|April 2001 · Vol. 50, No. 4
Patient Oriented Evidence that Matters
Is an extract of the fruit of agnus castus (chaste tree or chasteberry) effective for prevention of symptoms of premenstrual syndrome (PMS)?
University of Connecticut and Saint Francis Hospital and Medical Center Hartford
BACKGROUND: PMS is both common and troublesome, and there is no consensus on the most tolerable and effective therapy. Chasteberry fruit is commonly used in Europe for this condition. Given the strong placebo response noted with PMS1 and the increasing popularity and availability of herbal formulations in the United States, carefully controlled trials are needed to assess these new treatment options.
POPULATION STUDIED: Six general medicine outpatient clinics in Germany recruited 178 women aged 18 years or older with PMS as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Exclusion criteria included psychotherapy, any serious medical condition, pregnancy, breast-feeding, inadequate contraception, alcohol or drug dependence, hypersensitivity to chasteberry, fever, pituitary disease, or use of sex hormones other than oral contraceptives. The treatment groups did not differ significantly in terms of age (mean=36 years), weight, cycle characteristics, or initial assessments of severity.
STUDY DESIGN AND VALIDITY: In this prospective randomized double-blind placebo-controlled trial, participants received either a chasteberry (ZE 440) 20-mg tablet standardized for casticin (one of the presumed active principles) or matching placebo once daily. The authors assessed efficacy by comparing validated self-assessment scales at baseline (beginning of first menstrual cycle) and at the end of the third cycle. Tolerability was assessed using side effects reported at the last study visit, rather than by recording in a daily diary.
This is the appropriate study design for an efficacy trial. Of 178 participants initially screened and randomized, 170 had at least one baseline and one postbaseline value recorded. These 170 participants underwent intention-to-treat analysis and served as the basis for all study findings. The study may not have been randomized appropriately; although randomization occurred centrally in blocks of 4, an uneven number of patients were assigned to the 2 groups (91 vs 87). It is not clear whether concealed allocation occurred.
OUTCOMES MEASURED: The primary outcome was the change from baseline to end point in a combined score of 6 self-assessment items rated on a visual analog scale (irritability, mood alteration, anger, headache, other menstrual symptoms including bloating, and breast fullness). The secondary outcomes included each of the 6 items independently, 3 global assessment items (corroborated by physicians), and the responder rate, defined as 50% or more reduction in self-assessed symptoms from baseline.
RESULTS: Compared with placebo, patients who received chasteberry had a significant improvement in the combined symptom score (P <.001). In 5 of the 6 self-assessment items (irritability, mood alteration, anger, headache, and breast fullness), chasteberry was more effective than placebo (P <.01), with “other symptoms including bloating” being unaffected by treatment. All 3 global assessment items significantly favored the treated group, as did the responder rate (52% vs 24%, no statistical analysis presented). These results remained unchanged by subgroup analyses that excluded women taking oral contraceptives and included the 8 women initially screened but without postbaseline values who were removed from the initial intention-to-treat population. Side effect rates were similar in the 2 groups; all were mild, and none led to discontinuation.