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Planta Med 2013; 79(07): 562-575
DOI: 10.1055/s-0032-1327831
Women's Health
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Vitex agnus-castus Extracts for Female Reproductive Disorders: A Systematic Review of Clinical Trials

M. Diana van Die
1   Royal Melbourne Institute of Technology-University, Bundoora, Victoria, Australia
,
Henry G. Burger
2   Prince Henryʼs Institute of Medical Research, Clayton, Victoria, Australia
,
Helena J. Teede
3   Monash University, Clayton; Southern Health, Dandenong, Victoria, Australia
,
Kerry M. Bone
4   University of New England, Armidale, New South Wales; MediHerb/Integria, Warwick, Queensland, Australia
› Author Affiliations
Further Information

Publication History

received 10 August 2012
revised 09 September 2012

accepted 17 September 2012

Publication Date:
07 November 2012 (online)

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Abstract

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating womenʼs health.

Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.

Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.

Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials.

Key words

Vitex agnus-castus - Verbenaceae - premenstrual - mastalgia - hyperprolactinaemia - systematic review
 

  • References

  • 1 Upchurch DM, Chyu L, Greendale GA, Utts J, Bair YA, Zhang G, Gold EB. Complementary and alternative medicine use among American women: findings from The National Health Interview Survey, 2002. J Womenʼs Health (Larchmt) 2007; 16: 102-113
    PubMedGoogle Scholar
  • 2 Upchurch DM, Dye CE, Chyu L, Gold EB, Greendale GA. Demographic, behavioral, and health correlates of complementary and alternative medicine and prayer use among midlife women: 2002. J Womenʼs Health (Larchmt) 2010; 19: 23-30
    PubMedGoogle Scholar
  • 3 Domoney CL, Vashisht A, Studd JW. Use of complementary therapies by women attending a specialist premenstrual syndrome clinic. Gynecol Endocrinol 2003; 17: 13-18
    PubMedGoogle Scholar
  • 4 Christie S, Walker AF. 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 1997; 3: 29-45
    PubMedGoogle Scholar
  • 5 [no authors listed] Agnus castus also effective in fertility disorders. Exeter: The 5th Annual Symposium on Complementary Health Care; 1999
    Google Scholar
  • 6 Van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause 2009; 16: 156-163
    CrossrefPubMedGoogle Scholar
  • 7 Singh BB, Berman BM, Simpson RL, Annechild A. Incidence of premenstrual syndrome and remedy usage: a national probability sample study. Altern Ther Health Med 1998; 4: 75-79
    PubMedGoogle Scholar
  • 8 Winer SA, Rapkin AJ. Premenstrual disorders: prevalence, etiology and impact. J Reprod Med 2006; 51: 339-347
    PubMedGoogle Scholar
  • 9 Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology 2003; 28 (Suppl. 03) 1-23
    PubMedGoogle Scholar
  • 10 Frackiewicz EJ, Shiovitz TM. Evaluation and management of premenstrual syndrome and premenstrual dysphoric disorder. J Am Pharm Assoc (Wash) 2001; 41: 437-447
    PubMedGoogle Scholar
  • 11 Ader DN, South-Paul J, Adera T, Deuster PA. Cyclical mastalgia: prevalence and associated health and behavioral factors. J Psychosom Obstet Gynaecol 2001; 22: 71-76
    CrossrefPubMedGoogle Scholar
  • 12 Halbreich U, Ben-David M, Assael M, Bornstein R. Serum-prolactin in women with premenstrual syndrome. Lancet 1976; 2: 654-656
    PubMedGoogle Scholar
  • 13 Muhlenstedt D, Bohnet HG, Hanker JP, Schneider HP. Short luteal phase and prolactin. Int J Fertil 1978; 23: 213-218
    PubMedGoogle Scholar
