1. Integrative Women’s Health: Caring for the Menopausal Woman Priscilla Abercrombie, RN, NP, PhD, AHN-BC Assistant Clinical Professor UCSF, Dept of Community Health Systems Dept of Obstetrics, Gynecology, and Reproductive Sciences

2. © 2008 Priscilla Abercrombie NCCAM Definitions Complementary medicine is used together with conventional medicine. Alternative medicine is used in place of conventional medicine. Integrative medicine, as defined by NCCAM, combines mainstream medical therapies and CAM therapies for which there is some high- quality scientific evidence of safety and effectiveness. 2

3. © 2008 Priscilla Abercrombie 3 Tenets of Integrative Health Care Patients want health care that is safe, effective and affordable Patients want to be cared for as unique holistic beings; mind, body and spirit Patients want to explore and understand all of the health care options available to them; conventional, alternative and complementary

4. © 2008 Priscilla Abercrombie 4 Tenets of Integrative Health Care Patients are encouraged to be active participants in their health care and to seek a collaborative relationship with their provider that is empowering and supportive The provider guides the patient on their quest for health and healing based on experience, education and the ability to examine the scientific evidence to support recommended treatments Health care is healing oriented and engages the body’s natural and innate ability to heal itself whenever possible

5. © 2008 Priscilla Abercrombie 25- 36% of their patients are using them Only 45-56% will tell their provider about their use 68% of patients in one study felt the herbs improved their symptoms Use of CAM is common among many ethnicities (50% Hispanic, 50% Asian, 41% White, 22% African American) Why should providers care about CAM therapies? 5 (Brett, 2007; Dailey, 2003; Kuo, 2004)

6. Integrative Care for Menopausal Symptoms: Focus on Hot Flashes

7. © 2008 Priscilla Abercrombie Menopause 12 months of amenorrhea, retrospective diagnosis Usually occurs between 50-52 yrs old A variety of physiological changes occur that can have a profound impact on women’s lives. Menopause is the result of the natural decline in the hormones (estrogen, progesterone) produced in the ovaries. As hormone levels decrease, a number of symptoms may emerge, although their presentation and severity varies greatly from woman to woman. 7

8. © 2008 Priscilla Abercrombie 8 Menopausal symptoms VasomotorGenitourinaryOther Systemic Headache Palpitations Vaginal dryness Dyspareunia Fatigue Reduced sexual desire or arousal Night sweats Insomnia/ sleep disturbance Vaginal itching or burning Anxiety, irritability, depression Urinary frequency, dysuria, urgency Cognitive difficulties Backache, stiffness ARHP

9. © 2008 Priscilla Abercrombie Hot flashes Hot flashes typically begin when cycles become irregular, occur in 80% of women (Kronenberg,1990) Usually end 1-2 years after menstruation has ceased but can continue for 5 years or more. Symptoms range from flushing or warmth in the face and upper body to sweating and chills lasting an average of 4 min., 20% women find them intolerable. Can lead to severe sleep disturbances. Appear to be the result of mixed signals from the hypothalamus, resulting in altered thermoregulation, the exact mechanism is unknown 9

10. Conventional Treatment

11. © 2008 Priscilla Abercrombie 11 Hormone Therapy: Women’s Health Initiative - First randomized, controlled trial in women (50-79 years) treated with HRT 6700 women with 5.2 years of follow-up -37% -34% +29% +26% +41% +112% -80 -40 0 40 80 120 160 Intestinal cancer Difference % vs. placebo Vertebral fracture Hip fracture Cardiovascular diseases Stroke Breast cancer Advantages Tromb. venous Disadvantages Manson JE at al, N Engl J Med, 2003;349:523-534

12. © 2008 Priscilla Abercrombie Discuss Risks and Benefits Routes of administration Regimens Types of estrogens and progestogens Bioidentical hormones Compounding hormones Saliva or blood testing to monitor hormones What is “natural” to you? 12

13. © 2008 Priscilla Abercrombie Practice Guidelines Organizations:  American College of Obstetricians & Gynecologists  Food & Drug Administration  North American Menopause Society General Recommendations  Use close to menopause  Start at lowest dose  Use shortest time possible 13

