A Pilot Study to Examine a Combination Botanical for the Treatment of Menopausal Symptoms

1. A Pilot Study to Examine a Combination Botanical for the Treatment of Menopausal Symptoms Debi Smolinski, N.D., Debra Wollner, Ph.D., Jennifer Orlowski N.D., Jessica Curico N.D., Jennifer Nevels N.D., and Linda S Kim, N.D. By Anne Swinson

2. Background • Menopause- cessation of menses > 1 year • Changes in levels of progesterone and estrogen • 40 million postmenopausal women in the US • Average age of menopause is 51 years • Early menopause can be triggered • Smoking • Hysterectomy • Oophorectomy

3. Symptoms • Can have unbearable symptoms • Hot flashes • Mood changes • Depression • Cognitive changes • Decreased libido • Vaginal dryness • Urinary Tract infections • Decreased energy • Sleep disturbances • Weight gain • Osteoporosis

4. Staying Healthy • Don't smoke- it’s never too late to quit • Eat a healthy diet, low in fat, high in fiber, with plenty of fruits, vegetables, and whole-grain foods, as well as all the important vitamins and minerals • Make sure you get enough calcium and vitamin D—in your diet or with vitamin/mineral supplements • Learn what your healthy weight is, and try to stay there. • Do weight-bearing exercise, such as walking, jogging, or dancing, at least 3 days each week for healthy bones. • Take medicine as it’s prescribed • Use a water-based lubricant for vaginal discomforts • Get regular check-ups- Pap tests, breast exams, and mammograms

5. Current Therapy • Hormone Replacement Therapy • Estrogen and progesterone • Birth control pills • Still has risks and side effects • Stroke • Cardiovascular disease • Heart Disease • Breast Cancer • Complementary and Alternative Care (CAM) • Natural estrogenic activity

6. Purpose • “The purpose of this pilot study was to evaluate a combination of botanical formulation comprised of whole herbs for efficacy in reducing the severity of symptoms associated with menopause.” • Previously used botanicals studied individually • Combination could be more effective

8. Subjects • 8 women with menopausal symptoms • Recruitment through newspaper advertisement • Written consent was obtained • Inclusion Criteria • Age 40- 65 years • Natural menopause • Moderate severity of hot flashes • Avoidance of other treatments • Ability to take daily doses of botanicals for 3 months • Gynecological check-up prior to enrollment

9. Exclusion Criteria • Exclusion Criteria • Menopause due to chemical or surgical procedures • Abnormal blood/urine chemistry • Hepatic, blood, or renal disorders • Chronic constipation • Major disease • Heart, cancer, renal, or psychiatric disorders • Concurrent prescription or OTC drug use • CAM therapies for menopause treatment • Allergies or sensitivities

10. Treatment • One single treatment group • No placebo group • Blend of 15 whole herbs in 550 mg capsules taken twice daily between meals • Provided a total of 2200 mg/day

11. Outcome Measurement • Health history questionnaire and symptom instrument • Routine complete blood chemistry and urine analysis • Weekly telephone calls in the 1st month • Biweekly calls in the 2nd and 3rd months • Kupperman Index (KI) • Completed at baseline, 1, 2, and 3 months • Daily hot flash recording- VAS scale

12. Kupperman Index • Rating Scale • O = no symptoms • 1 = slight • 2 = moderate • 3 = severe • Hot flashes • Weight change • Insomnia • Irritability • Depression • Low sex drive • Fatigue • Muscle or joint pain • Headache • Heart palpitation • Vaginal dryness • Forgetfulness

13. SF-36 Health Survey • Assessed at baseline and 3 months • Responses were categorized in 8 domains • Physical functioning • Role physical • Bodily pain • General health • Vitality • Social functioning • Role emotional • Mental health

14. Statistics • Analyzed using • Mean • Standard deviation • Paired t-test • Wilcoxon signed rank test • Two-tailed test • Confidence interval of 95% • α of 0.05 • Improvement of 40% in daily hot flashes

15. Results • Mean age of 54 + 6 years • 8 enrolled, 7 completed the trial • No blood abnormalities • KI scores decrease was significant- 24.4% • Baseline: 30.3 + 7.5 • 3rd month: 22.9 + 8.4 • Hot flashes decrease was significant- 41.9% • Baseline: 68.1 + 14.3 • 3rd month: 39.6 + 9.7 • Mean changes in 4 domains indicate improved health • Physical function, role physical, general health, role emotional

16. Conclusion • All indicators proved significant improvement indicating reduced menopause-related symptoms • KI: 30.3 to 22.9 24.4% • Hot Flashes: 68.1 to 39.6 41.9% • More data is needed for efficacy, safety, toxicity, and long-term consequences

17. Limitations • Small sample size • No placebo group • Combination of botanicals- which one worked? • Lack of measurement tool/scale • Exclusion criteria • Any other Limitations?

18. Suggestions for the future… • Use a more objective scale • Track hormone changes • Larger study group • Have a placebo group • Any others?

19. Questions • Victoria: • “The greatest limitation that I immediately thought of while reading the method is the measurement of hot flash severity, forgetfulness, and irritability…. Even irritability is relative to the person reporting. It may also be difficult for subjects to define their severity of forgetfulness. In trying to think of a different way to measure this however, nothing really comes to mind. Is there another possible method that could have been used?”

20. Sarah • “My suggestion for future studies on the effects of supplementation for menopause symptoms would be to measure the women's follicle-stimulating hormone(FSH), estrogen (estrodial), and thyroid-stimulating hormone (TSH) before, during, and after the treatment. I am aware that there are fluctuations to these hormones during menopause, however, I am only assuming that these suggested markers could also, accurately represent severity. Do you know if this is true?”

21. Karen • “The researchers failed to provide any background information on this specific formulation except that they had been used before in treating hormone irregularities. Did you investigate whether more recent research/studies were available?”

22. Kirstie • “If further studies could look into the idea of this study and produce similar results, combination botanical's could replace costly and potentially harmful hormone treatment therapies in treating menopausal symptoms.”

23. Any other comments?

24. References: • Smolinski, Debi; Wollner, Debra; Orlowski, Jennifer; Curcio Jessica; Nevels, Jennifer; Kim, Linda. “A pilot study to examine a combination botanical for the treatment of menopausal symptoms.” Journal of Alternative and Complementary Medicine. Vol 11, No 3. June 2005. • http://www.nia.nih.gov/health/publication/menopause. Accessed online March 17, 2013. • Low Dog, Tieraona. Menopause: A review of botanical dietary supplements. The American Journal of Medicine (2005) Vol 118 (12B), 98S–108S. • Doyle, Brian, JonnaFrasor, Lauren Bellows, Tracie Locklear, Alice Perez, Jorge Gomez-Laurito, GaiMahady. Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms. Menopause. Issue 16, Volume 4. p 748-755. August 2009.