• Vitex agnus-castus (Abraham tree / Vitex sacred) in alleviating the symptoms of menopause
To content

Vitex agnus-castus (Abraham tree / Vitex sacred) in alleviating the symptoms of menopause

HEALTH OF WOMAN. 2018.9(135):26–35

Margaret Diane van Dee, Ph.D., Henry G. Burger, physician, member of the Royal Australian College of General Practitioners, Helena J. Teeda, Bachelor of Medicine and Bachelor of Surgery, Ph.D., member of the Royal Australian College of General Practitioners and Kerry M. Bown, Bachelor of Science, Certified Phytotherapist, Researcher at the National Institute of Mental Health, Member of the National Association of Herbal Therapists

Royal Melbourne University of Technology (RMIT), Bandoora, Victoria, Australia.
Prince Henry Institute for Medical Research, Clayton, Victoria, Australia

Gene Heils Foundation, Monash University Institute of Health, Monash University, Clayton, Victoria, Australia
MediHerb, Warwick, Queensland, Australia
University of New England, Armidale, New South Wales, Clayton, Victoria, Australia

Published: JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE. Volume 15, Number 8, 2009, pp. 835–862

© "Mary Ann Libert, Inc."

DOI: 10.1089 / acm.2008.0447


1. Mills S, Bone K. 2000. Principles and Practice of Phytotherapy. London: Churchill Livingstone.

2. Pizzorno J, Murray M. 2000. Textbook of Natural Medicine. New York: Churchill Livingstone

3. Hawley R, Levick B, eds. 1995. Women in Antiquity: New Assessments. London, New York: Routledge.

4. Hobbs C. 1990. Vitex: The Women’s Herb. 2nd ed. Santa Cruz, CA: Botanica Press.

5. Attelmann H, Bends K, Hellenkemper H, Warkalla H. 1972. Agnolyt_ in the treatment of gynecological complaints. Z Pra¨ klin Geriatr 2:239–243.

6. Fugh-Berman A. Herbs, phytoestrogens and other CAM therapies. 2007. In: Lobo R, ed. Treatment of the Postmenopausal Woman. Basic and Clinical Aspects. 3rd ed. Burlington, MA: Academic Press:683.

7. Bone K. 2003. A Clinical Guide to Blending Liquid Herbs. St. Louis: Churchill Livingstone.

8. Mills S. 1985. The Dictionary of Modern Herbalism. Wellingborough, UK: Thorsons.

9. Newall C, Anderson L, Phillipson J. 1996. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press.

10. Christie S, Walker AF. 1997. Vitex agnus-castus L.: (1) A Review of Its Traditional and Modern Therapeutic use; (2) Current Use from a Survey of Practitioners. Eur J Herbal Med 3:29–45.

11. Rotem C, Kaplan B. 2007. Phyto-female complex for the relief of hot flushes, night sweats and quality of sleep: Randomized, controlled, double-blind pilot study. Gynecol Endocrinol 23:117–122.

12. Newton KM, Reed SD, LaCroix AZ et al. 2006. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: A randomized trial. Ann Intern Med 145:869–879.

13. van Die MD, Burger HG, Bone KM et al. 2009. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms. Menopause 16:156–163.

14. Smolinski D, Wollner D, Orlowski J et al. 2005. A pilot study to examine a combination botanical for the treatment of menopausal symptoms. J Altern Complement Med 11:483–489.

15. Wuttke W, Gorkow C, Jarry H. 1995. Dopaminergic compounds in Vitex agnus-castus. In: Leow D, Rietbrock, N, ed. Herbal Medicine in Research and Clinical Application. Darmstadt, Germany, Steinkopff (Verlag):81–91.

16. Wuttke W, Jarry H, Christoffel V et al. 2003. Chaste tree (Vitex agnus-castus): Pharmacology and clinical indications. Phytomedicine 10:348–357.

17. Wuttke W. 2008. The use of chasteberry (Vitex agnus castus) extract in gynecology. Gynakol Endokrinol 6:82–86.

18. Meier B, Berger D, Hoberg E et al. 2000. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine 7:373–381.

19. Webster DE, Lu J, Chen SN et al. 2006. Activation of the muopiate receptor by Vitex agnus-castus methanol extracts: Implication for its use in PMS. J Ethnopharmacol 106:216–221.

20. Dericks-Tan JS, Schwinn P, Hildt C. 2003. Dose-dependent stimulation of melatonin secretion after administration of Agnus castus: Experimental and clinical endocrinology & diabetes 111:44–46.