14. © 2008 Priscilla Abercrombie 14 Bioidentical hormones Manufactured to have the same molecular structure as the hormones made in the body Individualized dosages can be made in compounding pharmacy Dose/formulation based upon results of blood or saliva tests for estrogen, testosterone, DHEA Dosage changes over time based upon symptoms and hormone levels Safety and efficacy not well studied Prometrium is bio-identical progesterone 17 ß-estradiol is bio-identical, available in patch

15. © 2008 Priscilla Abercrombie 15 Bioidentical HT Thought to mimic levels of estrogen in the body: 90% estriol, 3% estrone, 7% estradiol Tri-Est: estriol 1mg, estrone 0.125 mg, estradiol 0.125 mg taken BID (=0.625 premarin) Bi-Est: estriol 80% and estradiol 20% Estriol may have protective effect against breast cancer but not well studied Estriol alone does increase risk of endometrial hyperplasia and cancer Compounded hormones are more expensive

16. © 2008 Priscilla Abercrombie 16 “Natural” hormones What is “natural” to you? Many pharmaceuticals containing estradiol are derived from soybeans or wild yam (Ex: Estrace, Ortho-Est, Climara, Estraderm Premarin is derived from the urine of pregnant mares

17. © 2008 Priscilla Abercrombie Pharmaceuticals Paroxetine (Paxil): SSRI, 2 large trials, 10- 25mg/d, significant reduction in hot flash frequency, may interfere with tamoxifen, SEs: headache, nausea, dry mouth, loss of appetite Venlafaxine (Effexor): SNRI, 1 large trial, 37.5 or 75(ER) mg/d, decreased number of hot flashes, increased well being, higher doses more effective but more SE’s, can cause heavy uterine bleeding, galactorrhea, mastodynia Gabapentin (Neurotin): anti-convulsant, 2 trials effective, 900mg/d, SE: dizziness and sleepiness.

18. © 2008 Priscilla Abercrombie Pharmaceuticals con’t Clonidine: antihypertensive, 10 trials, half showing reduced hot flash frequency and severity, mostly studied with women taking tamoxifen, SE: difficulty sleeping Many of these drugs reduced frequency of hot flashes but not always severity, clinical significance? None of these drugs have FDA approval for the treatment of hot flashes. Be aware of drug interactions: MAO inhibitors, St John’s Wort, tamoxifen 18

19. © 2008 Priscilla Abercrombie 19 Bellergal Retard® 40 mg phenobarbital, 0.6 mg ergotamine tartrate, and 0.2 mg levorotatory alkaloids of belladonna, one twice daily Only non-hormonal drug approved by the FDA for hot flashes and other menopausal symptoms Side effects: addictive, dizziness, sleepiness

20. Botanicals Valerian

21. © 2008 Priscilla Abercrombie 21 Black Cohosh (Cimicifuga racemosa) Most studies have shown significant relief of vasomotor and other symptoms (psych, vaginal proliferation, etc.) but inconclusive Remifemin®: study doses ranged from 20-80 mg taken twice daily. German health authorities and WHO endorse its use for premenstrual discomfort, dysmenorrhea and menopause. NAMS for mild to moderate hot flashes. Mechanism of action unknown but likely nonhormonal

22. © 2008 Priscilla Abercrombie 22 Black Cohosh con’t Two extensive safety reviews concluded it is without significant adverse effects; 4 case reports linked black cohosh to acute liver disease. A causal relationship has not been established. Check liver enzymes. There is no evidence that it increases risk for breast cancer but safety not known in women with a history of breast cancer. NIH studies in process, negative study published 12/06

23. © 2008 Priscilla Abercrombie 23 Chastetree fruit (Vitex agnus castus) German E Commission endorsed for PMS, irregular menses, and mastalgia Has been found to increase progesterone thus stabilizing the endometrium (used in infertility) Dose: 500mg/d crude herb Few side effects; mostly GI No RCT evaluating its use in menopause Some estrogen receptor binding, not for use in women with breast cancer

