Elsevier

Maturitas

Volume 51, Issue 4, 16 August 2005, Pages 397-404
Maturitas

Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial

https://doi.org/10.1016/j.maturitas.2004.10.003Get rights and content

Abstract

Objectives:

To compare the efficacy and safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints.

Methods:

A multicenter, randomized, placebo-controlled, double-blind, parallel group study was conducted in 122 menopausal women (intention-to-treat population) with ≥3 hot flashes a day, treated over 12 weeks. Two main efficacy measures – weekly weighted score of hot flashes and Kupperman Index – and secondary efficacy variables, e.g. Menopause Rating Scale, were defined. Routine safety laboratory parameters and adverse events were documented.

Results:

The primary efficacy analysis showed no superiority of the tested black cohosh extract compared to placebo. However, in the subgroup of patients with a Kupperman Index  20 a significant superiority regarding this index could be demonstrated (P < 0.018). A decrease of 47% and 21% was observed in the black cohosh and placebo group, respectively. The weekly weighted scores of hot flashes (P < 0.052) and the Menopause Rating Scale (P < 0.009) showed similar results. Prevalence and intensity of the adverse events did not differ in the two treatment groups.

Conclusions:

The results indicate a superiority of the tested Cimicifuga racemosa extract compared to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index  20, but not in the intention-to-treat population as a whole.

Introduction

Due to the changing hormonal situation the menopausal transition period is associated with vasomotor, psychic and somatic disorders, particularly hot flashes, sweating, depressed mood, sleeping disorders and urogenital complaints. The symptoms are widespread with prevalences between 60% and 80% whereas duration and severity show a broad range.

In the last decades hormone replacement therapy (HRT) was a widely used and accepted medication for these climacteric disturbances. Numerous clinical studies have demonstrated efficacy and during short-term use safety. However, recent observational and randomized controlled trials suggest higher risks for long-term HRT use, particularly for combined estrogen-progestogen therapy started in the later postmenopause [1], [2], [3], [4], [5]. Newer findings show a growing evidence that HRT may increase the incidence of breast cancer, coronary heart disease and stroke in elderly women – whether the administration of unopposed estrogen increases breast cancer risk is doubtful. Thus, a significant number of women and physicians look for other treatment approaches [6], [7]. Progressive interest in phytotherapy for relief of climacteric symptoms is seen during the past years and black cohosh root extracts (Cimicifugae racemosae rhizoma) are considered as an important treatment alternative [8], [9], [10].

Preclinical in vitro and in vivo tests suggest that these plant extracts exert tissue specific estrogenic effects [11], [12], [13], [14], [15]. They may show agonistic actions regarding central nervous system and bone, whereas regarding uterus and breast such actions are unlikely. Additionally, dopaminergic effects – mediated via D2 or D3 receptors – as well as serotonergic and progestogenic effects are proposed [16], [17], [18], [19]. The data agree well with the observed improvement of vasomotor and psychic menopausal symptoms in several clinical studies [20], [21], [22], [23]. Most of these, however, were poorly designed and do not fulfill actual GCP guidelines.

Thus, the aim of the study was to compare efficacy and safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints following strict methodology.

Section snippets

Study design

The trial was conducted as a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel group study in Switzerland according to GCP guidelines of the European Union, the International Conference on Harmonization and the Declaration of Helsinki. It was approved by the ethic committees of Aargau, Basel, Bern und Zürich.

The patients were randomized in the ratio of 2:1, i.e. the number of patients in the active group was double the size of the placebo group.

The trial was

Study population

The study populations are shown in Table 1. Out of 127 treated patients, five patients were excluded from the intention-to-treat population because of serious protocol violations or a posteriori detected exclusion criteria. Fifteen patients discontinued the study prematurely. Table 2 lists demographic and diagnostic characteristics of the enrolled patients at study entry.

Efficacy results – primary efficacy analysis

In the primary efficacy analysis no superiority of the tested black cohosh extract compared to placebo could be demonstrated

Discussion

In the primary efficacy analysis no significant difference between the tested black cohosh extract and placebo could be demonstrated. The results, however, indicate a superiority of the active medication compared to placebo with respect to symptoms of menopausal disorders in patients with a Kupperman Index  20.

The Cimicifuga racemosa extract was significantly superior to placebo regarding the Kupperman Index and the Menopause Rating Scale in spite of the small number of patients of 35 and 18,

Acknowledgements

Dr. Kolkmann and Partner Oldenburg Germany supplied the study medication and funded the trial. The contribution of the investigators—Dr. Suzanne Aebi Basel, Dr. Christine Bodmer University Hospital Bern, Dr. Susanne Brüning Bern, Prof. Dr. Christian De Geyter University Hospital Basel, Dr. Sabine Dettwiler Riehen, Dr. Wolfgang Gattlen Basel, Dr. Susanne Kann und Dr. Gabrielle Neuhaus Basel, Dr. Karin Köhler Küsnacht, Dr. Christoph König Bern, Dr. Jürg Kuster Ammerswil, Dr. Beatrice Maerki Bern,

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