21. Chopin Lucks B. 2003. Vitex agnus castus essential oil and menopausal balance: A research update. Complement Ther Nurs Midwifery 9:157–160.

22. World Health Organisation. Research on the Menopause in the 1990s. Report of a WHO Scientific Group. WHO VITEX AGNUS-CASTUS IN MENOPAUSE 859 Technical Report Series No. 866. Geneva: WHO Library Cataloguing in Publication Data. 1996.

23. Lucks BC, Sørensen J, Veal L. 2002. Vitex agnus-castus essential oil and menopausal balance: A self-care survey. Complement Ther Nurs Midwifery 8:148–154.

24. Mitchell E, Woods NF, Mariella A. 2000. Three stages of the menopausal transition from the Seattle Midlife Women’s Health Study: Toward a more precise definition. Menopause 7:334–349.

25. Burger H. 1999. The endocrinology of the menopause. J Steroid Biochem Molecular Biol 69:31–35.

26. Burger H. 2005. The relationship between the endocrine characteristics and the regularity of menstrual cycles in the approach to menopause. Menopause 12:267–274.

27. Santoro N, Brown JR, Adel T, Skurnick JH. 1996. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 81:1495–1501.

28. Dennerstein L, Smith AM, Morse C et al. 1993. Menopausal symptoms in Australian women. Med J Aust 159:232–236.

29. Van Look PF, Lothian H, Hunter WM et al. 1977. Hypothalamic pituitary- ovarian function in perimenopausal women. Clin Endocrinol (Oxf ) 7:13–31.

30. Teede H, Buger H. 1998. The menopausal transition. In: Studd JW, ed. The Management of the Menopause. Annual Review. New York: Elsevier:1–18.

31. Guthrie JR, Dennerstein L, Taffe JR et al. 2005. Hot flushes during the menopause transition: A longitudinal study in Australian-born women. Menopause 12:460–467.

32. Dennerstein L, Dudley EC, Hopper JL et al. 2000. A prospective population-based study of menopausal symptoms. Obstet Gynecol 96:351–358.

33. Nilsson K, Heimer G. 1992. Endogenous estrogen levels in postmenopausal women with severe urogenital atrophy. Gynecol Obstet Invest 34:234–236.

34. Burger H, Dudley E, Robertson D, Dennerstein L. 2002. Hormonal changes in the menopause transition. Recent Prog Hormone Res 57:257–275.

35. Fraser IS, Baird DT. 1974. Blood production and ovarian secretion rates of estradiol-17 beta and estrone in women with dysfunctional uterine bleeding. J Clin Endocrinol Metab 39:564–570.

36. Bungay GT, Vessey MP, McPherson CK. 1980. Study of symptoms in middle life with special reference to the menopause. Br Med J 281:181–183.

37. Freeman EW, Sammel MD, Liu L et al. 2004. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry 61:62–70.

38. Robinson GE. 2001. Psychotic and mood disorders associated with the perimenopausal period: Epidemiology, aetiology and management. CNS Drugs 15:175–184.

39. Bromberger JT, Meyer PM, Kravitz HM et al. 2001. Psychologic distress and natural menopause: A multiethnic community study. Am J Public Health 91:1435–1442.

40. Hassan I, Ismail KM, O’Brien S. 2004. PMS in the perimenopause. J Br Menopause Soc 10:151–156.

41. Erlik Y, Tataryn IV, Meldrum DR et al. 1981. Association of waking episodes with menopausal hot flushes. JAMA 245:1741–1744.

42. Shaver J, Giblin E, Lentz M, Lee K. 1988. Sleep patterns and stability in perimenopausal women. Sleep 11:556–561.

43. Gonen R, Sharf M, Lavie P. 1986. The association between midsleep waking episodes and hot flashes in post-menopausal women. J Psychosom Obstet Gynecol 5:113–117.

44. Freedman RR, Roehrs TA. 2006. Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause 13:576–583.

45. Casper RF, Yen SS. 1985. Neuroendocrinology of menopausal flushes: An hypothesis of flush mechanism. Clin Endocrinol (Oxf ) 22:293–312.

46. Habib KE, Gold PW, Chrousos GP. 2001. Neuroendocrinology of stress. Endocrinol Metab Clin North Am 30:695–728; vii–viii.