  • 14 Dietrich M, Hinney B, Link M, Kuhn W, Wuttke W. Latent hyperprolactinaemia as a cause of mastodynia and luteal function impairment. Kyoto, Japan: 5th International Congress Prolactin; 1988
    Google Scholar
  • 15 Wuttke W, Gorkow C, Jarry H. Dopaminergic compounds in Vitex agnus-castus . In: Leow D, Rietbrock N, editors Phytopharmaka in Forschung und klinischer Anwendung. Darmstadt: Steinkopff Verlag; 1995: 81-91
    CrossrefGoogle Scholar
  • 16 Yen S. The human menstrual cycle: neuroendocrine regulation. In: Yen S, Jaffe RB, Barbieri RL, editors Reproductive endocrinology. Physiology, pathophysiology and clinical management. Philadelphia: WB Saunders Company; 1999: 191-217
    Google Scholar
  • 17 Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlova-Wuttke D. Chaste tree (Vitex agnus-castus)-pharmacology and clinical indications. Phytomedicine 2003; 10: 348-357
    Google Scholar
  • 18 Wuttke W. The use of chasteberry (Vitex agnus castus) extract in gynecology. Gynäkol Endokrinol 2008; 6: 82-86
    PubMedGoogle Scholar
  • 19 Noack M. Our experiences with Agnus castus oligoplex for increasing milk yield. Dtsch Med Wochenschr 1943; 9: 204-206
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Bautze HJ. Investigations on the influence of Agnus castus on the breastfeeding performance. Medwelt 1953; 4: 189-190
    PubMedGoogle Scholar
  • 21 Ciotta L, Pagano I, Stracquadanio M, Di Leo S, Ando A, Formuso C. Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus . Minerva Ginecol 2011; 63: 237-245
    PubMedGoogle Scholar
  • 22 Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ 2001; 322: 134-137
    CrossrefPubMedGoogle Scholar
  • 23 Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Med Iran 2012; 50: 101-106
    PubMedGoogle Scholar
  • 24 Turner S, Mills SY. A double-blind clinical trial on a herbal remedy for premenstrual syndrome: a case study. Complement Ther Med 1993; 1: 73-77
    CrossrefPubMedGoogle Scholar
  • 25 Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (version 5.0.1). The Cochrane Collaboration; 2008. Available at http://www.cochrane-handbook.org Accessed May 13, 2012
    CrossrefGoogle Scholar
  • 26 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17: 1-12
    CrossrefPubMedGoogle Scholar
  • 27 Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med 2006; 144: 364-367
    CrossrefPubMedGoogle Scholar
  • 28 Ma L, Lin S, Chen R, Wang X. Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Gynaecol Endocrinol 2010; 26: 612-616
    CrossrefPubMedGoogle Scholar
  • 29 Ma L, Lin S, Chen R, Zhang Y, Chen F, Wang X. Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Aust N Z J Obstet Gynaecol 2010; 50: 189-193
    CrossrefPubMedGoogle Scholar
  • 30 [no authors listed] Agnus castus . UK: Gerard House Promotional Brochure; 1988
    Google Scholar
  • 31 He Z, Chen R, Zhou Y, Geng L, Zhang Z, Chen S, Yao Y, Lu J, Lin S. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas 2009; 63: 99-103
    CrossrefPubMedGoogle Scholar
  • 32 Kilicdag EB, Tarim E, Bagis T, Erkanli S, Aslan E, Ozsahin K, Kuscu E. Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and mastalgia. Int J Gynaecol Obstet 2004; 85: 292-293
    CrossrefPubMedGoogle Scholar
  • 33 Lauritzen C, Reuter HD, Repges R, Bohnert KJ, Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus – Controlled, double-blind study versus pyridoxine. Phytomedicine 1997; 4: 183-189
    CrossrefPubMedGoogle Scholar
  • 34 Pakgohar M, Moradi M, Jamshidi AH, Mehran A. Assessment of Vitex agnus-castus L. extract effect on treatment of premenstrual syndrome. J Med Plants 2009; 8: 98-107 , 185
    PubMedGoogle Scholar
  • 35 Di Pierro F, Prazzoli R, Candidi C, Attolico M. Premenstrual syndrome: Controlled clinical trial with a fast acting form of a highly standardized extract of Vitex agnus castus . Giorn It Ost Ginecol 2009; 31: 153-157
