Vitex agnus-castus extract (Ze 440) improves symptoms in women with menstrual cycle irregularities


  • R. Eltbogen Department of Gynecology and Obstetrics, Bürgerspital, Solothurn, Switzerland
  • M. Litschgi Consultant for Gynecology and Obstetrics Schaffhausen, Switzerland
  • U. E. Gasser ClinResearch Ltd. Aesch, Switzerland
  • A. Flueeli Zeller Medical AG Romanshorn, Switzerland
  • S. Nebel Zeller Medical AG Romanshorn, Switzerland
  • C. Zahner Zeller Medical AG Romanshorn, Switzerland



Menstrual Cycle Irregularities (MCIs), menstrual cycle disorders, Chaste tree, Vitex agnus-castus (VAC), Ze 440, polymenorrhea, oligomenorrhea, amenorrhea, observational study


Principle: This noninterventional, observational study (NIS) had been conducted by Swiss gynaecologists and general practitioners in primary medical routine care.

The objective of this NIS was to evaluate the efficacy and safety of Vitex agnus-castus (VAC) extract (Ze 440: premens, Zeller Medical AG, Romanshorn, Switzerland) in women suffering from menstrual cycle irregularities, such as polymenorrhea, oligomenorrhea, or amenorrhea.

Methods: A total of 211 patients were included in this NIS and symptoms associated with menstrual cycle irregularities (MCIs) and menstrual bleeding were assessed at baseline visit (BV) and at a follow-up visit (FV) after treatment with VAC extract during 3 subsequent menstrual cycles. The median age of patients was 35.3 ± 8.8 years.

Results: The proportion of patients with remission or improvement of MCIs (all in all) and specific symptoms such as polymenorrhea, oligomenorrhea, and amenorrhea was 79–85% at the FV. The proportion of patients with remission or improvement of symptoms related to menstrual bleeding such as dysmenorrhea, intermenstrual bleeding, hypermenorrhea, menometrorrhagia, ovulation bleeding, premenstrual or postmenstrual bleeding was 60–88% at FV. Out of 53 patients who reported an unfulfilled desire to have children at BV, 12 women (23%) got pregnant during treatment with VAC extract. At the FV, 91% of the physicians and 92% of the patients were “satisfied” or “very satisfied” with the achieved treatment outcomes, and 80% of the patients confirmed their preference to continue treatment with VAC extract.

Conclusion: This observational study in routine medical care showed that treatment with VAC extract (Ze 440) clearly ameliorated MCIs, polymenorrhea, oligomenorrhea, and amenorrhea and was well tolerated. The majority of patients decided to continue treatment with VAC extract.

