Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome

Ruediger Schellenberg, Christian Zimmermann, Jurgen Drewe

Abstract


Background. Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS.

Methods. In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18–45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30 mg) over three menstrual cycles. PMS symptoms’ severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness.

Results. Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20 mg group was significantly higher than in the placebo and 8 mg treatment group. The higher dose of 30 mg, on the other hand, did not significantly decrease symptom severity compared to the 20 mg treatment, providing a rational for the usage of 20 mg.

Corresponding results were observed with the single PMS symptom scores.

Conclusion. This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20 mg. Therefore, for patients suffering from PMS, 20 mg Ze 440 should be the preferred daily dose.


Keywords


Vitex agnus castus; chasteberry; premenstrual syndrome; dose-response; randomized controlled trial; Ze 440

References


Rapkin, A.J., Winer, S.A. “Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and burden of illness.” Expert Review of Pharmacoeconomics & Outcomes Research 9.2 (2009): 157–70.

Doll, M. “The premenstrual syndrome: effectiveness of Vitex agnus castus.” Medizinische Monatsschrift fur Pharmazeuten 32.5 (2009): 186–91.

Dickerson, L.M., Mazyck, P.P.J., Hunter, M.H. “Premenstrual syndrome.” American Family Physician 67.8 (2003): 1743–52.

Sliutz, G., Speiser, P., Schultz, A.M., et al. “Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.” Hormone and Metabolic Research 25.5 (1993): 253–5.

Mansel, R.E., Dogliotti, L. “European multicentre trial of bromocriptine in cyclical mastalgia.” Lancet 335.8683 (1990): 190–3.

Singh, B.B., Berman, B.M., Simpson, R.L., Annechild, A. “Incidence of premenstrual syndrome and remedy usage: a national probability sample study.” Alternative Therapies in Health and Medicine 4.3 (1998): 75–9.

Roeder, D. “Therapie von Zyklusstorungen mit Vitex agnus-castus.” Zeitschrift fur Phytotherapie 15 (1994): 157–63.

Wuttke, W., Splitt, G., Garkow, C., Sieder, C. “Behandlung zyklusabhangiger Brustschmerzen mit einem Agnus castus-haltigen Arznei mittel – Egebnisse einer randomisierten plazebokontrollierten Doppelblindstudie.” Geburtshilfe Frauenheilkd 57 (1997): 569–74.

Milewicz, A., Gejdel, E., Sworen, H., et al. “Vitex agnus castus – Extrakt zur Behandlung von Regeltempoanomalien infolge latenter Hyperprolaktinamie – Ergebnisse einer randomisierten Plazebo-kontrollierten Doppelblindstudie.” Arzneimittel-Forschung 43.7 (1993): 752–6.

Gerhard, I., Patek, A., Monga, B., et al. “Mastodynon® bei weiblicher Sterilitat. Randomisierte, plazebokontrollierte, klinische Doppelblindstudie.” Forsch Komplementarmed 5 (1998): 272–8.

Lauritzen, C., Reuter, H.D., Repges, R., et al. “Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, doubleblind study versus pyridoxine.” Phytomed 4.3 (1997): 183–9.

Atmaca, M., Kumru, S., Tezcan, E. “Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder.” Human Psychopharmacology 18.3 (2003): 191–5.

Daniele, C., Thompson Coon, J., Pittler, M.H., Ernst, E. “Vitex agnus castus : a systematic review of adverse events.” Drug Safety 28.4 (2005): 319–32.

Webster, D.E., Lu, J., Chen, S.N., et al. “Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS.” Journal of Ethnopharmacology 106.2 (2006): 216–21.

Jarry, H., Spengler, B., Porzel, A., et al. “Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones.” Planta Medica 69.10 (2003): 945–7.

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.” Experimental and Clinical Endocrinology 102.6 (1994): 448–54.

E/S/C/O/P Monographs. The Scientific Foundation for Herbal Medicinal Products, 2nd ed. European Scientific Cooperative on Phytotherapy & Georg Thieme Verlag. Exeter/Stuttgart/New York (2003).

Schellenberg, R. “Treatment for the premenstrual syndrome with Agnus castus fruit extract: prospective, randomised, placebo controlled study.” British Medical Journal 322.7279 (2001): 134–7.

Berger, D., Schaffner, W., Schrader, E. et al. “Efficacy of Vitex agnus castus L. extract Ze 440 in patients with premenstrual syndrome (PMS).” Archives of Gynecology and Obstetrics 264.3 (2000):150–3.

Landen, M., Nissbrandt, H., Allgulander, C., et al. “Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.” Neuropsychopharmacology 32.1 (2007): 153–61.

He, Z., Chen, R., Zhou, Y., et al. “Treatment for premenstrual syndrome with Vitex agnus castus: a prospective, randomized, multicenter placebo controlled study in China.” Maturitas 63.1 (2009): 99–103.

Halaska, M., Beles, P., Gorkow, C., Sieder, C. “Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebocontrolled double-blind study.” Breast 8.4 (1999): 175–81.

Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Vitex agnus-castus L., fructus, vol. EMA/HMPC/144006/2009. Committee on Herbal Medicinal Products (HMPC)/European Medicines Agency, 25 Nov 2010.

Huber, J.C., Bentz, E.K., Ott, J., Tempfer, C.B. “Non-contraceptive benefits of oral contraceptives.” Expert Opinion on Pharmacotherapy 9.13 (2008): 2317–25.

Lopez, L.M., Kaptein, A.A., Helmerhorst, F.M. “Oral contraceptives containing drospirenone for premenstrual syndrome.” Cochrane Database Systematic Reviews 2 (2009): CD006586.

