Dealing with the Facts

Transcription

1 Phytoestrogen, Herbal Remedies and Women Health during Menopause: Dealing with the Facts Dr Doaa Genena MBChB, MPH, PhD (Public Health/Nutrition) Fellow Lecturer & Clinical Nutrition Consultant - Medical Research Institute- Alexandria University, Egypt. Member of the European Society of Clinical Nutrition and Metabolism (ESPEN) Associate member, International Union for Cancer Control (UICC), Switzerland. Scientific board member, The Egyptian Nutrition and Health Coaching Association (ENHCA), Egypt

2 Menopausal Facts End of menstruation and child-bearing years 12 months of amenorrhea, retrospective diagnosis Usually occurs between yrs. Old (North American Menopause Society) Menopause is the result of the natural decline in the hormones (estrogen, progesterone) produced in the ovaries. Prematurely from medical intervention (eg, bilateral oophorectomy, chemotherapy, medications)

3 What Is Menopause? A period of change: Hormonal Physical Emotional As hormone levels decrease, a number of symptoms may emerge, although their presentation and severity varies greatly from woman to woman.

4 estrogen receptors are located throughout the body, multiple systems are at risk : Brain Breasts Heart Liver Bones Vagina Skin & hair Uterus Ovaries May impact health and quality of life

5 What Happens With Hormonal Changes? Irregular periods Vaginal dryness Sexuality Decrease ability to remodel bones bone mass osteoporosis Joint discomfort Change in blood lipid levels cholesterol & LDL level- HDL Sleep disturbances Weight gain Hair loss and changes in hair Quality

6 What Happens With Hormonal Changes? Climacteric symptoms - physiological events caused by failure of ovarian function in women in their late 40 s. Including hot flashes in association with other vasomotor symptoms : palpitation, sweating esp. at night, irritability, anxiety. (Kronenberg,1990). No two women experience menopause in the same way

7 Estrogen Secretion Estrogen Loss and Manifestations of Health Risks Over Time Short-Term Symptoms Long-Term Diseases Development of Subclinical Disease Hot flushes Mood, sleep, and/or acute cognitive changes Urogenital symptoms, skin changes Cardiovascular disease Osteoporosis Cognitive decline (Alzheimer s disease) Age (years)

8 Hot Flashes Most common symptom of menopause (Affects 68-93% of women) Hot flashes typically begin when cycles become irregular Maximal prevalence is during first 2 years post menopause, after which the prevalence declines over time.

9 Hot Flashes Symptoms range from flushing in face and upper body to sweating and chills lasting an average of 4 min., 20% women find them intolerable. (Kronenberg F. 1990, Sturdee DW, 1978) Symptoms usually last 6 months to 5 years - 25% remain symptomatic for > 5 years. (Shanafelt TD. 2002, Stearns V. 2002) Primary reason women seek medical treatment

10 For decades, Hormone Replacement Therapy (HRT) has been recognized as the best treatment for problems related to menopause especially hot flashes and vaginal dryness, reducing risks of osteoporosis and fractures, endometrial and colorectal cancers.

11 In 2002, the Women s Health Initiative (WHI) trial of estrogen/progestin therapy was halted midtrial due to high incidence of breast cancer and cardiovascular disease. (for moderate doses of estrogen, the risk of breast cancer is probably in the range of 20% to 30% in those women who are susceptible.)

12 Contraindications to Hormone Therapy Breast cancer Estrogen-dependent cancer Abnormal genital bleeding Deep vein thrombosis / Blood clots Active liver disease

13 Now as a clinician / nutritionist: What is the important question? I AM HOT, IRRITABLE AND FEELING LOW; I M UNCERTAIN ABOUT TAKING HRT Is there alternative therapy for me?

14 Why should providers care about CAM therapies? 25-36% of their patients are using them Use of CAM is common among many ethnicities (50% Hispanic, 50% Asian, 41% White, 22% African American) Only 45-56% will tell their provider about their use

15 Why should providers care about CAM therapies? Common beliefs- : 100% natural origin and perception that natural means safe. Health benefits without any side effects Easily available without a prescription. More easily accepted than a professional consultation with a physician or a nutritionist. Formal education is not routinely provided in medical schools or postgraduate medical training programs.

