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With Comments from John La Puma, MD, FACP
May 2001; Volume 4; 59-60
Source: Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study BMJ 2001;322:134-137.
To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus-castus L extract Ze 440) with placebo for women with premenstrual syndrome, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparison over three menstrual cycles.
We used general medicine community clinics in the UK. We screened 178 women, and evaluated 170 (active 86; placebo 84). Subject mean age was 36 years; mean menstrual cycle length was 28 days; mean duration of menses was 4.5 days. We gave one tablet daily of agnus castus (dry extract tablets) or matching placebo for three consecutive menstrual cycles.
For our main variable, we measured change from baseline to endpoint (end of the third menstrual cycle) for the following self-assessed parameters: irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. For our secondary variable, we measured changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms).
Our results show improvement in the main variable was greater in the active group compared with placebo group (P < 0.001). Analysis of the secondary variables showed significant (P < 0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. We conclude that dry extract of agnus castus fruit is an effective and well-tolerated treatment for the relief of premenstrual syndrome symptoms.
Vitex agnus-castus is approved in Germany for use in disorders of the menstrual cycle, premenstrual syndrome, and mastodynia.
Five of the six self-assessment items (irritability, mood alteration, anger, headache, and breast fullness) were positive for vitex users. Analyses of subgroups—women who were taking oral contraceptives and screened women without post-baseline values—did not change the results.
This study is probably the best randomized, double-blind, controlled trial to date in this area. The authors applied DSM diagnostic criteria strictly, and used robust, validated, disease-specific instruments of assessment. The decision to test vitex against a placebo instead of an intervention is reasonable, given the high placebo response in this disorder and the modest effectiveness of vitamin B6, calcium, and other interventions. Though it is unclear how 91 patients were randomized to the active arm and 87 to placebo, given randomization in blocks of four, the authors minimized clinic visits to minimize bias from medical reassurance. The dosage was modest (active fruit extract ZE 440: 60% ethanol m/m, extract ratio 6-12:1; standardized for casticin; 20 mg/d) and there were few subjects lost to follow up, unlike other trials in this area.
The authors speculate that the mechanism of action also may be related to modulation of stress-induced prolactin secretion via dopamine, without directly affecting luteinizing hormone or follicle-stimulating hormone.
Adverse events were insignificant and not different between the two groups.
The author’s conclusion that vitex is effective in the treatment of the premenstrual syndrome, confirmed by women’s self-assessment and by the doctors’ evaluation, appears to be evidence-based. More than half the women had a 50% or greater improvement in their symptoms. As is the case for many studies of prescription pharmaceuticals, Zeller AG, Switzerland, supplied the study medication and sponsored the study.
Klepser and Nisly report, "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." (See Alternative Medicine Alert, June 1999, pp. 64-67.) Their paper lists five progestins in vitex flower and leaf. They conclude, "Vitex may be an option for women who have tried vitamin B6 and calcium, and who do not wish to use prescription hormonal treatment... 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."
For women with premenstrual syndrome who are not taking oral contraceptives and are not pregnant or lactating, a several month trial of Vitex agnus-castus appears warranted. Recommend it to women who want to try something new and for whom a careful diagnosis has been made.