Benefits
Premenstrual mood and physical comfort
In placebo-controlled trials in women with premenstrual symptoms, daily extracts for three to six cycles lowered self-rated irritability, mood changes, anger, headache and breast fullness more than placebo. Two pooled analyses agree on direction, but one found a high risk of bias and signs of publication bias and the other could use only 3 of 21 trials, so the benefit is likely smaller than reported.
Breast comfort during the menstrual cycle
In a double-blind trial of 97 women with cyclical breast pain, a liquid extract cut pain more than placebo after one and two cycles, but the gap after three cycles fell short of significance. In a second trial of 159 women in three groups, a chasteberry tablet lowered breast pain scores more than placebo after one and two months.
Mechanism of action
Dopamine receptor binding and prolactin
A pharmacology review reports that chasteberry compounds, mainly clerodadienol diterpenes, bind dopamine D2 receptors and suppress prolactin release in cell and animal studies. In a small placebo-controlled study, 37 women with short luteal phases and high prolactin responses who completed 3 months of a 20 mg extract had a lower prolactin release after a hormone challenge, longer luteal phases and higher luteal progesterone; these changes were not seen with placebo. European regulators say a drop in raised prolactin levels in people has not been conclusively proven, and whether this explains effects on premenstrual symptoms is not established.
Clinical trials
Randomized, double-blind, placebo-controlled, parallel trial over three menstrual cycles; one 20 mg dry extract tablet or placebo daily. Zeller AG, the extract's maker, supplied the tablets and sponsored the study (Schellenberg 2001, BMJ)
170 women with premenstrual syndrome evaluated (86 extract, 84 placebo); mean age 36.
Self-rated irritability, mood alteration, anger, headache, breast fullness and other symptoms improved more with the extract than placebo (P < 0.001). 52% vs 24% had at least a 50% drop in symptoms. Seven women reported mild adverse events (four extract, three placebo); none stopped treatment.
Systematic review and meta-analysis of randomized trials lasting at least two menstrual cycles in women with PMS or PMDD; it pools other trials and is not a separate trial (Verkaik et al. 2017, Am J Obstet Gynecol)
17 randomized trials found; 14 included in the pooled analysis.
13 of 14 studies reported positive effects on total symptom scores, and the pooled effect versus placebo was large (Hedges g -1.21). Heterogeneity was extremely high (I2 91%), most trials had high risk of bias, and funnel plot and Egger tests suggested publication bias. The authors called the pooled effect explorative and at best an overestimate.
Randomized, double-blind, placebo-controlled, parallel trial over three menstrual cycles; 30 drops of the extract solution twice daily. Two of the four authors were from Bionorica Arzneimittel GmbH, a maker of chasteberry products. The same trial was also published in Czech in 1998 (Halaska et al. 1999, Breast)
97 women with breast pain on at least 5 days of the pre-treatment cycle (48 extract, 49 placebo).
Pain on a visual scale fell by 21.4 mm vs 10.6 mm after one cycle (p=0.018) and 33.7 mm vs 20.3 mm after two cycles (p=0.006) with the extract vs placebo. After three cycles the drop was 34.3 mm vs 25.7 mm, which was not significant (p=0.064). Adverse events: 5 extract, 4 placebo.
Prospective, randomized, double-blind, placebo-controlled, multicenter trial for up to three cycles; BNO 1095 extract corresponding to 40 mg of herbal drug (He et al. 2009, Maturitas)
217 Chinese women with moderate to severe premenstrual syndrome randomized (108 extract, 109 placebo); 208 gave efficacy data.
The premenstrual diary score fell by 22.71 points with the extract vs 15.50 with placebo (p<0.0001), with a similar result on a second scale (p<0.01). The placebo response was about 50%. No serious adverse events occurred in either group.
Multicenter, randomized, double-blind, placebo-controlled, parallel trial over three cycles comparing 8, 20 and 30 mg a day. Three of the five authors were from Max Zeller Söhne AG, the maker of Ze 440 (Schellenberg et al. 2012, Phytomedicine)
162 women aged 18 to 45 with premenstrual syndrome.
Total symptom score improved significantly more with 20 mg than with placebo or 8 mg. The 30 mg dose did not lower symptoms significantly more than 20 mg. All doses were reported as well tolerated.
Randomized, double-blind, placebo-controlled trial; 40 drops of extract or placebo daily for 6 days before menses over 6 cycles (Zamani et al. 2012, Acta Med Iran)
128 women with mild to moderate premenstrual syndrome evaluated (62 extract, 66 placebo) of 134 enrolled; mean age about 31.
Self-rated headache, anger, irritability, low mood, breast fullness and bloating on visual scales improved more with the extract than placebo (P<0.0001).
Randomized, placebo-controlled, three-arm trial over two months: 25 g flaxseed a day, a 3.2 to 4.8 mg chasteberry tablet a day, or placebo (Mirghafourvand et al. 2016, Complement Ther Med)
159 women with cyclical breast pain in Tabriz, Iran (53 per group).
Breast pain scores were lower than placebo with the chasteberry tablet after the first month (adjusted difference -3.3) and the second month (-6.4). Longer-term effects were not studied.
Randomized, double-blind, placebo-controlled trial over three months in women with short luteal phases; one 20 mg capsule (Strotan) a day. A hormone marker study, not a symptom trial. Article in German (Milewicz et al. 1993, Arzneimittelforschung)
52 participants with luteal phase defects and latent hyperprolactinemia; 37 complete cases analyzed (17 extract, 20 placebo).
Prolactin release after a TRH challenge fell, short luteal phases lengthened and low luteal progesterone rose with the extract only. Other hormones did not change except a rise in luteal estradiol. No side effects were seen.