16 Most botanical supplements 1. Have no biological activity 2. Do not interact with prescription drugs 3. Are natural and therefore perfectly safe 4. Are like prescription meds and have potential for interactions

17 Counseling Integrating CAM and conventional medicine 1. Assess potential harm 2. Assess potential benefit: Direct harm (toxicity or injury) from the remedy Indirect harm (interaction with check the product or therapy for data on efficacy, wellperformed studies are hard to find in exploitation). this area, but they do exist. other treatments or financial 3. Assess the quality of the product/provider 4. Assess the integration with the conventional treatment plan

18 Phytoestrogen and Herbal Remedies

19 Phytoestrogens Nonsteroidal compounds that occur naturally in plants (Phyto). Estragon like action: Readily diffuses across cell membrane. Activate estrogen receptors. ER-a Uterus, testis, pituitary, ovary, epididymis, and adrenal gland. ER-b Brain, kidney, prostrate, ovary, lung, bladder, intestine, and epididymis.

20 Phytoestrogens 100 to 10,000 times weaker than endogenous estrogen. Depending on the tissue type and location in the body, phytoestrogens can act as estrogens or antiestrogens. have activity similar to selective estrogen receptor modulators (SERMs) such as tamoxifen.

21 Phytoestrogens in Human Health Cancer preventive Postmenopausal supplement Prevention of osteoporosis Cardiovascular health

22 Epidemiological data: Phytoestrogens 10-20% incidence of hot flushes in China/Japan, 70-80% in Western countries Cause could be > Soy factor < 1mg soy isoflavones in Western diets, mg in Japanese diets

23 Types of Phytoestrogens Isoflavones : soybeans, chickpeas, red clover, and other legumes. The most potent; most commonly investigated are genistein and daidzein, also thought to have the highest estrogenic properties. Lignans (enterolactone or enterodiol) : flaxseed (in huge quantities), lentils, whole grains, beans, fruits, and vegetables.

24 Foods containing Phytoestrogens Soy beans soy products and soy beverages Dried beans Tofu Lentils Sesame seeds Barley Flaxseed Apple Wheat Carrots Berries wheat germ Oats Rice

25 The Evidence Hot Flashes Soy protein may decrease hot flashes A 2007 Cochrane Review looked at phytoestrogens & in respect of soy extracts, 9 trials were included 5 had some positive results & 4 were negative. It all depends on the methodology. A review by V. Wong et al in Gynaecological Endocrinology 2009;25(3): : concluded that results were mixed, & did not conclusively demonstrate efficacy over placebo.

26 Flaxseed and hot flashes The Evidence Hot Flashes One pilot study at the Mayo Clinic enrolled 30 women and studied the effect of ingesting 40grams of crushed flax seed daily for 6 weeks and looking at the change in hot flash score as reported prospectively in a daily hot flash diary. The mean decrease in the hot flash frequency was 50%- from 7.3 hot flashes to 3.6, and the mean decrease in the hot flash scores was 57%. This small study suggests that further study is warranted regarding the use of flaxseed as a possible option the treatment of hot flashes.

27 The Evidence Hot Flashes Clinical practice guidelines issued in 2011 by the American Association of Clinical Endocrinologists for the diagnosis and management of menopause state that: Phytoestrogens, including soy-derived isoflavonoids, result in inconsistent relief of symptoms. Guidelines from the American College of Obstetricians and Gynecologists stated that phytoestrogens and herbal supplements have not been shown to be useful for treating hot flashes.

28 Variability in clinical trials of soy for menopausal symptoms Different products and foods contain varying levels of isoflavones Optimum dose is not known Formulated products may not contain stated levels Trial duration ranges from 1-4 months Variability and deficiencies in reporting of outcomes

29 The Evidence Hot Flashes While phytoestrogens did not bring a decrease in Kupperman menopause Index compared to placebo, their use was associated with a reduction in the hot flush frequency and their side-effects were no more common than those with placebo. The available data do not support the recommendation of phytoestrogens for relief of all menopausal symptoms, some patients may benefit from their use in reducing hot flushes as these compounds also seem to be well tolerated further study of phytoestrogens for the relief of menopausal symptoms and their potential long-term adverse effects is warranted.

30 How much each day? Consuming mg/day of isoflavones from food seems to be a safe amount that helps to relieve hot flashes. This would be equivalent to consuming one of the following: 1-2 cups soy milk (low fat, calcium enriched) 150 grams tofu ½ cup edamame 3-4 tbsp miso ¼- ½ cup soy nuts Regular intake for 1-2 months is usually necessary to notice any effects from isoflavones

31 How much each day? 2-4 slices flaxseed bread, or multigrain (for lignans) 30-40g Flaxseed 1 cup legumes

32 Phytoestrogen - Safety Not all women efficiently convert phytoestrogens into a form the body can use to relieve menopausal symptoms. Soy, can provoke hypersensitivity reactions. Soy can be allergenic or interfere with proper nutrient absorption and digestion.

