MAJOR CHEMICAL CONSTITUENTS

The principal constituents are two labdane diterpenoids, including rotundifuran, vitexilactone, as well as vitexilactam A; flavonoids, including casticin, penduletin, chrysosplenol, isoorientin, and isovitexin; iridoids, including aucubin and agnuside; fatty oils, including caprinic acid, palmitic acid, and stearic acid as well as possibly linolenic acid; and essential oils.

PRINCIPAL USES

TRADITIONAL AND HISTORICAL USES

Vitex agnus-castus is a deciduous shrub native to Mediterranean Europe and Central Asia. It has a long history of use for gynecologic complaints, as well as an alleged history of use as an aphrodisiac among monks (hence the common names monk’s pepper and chaste tree/berry). It is mentioned early in history by Greek philosopher and naturalist Plato (circa 428–348 bce), who described the herb’s aphrodisiac effects. The ability of chaste tree fruit to stimulate menstrual flow was reported by Lonicerus in 1582. It was mentioned in ancient herbals for the treatment of reproductive pain. For unknown reasons, chaste tree is not found in many Western herbals until the middle of the 1900s. Prior to that time it was not considered a primary herb in the US medical botany, Eclectic, or herbal literature. It is mentioned briefly by Felter and Lloyd in King’s American Dispensatory as a galactogogue, emmenagogue, and aphrodisiac.

CLINICAL INDICATIONS

Chaste tree is one of the most popular herbs in Europe, the United States, and other Western nations for the treatment of a number of gynecologic complaints. Its primary uses include the treatment of menstrual irregularities, especially secondary amenorrhea, oligomenorrhea, and dysmenorrhea; premenstrual symptoms and PMS; luteal phase dysfunction caused by luteal insufficiency, infertility (particularly secondary to endometriosis or anovulation), cyclic mastalgia, hyperprolactinemia, habitual miscarriage (attributed to progesterone insufficiency), insufficient lactation, and acne. Subclinical hyperprolactinemia has been suggested as a possible cause of endometriosis in some women, and is associated

Chaste tree (Vitex agnus-castus).

(Photo by Martin Wall.)

with amenorrhea and other menstrual irregularities, and cyclic mastalgia. Chaste tree has been shown to increase progesterone levels and lengthen the hyperthermic phase of the basal metabolic temperature curve when taken daily for a minimum of three consecutive months.

MECHANISMS OF ACTION

The pharmacodynamics of chaste tree are not yet entirely understood. Dopaminergic activity, and consequently prolactin-lowering effects, have been demonstrated in preclinical studies and animal studies in vitro and in vivo, lending credence to the traditional uses of this herb in the treatment of menstrual irregularities; however, it appears contradictory to the herb’s use as a lactagogue (see Use in Pregnancy and Lactation). There is also evidence that suggests mediation of the herb’s effects via luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and progesterone.

IN VITRO, ANIMAL, AND CLINICAL DATA

In vitro and animal studies have demonstrated binding of chaste tree extract and isolated constituents to dopamine (D2) receptors in a dose dependent manner, with a number of studies demonstrating subsequent reductions in prolactin release or levels. In vitro studies have suggested that chaste tree may exert benefits in PMS via a direct endorphin-like effect on opioid receptors as well as indirectly via estrogenic effects, which may lead to an increase in endogenous opioid levels. A weak binding of chaste tree extract components to serotonin receptors has been seen in animal models, hinting at another possible mediating effect of this herb on PMS. Elevations in progesterone levels have been seen with the herb. Ligand binding assays demonstrate competitive binding to estrogen receptors of both the α and β subtypes, although estrogenic effects have not been seen consistently in in vitro assays using methanol extracts of the herb.

