Presentaton of in depth review of literature on efficacy and safety of Black Cohosh as alternative to hormones for menopause symptom therapy

1. A Review of the Benefits and Risks
of Black Cohosh
(Cimicifuga racemosa syn Actaea racemosa)
in the Treatment of Vasomotor Irregularities
Resulting from Menopause
by Noelani Fox
for Issues in Nutrition and Health
at The University of Texas at Austin
November 22, 2011

2. Introduction
• Menopause and Hot Flashes
• Associated Risks
• Evaluation Scales
• Traditional and Alternative Treatments
• Black Cohosh
Methods
• Literature Search
• Inclusion / Exclusion
• Outcome Measures
Results
• Efficacy
• Safety

3. Discussion
• Effectiveness and Safety
• Concurrence and Disagreement
• Conflict
• Strengths / Weaknesses
• Conclusion
References

4. Introduction

5. ◦ 12 months of Menopause:
amenorrhea a fact of life
◦ Many, varied symptoms
Hot flashes
◦ 2/3 of women between Night sweats
Profuse sweating
40 and 60 Headaches
Depression
Irritability
Sleep disorders
◦ 80% severe Vaginal dryness
Heart discomfort
Anxiety
Sexual dysfunction
◦ Vasomotor symptoms are Bladder problems
the most common Joint pain
Muscular discomfort

6. ◦ 12 months of Menopause:
amenorrhea a fact of life
◦ Many, varied symptoms
Hot flashes
◦ 2/3 of women between Night sweats
Profuse sweating
40 and 60 Headaches
Depression
Irritability
Sleep disorders
◦ 80% severe Vaginal dryness
Heart discomfort
Anxiety
Sexual dysfunction
◦ Vasomotor symptoms are Bladder problems
the most common Joint pain
Muscular discomfort

7. Risks
Associated ◦ Greater aortic calcification
with Hot ◦ Coronary artery calcification
Flashes
◦ Higher cholesterol levels
 Longer history
◦ Higher blood pressure
of hot flashes
correlated
with: ◦ Increased BMI
◦ Reduced dilation of right
brachial artery

8. Risks
Associated ◦ Greater aortic calcification
with Hot ◦ Coronary artery calcification
Flashes
◦ Higher cholesterol levels
 Longer history
◦ Higher blood pressure
of hot flashes
correlated
with: ◦ Increased BMI
◦ Reduced dilation of right
brachial artery

9.  Kupperman Index
◦ Developed 1953
◦ Eleven symptoms
 Scale of 0 (none) to
3 (severe)
• Menopause Rating Scale
• Developed 1990’s
• Eleven symptoms
• Three subscales
• Scale of 0 (none) to
4 (severe)
Evaluation Scales

10. Symptoms Factor Severity Numerical conversion
(factor × severity)
Vasomotor
Paraesthesia
Insomnia
Nervousness
Melancholia
Vertigo
Weakness (fatigue)
Arthralgia and myalgia
Headaches
Palpitations
Formication
Menopausal index (sum)
0 (none)=0, S (slight)=1, M (moderate)=2, and + (severe)=3
Kupperman Index

11. Symptoms
Somatic 1 Hot flushes, night sweats (episodes of sweating)
2 Heart discomfort (unusual awareness of heart beat, heart skipping,
heart racing, tightness)
3 Sleep problems (difficulty in falling asleep, difficulty in sleeping
through, waking up early)
4 Depressive mood (feeling down, sad, on the verge of tears, lack of
Psychological
drive, mood swings)
5 Irritability (feeling nervous, inner tension, feeling aggressive)
6 Anxiety (inner restlessness, feeling panicky)
7 Physical and mental exhaustion (general decrease in performance,
impaired memory, decrease in concentration, forgetfulness)
8 Sexual problems (change in sexual desire, in sexual activity and
satisfaction)
Urogenital
9 Bladder problems ((difficulty in urinating, increased need to urinate,
bladder incontinence)
10 Dryness of vagina (sensation of dryness or burning in the vagina,
difficulty with sexual intercourse)
11 Joint and muscular discomfort (pain in the joints, rheumatoid
Som
complaints)
Menopause Rating Scale

12. ◦ Hormone Replacement Therapy
• Estrogen and progestin
◦ Women’s Health Initiative
• 16,608 women
• Terminated 3 years early
◦ Breast cancer
◦ Stroke
◦ Pulmonary embolism
Traditional Therapy (HRT)