47. Finkelstein JW, Roffwarg HP, Boyar RM et al. 1972. Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 35:665–670.

48. Van Cauter E, Plat L, Copinschi G. 1998. Interrelations between sleep and the somatotropic axis. Sleep 21:553–566.

49. Joffe H, Hall JE, Soares CN et al. 2002. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause 9:392–398.

50. Landgren BM, Collins A, Csemiczky G et al. 2004. Menopause transition: Annual changes in serum hormonal patterns over the menstrual cycle in women during a nine-year period prior to menopause. J Clin Endocrinol Metab 89:2763–2769.

51. Burger H, Teede H. 2007. Endocrine changes during the perimenopause. In: Lobo R, ed. Treatment of the Postmenopausal Woman. Basic and Clinical Aspects. 3rd ed. Burlington, MA: Academic Press: 67–76.

52. Richardson SJ, Senikas V, Nelson JF. 1987. Follicular depletion during the menopausal transition: Evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 65:1231–1237.

53. Metcalf MG, Donald RA, Livesey JH. 1981. Pituitary-ovarian function in normal women during the menopausal transition. Clin Endocrinol (Oxf ) 14:245–255.

54. Robertson DM, Burger HG. 2002. Reproductive hormones: Ageing and the perimenopause. Acta Obstet Gynecol Scand 81:612–616.

55. Lenton EA, Sexton L, Lee S, Cooke ID. 1988. Progressive changes in LH and FSH and LH: FSH ratio in women throughout reproductive life. Maturitas 10:35–43.

56. Santoro N, Chervenak JL. 2004. The menopause transition. Endocrinol Metab Clin North Am 33:627–636.

57. Burger HG. 1994. Diagnostic role of follicle-stimulating hormone (FSH) measurements during the menopausal transition: An analysis of FSH, oestradiol and inhibin. Eur J Endocrinol 130:38–42.

58. Rannevik G, Carlstrom K, Jeppsson S et al. 1986. A prospective long-term study in women from pre-menopause to postmenopause: Changing profiles of gonadotrophins, oestrogens and androgens. Maturitas 8:297–307.

59. Longcope C, Franz C, Morello C et al. 1986. Steroid and gonadotropin levels in women during the peri-menopausal years. Maturitas 8:189–196.

60. Burger HG, Dudley EC, Hopper JL et al. 1999. Prospectively measured levels of serum follicle-stimulating hormone, estradiol, and the dimeric inhibins during the menopausal transition in a population-based cohort of women. J Clin Endocrinol Metab 84:4025–4030.

61. Prior JC. 1998. Perimenopause: The complex endocrinology of the menopausal transition. Endocr Rev 19:397–428.

62. Miro F, Parker SW, Aspinall LJ et al. 2004. Origins and consequences of the elongation of the human menstrual cycle during the menopausal transition: The FREEDOM Study. J Clin Endocrinol Metab 89:4910–4915. 860 VAN DIE ET AL.

63. Weiss G, Skurnick JH, Goldsmith LT et al. 2004. Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA 292:2991–2996.

64. Yonkers KA, O’Brien PM, Eriksson E. 2008. Premenstrual syndrome. Lancet 371:1200–1210.

65. Genazzani AR, Salvestroni C, Spinetti A et al. 1998. Estrogens and neurotransmitters. In: Studd JWW, ed. The Management of the Menopause: Annual Review 1998. Carnforth, Lancs, UK: The Parthenon Publishing Group Limited: 169–175.

66. Sherwin BB. 1996. Hormones, mood, and cognitive functioning in postmenopausal women. Obstet Gynecol 87(2 Suppl):20S–26S.

67. Maggi A, Perez J. 1985. Role of female gonadal hormones in the CNS: Clinical and experimental aspects. Life Sci 37:893–906.

68. Da Sliva I, Naftolin F. 2007. Clinical effects of sex steroids on the brain. In: Lobo R, ed. Treatment of the Postmenopausal Woman. Basic and Clinical Aspects. 3rd ed. Burlington, MA: Academic Press: 199–215.

69. Nair NP, Hariharasubramanian N, Pilapil C et al. 1986. Plasma melatonin: An index of brain aging in humans? Biol Psychiatry 21:141–150.

70. Haimov I, Laudon M, Zisapel N et al. 1994. Sleep disorders and melatonin rhythms in elderly people. BMJ 309:167.

71. Vakkuri O, Kivela A, Leppaluoto J et al. 1996. Decrease in melatonin precedes follicle-stimulating hormone increase during perimenopause. Eur J Endocrinol 135:188–192.

72. Zimmerman R, Olcese J. 2007. Melatonin. In: Lobo R, ed. Treatment of the Postmenopausal Woman. Burlington, MA: Academic Press.

