The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers.

OBJECTIVES: In the present study, therapeutic effects of the Cimicifuga racemosa preparation CR BNO 1055 (Klimadynon/Menofem) on climacteric complaints, bone metabolism and endometrium will be compared with those of conjugated estrogens (CE) and placebo. The question whether CR BNO 1055 contains substances with selective estrogen receptor modulator (SERM) activity will be investigated. METHODS: Sixty-two evaluable postmenopausal women were included in the double-blind, randomized, multicentre study, and treated either with CR BNO 1055 (daily dose corresponding to 40 mg herbal drug), 0.6 mg CE, or matching placebo, for 3 months. Menopausal symptoms were assessed by the menopause rating scale (MRS) and a diary. Levels of CrossLaps (marker of bone degradation) were determined by ELECSYS system and bone-specific alkaline phosphatase (marker of bone formation) by an enzymatic assay. Endometrial thickness was measured via transvaginal ultrasound; vaginal cytology was also studied. The primary efficacy criterion was the change from baseline to end point in the MRS. Change from baseline was analyzed for the secondary variables too. RESULTS: CR BNO 1055 proved to be equipotent to CE and superior to placebo in reducing climacteric complaints. Under both verum preparations, beneficial effects on bone metabolism have been observed in the serum. CR BNO 1055 had no effect on endometrial thickness, which was significantly increased by CE. Vaginal superficial cells were increased under CE and CR BNO 1055 treatment. CONCLUSION: The results concerning climacteric complaints and on bone metabolism indicate an equipotent effect of CR BNO 1055 in comparison to 0.6 mg CE per day. It is proposed that CR BNO 1055 contains substances with SERM activity, i.e. with desired effects in the brain/hypothalamus, in the bone and in the vagina, but without exerting uterotrophic effects.

[Effectiveness of Vitex agnus-castus preparations]. / Zur Wirksamkeit von Vitex agnus castus-Präparaten.

The prolactin-inhibiting effect of ACF-preparations, which is due to dopaminergic activities, has been shown in humans too and gives a pharmacological rationale for the clinical effects observed in the different indications (2, 11, 25, 26, 35, 41). Confirmation of efficacy in the treatment of mastalgia has been best endorsed by two recently published double-blind studies conducted according to the principles of GCP (14, 41). One double-blind study, several open and postmarketing surveillance studies have shown that the premenstrual syndrome, or individual symptoms, can be influenced positively (3, 6, 7, 9, 19, 21, 37). Design shortcomings in a second double-blind study should be eliminated in future studies in this indication to improve the body of evidence (18). Hither to there has been one controlled double-blind study of cycle disorders in the case of corpus luteum insufficiency with significant results and a number of non-controlled open studies (1, 4, 15, 16, 20, 24, 26, 27, 32, 35, 36). The high success rates in the open studies indicate therapeutic effects, and it should be possible to reproduce these results under double-blind conditions. The success rates on fertility disorders should be confirmed in controlled double-blind studies (10, 33, 34).

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.

In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p=0.018; p=0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p=0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

Mastodynon(R) bei weiblicher Sterilität.

Mastodynon(R) for Female Infertility. Randomized, Placebo-Controlled, Clinical Double-Blind Study OBJECTIVE AND DESIGN: The effects of Mastodynon(R), an Agnus castus-containing preparation, were investigated in 96 women with fertility disorders in a prospective, randomized, placebo-controlled, double-blind study. PATIENTS AND METHODS: 38 women with secondary amenorrhoea, 31 women with luteal insuffciency and 27 women with idiopathic infertility received 30 drops of Mastodynon or placebo twice a day over a period of 3 months. OUTCOME MEASURE AND RESULTS: The outcome measure, which was pregnancy or spontaneous menstruation in women with amenorrhoea and pregnancy or improved concentrations of luteal hormones in both other groups, was achieved in 31 out of 66 women who were suitable for evaluation. It was achieved more often in the Mastodynon group compared to the placebo group (57.6% versus 36.0%, p = 0.069). 15 women conceived during the observation period (n = 7 with amenorrhoea, n = 4 with idiopathic infertility, n = 4 with luteal insufficiency). In women with amenorrhoea or luteal insufficiency, pregnancy occurred in the Mastodynon group more than twice as often as in the placebo group. Under therapy no hormonal changes were found at a 5% significance level. Only very few undesirable drug effects were observed. CONCLUSION: In women with sterility due to secondary amenorrhoea and luteal insufficiency, a treatment with Mastodynon can be recommended over a period of 3 to 6 months.

