Black Cohosh Does Not Exert an Estrogenic Effect on the Breast

Abstract

Women's Health Initiative findings indicate that hormone replacement therapy may increase breast cancer and cardiovascular disease risk. Black cohosh extract (BCE) is a popular alternative that reduced menopausal symptoms in several clinical trials. Preclinical studies have addressed the estrogenic properties of BCE, with conflicting results. The estrogenic influence of BCE on the breast has not been investigated. Black cohosh is standardized to triterpenes, but the activity and mechanism of action of these compounds are unknown. The study goals were to determine 1) triterpene content of 2 commercially available BCE preparations and 2) the effect of BCE on circulating and breast-specific estrogenic markers. Two black cohosh preparations were analyzed for triterpene content. Postmenopausal women took BCE for 12 wk followed by a 12-wk washout. One BCE preparation contained trace amounts and another contained 2.5% triterpenes. Women taking BCE with 2.5% triterpenes experienced relief of menopausal symptoms, with reversion toward baseline after washout. BCE had no effect on estrogenic markers in serum and no effect on pS2 or cellular morphology in nipple aspirate fluid. Triterpene content in commercially available black cohosh preparations varies. BCE standardized to 2.5% triterpenes relieved menopausal symptoms without systemic or breast-specific estrogenic effects.

Acknowledgments and Notes

National Institutes of Health grant AT01102 provided funds for the study and ensured that the side effects were acceptable to the Data Safety Monitoring Board. R.L. Ruhlen was supported by National Institutes of Health NRSA F32AT002420-01. The study was designed and coordinated by E. R. Sauter, sample collection by J. Haubner, HPLC analysis by J. K. Tracy and G. E. Rottinghaus, biomarker analysis by W. Zhu and R. L. Ruhlen, cytological analyses by H. Ehya, data analyses by W. R. Lamberson and R. L. Ruhlen, and the manuscript was drafted by R. L. Ruhlen and E. R. Sauter. All authors had no conflict of interest. We would like to thank Karen Bromert for technical assistance and the women who participated in this study.

Notes

a: Abbreviations are as follows: NAF, nipple aspirate fluid, BCE, black cohosh extract; E2, estradiol; LH, luteinizing hormone; FSH, follicle stimulating hormone. E2 (pg/ml), LH (mIU/ml), FSH (mIU/ml), and pS2 (pg/ml) were not affected by BCE treatment. Mean ± SEM (n). E2 was analyzed with age as a cofactor, and FSH was analyzed with body mass index as a cofactor. Sample size for E2, LH, and FSH varied due to limited volume of sample. pS2 enzyme-linked immunoabsorbent assay kit was discontinued by manufacturer, so further samples could not be analyzed.

a: Abbreviations are as follows: NAF, nipple aspirate fluid, BCE, black cohosh extract. Hyperplasia without atypia or atypical hyperplasia out of total number of samples at each time point. Right and left breast NAF were analyzed separately. All subjects provided NAF from at least 1 breast at baseline. BCE did not affect the number of subjects with hyperplasia. Few subjects had atypia at any time.

a: Abbreviations are as follows: BCE, black cohosh extract; WVSS, Wiklund Vasomotor Symptom Subscale; KMI, Kupperman Menopausal Index; MRS, Menopause Rating Scale. Summary of clinical trials of BCE since 1985. If not directly reported, magnitude of efficacy (% reduction in symptoms) was estimated from the data shown, if possible.

b: Study included breast cancer patients taking tamoxifen, which increases menopausal symptoms.

c: Sample size of largest BCE-treated group within study.