Reviewed: 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 NZ J Obstet Gynaecol. 2010;50(2):189-193.

Premenstrual Syndrome (PMS) has been estimated to have a prevalence ranging from 30-87% in women of reproductive age. It can be described as a range of physical symptoms—such as abdominal cramps, breast fullness and tenderness, water retention, pelvic and back pain, chest pain, change in appetite—to emotional symptoms that include anxiety, depression, mood swings, irritability, fatigue, and tension.

The purpose of this prospective, randomized, double-blind, placebo-controlled trial was to investigate the degree of efficacy of chaste tree (Vitex agnus-castus, Verbenaceae) berry extract’s ability to relieve 17 different symptoms associated with PMS. Previous studies have shown that various chaste tree extract preparations are effective at reducing and eliminating PMS symptoms. Chaste tree extracts have also been shown to have a dopaminergic effect in animal and clinical trials.¹ The study was conducted at the Gynecological Endocrinology and Women’s Health Center of Peking Union Medical College Hospital in Beijing, China between February 2005 to January 2007.

This trial included 67 women with moderate to severe PMS, ages 21-44 years. Inclusion criteria included an increased score of at least 16 points on the Premenstrual Syndrome Diary (PMSD) in the luteal phase (7 days before menses) compared with the follicular phase (day 3 to day 9 of the menstrual cycle). The average PMSD score must have been at least 20 in the follicular phase and/or more than 15 points during days 6-19 of the cycle, which should be the symptom-free days. The PMSD was used as a self assessment tool prior to and during the trial to chart premenstrual symptoms according to severity, negative mood effects, water retention, appetite, pain, and insomnia (0=absent to 3=severe). A 36-item questionnaire called the Premenstrual Tension Syndrome Self-Rating Scale (PMTS) was also used as a self-assessment tool by the subjects at the first and second visits with a sum score of ≥18 as part of the inclusion criteria.

The chaste tree extract used for the study was BNO 1095 (Bionorica AG; Neumarkt, Germany), which contained 4.0 mg of a proprietary dry extract (70% ethanol) in tablet form, derived from 28 to 44 mg of dried chaste tree fruit. This extract is contained in Cyclopret^®, and the identical formulation is sold as Agnucaston^® or Cyclodynon^® in European and Asian countries. The subjects were given either 1 tablet of BNO 1095 (33 subjects) or 1 tablet of an identical-looking placebo (34 subjects) daily for 3 menstrual cycles.

Completed data were available for 64 of the subjects (3 subjects withdrew including 1 in the treatment group due to a prolonged menstrual period). Comparisons were made between scores from baseline and the third treatment cycle. The treatment group experienced reduction percentages in 17 symptoms from 80.1% to 92.46%. The improved symptoms ranged from pain to depression, headache, tension-irritability, and anxiety-nervousness. The reduction percentage lowered, but remained above 80%, for breast tenderness, fatigue, and abdominal bloating.

The placebo group had a percentage reduction of 48.95% to 73.7%, mostly in different symptoms from the treatment group (P=0.042). Abdominal cramping, change in appetite, pain, and lower-backache symptoms improved most with placebo. Symptoms including anxiety-nervousness, tension-irritability, crying, and depression were less improved than other symptoms in the chaste tree group.

Treatment differences were significantly better than placebo for 16 symptoms. Reduction percentages were highest in the luteal phase of the third menstrual cycle in the active group compared to placebo (P<0.05), with the exception of abdominal cramping (P=0.17). There was no significant difference in serum prolactin levels between the groups (P=0.942). There was also no significant difference in serum prolactin levels at the end of the third cycle compared to baseline between the 2 groups (P=0.952 vs. P=0.726).

Chaste tree extract tablets were found to reduce symptoms in almost all of the PMSD test categories more than placebo. In a previous study using BNO 1095 (Agnucaston), irritability, breast tenderness, swelling, food cravings, and cramps were reduced by at least 50%.²

These results are consistent with research on other chaste tree extracts which have shown benefit for PMS symptoms. In one trial 42% of the subjects in the chaste tree group (fruit extract ZE 440 [made by Zeller AG; Romanshorn, Switzerland]: 60% ethanol m/m, extract ratio 6-12:1; standardized for casticin; one 20 mg tablet once daily) had a complete absence of all PMS symptoms by the end of the trial, 51% had a decrease in their symptoms, and 1% experienced an increase in their symptoms.³ In a similar study using ZE 440, the authors found symptoms that were the most improved by the use of chaste tree were irritability, mood alteration, anger, headache, and breast fullness compared to the placebo.⁴

In conclusion, there is consistent evidence that the Bionorica chaste tree berry extract BNO 1095 exhibits improvement on PMS symptoms. The most improved symptoms in the trial were pain symptoms and emotional negative-effect symptoms. However, all symptoms were improved in the chaste tree group more than in the placebo group except abdominal cramping. Further research with a longer duration and a larger test population would benefit the evaluation of the BNO 1095 chaste tree extract for PMS.

—Erin Miner

References

1. Wuttke W, Gorkow C, Jarry H. Dopaminergic compounds in Vitex agnus castus. In: Loew D, Rietbrock N, eds
2. Phytopharmaka in Forschung und klinischer Anwendung. Darmstadt: Steinkopff, Verlag. 1995;81-91
3. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol. 2003;18(3):191-195.
4. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med. 2000;9(3):315-320.
5. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134-137.