First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055

Objective: To investigate endometrial safety by assessment of endometrial biopsy samples and the tolerability and efficacy of the special Actaea or Cimicifuga racemosa extract (CR BNO 1055). Design: Four hundred postmenopausal women with symptoms related to estrogen deficiency were enrolled into a prospective, open-label, multinational, multicenter study. Treatment duration (daily dose corresponds to 40 mg of herbal drug) was 52 weeks. To determine the probability of endometrial hyperplasia and more serious adverse endometrial outcome, the point estimator and upper limit of 95% CI were calculated. Descriptive statistics was used to assess the secondary endpoints. Results: Endometrial safety has been proven because no case of hyperplasia or more serious adverse endometrial outcome occurred (point estimate: 0.0; upper limit of 95% CI: 0.011). Endometrial thickness, which was measured by endovaginal ultrasonography, did not show an increase. The number and intensity of hot flushes were markedly decreased. The dropout rate was less than 10%. The overall tolerability was good. Conclusions: The lack of endometrial proliferation and improvement of climacteric complaints as well as only few gynecologic organ-related adverse events are reported for the first time after a treatment period of 1 year. Due to the improved benefit:risk ratio, it must be assumed that the Cimicifuga racemosa special extract BNO 1055 is a safe alternative for treatment of climacteric complaints.

[1]  E. Liske,et al.  Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms , 2005, Obstetrics and gynecology.

[2]  R. Freedman.  Pathophysiology and treatment of menopausal hot flashes. , 2005, Seminars in reproductive medicine.

[3]  L. Mozley,et al.  Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women. , 2004, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[4]  V. Unfer,et al.  Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. , 2004, Fertility and sterility.

[5]  B. Alving.  NIH asks participants in Women's Health Initiative estrogen-alone study to stop study pills, begin follow-up phase. , 2004, Southern medical journal.

[6]  T. Rollason.  Blaustein’s Pathology of the Female Genital Tract , 2003, Springer New York.

[7]  J. Pezzuto,et al.  Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. , 2003, Journal of agricultural and food chemistry.

[8]  H. Jarry,et al.  Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus. , 2003, Maturitas.

[9]  D. Seidlová-Wuttke,et al.  The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. , 2003, Maturitas.

[10]  B. Spengler,et al.  In vitro effects of the Cimicifuga racemosa extract BNO 1055. , 2003, Maturitas.

[11]  H. Jarry,et al.  Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy? , 2003, Maturitas.

[12]  T. Shanafelt,et al.  Pathophysiology and treatment of hot flashes. , 2002, Mayo Clinic proceedings.

[13]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[14]  B. V. VON Schoultz,et al.  Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. , 2002, American journal of obstetrics and gynecology.

[15]  E. Liske,et al.  Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. , 2002, Journal of women's health & gender-based medicine.

[16]  G. Bachmann.  Vasomotor flushes in menopausal women. , 1999, American journal of obstetrics and gynecology.

[17]  E. Vittinghoff,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[18]  E. Liske,et al.  P-l. Therapy of Climacteric Complaints with Cimicifuga racemosa: Herbal Medicine with Clinically Proven Evidence , 1998 .

[19]  G. Harnischfeger,et al.  Flavones in Extracts of Cimicifuga racemosa , 1997, Planta medica.

[20]  N. Einer-jensen,et al.  Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats. , 1996, Maturitas.

[21]  G A Colditz,et al.  The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. , 1995, The New England journal of medicine.

[22]  A. Miller,et al.  Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. , 1995, Journal of the National Cancer Institute.

[23]  F. Kronenberg.  Hot flashes: Phenomenology, quality of life, and search for treatment options , 1994, Experimental Gerontology.

[24]  M. Michell,et al.  The mammographic parenchymal patterns of women on hormonal replacement therapy. , 1991, Clinical radiology.

[25]  H. Jarry,et al.  [The endocrine effects of constituents of Cimicifuga racemosa. 2. In vitro binding of constituents to estrogen receptors]. , 1985, Planta medica.

[26]  H. Jarry,et al.  Studies on the endocrine effects of the contents of Cimicifuga racemosa 2. In vitro binding of compounds to estrogen receptors. , 1985, Planta medica.

[27]  K. Lu,et al.  LH, FSH and skin temperaure during the menopausal hot flash. , 1979, The Journal of clinical endocrinology and metabolism.

[28]  J. Wolfe.  Risk for breast cancer development determined by mammographic parenchymal pattern , 1976, Cancer.

[29]  Vladimír Soška.  Poruchy metabolizmu lipidů : diagnostika a léčba. , 2001 .

[30]  U. Albert,et al.  Einfluß der Hormone Replacement Therapy (HRT) auf die bildgebende Diagnostik , 2001 .

[31]  P. Potthoff,et al.  [The Menopause Rating Scale (MRS II): methodological standardization in the German population]. , 2000, Zentralblatt fur Gynakologie.

[32]  E. Cornier.  The Pipelle: a disposable device for endometrial biopsy. , 1984, American journal of obstetrics and gynecology.