13. Alternatives to Hormone
Replacement
 Over 80 trials reviewed
 20 alternative treatments
Botanical Extracts
Multibotanicals
Pharmaceuticals

14. History
 Used in US for over 100 years
◦ Coughs and colds
◦ Constipation
◦ Fatigue
◦ Rheumatism
 Menstrual maladies since 1950’s
Black Cohosh

15. Mechanism of Action
 Estrogen-receptor mediation unlikely
 Thermogenesis regulated by serotonergic receptors
◦ Nω-methylserotonin
 Binds to receptors
 Induces cAMP activity
 Prevents serotonin reuptake
Black Cohosh

16. Safety
 Hepatic perfusion and liver function
◦ No change in blood flow
◦ No negative change in liver enzymes
 Lipid and glucose profiles
◦ No effect on glucose or insulin
◦ No effect on lipids or fibrinogen
Black Cohosh

17. Methods

18. Menopause • 47,873
Hot flash • 1,659
Black cohosh • 104
English
language • 99
Currency
(post 2005) • 70
Literature Search

19. Inclusion Exclusion
Original study Reviews
Monopreparation of Black Meta-analyses
Cohosh
Hot flashes as primary or Related to breast cancer
secondary outcome measure survivors
Assessment of safety or risk Published previous to 2005
factors
Criteria for Consideration

20.  Efficacy  Safety
◦ Self assessment ◦ Adverse events
 Kupperman Index
◦ Liver function
 Menopause Rating
Scale ◦ Lipid profiles
 Frequency of hot
◦ Endometrial changes
flashes
 Severity of hot flashes
Outcome Measures

21. Results

22. 1 2 3
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Results
Efficacy Measures

23. Fluoxetine Tibolone
30 30
25.1 25.2 24.7 24.7
25 25
20 18.5 20
15 13 15 11.2 11.2
10 10 7.7 7.5
Baseline Baseline
5 5 4 weeks
0 12 Weeks
0
12 weeks
Kupperman Index

24. Fluoxetine Tibolone
30 30
25.1 25.2 24.7 24.7
25 25
20 18.5 20
15 13 15 11.2 11.2
10 10 7.7 7.5
Baseline Baseline
5 5 4 weeks
0 12 Weeks
0
12 weeks
Kupperman Index

25. Placebo Combination Therapy
Monotherapy Combination
 Difference in Therapy
treatment in favor Base- Mo 3 Mo 6 Base- Mo 3 Mo 6
of Black Cohosh line line
0.52 0.33 0.25 0.56 0.34 0.25
(p=0.027)
Flashes
± ± ± ± ± ±
Hot
0.21 0.19 0.16 0.21 0.19 0.16
◦ Covariates
0.31 0.21 0.16 0.42 0.26 0.19
eliminated (p=0.02)
Total MRS Psyche
± ± ± ± ± ±
0.22 0.18 0.14 0.23 0.18 0.15
◦ Confounders 0.30 0.20 0.16 0.36 0.24 0.18
considered (p<0.001) ± ± ± ± ± ±
Score
0.17 0.14 0.11 0.17 0.14 0.12
Menopause Rating Scale

26. Placebo Combination Therapy
Monotherapy Combination
 Difference in Therapy
treatment in favor Base- Mo 3 Mo 6 Base- Mo 3 Mo 6
line line
of Black Cohosh
0.52 0.33 0.25 0.56 0.34 0.25
(p=0.027)
Flashes
± ± ± ± ± ±
0.21 0.19 0.16 0.21 0.19 0.16
Hot
◦ Covariates 0.31 0.21 0.16 0.42 0.26 0.19
eliminated (p=0.02)
Total MRS Psyche
± ± ± ± ± ±
0.22 0.18 0.14 0.23 0.18 0.15
◦ Confounders 0.30 0.20 0.16 0.36 0.24 0.18
considered (p<0.001) ± ± ± ± ± ±
Score
0.17 0.14 0.11 0.17 0.14 0.12
Menopause Rating Scale

27. Placebo Combination Therapy
Monotherapy Combination
 Difference in Therapy
treatment in favor Base- Mo 3 Mo 6 Base- Mo 3 Mo 6
line line
of Black Cohosh
0.52 0.33 0.25 0.56 0.34 0.25
(p=0.027)
Flashes
± ± ± ± ± ±
0.21 0.19 0.16 0.21 0.19 0.16
Hot
◦ Covariates 0.31 0.21 0.16 0.42 0.26 0.19
eliminated (p=0.02)
Total MRS Psyche
± ± ± ± ± ±
0.22 0.18 0.14 0.23 0.18 0.15
◦ Confounders 0.30 0.20 0.16 0.36 0.24 0.18
considered (p<0.001) ± ± ± ± ± ±
Score
0.17 0.14 0.11 0.17 0.14 0.12
Menopause Rating Scale