24. © 2008 Priscilla Abercrombie 24 Sage (Salvia officinalis L ) Traditionally combined with other herbs for hot flashes or night sweats German E Commission recognizes its use for dyspepsia and excessive sweating May exert some weak estrogenic activity A small number of uncontrolled studies show that it was effective for hot flashes and night sweats Dose: Ex: Menopause Feminine®, 15mg taken BID

25. © 2008 Priscilla Abercrombie 25 St John’s Wort (Hypercium perforatum) Effective for mild to moderate depression Not studied in menopause but found in many menopause formulas Dose: 300mg 3x daily, of 0.3% hypericin standardize extract Precautions: interactions with many drugs, including OC’s National Cancer Institute-funded Hypericum perforatum (St. John's wort) in Relieving Hot Flashes in Women with Non-Metastatic Breast Cancer phase II trial in process

26. © 2008 Priscilla Abercrombie 26 Ginseng Panax ginseng (Asian ginseng) and Panax quinquefolius (American ginseng) have been traditionally used as tonics 2 studies (American ginseng) conducted showed no significant change in hot flashes (Wiklund1999; Tode, 1999) But both studies showed improved sense of wellbeing, depression, mood and sleep consistent with its traditional use as a tonic (invigoration or fortification) Dose: standardized extract ranging from 100-600 mg per day Side effects: well tolerated, comparable to placebo

27. © 2008 Priscilla Abercrombie 27 What doesn’t seem to work Soy Red clover Evening primrose oil Don Quai Wild yam Don Quai

28. © 2008 Priscilla Abercrombie 28 Phytoestrogens: Soy (Glycine max) Asian women report less hot flashes, this is thought to be due to dietary intake of soy Non-fermented soy contains isoflavones predominantly in their glycoside form (e.g. genistin, daidzin). When eaten these are converted to their more active aglycone form (e.g., genistein, daidzein). The intestinal micoflora then further change them to more biologically active compounds. Not everyone has the microflora needed to make this last conversion - only 35% of Westerners Fermented soy products have higher levels of the active compounds

29. © 2008 Priscilla Abercrombie 29 More on soy Appears to have weak estrogenic and anti-estrogenic activities Studies used a variety of soy isoflavones in different dosages and combinations, doses ranged from 50- 100mg/day There is some evidence that increasing the intake of soy foods may help with menopausal symptoms though results of randomized clinical trials are contradictory (Nelson, 2006; Low Dog, 2005) Does not appear to effect mammographic breast density Long term treatment with soy (high dosages of isoflavones) has been associated with endometrial hyperplasia

30. © 2008 Priscilla Abercrombie 30 Phytoestrogens: Red Clover (Trifolium pratense) Semi-purified isoflavones from the blossoms have been studied as Promensil® and Rimostil® They have differing types and amounts of isoflavones 5 controlled trials have been conducted: no significant reduction in hot flashes in systematic reviews (Nelson, 2006; Low Dog, 2005; Krebs, 2004) Does not appear to effect mammographic breast density (Atkinson, 2004) or endometrium (Clifton- Bligh, 2001) Safety in women with breast cancer unknown

31. © 2008 Priscilla Abercrombie 31 Don Quai (Angelica sinensis) Traditionally used as a tonic in TCM for many centuries (not for menopause), combined with other herbs Usual dose is 3-6 g/day in 3 doses One study failed to find a reduction in hot flashes (Hirata, 1997) May interfere with warfarin, may increase menstrual bleeding, safety in women with a history of breast cancer not known

32. © 2008 Priscilla Abercrombie 32 Evening primrose oil (Oenothera biennis) Extracted from the wildflower's seeds, rich in linoleic acid Standardized to 320-360 mg of linoleic acid and 40 mg y-linolenic acid per capsule Usual dose: 3-6 g/day Well tolerated, some GI side effects, aggravation of temporal lobe epilepsy? One small study did not find benefit for hot flashes (Chenoy1994)