73. Freedman RR. 2001. Physiology of hot flashes. Am J Hum Biol 13:453–464.

74. Bruck K, Zeisberger E. 1987. Adaptive changes in thermoregulation and their neuropharmacological basis. Pharmacol Ther 35:163–215.

75. Biegon A, Reches A, Snyder L, McEwen BS. 1983. Serotonergic and noradrenergic receptors in the rat brain: Modulation by chronic exposure to ovarian hormones. Life Sci 32:2015–2021.

76. Tuchman E. 2007. Exploring the prevalence of menopause symptoms in midlife women in methadone maintenance treatment. Soc Work Health Care 45:43–62.

77. Simpkins JW, Katovich MJ, Song IC. 1983. Similarities between morphine withdrawal in the rat and the menopausal hot flush. Life Sci 32:1957–1966.

78. Barros RC, Branco LG, Carnio EC. 2004. Evidence for thermoregulation by dopamine D1 and D2 receptors in the anteroventral preoptic region during normoxia and hypoxia. Brain Res 1030:165–171.

79. Cagnacci A, Melis GB, Soldani R et al. 1989. Regulation of body temperature in postmenopausal women: Interactions between bromocriptine and the endogenous opioid system. Life Sci 44:1395–1402.

80. Zichella L, Falaschi P, Fioretti P et al. 1986. Effects of different dopamine agonists and antagonists on post-menopausal hot flushes. Maturitas 8:229–237.

81. Blum I, Vered Y, Lifshitz A et al. 1996. The effect of estrogen replacement therapy on plasma serotonin and catecholamines of postmenopausal women. Isr J Med Sci 32:1158–1162.

82. Gonzales GF, Carrillo C. 1993. Blood serotonin levels in postmenopausal women: Effects of age and serum oestradiol levels. Maturitas 17:23–29.

83. Fink G, Sumner BE. 1996. Oestrogen and mental state. Nature 383:306.

84. Dennerstein L, Lehert P, Guthrie JR, Burger HG. 2007. Modeling women’s health during the menopausal transition: A longitudinal analysis. Menopause 14:53–62.

85. Ballinger CB, Browning MC, Smith AH. 1987. Hormone profiles and psychological symptoms in peri-menopausal women. Maturitas 9:235–251.

86. Chakravarti S, Collins WP, Newton JR et al. 1977. Endocrine changes and symptomatology after oophorectomy in premenopausal women. Br J Obstet Gynaecol 84:769–775.

87. Soares CN, Cohen LS. 2001. The perimenopause, depressive disorders, and hormonal variability. Sao Paulo Med J 119:78–83.

88. Freeman EW, Sammel MD, Lin H, Nelson DB. 2006. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 63:375–382.

89. Avis NE, Kaufert PA, Lock M et al. 1993. The evolution of menopausal symptoms. Baillieres Clin Endocrinol Metab 7:17–32.

90. Barden N, Merand Y, Rouleau D et al. 1981. Changes in the betaendorphin content of discrete hypothalamic nuclei during the estrous cycle of the rat. Brain Res 204:441–445.

91. Genazzani AR, Petraglia F, Mercuri N et al. 1990. Effect of steroid hormones and antihormones on hypothalamic betaendorphin concentrations in intact and castrated female rats. J Endocrinol Invest 13:91–96.

92. Wise PM, Rance N, Barraclough CA. 1981. Effects of estradiol and progesterone on catecholamine turnover rates in discrete hypothalamic regions in ovariectomized rats. Endocrinology 108:2186–2193.

93. Jacobs PA, Hyland ME. 2003. An evaluation of the benefits of taking hormone replacement therapy with other prescription drugs. Maturitas 46:273–281.

94. Paoletti AM, Floris S, Mannias M et al. 2001. Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause. J Clin Endocrinol Metab 86:608–612.

95. Parry BL, Newton RP. 2001. Chronobiological basis of femalespecific mood disorders. Neuropsychopharmacology 25(S5):S102–S108.

96. Khan SA, Pace JE, Cox ML et al. 1994. Climacteric symptoms in healthy middle-aged women. Br J Clin Pract 48:240–242.

97. Schmidt PJ, Nieman LK, Grover GN et al. 1991. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. NEJM 324:1174–1179.

98. Winer SA, Rapkin AJ. 2006. Premenstrual disorders: Prevalence, etiology and impact. J Reprod Med 51(4 suppl):339–347.

99. Richards M, Rubinow DR, Daly RC, Schmidt PJ. 2006. Premenstrual symptoms and perimenopausal depression. Am J Psychiatry 163:133–137.

