1. Menopause and Complementary and Alternative Therapies (CAM) Katie Jackson and Soraya Valencia Benedictine University October, 2014

2. Definition of Menopause Definition of Menopause “Menopause is the cessation of menstruation that results from loss of ovarian follicular activity or depletion” 1 Eden KJ, Wylie KR, 2009

3. Menopause Onset Menopause Onset Occurs 12 months after the last period. 2 Can happen between the ages 40-55. 3 Premature menopause before age 40. 3 Mean average age in United States is 51. 2 Smokers often begin earlier than non- smokers. 3 Mayo Clinic and WebMD

5. Epidemiology Epidemiology Women’s Health Initiative (WHI) ◦ 60% of women aged 50-54 have hot flashes ◦ 23% reported moderate to severe hot flashes ◦ The prevalence decreases with age 4 The study of Women’s Health Across the Nation (SWAN) ◦ Hot flashes differ by ethnicity, lifestyle factors, and socioeconomic status. 5 ◦ Higher body mass index associated with physiological and vasomotor symptoms. 4 Moilanen et al, 2010

6. Epidemiology Epidemiology Failure to produce estrogen begins in the late 30s. 6 70 million women is affected by estrogen 6 deficiency in the U.S.A age > 50 years. 85% of menopausal women are affected by discomfort. 6 Goodman et al, 2011

7. Signs and Symptoms Signs and Symptoms Hot flashes and night sweats Vaginal dryness Changes in mood Sleep problems Weight gain and slow metabolism Thinning hair and dry skin Loss of breast fullness 2 Most women with menopause symptoms may experience cessation 5 years after onset. 6 Mayo Clinic and Goodman et al., 2011

8. Etiology Etiology Natural decline of the reproductive 2 hormones estrogen and progesterone. 2 Hysterectomy that removes the uterus, not the ovaries. 2 Chemotherapy and radiation therapy. 2 Ovarian insufficiency: 1% of women experience menopause < 40 years. 2 Mayo Clinic

9. Menopause Pathophysiology

10. Menses cessation or amenorrhea 16 Ovaries age   response to pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone  follicular phase and ovulations shortened  production of progesterone lowered 16 Follicle production drops  unresponsive  estradiol production lowered 16 Androstenedione levels are reduced by half 16 Ovarian inhibin and estrogen   pituitary release of LH and FSH is inhibited  LH and FSH  significantly in circulation 16

11. Complications After Menopause 2 Heart and blood vessel disease Osteoporosis Urinary incontine nce Sexual function Weight gain

12. Conventional Therapy Conventional Therapy Hormone Therapy: ◦ Estrogens: helps relief symptoms or bone protection in the lowest dose. 6 ◦ Progestagens: provide endometrial protection. Hormone replacement therapy (HRT): ◦ combination of estrogen and progesterone. 2 Bioidentical Hormone Therapy: 6 ◦ Identical in structure to human endogenous. Testosterone with estrogen. 7 Mayo Clinic, WebMD, Goodman et al. 2011

13. Other Therapies Low-dose antidepressants Phytoestrogens: Isoflavones and lignans Gabapentin (Neurontin) Medications to prevent or treat osteoporosis Lifestyle modification Yoga Acupuncture Goodman et al, 2011

14. CAM Usage CAM Usage Therapy Usage Claims Side Effects Black CohoshReduces hot flashesAbdominal pain, dark urine, jaundice, liver failure Dong quiReduces hot flashes, No estrogen activity Bleeding complications KavaDecreases hot flashes and anxiety Potential to damage the liver Red cloverReduces hot flashesContains phytoestrogen, may have effects on hormone sensitive-tissue GinsengHelp with mood symptoms and sleep disturbances Allergic reactions SoyReduces hot flashesLong-term use thickening of the lining of the uterus

15. Red Clover/Vasomotor and menopausal symptoms Red clover is a plant to make medicine with the red flower. 7 Used for many conditions, not enough scientific evidence. 7 Contains hormone-like chemicals (isoflavones). 9 The use of red clover supplementation has reported positive effects on menopausal symptoms. 9 NIH and Lipovac et al, 2012