28. Low-dose estradiol Placebo
14 18
12 16
10 14
8
TTSE2 12
6
10 Placebo
4
Black 8
2
0 Cohosh 6 Black
4 Cohosh
2
0
Symptom Diary

29. Low-dose estradiol Placebo
14 18
12 16
10 14
8 12
6 TTSE2
10 Placebo
4
Black 8
2
0 Cohosh 6 Black
4 Cohosh
2
0
Symptom Diary

30. Results
Safety

31.  Gastrointestinal distress
 Allergic skin reactions
 Infections
 Sleep disturbances
 Gynecological
 Headaches
Adverse Events

32. 60 150
40 100
20 50 Total
Total
0 0
Adverse Adverse
Events Events
6800
5100 200
Total 150
3400
100
Total
1700 Adverse 50
Events
0 Adverse
0
Events
Black
Cohosh
Adverse Events

33.  Liver function
◦ AST, ALT
◦ γ-glutamyl transpeptidase
◦ GOT, GPT
 Heart rate, blood pressure, weight
 Total cholesterol
◦ HDL, LDL
Laboratory Measures

34.  No change in estradiol study
 Clinically irrelevant change in tibolone
study
◦ Both peri- and postmenopausal women on
tibolone
◦ Only perimenopausal women on black cohosh
Endometrial Change

35. Discussion

36.  Five of six studies found reductive effect
◦ Equivalent to HRT
◦ More effective than SSRI, placebo
◦ Effective as monopreparation or combination
 Good tolerability and safety
◦ Low rate of adverse events
 Less common than HRT, comparable to placebo
 None serious
◦ No adverse effect on liver, cardiovascular
function
Overview of Efficacy and Safety

37.  Cumulative findings consistent with literature
 One of six studies found no significant
benefit to Black Cohosh vs placebo
◦ Only study with crossover design
◦ Shortest treatment period
◦ Enhanced placebo effect?
Concurrence and Disagreement

38.  Hans-Heinrich Henneicke-von Zepelin
◦ Co-author of three studies
 Ute Stammwitz
◦ Co-author of one study
 Schaper and Brümmer, Salzgitter, Germany
◦ Manufacturer of Remifemin®
Conflict of Interest

39.  Strengths  Weaknesses
◦ Current studies ◦ Reliance on self
◦ Peer reviewed reporting of symptoms
◦ Reputable journals ◦ Short term treatment
◦ Monopreparation as ◦ All studies not same
one treatment formulation
◦ Range of locations/ ◦ Limited to six studies
populations ◦ English language only
(US, China, Turkey, Ger ◦ PubMed only
many and Italy) database searched
Strengths and Weaknesses

40.  Effective alternative
◦ Reduce health risk
 Long history of hot flashes
 Hormone replacement therapy
◦ Maintain higher quality of life
Conclusion

41.  Safe for short term use
◦ Additional trials needed
 Recommend Black Cohosh as valid
alternative for management of vasomotor
irregularities in menopausal women
Conclusion

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and fluoxetine in the treatment of postmenopausal symptoms: A
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Review Articles

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E. Powell SL, Godecke T, Nikolic D, Chen SN, Ahn S, Dietz B, Farnsworth NR, van Breemen RB, Lankin DC, Pauli GF, Bolton JL, In
vitro serotonergic activity of black cohosh and identification of Nω-methylserotonin as a potential active constituent, J
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G. Gast GCM, Grobbee DE, Pop VJM, Keyzer JJ, Wijnands-van Gent CJM, Samsioe GN, Nilsson PM, van der Schouw
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H. Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA, Hot flashes and subclinical cardiovascular
disease, Circulation, 2008; 118: 1234-1240
I. Mahady GB, Fabricant D, Chadwick LR, Dietz B, Black cohosh: An alternative therapy for menopause? Nutr Clin Care, 2002;
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J. Cheema D, Coomarasamy A, El-Toukhy T, Non-hormonal therapy of post-menopausal vasomotor symptoms, Arch Gynecol
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K. Rotem C, Kaplan B, Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep, Gynecol
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45. Questions?