Author Biography

R. Eltbogen, Department of Gynecology and Obstetrics, Bürgerspital, Solothurn

President of the Swiss Medical Society for Phytotherapy, MD


  1. Van Hooff, M.H., Voorhorst, F.J., Kaptein, M.B., et al. “Endocrine features of polycystic ovary syndrome in a random population sample of 14–16 year old adolescents.” Hum Reprod 14 (1999): 2223–9.
  2. Ginsburg, K.A., Dinsay, R. “Premenstrual syndrome.” In: Practical Strategies in Obstetrics and Gynecology. Ed. by S.B. Ransom. WB Saunders. Philadelphia, Pa (2000): 684–94.
  3. Mishell, D.R. “Premenstrual disorders: epidemiology and disease burden.” Am J Manag Care 11 (2005): 473–9.
  4. Rapkin, A.J., Winer, S.A. “Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and burden of illness.” Expert Rev Pharmacoecon Outcomes Res 9 (2009): 157–70.
  5. Tschudin, S., Coda Bertea, P., Zemp, E. “Prevalence and predictors of premenstrual syndrome and premenstrual dysphoric disorder in a population-based sample.” Arch Womens Ment Health 13 (2010): 485–94.
  6. Meier, B., Berger, D., Hoberg, E., et al. “Pharmacological activities of Vitex agnus castus extract in vitro.” Phytomedicine 7 (2000): 373–81.
  7. Mansfield, M.J., Emans, S.J. “Adolescent menstrual irregularity.” J Reprod Med 29 (1984): 399–410.
  8. Dickerson, L.M., Mazyck, P.J., Hunter, M.H. “Premenstrual syndrome. Am Fam Physician 67 (2003): 1743–52.
  9. Sliutz, G., Speiser, P., Schultz, A.M., et al. “Agnus castus extract inhibit prolactin secretion of rat pituitary cells.” Horm Metab Res 25 (1993): 253–5.
  10. Jarry, H., Leonhardt, S., Gorkow, C., et al. “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 102 (1994): 448–54.
  11. Wuttke, W., Jarry, H., Christoffel, V., et al. “Chaste tree (Vitex agnus castus) – pharmacology and clinical indications.” Phytomedicine 10 (2003): 348–57.
  12. Singh, B.B., Berman, B.M., Simpson, R.L., et al. “Incidence of premenstrual syndrome and remedy usage: a national probability sample study.” Altern Ther Health Med 4 (1998): 75–9.
  13. Mergner, R. “Zyklusstörungen: Therapie mit einem Vitex-agnus-castushaltigen Kombinationsarzneimittel.” Der Kassenarzt 7 (1992): 51–60.
  14. Roemheld-Hamm, B. “Chasteberry.” Am Fam Physician 72 (2005): 821–4.
  15. European Scientific Cooperative on Phytotherapy (ESCOP). Agni Casti Fructus (Agnus Castus). ESCOP Monographs. 2nd ed. Thieme. New York (2003): 8–13.
  16. Halaska, M., Beles, P., Gorkow, C., et al. “Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.” Breast 8 (1999): 175–81.
  17. Kayser, H.W., Istanbullouglu, S. “Eine Behandlung von Menstruationsstörungen ohne Hormone.” Hippokrates 25 (1954): 717–8.
  18. Fikentscher, H. “Ätiologie, Diagnose und Therapie der Mastopathie und Mastodynie. Erfahrungen bei der Behandlung mit Mastodynie.” Med Klein 72 (1977): 1327–30.
  19. Loch, E.G., Bohnert, K.J., Peeters, M., et al. “Die Behandlung von Blutungsstörungen mit Vitex agnuscastus- Tinktur.” Frauenarzt 32 (1991): 867–70.
  20. Dittmar, F.W., Bohnert, K.J., Peeters, M., et al. “Prämenstruelles Syndrom: Behandlung mit einem Phytopharmakon.” TW Gynäkologie 5 (1992): 60–8.
  21. Berger, D., Schaffner, W., Schrader, E., et al. “Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS).” Arch Gynecol Obstet 264 (2000): 150–3.
  22. Feldmann, H.U., Albrecht, M., Lamertz, M., et al. “Therapie bei Gelbkörperschwache bzw. prämenstruellem Syndrom mit Vitex agnus castus Tinktur.” Gyne 11 (1990): 421–5.
  23. Propping, D., Bohnert, K.J., Peeters, M., et al. “Vitex agnus-castus. Behandlung gynäkologischer Krankheitsbilder.” Therapeutikon 5 (1991): 581–5.
  24. Milewicz, A., Gejdel, E., Sworen, H., et al. “Vitex agnus castus Extrakt zur Behandlung von Regeltempoanomalien infolge latenter Hyperprolactinaemie. Ergebnisse einer randomisierten, Placebokontrollierten Doppelblindstudie.” Arzneimittelforschung 43 (1993): 752–6.
  25. Wuttke, W., Splitt, G., Gorkow, C., et al. “Behandlung zyklusabhängiger Brustschmerzen mit einem Agnus-castus haltigen Arzneimittel.” Geburtshilfe Frauenheilkd 57 (1997): 569–74.
  26. Schellenberg, R. “Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.” BMJ 322 (2001): 134–7.
  27. Gerhard, I., Patek, A., Monga, B., et al. “Mastodynon® bei weiblicher Sterilität.” Forsch Komplementärmed 5 (1998): 272–8.
  28. Westphal, L.M., Polan, M.L., Trant, A.S., et al. “A nutritional supplement for improving fertility in women: a pilot study.” J Reprod Med 49 (2004): 289–93.
  29. Daniele, C., Thompson Coon, J., Pittler, M.H., et al. “Vitex agnus castus: a systematic review of adverse events.” Drug Saf 28 (2005): 319–32.
  30. Peters-Welte, C., Albrecht, M. “Regeltempostörungen und PMS. Vitex agnus-castus in einer Anwendungsbeobachtung.” TW Gynäkologie 7 (1994): 49–52.
  31. Chaste tree fruit (Vitex agnus-castus). Standards of analysis, quality control and therapeutics. American Herbal Pharmacopoeia. Santa Cruz (CA) (2001).
  32. Blumenthal, M. “Monographie zu Agni casti fructus.” Bundesanzeiger 226 (1992).
  33. Schellenberg, R., Zimmermann, C., Drewe, J., et al. “Dosedependent effi cacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome.” Phytomedicine 19 (2012): 1325–31.
  34. Committee on Herbal Medicinal Products (HMPC). Community herbal monograph on Vitex agnus-castus L., fructus. European Medicines Agency ( 2010).
  35. Johnson, S.R. “Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners.” Obstet Gynecol 104 (2004): 845–59.
  36. Atmaca, M., Kumru, S., Tezcan, E. “Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder.” Hum Psychopharmacol 18 (2003): 191–5.
  37. Falch, B.S., Bitzer, J., Polasek, W. “Die Behandlung des prä- menstruellen Syndroms (PMS).” Phytotherapie 3 (2003): 1–8.
  38. Ludwig, M. “Vitex agnus castus: Klinische Anwendung.” Gynäkologische Endokrinologie 7 (2009): 33–8.



How to Cite

Eltbogen, R., Litschgi, M., Gasser, U. E., Flueeli, A., Nebel, S., & Zahner, C. (2016). Vitex agnus-castus extract (Ze 440) improves symptoms in women with menstrual cycle irregularities. REPRODUCTIVE ENDOCRINOLOGY, (28), 86–91.



Reproductive endocrinology

Most read articles by the same author(s)