicine 1997;4:183-189.

    2. Chaste Tree. In: The Review of Natural Products. St. Louis, MO: Facts and Comparisons; 1998.

    3. Odenthal KP. Vitex agnus-castus L., traditional drug and actual indications. Phytotherapy Research 1998;12:S160-S161.

    4. Foster S. Herbs for Your Health. Loveland, CO: Interweave Press; 1996.

    5. Robbers JE, Tyler VE. Tyler’s Herbs of Choice: The Therapeutic Use of Phytomedicinals. Binghamton, NY: Haworth Press; 1999.

    6. Leigh E. Vitex more effective than pyridoxine in PMS. HerbalGram 1998;42:16.

    7. PDR for Herbal Medicines. Montvale, NJ: Medical Economics Company; 1998.

    8. Dr. Duke’s Phytochemical and Ethnobotanical Databases. Agricultural Research Service. Available at: http://www.ars-grin.gov/cgi-bin/duke/index.html.

    9. Winterhoff H, et al. Die hemmung der laktation bei ratten als indirekter beweis fur die senkung von prolaktin durch Agnus castus. Zeitschrift fur Phytotherapie 1991;12:175-79.

    10. Sliutz G, et al. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Horm Metab Res 1993;25:253-255.

    11. Jarry H, 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;102:448-454.

    12. Betz W. Commentary. Forschende Komplementarmedizen 1998;5:146-147.

    13. Brown D. Integrating Herbal Medicine into Clinical Practice. Presented at: Western States Chiropractic College and the University of Colorado Health Science Center School of Pharmacy’s Botanical Medicine Continuing Education; April 1998; Chicago, IL.

    14. Reichert R. Comparing vitex and vitamin B6 for PMS. Quarterly Review of Natural Medicine 1998;Spr:19-20.

    15. Milewicz A, et al. Vitex agnus castus extrakt zur behandlung von regeltempoanomalien infolge latenter hyperprolaktinamie. Arzneimittelforschung 1993;43:752-756.

    16. Murray MT. Encyclopedia of Nutritional Supplements: The Essential Guide for Improving Your Health Naturally. Rocklin, CA: Prima Publishing; 1996.

    17. Hoffman D. The Herbal Handbook: A User’s Guide to Medical Herbalism. Rochester, VT: Healing Arts Press; 1988.

Which of the following has not been reported as a side effect of chaste tree berry?

a. Rash

b. Increased menstrual flow

c. Lower abdominal complaints

d. Blurry vision

e. Headache

Which of the following drugs may weaken the effects of Vitex agnus-castus?

a. Bromocriptine

b. Aspirin

c. Haloperidol

d. Atenolol