16. The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. (Lipovac et al, 2012) Randomized double-blind Placebo-controlled Control group A: 2 capsules of red clover isoflavone 40mg each Placebo group B: 2 capsules identical manufactured 90-day period After 7-day washout period, subjects received opposite treatment for 90-days more Control group A: 2 capsules of red clover isoflavone 40mg each Placebo group B: 2 capsules identical manufactured 90-day period After 7-day washout period, subjects received opposite treatment for 90-days more 109 postmenopausal women aged >40 years Non-users of HT Moderate to severe menopausal symptoms More than 5 hot flashes per day 109 postmenopausal women aged >40 years Non-users of HT Moderate to severe menopausal symptoms More than 5 hot flashes per day

18. Study Results and Conclusion Study Results and Conclusion Fifty-three women completed the trial No significant effect on BMI, weight or blood pressure Red clover isoflavones significantly decreased menopausal symptoms Positive effect on vaginal cytology Lipid levels decreased No side effects in either active compound or placebo Despite the results, the effects over vasomotor symptoms continues being a controversial issue. Lipavac et al, 2012

19. Oral Evening Primrose oil and Menopausal hot flashes Oil from the seed of evening primose plant, Oenothera biennis 10,11 Obtained through cold expression from the plant 11 Rich source of omega-6 fatty acids, which may help alleviate inflammation 10,11 Studies mostly on its usage to treat systemic disease Targets women’s health problems, including menopausal symptoms (i.e. hot flashes) 10 EPO tolerated well with documented side effects, including gastrointestinal and headaches. Most recent studies are limited and appropriate dosing standards anticipate clarification

20. The effect of oral evening primrose oil on menopausal hot flashes. (Farzaneh F et al, 2013) Six-week randomized clinical trial Hot flashes commonly occur in menopausal women May affect quality of life due to symptom severity Study aim: compare efficacy of EPO versus placebo in menopausal hot flash symptom severity Hot flashes commonly occur in menopausal women May affect quality of life due to symptom severity Study aim: compare efficacy of EPO versus placebo in menopausal hot flash symptom severity Total of 56 menopausal women 45-59 age range Pre and post intervention, participants reported characteristic of hot flash symptoms (i.e. hot flash related daily interference scale) Randomly assigned to 2 capsules per day Improvements reported Total of 56 menopausal women 45-59 age range Pre and post intervention, participants reported characteristic of hot flash symptoms (i.e. hot flash related daily interference scale) Randomly assigned to 2 capsules per day Improvements reported

21. Study Results and Conclusion Study Results and Conclusion Improvement for frequency, severity of hot flashes improved from 32, 32 and 18% in placebo to 39, 42 and 19% in EPO group 12 The score from the HFDIS increased in two groups 12 Improvement in social activities and relationships, and sexual life had a significant increase in EPO group (p <0.05) 12 Oral EPO shown to alleviate hot flashes through lessened intensity and a better HFDIS score 12

22. Valerian root and sleep quality in menopause Flowering plant native to Europe and Asia 13 Grown in North America 13 Used for its medicinal properties as a sleep aid 13 Hot flashes commonly disrupt sleep in menopausal women 13

23. The effect of valerian on sleep quality in post- menopausal women. (Taavoni S et al, 2011) Approximately half of postmenopausal women have sleep disturbances Aim of study is to evaluate valerian extract effects on sleep quality improvement in postmenopausal women Approximately half of postmenopausal women have sleep disturbances Aim of study is to evaluate valerian extract effects on sleep quality improvement in postmenopausal women 100 postmenopausal women 50 to 60 years of age Insomnia symptoms pre- study Data obtained from demographic form and Pittsburgh Sleep Quality Index Two groups randomly assigned, given 530 mg valerian extract concentrate or placebo Administered twice daily, 4 weeks 100 postmenopausal women 50 to 60 years of age Insomnia symptoms pre- study Data obtained from demographic form and Pittsburgh Sleep Quality Index Two groups randomly assigned, given 530 mg valerian extract concentrate or placebo Administered twice daily, 4 weeks Randomized Placebo-controlled Clinical trial Triple-blind Randomized Placebo-controlled Clinical trial Triple-blind

24. Study Results and Conclusion Study Results and Conclusion Intervention group had significant increase in sleep quality, P <0.001 14 Thirty percent of subjects in valerian group versus four percent in placebo group had noted improvements in sleep quality 14 Menopausal women with insomnia have higher quality sleep with the use of Valerian 14 Results support reported efficacy of valerian through clinical findings of positive effects on insomnia 14 Need for long-term trials