    PubMedGoogle Scholar
  • 36 Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol 2003; 18: 191-195
    CrossrefPubMedGoogle Scholar
  • 37 Milewicz A, Gejdel E, Sworen H, Sienkiewicz K, Jedrzejak J, Teucher T, Schmitz H. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimittelforschung 1993; 43: 752-756
    PubMedGoogle Scholar
  • 38 Dante G, Facchinetti F. Herbal treatments for alleviating premenstrual symptoms: a systematic review. J Psychosom Obstet Gynaecol 2011; 32: 42-51
    CrossrefPubMedGoogle Scholar
  • 39 Carmichael AR. Can Vitex agnus castus be used for the treatment of mastalgia? What is the current evidence?. Evid Based Complement Alternat Med 2008; 5: 247-250
    CrossrefPubMedGoogle Scholar
  • 40 Daniele C, Thompson Coon J, Pittler MH, Ernst E. Vitex agnus castus: a systematic review of adverse events. Drug Saf 2005; 28: 319-332
    Google Scholar
  • 41 Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994; 102: 448-454
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Mertz PG, Gorkow C, Schrodter A, Rietbrock S, Sieder C, Loew D, Dericks-Tan JS, Taubert HD. The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects. Exp Clin Endocrinol Diabetes 1996; 104: 447-453
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Dericks-Tan JSE, Schwinn P, Hildt C. Dose-dependent stimulation of melatonin secretion after administration of Agnus castus . Exp Clin Endocrinol Diabetes 2003; 111: 44-46
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Van Die M, Burger H, Teede H, Bone K. Vitex agnus-castus (Chaste-tree/berry) in the Treatment of Menopause-related Complaints. J Altern Complement Med 2009; 15: 853-862
    CrossrefPubMedGoogle Scholar
  • 45 Diaz BL, Llaneza PC. Endocrine regulation of the course of menopause by oral melatonin: first case report. Menopause 2008; 15: 388-392
    CrossrefPubMedGoogle Scholar
  • 46 Jarry H, Spengler B, Porzel A, Schmidt J, Wuttke W, Christoffel V. Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Planta Med 2003; 69: 945-947
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol 2009; 16: 407-429
    PubMedGoogle Scholar
  • 48 Bryant M, Cassidy A, Hill C, Powell J, Talbot D, Dye L. Effect of consumption of soy isoflavones on behavioural, somatic and affective symptoms in women with premenstrual syndrome. Br J Nutr 2005; 93: 731-739
    CrossrefPubMedGoogle Scholar
  • 49 Cos P, De Bruyne T, Apers S, Vanden Berghe D, Pieters L, Vlietinck AJ. Phytoestrogens: recent developments. Planta Med 2003; 69: 589-599
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr 2000; 19: 3-12
    CrossrefPubMedGoogle Scholar
  • 51 Hagen I, Nesheim BI, Tuntland T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet Gynecol Scand 1985; 64: 667-670
    CrossrefPubMedGoogle Scholar
  • 52 Doll H, Brown S, Thurston A, Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract 1989; 39: 364-368
    PubMedGoogle Scholar
  • 53 Wyatt KM, Dimmock PW, Jones PW, Shaughn OʼBrien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ 1999; 318: 1375-1381
    CrossrefPubMedGoogle Scholar
  • 54 Gumm R, Cunnick GH, Mokbel K. Evidence for the management of mastalgia. Curr Med Res Opin 2004; 20: 681-684
    CrossrefPubMedGoogle Scholar
  • 55 Mansel RE, Dogliotti L. European multicentre trial of bromocriptine in cyclical mastalgia. Lancet 1990; 335: 190-193
    CrossrefPubMedGoogle Scholar
  • 56 Van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med 2009; 15: 1045-1048
    CrossrefPubMedGoogle Scholar
  • 57 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd. edition, revised (DSM-III-R). Washington DC: APA; 1987: 715-718
    Google Scholar