The standardized black cohosh extract in Remifemin is:

• Backed by nearly 50 years of clinical studies.
• Proven to be effective, safe, and well tolerated.^†
• Rated number one in recommended non-prescription menopausal therapies by obstetricians and gynecologists.
• Clinically proven to reduce hot flashes, night sweats, related occasional sleeplessness, irritability, and mood swings associated with menopause.^†

Hot flashes (also referred to as hot flushes) are a sudden sensation of heat often accompanied by facial flushing and sweating that generally lasts a few seconds to a few minutes. When hot flashes occur during sleep they are referred to as night sweats. Their presence often leads to occasional sleeplessness, irritability, and mood swings. Some women experience few symptoms, while others experience various symptoms ranging from mild to fairly severe. This variation is normal and expected. ^1-3

Until July of 2002, hormone replacement therapy (HRT) was the most common treatment to relieve the discomforts of menopause.⁴ Since that time, repeated findings from clinical research have concluded that, for most women, the harmful effects of estrogen and progestin are likely to exceed the benefits. ^4-7 Health organizations world wide are strongly encouraging women with a personal or family history of heart disease, blood clots, and breast cancer not use HRT for menopausal symptom relief.^5-8

Research to date suggests that black cohosh has no estrogenic activity. ^9-11 No significant adverse effects have reported in clinical trials. It has been determined safe for use by women who have had breast cancer who cannot take estrogen.

Several European studies indicate that black cohosh, specifically Remifemin, may be as effective as hormone replacement therapy (HRT) in reducing hot flashes, night sweats, related occasional sleeplessness, irritability, and mood swings associated with menopause.^{† 16-22} As Remifemin does not exert an estrogenic effect on breast tissue, it is suggested that it can be safely used by women with a history of breast cancer who cannot take estrogen.^{† 9,12,13}

Clinical Research Findings
There have been numerous clinical and scientific studies of Remifemin. The most recent (Osmers, et al; 2005), a randomized, multicenter, double-blind clinical trial, compared the efficacy and tolerability of Remifemin in the treatment of menopausal symptoms compared with placebo.²³ A total of 304 women were randomly allocated to receive 40mg of Remifemin or matching placebo daily for 12 weeks. The results showed that women in the Remifemin group experienced a significant decrease in hot flashes.^† No significant adverse effects were reported.^{† 23}

The following charts summarize findings in clinical studies of Remifemin:

Author, year	Subjects	Dose	Study Duration	Study Population	Primary Measures	Study Conclusions
Double-Blind Studies Using Remifemin
Osmers R. Obstet Gynecol 2005;105:1074-83.	304	40mg daily	12 weeks	Women greater than or equal to 45 with menopausal symptoms	MRS units, proliferation of vaginal epithelium	Statistically significant improvement in all scales especially in early menopause.†23
Liske, E. J Womens Health Gend Based Med. 2002:11:163-74	152	40mg daily	6 months	Women aged 42 to 60 with menopausal symptoms	Kupperman Index, SRDS	Statistically significant improvement in all scales.†24
Stoll, Therapeutikon 1987;1:23-31.	80	40mg daily	12 weeks	Women aged 46 to 58 with climacteric complaints	Kupperman index, HAM A scale vaginal epithelium proliferation	Statistically significant improvement in all scales.†19

Author, year	Subjects	Dose	Study Duration	Study Population	Primary Measures	Study Conclusions
Open Studies Using Remifemin
Pockaj BA, Cancer Invest. 2004;22:515-21.	21	40mg daily	4 weeks	Women aged 38 to 80 with report of hot flash greater than or eual to 14 per week	Self report of hot flash reduction	Statistically significant improvement in daily and weekly hot flash scores†25
Lehmann-Willebrock, Zent bl Gynaekol 1988; 110:611-8.	60	40mg daily	24 weeks	Hysterectomized women, under 40 with at least one ovary	Kupperman Index	All groups showed statistically significant improvement in Kupperman index; no statistical difference between groups†26
Petho, Aerztl Prax 1987;38:1551-3.	50	40mg daily	6 months	Women previously treated with hormones for menopausal symptoms	Kupperman Index	Statistically significant improvement in Kupperman Index, decrease in number of hormone injections, and decrease in subjective complaints.†18
Warnecke, Med Welt 1985;36:871-4.	19	40 drops twice daily	12 weeks	Women aged 45 to 60, with irregular or no bleeding and menopausal symptoms	Kupperman index, CGI scale, HAM-A scale, SDS	All groups showed statistically significant improvement in scales; no statistical difference between groups.†21
Vorberg, ZFA 1984;60(13):626-9	50	40 drops twice daily	12 weeks	Women having contraindications to hormone therapy or reject it	Kupperman index, POMS scale, CGI scale	Kupperman index, POMS scale, CGI scale 22
Daiber, Aerztl Prax 1983;35(65):1946-7.	36	40 drops twice daily	12 weeks	Women having contraindications to hormone therapy or reject it	Kupperman index, CGI scale	Significant improvement in all scales decrease in the most frequent symptoms of menopause†27
Stolze, Gyne 1982;3(1):14-6.	629	40 drops twice daily	8 weeks	Women with menopausal symptoms	Physician evaluation	80% showed improvement†20