Wuttke, W., Jarry, H., Christoffel, V., et al. “Chaste tree (Vitex agnus-castus) – pharmacology and clinical indications.” Phytomed 10.4 (2003): 348–57.


GOST Style Citations


1. Rapkin, A.J., Winer, S.A. “Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and burden of illness.” Expert Review of Pharmacoeconomics & Outcomes Research 9.2 (2009): 157–70.

2. Doll, M. “The premenstrual syndrome: effectiveness of Vitex agnus castus.” Medizinische Monatsschrift fur Pharmazeuten 32.5 (2009): 186–91.

3. Dickerson, L.M., Mazyck, P.P.J., Hunter, M.H. “Premenstrual syndrome.” American Family Physician 67.8 (2003): 1743–52.

4. Sliutz, G., Speiser, P., Schultz, A.M., et al. “Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.” Hormone and Metabolic Research 25.5 (1993): 253–5.

5. Mansel, R.E., Dogliotti, L. “European multicentre trial of bromocriptine in cyclical mastalgia.” Lancet 335.8683 (1990): 190–3.

6. Singh, B.B., Berman, B.M., Simpson, R.L., Annechild, A. “Incidence of premenstrual syndrome and remedy usage: a national probability sample study.” Alternative Therapies in Health and Medicine 4.3 (1998): 75–9.

7. Roeder, D. “Therapie von Zyklusstorungen mit Vitex agnus-castus.” Zeitschrift fur Phytotherapie 15 (1994): 157–63.

8. Wuttke, W., Splitt, G., Garkow, C., Sieder, C. “Behandlung zyklusabhangiger Brustschmerzen mit einem Agnus castus-haltigen Arznei mittel – Egebnisse einer randomisierten plazebokontrollierten Doppelblindstudie.” Geburtshilfe Frauenheilkd 57 (1997): 569–74.

9. Milewicz, A., Gejdel, E., Sworen, H., et al. “Vitex agnus castus – Extrakt zur Behandlung von Regeltempoanomalien infolge latenter Hyperprolaktinamie – Ergebnisse einer randomisierten Plazebo-kontrollierten Doppelblindstudie.” Arzneimittel-Forschung 43.7 (1993): 752–6.

10. Gerhard, I., Patek, A., Monga, B., et al. “Mastodynon® bei weiblicher Sterilitat. Randomisierte, plazebokontrollierte, klinische Doppelblindstudie.” Forsch Komplementarmed 5 (1998): 272–8.

11. Lauritzen, C., Reuter, H.D., Repges, R., et al. “Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, doubleblind study versus pyridoxine.” Phytomed 4.3 (1997): 183–9.

12. Atmaca, M., Kumru, S., Tezcan, E. “Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder.” Human Psychopharmacology 18.3 (2003): 191–5.

13. Daniele, C., Thompson Coon, J., Pittler, M.H., Ernst, E. “Vitex agnus castus : a systematic review of adverse events.” Drug Safety 28.4 (2005): 319–32.

14. Webster, D.E., Lu, J., Chen, S.N., et al. “Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS.” Journal of Ethnopharmacology 106.2 (2006): 216–21.

15. Jarry, H., Spengler, B., Porzel, A., et al. “Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones.” Planta Medica 69.10 (2003): 945–7.

16. 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.” Experimental and Clinical Endocrinology 102.6 (1994): 448–54.

17. E/S/C/O/P Monographs. The Scientific Foundation for Herbal Medicinal Products, 2nd ed. European Scientific Cooperative on Phytotherapy & Georg Thieme Verlag. Exeter/Stuttgart/New York (2003).

18. Schellenberg, R. “Treatment for the premenstrual syndrome with Agnus castus fruit extract: prospective, randomised, placebo controlled study.” British Medical Journal 322.7279 (2001): 134–7.

19. Berger, D., Schaffner, W., Schrader, E. et al. “Efficacy of Vitex agnus castus L. extract Ze 440 in patients with premenstrual syndrome (PMS).” Archives of Gynecology and Obstetrics 264.3 (2000):150–3.

20. Landen, M., Nissbrandt, H., Allgulander, C., et al. “Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.” Neuropsychopharmacology 32.1 (2007): 153–61.

21. He, Z., Chen, R., Zhou, Y., et al. “Treatment for premenstrual syndrome with Vitex agnus castus: a prospective, randomized, multicenter placebo controlled study in China.” Maturitas 63.1 (2009): 99–103.

22. Halaska, M., Beles, P., Gorkow, C., Sieder, C. “Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebocontrolled double-blind study.” Breast 8.4 (1999): 175–81.

23. Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Vitex agnus-castus L., fructus, vol. EMA/HMPC/144006/2009. Committee on Herbal Medicinal Products (HMPC)/European Medicines Agency, 25 Nov 2010.

24. Huber, J.C., Bentz, E.K., Ott, J., Tempfer, C.B. “Non-contraceptive benefits of oral contraceptives.” Expert Opinion on Pharmacotherapy 9.13 (2008): 2317–25.

25. Lopez, L.M., Kaptein, A.A., Helmerhorst, F.M. “Oral contraceptives containing drospirenone for premenstrual syndrome.” Cochrane Database Systematic Reviews 2 (2009): CD006586.

26. Wuttke, W., Jarry, H., Christoffel, V., et al. “Chaste tree (Vitex agnus-castus) – pharmacology and clinical indications.” Phytomed 10.4 (2003): 348–57.





DOI: http://dx.doi.org/10.18370/2309-4117.2016.30.111-118

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