33 Phytoestrogen - Safety the American Association of Clinical Endocrinologists for the diagnosis and It s best to get isoflavones from food rather than management of menopause :Clinical practice guidelines (2011) : supplements. women with a personal or strong family history of Isoflavone supplements might interfere with thyroid hormone-dependent cancers, thromboembolic events, function and inhibit mineral absorption. or cardiovascular events should not use soy-based Avoid consuming more than 150 mg of isoflavones per day. therapies.

34 Black Cohosh Cimifuga racemosa Black cohosh

35 Black Cohosh Traditionally used for both PMS and menopause Mechanism of action still uncertain but not believed to be estrogenic May have action on central serotonergic receptors Main commercial product is Remifemin - containing 20mg of black cohosh as an isopropanolic extract

36 Black Cohosh The North American Menopause Society reports that black cohosh may be helpful in the very short term (six months or less) for treatment of hot flashes, night sweats, and vaginal dryness, but the evidence of its effectiveness is mixed. Moderate side effects are rare (GI upset) Effects of long term use unknown > 6 mths German health authorities and WHO endorse its use for premenstrual discomfort, dysmenorrhea and menopause.

37 Black Cohosh CLINICAL EVIDENCE SO FAR Randomized, placebo-controlled trials evaluating black cohosh Stoll, 1987 Studied 80 women using the black cohosh extract Remifemin 4mg twice daily. Significant symptom improvement in black cohosh group No improvement with placebo group or estrogen treatment arm

38 Black Cohosh CLINICAL EVIDENCE SO FAR Jacobsen et al, 2001 No significant differences between groups in frequency and intensity of hot flashes Wuttke et al, 2003 Black cohosh as effective as conjugated estrogens in symptom improvement

39 HALT STUDY Most rigorous trial is the Herbal Alternatives for Menopause (HALT) study (2005) 1 American year double-blind Botanical RCT Council with 351 Clarifies subjects Clinical Trial (2008) Subjects They followed issued a up response at 3,6 and stating 12 months that HALT study findings are contradictory to the majority of results from other studies of black cohosh.

40 89 women were randomized to the study The HT arm, the conventional and recognized approach for the relief of vasomotor symptoms in perimenopausal and postmenopausal women, was included as a positive control

41 Black Cohosh CLINICAL EVIDENCE SO FAR The average number of vasomotor symptoms per week decreased over time across all groups (black cohosh, 34% reduction; red clover, 57%; placebo, 63%; and, CEE/MPA, 94%). There were no significant differences between the botanical treatments and placebo for any of the safety parameters including breast and endometrial safety, liver enzymes, complete blood count, or lipid profiles.

42 Black Cohosh CLINICAL EVIDENCE SO FAR There was no evidence for hepatotoxicity of black cohosh during the 12-month intervention. Prothrombin time was unchanged in any arm of the study, indicating that red clover, in particular, did not interfere with blood coagulation

43 Black Cohosh Safety Two extensive safety reviews concluded it is without significant adverse effects; 4 case reports linked black cohosh to acute liver disease. 30 reports of serious liver damage with supplementation A causal relationship has not been established. Check liver enzymes. No evidence that it increases risk for breast cancer but safety not known in women with a history of breast cancer

44 Evening Primrose

45 Evening Primrose Oil Extracted from the wildflower's seeds. Approved in England for treatment of breast tenderness A report published in Menopause in 2015 surveyed postmenopausal women aged 50 to 65 years and found that 70.4 percent used natural remedies, with evening primrose oil being the most commonly used.

46 Evening Primrose Oil Evening primrose oil is rich in gamma-linolenic acid (GLA), an essential fatty acid involved in the production of hormone-like substances - prostaglandins. By increasing production of prostaglandins, EPO is thought to help counter hormonal changes associated with menopause.

47 Evening Primrose Oil- The Evidence Most of the available research has yielded negative findings A review published in American Family Physician in 2009, researchers stated that there is insufficient evidence to determine if evening primrose oil is effective for "most clinical indications" (including symptoms associated with menopause). Downloaded from the American Family Physician Web site at Copyright 2009 American Academy of Family Physicians

48 Evening Primrose Oil- The Evidence In a small study published in Archives of Gynecology and Obstetrics in 2013, women aged 45 to 59 years who were experiencing menopause-related changes took either an evening primrose oil supplement or a placebo for six weeks. At the study's end, there was an improvement in the severity of hot flashes, but not hot flash frequency or duration.