100. Hale G, Hughes C, Burger H et al. 2009. Atypical oestradiol secretion and ovulation patterns caused by Luteal Out- Of-Phase (‘‘LOOP’’) events underlying irregular ovulatory menstrual cycles in the menopausal transition. Menopause 16:50–59.

101. Jarry H, Spengler B, Porzel A et al. 2003. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Planta Med 69:945–947.

102. Yen SSC, Jaffe RB. 1999. Prolactin in human reproduction. In: Yen SSC, Jaffe RB, Barbieri RL, ed. Reproductive VITEX AGNUS-CASTUS IN MENOPAUSE 861 Endocrinology. 4th ed. Philadelphia: WB Saunders: 276–277.

103. Halbreich U, Ben-David M, Assael M, Bornstein R. 1976. Serumprolactin in women with premenstrual syndrome. Lancet 2:654–656.

104. Muhlenstedt D, Bohnet HG, Hanker JP, Schneider HP. 1978. Short luteal phase and prolactin. Int J Fertil 23:213–218.

105. Dietrich M, Hinnery B, Link M et al. 1988. Latent hyperprolactinaemia as a cause of mastodynia and luteal function impairment. Vth International Congress Prolactin,

106. Giannini AJ, Martin DM, Turner CE. 1990. Beta-endorphin decline in late luteal phase dysphoric disorder. Int J Psychiatry Med 20:279–284.

107. Chuong CJ, Hsi BP, Gibbons WE. 1994. Periovulatory betaendorphin levels in premenstrual syndrome. Obstet Gynecol 83(5; 1):755–760.

108. Facchinetti F, Moglia A, Bonuccelli U et al. 1986. Pattern of plasma opioids in menstrually-related migraine and epilepsy. Funct Neurol 1:415–419.

109. Facchinetti F, Martignoni E, Petraglia F et al. 1987. Premenstrual fall of plasma beta-endorphin in patients with premenstrual syndrome. Fertil Steril 47:570–573.

110. Diaz BL, Llaneza PC. 2008. Endocrine regulation of the course of menopause by oral melatonin: First case report. Menopause 15:388–392.

111. Wuttke W, Seidlova-Wuttke D, Gorkow C. 2003. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a doubleblind placebo-controlled study: Effects on menopause symptoms and bone markers. Maturitas 44(suppl 1):S67–S77.

112. Osmers R, Friede M, Liske E et al. 2005. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 105(5; 1):1074–1083.

113. Nappi RE, Malavasi B, Brundu B, Facchinetti F. 2005. Efficacy of Cimicifuga racemosa on climacteric complaints: A randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 20:30–35.

114. Geller SE, Studee L. 2006. Contemporary alternatives to plant estrogens for menopause. Maturitas 55(suppl 1):S3–S13.

115. US Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER). Guidance for industry: Labeling guidance for noncontraceptive estrogen drug products for the treatment of vasomotor symptoms and vulvar and vaginal atrophy symptoms— prescribing information for health care providers and patient labeling. revision 1. Rockville, MD: Division of Drug Information, Center for Drug Evaluation and Research, CDER. 2004.

116. MacLennan AH, Broadbent JL, Lester S, Moore V. 2004. Oral oestrogen and combined oestrogen=progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 4:CD002978.

117. Albertazzi P, Pansini F, Bonaccorsi G et al. 1998. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 91:6–11.

118. Davis S, Briganti E, Chen RQ et al. 2001. The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women. Med J Austr 174:68–71.

119. Knight DC, Howes JB, Eden J. 1999. The effect of PromensilTM, an isoflavone extract, on menopausal symptoms. Climacteric 2:79–84.

120. Schellenberg R. 2001. Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study. BMJ 322:134–137.

121. Lauritzen CH, Reuter HD, Repges R et al. 1997. Treatment of premenstrual tension syndrome with Vitex agnus castus: Controlled, double-blind study versus pyridoxine. Phytomedicine 4:183–189.

122. Atmaca M, Kumru S, Tezcan E. 2003. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol 18:191–195.

123. Propping D, Bohnert KJ, Peeters M et al. 1991. Vitex agnus castus. The treatment of gynaecological syndromes.  Therapeutikon 5:581–585.

124. Loch EG, Selle H, Boblitz N. 2000. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med 9:315–320.

125. Berger D, Schaffner W, Schrader E et al. 2000. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with premenstrual syndrome (PMS). Arch Gynecol Obstet 264:150–153.

126. Linde K, Mulrow CD. 2000. St John’s wort for depression. Cochrane Database Sys Rev Abstracts 2:CD000448.