Clinical studies using chaste tree have focused on PMS and cyclic mastalgia. One of the strongest trials was a randomized, double-blind placebo-controlled trial of 170 women with PMS who received a chaste tree extract of 20 mg standardized to casticin daily for 3 months, at the end of which they reported significant improvements in PMS symptoms, including irritability, mood alteration, headache, breast fullness, and bloating compared with the placebo. Other, less robust clinical trials have also shown positive outcomes in the reduction of PMS symptoms. In a double-blind placebo-controlled study of 37 women with luteal insufficiency and latent hyperprolactinemia, the luteal phase was increased from 3.4 to 5.5 days to 10.5 days in the group taking chaste tree extract (n = 17) compared with the control group (n = 20). Results of two separate randomized, double-blind placebo-controlled trials (n = 104, n = 97) have provided evidence of efficacy for the treatment of mastalgia, with significant improvements in chaste berry groups compared with controls. Small trials, including randomized, double-blind placebo-controlled trials and several open uncontrolled studies, have shown achievement of pregnancy, and in cases with hyperprolactinemia, reported decreases in prolactin levels compared with baseline. Interestingly, in two studies looking at parameters not related to pregnancy, a total of 28 women in vitex groups only became pregnant; of these, 19 reported having some difficulty in achieving pregnancy prior to taking the herb. Preliminary reports suggest positive findings in the treatment of acne. Not all trials of chaste tree have shown consistently beneficial effects in the treatment of gynecologic conditions or improvements from baseline hormonal parameters; however, there have been a number of promising results, including the examples presented herein. Because gynecologic problems remain a significant cause of discomfort and distress to women, and represent significant social and economic costs to women and society (e.g., work absenteeism), further rigorous studies are needed to determine whether the use of chaste tree for common gynecologic complaints is supported by substantial evidence. In spite of limited trials, herbal practitioners and women continue to rely on this herb, reporting many positive outcomes.

RATINGS

PREPARATIONS USED CLINICALLY

DOSAGE

As with many herbs, dose discrepancies exist for chaste tree in the herbal and scientific literature. Ranges are provided in the following reflecting these inconsistencies.

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

A number of transient side effects have been associated with the use of chaste tree. The most common are gastrointestinal complaints/nausea; acne, skin reactions, or urticaria; menstrual cycle changes, including intermenstrual bleeding; and headache. The adverse events following use of chaste tree are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus, and erythematous rash. No herb–drug interactions have been reported. On theoretical grounds, it is thought prudent to avoid use of chaste berry in conjunction with dopamine agonists and antagonists. Case reports from herbalists have demonstrated that rarely, women with a history of depression taking chaste tree for the treatment of menstrual irregularity experience an exacerbation of depressive symptoms. This is also a reversible adverse effect, but one that practitioners and patients should be aware of prior to commencing use. A review of clinical trials, postmarket surveillance studies, surveys, spontaneous reporting schemes, manufacturers, and herbalist organizations indicate a high level of safety for this herb. See the following for safety during pregnancy and lactation.

USE IN PREGNANCY AND LACTATION

It has been postulated that increased progesterone levels as a result of improved luteal function associated with the use of chaste tree may partially explain positive results seen by herbal practitioners and midwives when using this herb for the prevention of subsequent miscarriage in women with a history of prior repeated miscarriages. No trials have been conducted to evaluate these claims, and specific data on the use and safety of chaste tree during pregnancy are lacking. Improvements in fertility were discussed earlier in this section. In studies in which pregnancy has been achieved while taking chaste tree, no follow-up studies have been conducted on the pregnancy outcomes or newborn health in those who did not discontinue the herb upon becoming pregnant. Reproductive toxicity studies in female rats at up to 80 times the concentration used clinically in humans showed no difference in offspring compared with controls, and no teratogenicity was seen in the offspring of rabbit dams given up to 74 times the recommended daily dose for humans. A nonsignificant increase in the number of resorptions and placental weight was seen in groups receiving the highest dose, and it is not known whether this was attributable to the alcohol, the herb, or spontaneous events. As stated, the Botanical Safety Handbook gives chaste tree a Class 1: rating, suggesting an ease on prior restrictions during pregnancy.

Historically and traditionally, the herb has been used to increase milk supply in breastfeeding mothers. Although research has shown prolactin-lowering effects that suggest quite the opposite result, effects may be dose dependent. Chaste tree has been reported to increase milk production without changing the composition of the breast milk. There is no known risk to consumption of chaste tree during lactation; however, use is commonly discouraged because of lack of evidence for or against safety.