49 Evening Primrose Oilsafety Minor gastrointestinal adverse effects, including abdominal pain, nausea, increased bowel movements, and diarrhea; headaches

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51 Alternatives to hormone therapy

52 Alternatives to hormone therapy Lifestyle changes Try relaxation techniques (eg, yoga, meditation) Eat a healthy diet Get regular exercise Keep cool Dress in layers (eg, light or wicking clothing) Sleep in cool room (eg, fan, thermoregulating pillow) Reduce sexual discomfort and increase sensitivity with moisturizers, and lubricants.

53 Basic Nutrition Prescription for the Menopausal women 5-9 servings of vegetables and fruits Whole grains (fibers) Healthy fats 2 to 3 servings weekly of oily fish (omega 3) 5 servings weekly of nuts and seeds Calcium rich foods

54 Basic Nutrition Prescription for the Menopausal women Include phytoestrogens: Ground flaxseed (start with one tsp\d increasing to 2 tbsp\day ½ cup of soy milk ½ cup of beans Eat organic: fewer hormone- disrupting pesticides Avoid hot flash triggers: hot foods, spicy foods, alcohol, limit caffeine containing beverages (may also reduce stress and sleep problems)

55 In Summary Providing integrative health care for women during the menopause transition involves incorporating many different avenues of healing. Menopause is a normal event, but many women have problematic vasomotor symptoms (hot flushes and night sweats) that impair quality of life and might require treatment. Management of menopausal symptoms should be individualized and address patient aims and preferences for treatment. Therapies should target the symptoms that most affect function and quality of life. Scientists have found little evidence that natural products, such as herbs and other dietary supplements, are helpful. Further studies are needed.

56 References Abdali K, et al. Effect of St. John s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17: Cassidy A. Diet and menopausal health. Nursing Standard. 2005;19: Crawford AM. The Natural Menopause Handbook. Crossing Press. Berkeley, CA Cheung T. The all-natural menopause diet. Pegasus Books. New York, NY Dennehy C, Tsourounis C. (2010) A review of select vitamins and minerals used by postmenopausal women. Maturitas 66(4) Edelman JS. Menopause Matters. The Johns Hopkins University Press. Baltimore, MD Glenville M. Healthy eating during menopause. National Book Network. Lanham, MD Hagey AR & Warren MP. Role of exercise and nutrition in menopause. Clin Obstet Gynecol 2008;51: Huntley A & Ernst E. A systematic review of the safety of black cohosh. Menopause 2003;10(1): Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor systems. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No: CD DOI: / CD Messina MJ & Wood CE. Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J 2008;7: Messina M. A brief historical overview of the past two decades of soy and isoflavone research. J Nutr 2010;140:1350S-1354S. Mahady GB, et al. United States Pharmacopeia review of black cohosh case reports of hepatotoxicity. Menopause 2008;15(4 Pt. 1): ).

57 References Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonal Therapies for Menopausal Hot Flashes: systematic review and meta-analysis. JAMA 295 (17): , 2006 Pruthi S, Thompson SL, Novotny PJ, Barton DL, Kottschade LA, Tan AD, Sloan JA, Loprinzi CL. Pilot evaluation of flaxseed for the management of hot flashes. J Soc Integr Oncol. 5(3): , 2007 Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci. 1990;592: Taylor N. Natural Menopause Remedies. New American Library. New York, NY Thacker HL. The Cleveland Clinic Guide To Menopause. Kaplan Publishing. New York, NY Teschke R et al. Suspected hepatotoxicity by Cimicifugae recemosae rhizoma. Phytomedicine 2009;16: Teschke R et al. Suspected black cohosh hepatotoxicity. Maturitas 2009;63: Tice JA, Grady, D. Alternatives to Estrogen for Treatment of Hot Flashes. JAMA 295 (17): , Saxena T, et al. Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study. Cancer Epidemiol Biomarkers Prev. 2010;Online First. Shanafelt TD, Barton DL, Adjei AA, et al. Pathophysiology and treatment of hot flashes. Mayo Clin Proc. 2002; 77(11): Stearns V, Ullmer L, Lopez JF, et al. Hot flushes. Lancet. 2002;360(9348): Sturdee DW, Wilson KA, Pipili E, et al. Physiological aspects of menopausal hot flush. Br Med J. 1978;2(6130):79-80.

58 Thank you