The efficacy of Hypericum perforatum (St John’s wort for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial

St. John’s Wort (Hypericum perforatum) shows promise in aiding those suffering from premenstrual syndrome.  In a recent study from the University of Leeds researchers found that St John’s Wort was “statistically superior to placebo in improving physical and behavioral symptoms of PMS (p<0.05).”  Other outcomes of the study including hormonal assessments, anxiety, depression, and other variables did not improve significantly.  Another study of PMS-like symptoms among perimenopausal women found significant reduction in anxiety and hydration along with other outcomes using a combination of St. John’s Wort and chaste tree/berry (Vitex agnus-castus).  These additional studies from the last year will help pave the way for future research to isolate issues like dose, clinical prediction variables and underlying mechanisms for action.

The efficacy of Hypericum perforatum (St John’s wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial.

Canning S, Waterman M, Orsi N, Ayres J, Simpson N, Dye L.
Institute of Psychological Sciences, University of Leeds, Leeds, UK.

BACKGROUND: Premenstrual syndrome (PMS) is a common condition. Some of the most widely prescribed medications are selective serotonin reuptake inhibitors (SSRIs), based on the hypothesized role of serotonin in the production of PMS symptoms. PMS sufferers, especially those experiencing mild to moderate symptoms, are often reluctant to take this form of medication and instead buy over-the-counter preparations to treat their symptoms, for which the evidence base with regard to efficacy is limited. Hypericum perforatum (St John’s wort) influences the serotonergic system. As such, this widely available herbal remedy deserves attention as a PMS treatment.

OBJECTIVE: To investigate the effectiveness of Hypericum perforatum on symptoms of PMS.

STUDY DESIGN: This randomized, double-blind, placebo-controlled, crossover study was conducted between November 2005 and June 2007.

SETTING: Institute of Psychological Sciences, University of Leeds, Leeds, UK.

PARTICIPATION: 36 women aged 18-45 years with regular menstrual cycles (25-35 days), who were prospectively diagnosed with mild PMS.

INTERVENTION: Women who remained eligible after three screening cycles (n = 36) underwent a two-cycle placebo run-in phase. They were then randomly assigned to receive Hypericum perforatum tablets 900 mg/day (standardized to 0.18% hypericin; 3.38% hyperforin) or identical placebo tablets for two menstrual cycles. After a placebo-treated washout cycle, the women crossed over to receive placebo or Hypericum perforatum for two additional cycles.
MAIN OUTCOME MEASURES: Symptoms were rated daily throughout the trial using the Daily Symptom Report. Secondary outcome measures were the State Anxiety Inventory, Beck Depression Inventory, Aggression Questionnaire and Barratt Impulsiveness Scale. Plasma hormone (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone, prolactin and testosterone) and cytokine (interleukin [IL]-1beta, IL-6, IL-8, interferon [IFN]-gamma and tumour necrosis factor [TNF]-alpha) levels were measured in the follicular and luteal phases during Hypericum perforatum and placebo treatment.
RESULTS: Hypericum perforatum was statistically superior to placebo in improving physical and behavioural symptoms of PMS (p < 0.05). There were no significant effects of Hypericum perforatum compared with placebo treatment for mood- and pain-related PMS symptoms (p > 0.05). Plasma hormone (FSH, LH, estradiol, progesterone, prolactin and testosterone) and cytokine (IL-1beta, IL-6, IL-8, IFNgamma and TNFalpha) levels, and weekly reports of anxiety, depression, aggression and impulsivity, also did not differ significantly during the Hypericum perforatum and placebo cycles (p > 0.05).
CONCLUSION: Daily treatment with Hypericum perforatum was more effective than placebo treatment for the most common physical and behavioural symptoms associated with PMS. As proinflammatory cytokine levels did not differ significantly between Hypericum perforatum and placebo treatment, these beneficial effects are unlikely to be produced through this mechanism of action alone. Further work is needed to determine whether pain- and mood-related PMS symptoms benefit from longer treatment duration. Trial registration number (International Standard Randomised Controlled Trial Number Register) ISRCTN31487459.
Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review

Can J Clin Pharmacol. 2009 Fall;16(3):e407-29. Epub 2009 Oct 29.

Can J Clin Pharmacol. 2009 Fall;16(3):e407-29. Epub 2009 Oct 29.

Whelan AM, Jurgens TM, Naylor H.
College of Pharmacy, Dalhousie University, Halifax, Nova Scotia. Anne.Marie.Whelan@Dal.Ca

BACKGROUND: As many women experiencing symptoms of premenstrual syndrome (PMS) seek relief from natural products (NP), health care providers should have quality information available to aid women in making evidence-based decisions regarding use of these products.

OBJECTIVE: To identify herbs, vitamins and minerals advocated for the treatment of PMS and/or PMDD and to systematically review evidence from randomized controlled trials (RCTs) to determine their efficacy in reducing severity of

PMS/PMDD symptoms.

METHODS: Searches were conducted from inception to April 2008 in Clinical Evidence, The Cochrane Library, Embase, IBID, IPA, Mayoclinic, Medscape,

MEDLINE Plus, Natural Medicines Comprehensive Database and the Internet to identify RCTs of herbs, vitamins or minerals advocated for PMS. Bibliographies of articles were also examined. Included studies were published in English or French. Studies were excluded if patient satisfaction was the sole outcome measure or if the comparator was not placebo or recognized therapy.

RESULTS: Sixty-two herbs, vitamins and minerals were identified for which claims of benefit for PMS were made, with RCT evidence found for only 10. Heterogeneity of length of trials, specific products and doses, and outcome measures precluded meta-analysis for any NP. Data supports the use of calcium for PMS, and suggests that chasteberry and vitamin B6 may be effective. Preliminary data shows some benefit with ginkgo, magnesium pyrrolidone, saffron, St. John’s Wort, soy and vitamin E. No evidence of benefit with evening primrose oil or magnesium oxide was found.

CONCLUSION: Only calcium had good quality evidence to support its use in PMS. Further research is needed, using RCTs of adequate length, sufficient sample size, well-characterized products and measuring the effect on severity of individual PMS symptoms.
Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis.

J Altern Complement Med. 2009 Sep;15(9):1045-8.

van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ.
Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia.
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.