The Efficacy of Hypericum perforatum (St John’s Wort) for the Treatment of Premenstrual Syndrome
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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]-1β, IL-6, IL-8, interferon [IFN]-γ and tumour necrosis factor [TNF]-α) 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-1β, IL-6, IL-8, IFNγ and TNFα) 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
KeywordsBeck Depression Inventory Luteal Phase Placebo Treatment Hypericin Hypericum Perforatum
Thanks are due to Lichtwer Pharma AG (Berlin, Germany) for the donation of the supplements and the Rosalind Bolton Bequest for funding the PhD studentship of the corresponding author. The Rosalind Bolton Bequest played no role in the production or submission of this manuscript. Thanks are also due to Biss Hartley for assisting Dr Julie Ayres with clinical interviews and to Uma Ekbote and Sarah Field for technical assistance.
No other sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.
Authors’ contributions: SC, LD, MW and NS designed the study and interpreted the data. SC collected the data. SC and LD analysed the data. SC wrote the paper. LD, MW, NS and NO made suggestions for revisions. NO supervised the hormone and cytokine assays. JA undertook clinical interviews with each participant. JA and NS were the physicians responsible for the study.
- 6.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; Department of Health and Human Services, 1994Google Scholar
- 7.Steiner M, Wilkins A. Diagnosis and assessment of premenstrual dysphoria. Psychiatr Ann 1996 Sep; 26(9): 571–5Google Scholar
- 18.Wyatt KM, Dimmock PW, O’Brien PM. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2002; (4): CD001396Google Scholar
- 28.Goodale IL, Domar AD, Benson H. Alleviation of premenstrual syndrome symptoms with the relaxation response. Obstet Gynecol 1990 Apr; 74(4): 649–55Google Scholar
- 55.Linthorst AC, Flachskamm C, Holsboer F, et al. Local administration of recombinant human interleukin-1 beta in the rat hippocampus increases serotonergic neurotransmission, hypothalamic-pituitary-adrenocortical axis activity, and body temperature. Endocrinology 1994 Aug; 135(2): 520–32PubMedCrossRefGoogle Scholar
- 69.Kapas L, Krueger JM. Tumor necrosis factor-beta induces sleep, fever, and anorexia. Am J Physiol Regul Integr Comp Physiol 1992 Sep; 263 (3 Pt 2): 703–7Google Scholar
- 75.Van Gool AR, Fekkes D, Kruit WH, et al. Serum amino acids, biopterin and neopterin during long-term immunotherapy with interferon-alpha in high-risk melanoma patients. Psychiatry Res 2003 Jul; 119(1–2): 125–32Google Scholar
- 86.Hicks SM, Walker AF, Gallagher J, et al. The significance of “nonsignificance” in randomized controlled studies: a discussion inspired by a double-blinded study on St. John’s wort (Hypericum perforatum L.) for premenstrual symptoms. J Altern Complement Med 2004 Dec; 10(6): 925–32Google Scholar
- 88.Pakgohar M, Mehran A, Salehi MS, et al. Comparison of hypericum perforatum and placebo in treatment of physical symptoms of premenstrual syndrome [in Persian]. HAYAT J Tehran Fac Nurs Midwifery 2004; 10(22): 99Google Scholar
- 89.Pakgohar M, Ahmadi M, Surmaghi MH, et al. Effect of Hypericum perforatum L. for treatment of premenstrual syndrome [in Persian]. J Med Plants 2005 Sep; 4(15): 33–42Google Scholar
- 92.Montgomery S, Hubener W, Gregoleit H. Efficacy and tolerability of St John’s wort extract compared with placebo in patients with a mild to moderate depressive disorder. Phytomedicine 2000; 7Suppl. 2: 107Google Scholar
- 95.Hamilton JA, Parry BL, Alagna S, et al. Premenstrual mood changes: a guide to evaluation and treatment. Psychiatr Ann 1984 Jun; 14(6): 426–35Google Scholar
- 96.NIMH Workshop on Pre-menstrual Syndrome. Co-sponsored by the Centre for Studies of Affective Disorders and the Psychobiological Processes and Behavioral Medicine Section. Rockville (MD): 1983 Apr: 14-15Google Scholar
- 98.Lampe L. Antidepressants: not just for depression. Aust Prescr 2005 Aug; 28(4): 91–3Google Scholar
- 100.Wyatt KM, Dimmock PW, Frischer M, et al. Prescribing patterns in premenstrual syndrome. BMC Womens Health 2002 Jun; 2(4): 1–8Google Scholar
- 106.Spielberger CD. Manual for the State-Trait Anxiety Inventory: STAI (Form Y). Palo Alto (CA): Consulting Psychologists Press, 1983Google Scholar
- 107.Pocock SJ. Clinical trials: a practical approach. Chichester: John Wiley, 1983Google Scholar
- 119.Rosenthal R, Rosnow RL. Essentials of behavioral research: methods and data analysis. 2nd ed. Singapore: McGraw-Hill, 1999Google Scholar
- 120.Machin D, Campbell MJ. Statistical tables for the design of clinical trials. Oxford: Blackwell Scientific Publications, 1987Google Scholar
- 122.Carlson NR. Foundations of Physiological Psychology. Boston (MA): Allyn and Bacon, 1988Google Scholar
- 130.First MB, Spitzer RL, Gibbon M, et al. Structured Clinical Interview for DSM-IV Axis I Disorders — Patient Edition (SCID-I/P, version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute, 1995Google Scholar
- 134.De Souza MC, Walker AF, Robinson PA, et al. A synergistic effect of a daily supplementation for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med 2000 Mar; 9(2): 131–9PubMedCrossRefGoogle Scholar