Summary

Remifemin, a unique extract of black cohosh (Cimicifuga racemosa), is the most studied form of black cohosh, with more than 20 clinical trials and open scientific monitoring trials in physicians' practices. No significant drug interactions have been reported in over 50 years of worldwide use; adverse events have been limited to mild, temporary stomach upset. Remifemin is the number one obstetrician and gynecologist recommended over-the-counter menopausal therapy.

2. Mehring PM. Menopause. In: Porth CM. Pathophysiology: Concepts of Altered Health States. 6th ed. Philadelphia, Pa: Lippincott; 2002: 991-993.

3. The North American Menopause Society (NAMS). Basic facts about menopause. Available at: http://www.menopause.org/edumaterials/guidebook/guidebook.htm. Accessed on May 12, 2005.

4. The Woman's Health Initiative Study Group. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.

5. Kirkby R, Al Saif A. Screening, supplements and the use of hormonal replacement therapy in postmenopausal women in a family medicine department prior to the publication of the Woman's Health Initiative report.Ann Saudi Med. 2004;24:175-8.

6. Pitkin J, Rees MC, Gray S, et al. British Menopause Society Council. Managing the menopause: BMS Council Consensus statement on HRT. J Br Menopause Soc. 2004;10:33-6.

7. Lea R, Bannister E, Case A, Levesque P, et al. Society of Obstetricians and Gynaecologists of Canada. Use of hormonal replacement therapy after treatment of breast cancer. J Obstet Gynaecol Can. 2004;23:49-60.

8. Vogel RA. The changing view of hormone replacement therapy. Rev Cardiovasc Med. 2003;4:68-71.

9. Borrelli F, Izzo AA, Ernst E. Pharmacological effects of Cimicifuga racemosa. Life Sci. 2003;73:1215-29.

10. Foster S. Black cohosh (Cimicifuga racemosa) [literature review]. Herbalgram. 1999;45:35-49.

11. Huntley A, Ernst E. A systematic review of the safety of black cohosh. Menopause. 2003;10:58-64.

12. Low Dog TL, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. 2003;10:299-313.

13. Lupu R, Mehmi I, Atlas E, et al. Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth. Int J Oncol. 2003;23:1407-12.

14. Mahady GB. Is black cohosh estrogenic? Nutr Rev. 2003;61:183-6.

15. Duker E, Kopanski L, Jarry H, Wuttle W. Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Medicia. 1991;57:420-424.

16. Einer-Jensen N, Zhao J, Anderson K, Kristoffersen K. Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats. Maturitas. 1996;25:149-153.

17. Lehmann-Willenbrock E, Reidel H. (Clinical and endocrinological examinations concerning therapy of climacteric symptoms following hysterectomy with remaining ovaries). Zent Bl Gynakol. 1988;110:611-618.

18. Petho A. Menopausal complaints: change-over of a hormone treatment to a herbal gynecological remedy practicable? Arztliche Praxis. 1987;38, 47:1551-1553.

19. Stoll W. Phytopharmacon influences atrophic vaginal epithelium: double-blind study: Cimicifuga vs estrogenic substances. Therapeutikon. 1987;1:1-14.

20. Stolze H. An alternative to treat menopausal complaints. Gyne. 1982;1:14-16.

21. Vorberg G. Treatment of menopausal complaints. Z. Allgemeinmed. 1984;13:626-629.

22. Warnecke G. Influencing menopausal symptoms with a phytotherapeutic agent: successful therapy with Cimifuga mono-extract. Medwelt. 1985;36:871-874.

23. Osmers R, Friede M, Liske E, et al. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol. 2005;105:1074-83.

24. Liske E, Hanggi W, Henneicke-von Zepelin HH, et al.Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med. 2002;11:163-74.

25. Pockaj BA, Loprinzi CL, Sloan JA, et al. Pilot evaluation of black cohosh for the treatment of hot flashes in women. Cancer Invest. 2004;22(4):515-21.

26. Lehmann-Willenbrock E, Riedel HH. Clinical and endocrinological examinations concerning therapy of climacteric symptoms following hysterectomy with remaining ovaries. Zent. Bl. Gynäkol. 1988;110:611-18.

27. Daiber W. Climacteric complaints: success without using hormones: a phytotherapeutic agent lessens hot flushes, sweating, and insomnia. Arztliche Praxis. 1983;65:1946-47.