Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study.

OBJECTIVES: To evaluate usage pattern, effectiveness and safety of Black cohosh alone or in fixed combination with St. John's wort on menopausal symptoms in general clinical practice. METHOD: Prospective, controlled open-label observational study of 6141 women at 1287 outpatient gynecologists in Germany. Subjects were treated with recommended doses of study therapies, with treatment chosen by the participating physicians. Patients were followed up for 6 months, optionally 12 months. The primary effectiveness variable was Menopause Rating Scale (MRS) subscore PSYCHE at Month 3 evaluated by ANCOVA. RESULTS: The treatment groups were comparable at baseline, excepting the main MRS score and the PSYCHE score (monotherapy: 0.31+/-0.22; combination therapy: 0.42+/-0.23). Reductions from baseline were seen with both regimens for all variables. The changes in the primary variable remained significantly different between groups (p<0.001) when adjusted for differences at baseline with the combination therapy being superior: from 0.37 (adjusted) to 0.25 (95% CI: 0.24-0.25) and 0.23 (95% CI: 0.22-0.23) at Month 3 in the monotherapy and combination-therapy groups, respectively. The improvement by both therapies was maintained at 6 and 12 months. The rate of possibly treatment-related adverse events was 0.16%, all non-serious. CONCLUSION: The results support the effectiveness and tolerability profiles of two Black cohosh-based therapies for menopausal symptoms in general practice. They were used differentially: the monotherapy for neurovegetative symptoms, the combination for patients with more pronounced mood complaints. The fixed combination of Black cohosh and St. John's wort was superior to Black cohosh alone in alleviating climacteric mood symptoms.

Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms.

OBJECTIVE: Several clinical studies suggest that black cohosh may be effective in climacteric complaints. However, evidence of its efficacy based on current quality standards has been limited. METHODS: This randomized, multicenter, double-blind clinical trial compared the efficacy and tolerability of the isopropanolic black cohosh extract in the treatment of climacteric complaints compared with placebo. A total of 304 patients were randomly allocated to receive tablets corresponding to 40 mg drug or matching placebo daily for 12 weeks. The primary efficacy measure was the change from baseline on the Menopause Rating Scale I; secondary measures included changes in its subscores and safety variables. RESULTS: Patient groups did not differ in baseline characteristics. The isopropanolic black cohosh extract was more effective than placebo (P < .001) depending on time from symptom onset (P = .014) and follicle-stimulating hormone level (P = .011). The effect size was 0.03 to 0.05 Menopause Rating Scale units which is similar to recent hormone replacement therapy study results (0.036 Menopause Rating Scale units) and may therefore be considered clinically relevant. Women in the early climacteric phase benefited more than in the late phase. The hot flush subscore was the most effective measure of the isopropanolic black cohosh extract's efficacy. There were no relevant group differences in adverse events, laboratory findings, or tolerability. CONCLUSION: This isopropanolic extract of black cohosh root stock is effective in relieving climacteric symptoms, especially in early climacteric women.

No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract.

We evaluated the pharmacokinetic interaction between a low-hyperforin St John's wort (SJW) extract and alprazolam, caffeine, tolbutamide, and digoxin. Previous reports on other SJW products had shown remarkably decreased plasma concentrations of certain co-medicated drugs, which was attributed to an inducing effect of SJW on cytochrome P-450 (CYP) and p-glycoprotein (p-gp) activity. Two randomised, placebo-controlled studies were performed with 28 healthy volunteers (age 18 - 55 years) in each study. In study A, single doses of alprazolam (1 mg; substrate of CYP3A4) and caffeine (100 mg; CYP1A2) were given on days 1 and 11. In study B, single doses of tolbutamide (500 mg, days 1 and 11; CYP2C9) and multiple doses of digoxin (0.75 mg on days -2 and -1, 0.25 mg/die on days 1 to 11; p-gp) were given. The participants received SJW (Esbericum capsules; 240 mg/die of extract, 3.5 mg hyperforin) or placebo on days 2 to 11. Blood for pharmacokinetic analysis was drawn on days 1 and 11. No statistically significant differences were found in the primary kinetic parameter, AUC0 - 24, of alprazolam, caffeine (AUC0 - 12), paraxanthine, tolbutamide, 4-hydroxytolbutamide, and digoxin between the placebo group and the SJW group at the end of the study. The SJW-induced change in AUCs was less than 12 % of the initial median AUC of the participants in studies A and B, thus clinically irrelevant. On day 11, trough concentrations were 2.0 (range 0.6 - 4.1) microg/L and 1.0 (0.2 - 3.9) microg/L for hypericin and pseudohypericin, respectively, whereas hyperforin concentrations were below the quantification limit (< 1 microg/L). Kinetics of investigated probe drugs were only marginally influenced by concomitant treatment with Esbericum capsules. This may be due in particular to the low hyperforin plasma concentration as this SJW component has been shown to activate the PXR receptor which regulates expression of CYP3A4 and p-gp. Our findings corroborate the view that reports about interactions of other SJW extracts seem not to be predictive for the product we studied.