25. Conclusions Red Clover ◦ More research needed for effects on human body Oral Evening Primrose Oil ◦ Recent studies limited ◦ Dosing standards need to be clarified Valerian root ◦ Need for long-term studies on efficacy and safety

26. Conclusion Whole foods first Supplements secondary, if necessary, as long as documented efficacy and safety are present Continued support with health care professional

27. References References 1. Eden KJ, Wylie KR. Quality of sexual life and menopause. Women’s Health. 2009;5(4):385-396. 2. Mayo Clinic. Menopause. Available at: http://www.mayoclinic.org/diseases- conditions/menopause/basics/definition/con-20019726. Accessed on October 10, 2014. 3. WebMD. Premature menopause. Available at: http://www.webmd.com/menopause/guide/premature-menopause. Accessed on October 10, 2014. http://www.webmd.com/menopause/guide/premature-menopause 4. Moilanen J, Aalto AM, Hemminki E, Aro AR, Raitanen J, Luoto R. Prevalence of menopause symptoms and their association with lifestyle among finish middle-aged women. Maturiatas. 201; 67: 368-374. 5. BMJ. Menopause. Epidemiology. Available at: https://online.epocrates.com/u/2923194/Menopause. Accessed on October 10, 2014. https://online.epocrates.com/u/2923194/Menopause 6. Goodman FN, Cobin RH, Ginzburg SB, Katz IA, Woode DE. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice For the Diagnosis and Treatments of Menopause. AACE menopause guidelines revision task force. Endocrine Practice. 2011; 17(6): 1-25.

28. References References 7. WebMD. Menopause and perimenapause. Available at: medicationshttp://www.webmd.com/menopause/tc/menopause-and-perimenopause-medications. Accessed on October 10, 2014. 8. NIH. Menopausal symptoms and complementary health practices. Available At: http://nccam.nih.gov/health/menopause/menopausesymptoms. Accessed on October 11, 2014. http://nccam.nih.gov/health/menopause/menopausesymptoms 9. Lipovac M, Chedraui P, Gruenhut C, Gocan A, Kurz C. The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. Gynecological Endocrinology. 2012; 28(3): 203-207. 10. WedMD. Find a vitamin or supplement: Evening primrose oil. 2005-2014. Available at http://www.webmd.com/vitamins-supplements/ingredientmono-1006- evening%20primrose%20oil.aspx?activeingredientid=1006&activeingredientname=evening%20primrose %20oil http://www.webmd.com/vitamins-supplements/ingredientmono-1006- evening%20primrose%20oil.aspx?activeingredientid=1006&activeingredientname=evening%20primrose %20oil 11. Bayles B et al. Evening primrose oil. American Family Physician. 2009; (12):1405-1408. Available at http://www.aafp.org/afp/2009/1215/p1405.html. Accessed October 16, 2014. http://www.aafp.org/afp/2009/1215/p1405.html 12. Farzaneh F et al. The effect of oral evening primrose oil in menopausal hot flashes: a randomized clinical trial. Arch Gynecol Obstet. 2013; (5):1075-9. Available at http://www.ncbi.nlm.nih.gov/pubmed/23625331. Accessed October 16, 2014. 13. Breus, M. Valerian: Help for post-menopausal insomnia. 2014. Huffpost Healthy Living. Available at http://www.huffingtonpost.com/dr-michael-j-breus/valerian-insomnia_b_1028544.html. Accessed October 16, 2014. http://www.huffingtonpost.com/dr-michael-j-breus/valerian-insomnia_b_1028544.html 14. Taavoni S et al. Effect of valerian on sleep quality in postmenopausal women: a randomized placebo- controlled clinical trial. Menopause. 2011; (9):951-5. Available at http://www.ncbi.nlm.nih.gov/pubmed/21775910. Accessed October 16, 2014. http://www.ncbi.nlm.nih.gov/pubmed/21775910 15. Nordstrom S. Menopause: What every medical student should know. UIC College of Medicine Lecture. Available at http://www.medicine.uic.edu/UserFiles/Servers/Server_442934/File/OBGYN%20Med%20Ed/STUDENTS/Lectures/NORD STROMMenopause%20talk.pdf. Accessed October 17, 2014. 16. Gass, M. Menopause. The Mercky Manual Professional Edition. 2014. Available at http://www.merckmanuals.com/professional/gynecology_and_obstetrics/menopause/menopause.html. Accessed October 17, 2014.