A Controlled Trial of Chinese Herbal Medicine for Premenstrual Syndrome Patsy Bin-Yo Chou 2007 A thesis submitted in fulfilment of the Degree of Doctor of Philosophy School of Health Sciences Faculty of Health, Engineering and Science Victoria University Melbourne, Australia ii Abstract Premenstrual syndrome is a common disorder troubling many women during their reproductive years. The Chinese have been using herbal medicines to treat menstrual cycle related symptoms for centuries. Traditional Chinese medicine provides the aetiology and pathogenesis of the symptoms of this disorder by applying Pattern Identification to diagnose the signs and symptoms of individual patients and to design individualised treatments which seek to address the entire pattern/s of disharmony. It follows that PMS, which has many symptoms and an idiosyncratic nature, is precisely an area for which Chinese medicine is most suitable. The aim of this study is to scientifically evaluate the effectiveness of Chinese herbal medicine on Australian women for the treatment of PMS within the theoretical frame-work of TCM. A double-blind randomized placebo-controlled crossover clinical trial was conducted by a qualified Chinese herbal practitioner and pharmacist. Following two months confirmatory assessment, sixty-one subjects were assigned randomly into two groups within different TCM patterns of Liver Qi Stagnation, Liver and Kidney Yin Deficiency, Liver and Spleen Disharmony and Heart and Spleen Deficiency. Herbal medicine (n=31) and placebo (n=30) were provided sequentially for a period of three months. There were significant differences (p < .01) in scores after three months of treatment between Chinese herbal medicine and placebo in premenstrual physical and psychological symptoms, depression, anxiety and anger, but with no difference in perceived stress (p > .05). There were highly significant reductions (p< .001) in all assessments in both groups except that a significant result (p < .05) was recorded on perceived iii stress only in the treatment-first group between baseline and the end of the third herbal treatment month. Also, there was no significant difference on treatment effects shown between TCM patterns. No adverse effects were reported by any participant. The results support the hypothesis that the symptoms occurrence and severity of PMS can be effectively reduced by the use of Chinese herbal medicine. On this basis, it is considered that Chinese herbal medicine may offer an alternative treatment method to western drugs for PMS sufferers who either do not accept the current treatment options or are having unwanted side-effects with their current treatment. iv Declaration “I, Patsy Bin-Yo Chou, declare that the PhD thesis entitled A Controlled Trial of Chinese Herbal Medicine for Premenstrual Syndrome is no more than 100,000 words in length, exclusive of tables, figures, appendices, references and footnotes. This thesis contains no material that has been submitted previously, in whole or in part, for the award of any other academic degree or diploma. Except where otherwise indicated, this thesis is my own work”. Signature Date v Acknowledgments I am most grateful to my principal supervisor, Professor Carol Morse, for her constant support, guidance, and encouragement throughout the entire course of this study, and for her advice in the preparation of the clinical trial and drafting of this thesis. I would also like to thank Dr Xu Hong, my co-supervisor, for her assistance and support during the study. My sincere thanks also extend to: Ms Maja Rechsteiner and Mr Chris Mills, for their contribution in the preparation of herbal medicine. Ms Pei Shan Wang and all the students in the King Street clinic, for their assistance and co-operation. Ms Dawn Bannon, for her help in arranging consultation rooms and ordering herbal medicine. Sun Ten and Meridian Herbals for providing discounts on herbal granules. Finally, I would like to express my gratitude to my husband Peter for his unwavering support, patience and proof reading of my drafts, to my daughter Eugenia for her support and encouragement, and my deceased father who taught me how to deal with challenges patiently, systematically and wisely. vi Table of Contents Abstract ii Declaration ⅳ Acknowledgments ⅴ Table of Contents ⅵ List of Tables ⅶ List of Figures ⅹ List of Appendices ⅹⅰ Section I: Introduction of the thesis Page Chapter 1: Introduction 1 Section II: Literature Review Chapter 2: Western Biomedical Perspective on Issues for Premenstrual 8 Syndrome Chapter 3: Traditional Chinese Medical Perspective on Issues for 47 Premenstrual Syndrome Chapter 4: Methodological Issues for Research on Premenstrual 127 Syndrome Chapter 5: A Review of Clinical Research of Premenstrual Syndrome 144 