Chasteberry, the fruit of the chaste tree or Vitex agnus castus, has long been touted as a remedy for a range of reproductive problems, including premenstrual symptoms or PMS.  Two recent publications have reviewed data on the use of Vitex agnus castus (VAC) for the treatment of premenstrual syndrome and premenstrual dysphoric disorder (PMDD) and discuss how VAC may be incorporated into clinical practice.

Verkaik and colleagues identified 17 randomized controlled trials of Vitex agnus castus in the treatment of premenstrual syndrome and PMDD, incorporating 14 of these studies in the final meta-analysis.  Thirteen of the 14 studies reported positive effects of VAC on total premenstrual symptoms as compared to placebo, dietary supplements, or active comparators (e.g., oral contraceptives, SSRIs).

The review from Cerqueira and colleagues included a smaller subset of studies — only eight — because they excluded studies which did not provide descriptions of rater and treater blinding or  information on rates of dropouts and withdrawals. All of the eight studies included in this analysis demonstrated positive effects for VAC in the treatment of PMS or PMDD.

While most of the studies demonstrated beneficial effects of VAC, the results were very heterogeneous, making it somewhat difficult to interpret the findings.  Most of the studies focused on PMS; however, the diagnostic criteria for PMS and PMDD have changed over time which has contributed to diagnostic variability across the studies. There was also considerable variation in the instruments used to assess premenstrual symptoms.   

The pooled effect of Vitex agnus castus in placebo-controlled trials was large (Hedges g, -1.21; 95% confidence interval, -1.53 to -0.88), but there was extremely high heterogeneity across the studies analyzed (I2, 91%).  The authors were not able to identify factors that could explain this heterogeneity.

Only two of the studies compared VAC to an SSRI, a well-established treatment for PMS and PMDD.  In the first study (Atmaca et al, 2002), 41 women with PMDD were randomized to either fluoxetine or VAC for 2 months.  In this study, a similar percentage of patients responded to fluoxetine (68.4%, n?=?13) and to VAC (57.9%, n?=?11). The second study (Ciotta et al, 2011) randomized 57 women to either VAC of fluoxetine for 2 months.  Although women receiving VAC experienced some improvement in their symptoms, fluoxetine appeared to have a greater effect on PMS symptoms.

Although most of the studies demonstrated positive effects, an analysis of the various studies using funnel plot and Egger tests suggested the presence of publication bias.  Specifically, Verkaik and colleagues observed that smaller studies reporting larger effects were more often represented among the publications included, and many trials of VAC were published in low-impact-factor journals. They concluded that the magnitude of the reported VAC treatment effects were most likely overestimated.

Should We Use Vitex Agnus Castus to Treat Premenstrual Symptoms?

Although the Association of Reproductive Health Professionals includes VAC as a treatment option for women with PMS, these reviews indicate that while there is some suggestion of the beneficial effects of VAC, there is no conclusive evidence that VAC effectively diminishes the symptoms of PMS or PMDD.

Nonetheless, there may be situations where clinicals might consider the use of this alternative treatment.  For example, some women may be opposed to using or unable to tolerate the side effects of SSRIs.

One very important issue, however, is that our information regarding the safety of this supplement is incomplete.  Looking a the side effects reported in these two reviews, the most commonly reported adverse events were nausea and headache.  It is not clear how VAC may work to relieve premenstrual symptoms.  Extracts or concentrates of the VAC fruit contains flavonoids (casticin, isovitexin, orientin), iridoids (aucubin, agnuside, eurostide), and volatile oils (monoterpenes, sesquiterpenes). In vitro studies have shown that VAC extracts bind to the dopamine-2 receptor, the human opioid receptor, and the ?-estrogen receptor.

According to data collected by WebMD, VAC may alter hormone levels and may thus interfere with the effectiveness of hormonal contraceptives and may negatively affect infertility treatment.  Because VAC interacts with dopamine receptors, there is also concern that VAC may affect how antipsychotic medications work.

In other words, just because it’s natural doesn’t mean it’s safe.


Ruta Nonacs, MD PhD

Cerqueira RO, Frey BN, Leclerc E, Brietzke E.  Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review.  Arch Womens Ment Health. 2017 Dec;20(6):713-719.

Verkaik S, Kamperman AM, van Westrhenen R, Schulte PFJ.  The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis.  Am J Obstet Gynecol. 2017 Aug;217(2):150-166.

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