Original Article Vitex agnus-castus (Chaste-Tree=Berry) in the Treatment of Menopause-Related Complaints Margaret Diana van Die, Ph.D., 1 Henry G. Burger, M.D., F.R.A.C.P., 2 Helena J. Teede, M.B.B.S., Ph.D., F.R.A.C.P., 3 and Kerry M. Bone, B.Sc., Dip.Phyt., F.N.I.M.H., F.N.H.A.A. 4,5 Abstract Background: The origin of the current practice of administering Vitex agnus-castus in menopause-related com- plaints 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. Introduction T he practice of administering Vitex agnus-castus (chaste-tree=berry or Monk’s pepper, family Verbena- ceae) in the treatment of menopause-related complaints appears to be of relatively recent origin. In current Anglo- American and European phytotherapeutic practice, Vitex fruit is most widely used for female reproductive problems, finding an application in conditions such as premenstrual syndrome, anovulatory cycles, infertility, and hyperprolacti- nemia, among others. 1,2 It is said to have a normalizing action on the menstrual cycle. 1,2 References to its value for ‘‘diseases of the uterus’’ appear as far back as the works of Hippocrates in 4th century bc and Dioscorides in ad 77. 3 Gerard, one of the great Renaissance herbalists, recommended it for inflamma- tion of the uterus and as an emmenagogue to promote men- struation. 4 The earliest overt reference in the literature to the applica- tion of Vitex in menopause-related complaints, however, does not appear until the 20th century. A 1972 publication of a collective report on the clinical experience of 5 practitioners with AgnolytÒ (a patent medicine extracted from dried Vitex fruit) reported on its efficacy for menopausal bleeding and menopausal complaints. 5 Its use in this context appears to have now become relatively popular in the Anglo-American tradition. 6–9 A practitioner survey of 276 UK herbalists reported that 86.3% prescribed it for the treatment of peri- menopausal complaints, including hot flushes. 10 It is also used in clinical practice to assist with withdrawal from hor- mone therapy (HT). 1,7,10 The fruit is a common ingredient of phytotherapeutic formulations for menopause-related com- plaints in several Western countries (Table 1). 11–14 While ev- idence for Vitex as a sole agent in this context is lacking from randomized controlled trials (RCTs), emerging pharmaco- logical evidence, relating to its dopaminergic activity, 15–17 affinity for opioid receptors, 18,19 and enhancement of mela- tonin secretion, 20 supports a role for V. agnus-castus in the alleviation of menopausal symptoms. This paper reviews the clinical and pharmacological evidence supporting this prac- tice, and possible rationale for such an application. Inconsistency of Definitions Used in Reference to Menopause The practice of administering Vitex for menopausal com- plaints is not universally supported. One possible explanation for the differences in observations from clinical experience and from research is the lack of consistency in the use of ter- minology relating to the menopausal stages. As a result, it is often unclear from the literature which menopausal phases, 1 Royal Melbourne Institute of Technology (RMIT) University, Bundoora, Victoria, Australia. 2 Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia. 3 Jean Hailes Foundation, Monash Institute of Health Services Research, Monash University, Clayton, Victoria, Australia. 4 MediHerb, Warwick, Queensland, Australia. 5 University of New England, Armidale, New South Wales, Australia. THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 15, Number 8, 2009, pp. 853–862 ª Mary Ann Liebert, Inc. DOI: 10.1089=acm.2008.0447 853