Treatment Using Herbal Medicine in Chinese Medical Journals 1996-2005 Section III: Empirical Research Study Chapter 6: Objectives, Significances and Hypotheses of the Study 166 Chapter 7: Methodology of the Intervention Study Using Chinese 170 Herbal Medicine vs. Placebo Chapter 8: Descriptive Findings of Assessment at Baseline 196 Chapter 9: Multivariate Analyses of Group Treatments 213 Chapter 10: Individual Symptoms Ratings, TCM Issues and Others 243 Chapter 11: Discussion 260 Chapter 12: Conclusions, Recommendations and Future Direction 291 References 297 Appendices 336 vii List of Tables Page Table 2.1 The order and frequency of the most common PMS 26 symptoms in different countries Table 2.2 MDQ Subscales (Moo’s 1968) 28 Table 2.3 Subgroups in Abraham’s Menstrual Symptom Diary 29 Table 3.1 22 TCM Patterns of PMS 81 Table 3.2 Pharmacological effects of liver coursing herbs 115 Table 3.3 Pharmacological effects of liver clearing and heat 116 purging herbs Table 3.4 Pharmacological effects of liver and kidney nourishing 117 herbs Table 3.5 Pharmacological effects of spleen strengthening herbs 118 Table 3.6 Pharmacological effects of blood moving and stasis 119 transforming herbs Table 5.1 Premenstrual syndrome or symptoms studied at the 124 149 trials Table 5.2 Samples sizes of the 124 trials 150 Table 5.3 Total effective rates of 21 trials 155 Table 5.4 Frequency of formulas used (more than once) in the 162 trials Table 7.1 Signs and symptoms of TCM patterns of disharmony of 190 PMS Table 7.2 Treatment for TCM patterns of disharmony 191 Table 8.1 Demographic Profiles 199 Table 8.2 Cigarette and alcohol consumption 201 Table 8.3 Happiness at work and family life 201 Table 8.4 Menstrual history 202 Table 8.5 Menstrual characteristics 204 Table 8.6 PMS experiences 205 Table 8.7 Comparisons of Group I and Group II on symptoms by 206 categorical clusters Table 8.8 Most common presenting symptoms 207 Table 8.9 Psychological Characteristics 208 Table 8.10 The distribution of Chinese patterns in groups 210 Table 8.11 Tongue signs recorded at the first interview 211 Table 8.12 Pulses recorded at the first interview 212 viii Table 9.1 Mean differences and percentages of reduction between 217 baseline and month 3 of Group I (herb) and Group II (placebo) Table 9.2 Significance of mean differences between time phases 220 of Group II Table 9.3 Time effects on all clinical assessments in Group II 220 Table 9.4 Mean differences of clinical assessment scores between 223 baseline, placebo and herbal treatment months in Group II Table 9.5 Time and Measurement Effects between baseline and 225 three months herbal treatment in Group I Table 9.6 Effects of herbal treatment on symptom reports in 226 Group I Table 9.7 Comparisons between baseline and three months of 228 herbal treatment on Physical symptoms, Psychological symptoms, Depression, Anxiety, Anger and Perceived Stress in Group I Table 9.8 Time and Measures Effects and Measures by Time 230 Interactions between baseline and three months herbal treatment in Group II Table 9.9 Significant differences over the four time periods (the 231 last month of placebo treatment and the three months of herbal treatment) in Group II Table 9.10 Comparisons between baseline and three months of 233 herbal treatment period of Physical symptoms, Psychological symptoms, Depression, Anxiety, Anger and Perceived Stress in Group II Table 9.11 Time and measures effects and measures by time 235 interactions between baseline, herbal treatment month 3 and follow-up on physical and psychological symptoms of Group II Table 9.12 Effects between baseline, herbal treatment month 3 and 236 follow-up on physical and psychological symptoms of Group II Table 9.13 Comparisons between baseline, herbal treatment month 236 3 and follow-up of Physical and Psychological symptoms in Group II Table 9.14 Significant clinical changes after three months herbal 239 treatment of Group I ix Table 9.15 Significant clinical changes after three months herbal 241 treatment of Group II Table 9.16 Clinically significant changes at follow-up of Group II 242 Table 10.1 Treatment effects on premenstrual symptoms collected 246 from MSD and MDQ at baseline and the three herbal treatment months in Group I and Group II Table 10.2 Comparison of baseline scores between women who 247 completed all MSD diaries and those not Table 10.3a Correlation between clients’ satisfaction rating and 249 clinical assessment scores at the third month of experimental period Table 10.3b Correlation between clients’ satisfaction rating and 249 clinical assessment scores at the sixth month of experimental period Table 10.4 Time, Measure and Pattern interactions between three 251 herbal treatment month Table 10.5a Treatment effects between TCM patterns at the