The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects.

The effects of three doses of a special Agnus castus extract (BP1095E1)--extracts from 120 mg, 240 mg and 480 mg of drug per day--were examined within the framework of a placebo-controlled clinical study of tolerance and prolactin secretion in 20 healthy male subjects during a period of 14 days. There was good tolerance during the study as regards the following: adverse effects, the effects on blood pressure and heart rate, blood count, Quick's test, clinical chemistry as well as testosterone, FSH and LH values. During each study phase the 24-hour prolactin secretion profile was measured from the penultimate to the final day, and the amount of prolactin release was monitored an hour after TRH stimulation on the last day. A significant increase in the 24-hour profile was registered with the lowest dose in comparison to placebo, the opposite being the case with the higher doses, i.e. a slight reduction. In contrast to the administration of placebo, the 1-hour AUC after TRH stimulation resulted in a significant increase with the lowest dose and a significant reduction with the highest dose. The results suggest effects of the special Agnus castus extract which are dependent on the dose administered and the initial level of prolactin concentration.

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.

Women suffering from premenstrual mastodynia often respond to stimuli of prolactin (Prl) release with a hypersecretion of this hormone. Pharmacological reduction of Prl release by dopamine agonists or treatment with extracts of Agnus castus (AC) improve the clinical situation of patients with such premenstrual symptoms. Extracts of AC contain compounds which inhibit in vivo Prl release in women as well as in vitro from dispersed rat pituitary cells. It is yet unknown whether this inhibitory action of AC is only exerted on Prl release or whether release of other pituitary hormones like LH and FSH is also affected. The effects of AC on LH and FSH release were examined in vitro using rat pituitary cell cultures. To rule out that the Prl-inhibiting properties of AC are at least in part due to a cytotoxic component, pituitary cell cultures were subjected to the MTT test. To assess whether the Prl inhibitory effect of AC preparations is due to compounds acting as dopamine (DA) agonists, we used the corpus striatum membrane DA receptor binding assay. Our results demonstrate for the first time that AC extract contains an active principle that binds to the D2 receptor. Thus, it is very likely that it is this dopaminergic principle which inhibits Prl release in vitro from rat pituitary cells. Furthermore we give evidence for the specificity of action of AC on hormone release, since gonadotropin secretion remained unaffected. The findings of the present study support the therapeutical usefulness of AC extracts for treatment of premenstrual mastodynia which is associated with hypersecretion of Prl. Furthermore, the beneficial effects of AC appear to be due to the inhibition of pituitary Prl release.

Reaginic and homocytotropic IgG antibodies in Schistosoma mansoni infected Mastomys natalensis: time courses in untreated infections and after chemoprophylactic and chemotherapeutic treatment.

Mastomys natalensis were infected percutaneously with 250 cercariae of Schistosoma mansoni and treated effectively with 5 X 50 mg amoscanate/kg body-weight 12-16 (I), 28-32 (II), 56-60 (III) and 101-105 days p.i. (IV) respectively. Levels of reaginic antibodies (RAb) and homocytotropic IgG antibodies (GAb) were assessed by passive cutaneous anaphylaxis tests (PCA) and compared with those in infected, untreated animals. In untreated animals RAb were first detected in the 6th week p.i. Maximum titres around 1:80 were reached after 100 days. High levels persisted until the end of the experiment 185 days p.i. RAb did not develop after treatment I. After treatment II only low PCA titres occurred. After treatment III the time course was similar to the controls but levels were reduced. Treatment IV did not interfere with the occurrence of specific RAb. In the case of GAb, independent of any treatment, after a first peak of PCA titres in the 5th week either a negative pattern or only very low titres were found in week 7. In untreated infected Mastomys GAb levels increased thereafter to maximum titres of about 1:80 at day 70. Later than 100 days p.i. relatively constant titres were observed. The second rise of antibody levels did not occur after early treatment. After treatment II only low transient titres developed. Animals treated in the early patency (III) showed reduced PCA titres and were negative at the end of the observation period. Treatment given 101 to 105 days p.i. rather enhanced the development of GAb.