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. Participants: 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]-1 beta, 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-1 beta, IL-6, IL-8, IFN gamma and TNF alpha) 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.