33. © 2008 Priscilla Abercrombie 33 Wild Yam (Dioscorea villosa) Wild yam contains diosgenin which can not be converted in the body Is converted in the lab to make a number of steroids including progesterone Sold as herbal cream sometimes with progesterone OTC One RPCT showed no effect on menopausal symptoms or blood hormone levels (Komesaroff, 2001)

34. Preventive Health

35. © 2008 Priscilla Abercrombie Medical Conditions More Common After Menopause Osteoporosis  Incidence substantially increased after menopause  Estrogen reduction increases bone resorption Atherosclerotic disease  Rates in women increase after age 50  Total cholesterol, LDL cholesterol, and triglyceride levels increase; HDL cholesterol level decreases  The leading cause of death in both women and men 35

36. © 2008 Priscilla Abercrombie Recommended Screening Exams Clinical breast exam Mammogram Pap smear Cholesterol, glucose, liver enzymes Colon cancer screening Others as appropriate: TSH, CBC, FSH etc. 36

37. © 2008 Priscilla Abercrombie Supplements Multivitamin: natural vitamin E, mixed carotenoids, B vitamins Calcium Vitamin D Magnesium Fish Oil Others as appropriate 37

38. Nutrition

39. © 2008 Priscilla Abercrombie 39 General Recommendations 5-7 servings of vegetables and fruits Whole grains Healthy fats Calcium rich foods Anti-inflammatory herbs and spices Mushrooms Hydrate Avoid hot flash triggers: hot foods, spicy foods, alcohol, limit caffeine

40. Physical Activity

41. © 2008 Priscilla Abercrombie General Recommendations Aerobic exercise thought to reduce hot flashes and improve quality of life, mixed results in studies Physical activity reduces cardiac disease, cancer, obesity (CDC) and depression (Dunn, 2005) Essential for weight management Moderate intensity exercise 5-7 times a week (CDC) Walking for weight bearing: pedometer for objective measurement Resistance training and strengthening important Identify barriers and preferences Provide resources 41

42. Mind/Body/Spirit

43. © 2008 Priscilla Abercrombie 43 Mind/Body Health Paced breathing found to be more beneficial than neurofeedback with alpha wave training (Freedman, 1995) Trained relaxation techniques for 20 minutes each day better than diary (Irwin, 1996) Recommendation:  Try mind/body practices for symptom relief and stress reduction: guided imagery, MBSR, breath work, yoga, tai chi, qi gong, massage  Seek therapy for depression

44. © 2008 Priscilla Abercrombie 44 Lifestyle and behavioral changes Identify hot flash triggers Modify environment: keep ambient temperature cool, wear cool clothes, drink chilled beverages Practice journaling Learn sleep hygiene strategies Seek social support and ability to share experiences Address spiritual needs: life transition, finding meaning in the experience

45. © 2008 Priscilla Abercrombie 45 Alternative Therapies Acupuncture studies show mixed results (Vincent, 2007; Huang, 2006; Wyon, 2004) Homeopathy studies show improvement in symptoms and quality of life (Jacobs, 2005; Clover, 2002)

46. © 2008 Priscilla Abercrombie 46 Resources Reviews:  Low Dog, T. (2005) Menopause: a review of botanical dietary supplements, American Journal of Medicine, 118, 985.  Nelson, H., et al. (2006). Nonhormonal therapies for menopausal hot flashes. Systematic review and meta- analysis. JAMA, 295, 2057.  Hickey, M. et al. (2005) Treatment of menopausal symptoms, what should we do now? Lancet, 366(9483):409 Natural Standard or Natural Medicine database for herbs and supplements, CAM therapies Consumerlabs.com evaluates supplements

47. © 2008 Priscilla Abercrombie Providing integrative health care for women during the menopause transition involves incorporating many different avenues of healing. There are a number of CAM treatments that can be safely integrated into care although their effectiveness has not been adequately studied in many cases. Integrative practitioners are ideally suited to provide holistic care for the perimenopausal woman; addressing her mind, body and spirit. Summary 47

48. © 2008 Priscilla Abercrombie 48 Contact Information Subscribe to the monthly eNewsletter at the website