Phytotherapeutic interventions in the management of biochemically recurrent prostate cancer: a systematic review of randomised trials.

OBJECTIVE: To evaluate the evidence from randomised trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent (BCR) prostate cancer, indicated by prostate-specific antigen (PSA) progression, numbers progressing to/time to initiation of androgen-deprivation therapy or salvage therapy. PATIENTS AND METHODS: MEDLINE (Ovid), EMBASE (Ovid), AMED (Ovid), CINAHL (EBSCO) and the Cochrane Library databases were searched. Clinical trials investigating phytotherapeutic interventions as dietary supplements or dietary components, including multi-component herbal formulations, in men with BCR prostate cancer were located. Eight of nine authors contacted for further information responded. Methodological quality was assessed using the Cochrane Collaboration's risk of bias assessment tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews was followed. RESULTS: Of 23 full-text articles assessed for eligibility, five met the criteria for inclusion. Two studies were placebo controlled; two were active control trials; and one a high-/low-dose trial. The interventions were administered as isolated phytochemicals (sulphoraphane), phytotherapeutic extracts [Pomi-T (pomegranate, turmeric, green tea and broccoli sprout extract), soy, lycopene, and POMx (pomegranate extract)], or plant-derived dietary items (soy and lycopene). All studies found serum PSA levels to stabilise, decrease or rise more slowly in a significant number of men, and three studies reported stabilising or lengthening of PSA-doubling time. Studies were generally of good quality, but sample sizes were predominantly small, and durations short. CONCLUSIONS: High-quality studies in this area are lacking. Sulphoraphane, lycopene, soy isoflavones, POMx, and Pomi-T are safe and well tolerated. There is limited evidence that they can affect PSA dynamics. No recommendation can be made for the use of these agents in managing prostate cancer morbidity and mortality until high-quality, fully powered studies are available. Recommendations are made for improving reproducibility and translation of findings with regard to study population, study endpoints, design, and the reporting of phytotherapeutic interventions.

Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis.

BACKGROUND: It has been suggested that some of the symptoms typically attributed to menopause may be more related to premenstrual syndrome (PMS) than menopause, as perimenopausal women appear to be more prone to PMS-like symptoms, or at least to tolerate them less well. OBJECTIVE: The objective of this study was to evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (chaste tree/berry) in the management of PMS-like symptoms in perimenopausal women. DESIGN: A double-blind, randomized, placebo-controlled parallel trial was conducted over 16 weeks on menopause-related symptoms. Data on PMS-like symptoms were collected at 4-weekly intervals from a small subgroup of late-perimenopausal women (n = 14) participating in this study. The primary endpoint was PMS scores measured on the Abrahams Menstrual Symptoms Questionnaire, comprising the subclusters of PMS-A (anxiety), PMS-D (depression), PMS-H (hydration), and PMS-C (cravings). Herbal combination therapy or placebo tablets were administered twice daily. RESULTS: At the end of the 16-week treatment phase, analyses of covariance showed the herbal combination to be superior to placebo for total PMS-like scores (p = 0.02), PMS-D (p = 0.006), and PMS-C clusters (p = 0.027). The active treatment group also showed significant reductions in the anxiety (p = 0.003) and hydration (p = 0.002) clusters, using paired-samples t tests. Results of trend analyses showed significant treatment group effects across the five phases for total PMS and all subscales, all in the clinically expected direction. No significant trends were evident in the placebo group. CONCLUSIONS: These results suggest a potentially significant clinical application for this phytotherapeutic combination in PMS-like symptoms among perimenopausal women. Further research is warranted through a randomized, controlled trial dedicated to investigation of these symptoms.

Predictors of placebo response in a randomized, controlled trial of phytotherapy in menopause.

OBJECTIVE: The aim of this study was to evaluate predictors of the placebo response in a randomized, placebo-controlled, double-blind trial of a phytotherapeutic combination for the treatment of menopausal symptoms. METHODS: A post hoc analysis was conducted on data from 46 placebo participants completing the study. Variables at baseline were investigated for prediction of improvement on any of the endpoints of flushing, depression measured on the Hamilton Depression Inventory, and menopausal symptoms measured on the Greene Climacteric Scale. Hierarchical linear regression analyses were carried out on the individual endpoints, controlling for baseline scores. Multivariate linear regression analysis was also conducted on these three endpoints in combination. RESULTS: Higher anxiety at study entry predicted placebo response on all three outcome measures individually (flushing: R = 0.33, P = 0.03; depression: R = 0.34, P < 0.001; and Greene Climacteric score: R = 0.24, P = 0.04); and in combination (P = 0.002), as did total Greene Climacteric scores at study entry (R = 0.24, P = 0.005). Improvement during nontreatment run-in predicted placebo response for depression (P = 0.005), menopausal symptoms (R = 0.28, P = 0.013), and the three combined endpoints (P = 0.015). Severity of scores at baseline predicted subsequent improvement on the Greene Climacteric scores only (r = 0.038, P = 0.009). CONCLUSIONS: These findings may facilitate identification of potential placebo responders in future randomized controlled trials on menopausal symptoms and have relevance to study design in this context. Further research is required.

Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints.

BACKGROUND: The origin of the current practice of administering Vitex agnus-castus in menopause-related complaints is uncertain, but appears to be relatively recent. Here we review the evidence for this application of Vitex based on evidence from pharmacological studies and clinical research. METHODS: The mechanisms of potential relevance in the context of menopause are explored with reference to the current understanding of the endocrinology and neuroendocrinology of menopause and associated symptoms. CONCLUSIONS: We conclude that, while evidence from rigorous randomized controlled trials is lacking for the individual herb in this context, emerging pharmacological evidence supports a role for V. agnus-castus in the alleviation of menopausal symptoms and suggests that further investigation may be appropriate.