Overview. Hormones of interest. Disclosure. Natural Estrogens in the Body. Estrogen 4/7/15 NON-HORMONAL MANAGEMENT OF MENOPAUSE IPAS APRIL 20, 2015

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Overview NON-HORMONAL MANAGEMENT OF MENOPAUSE IPAS APRIL 20, 2015 A whole new look at estrogen Promoting healthy forms of estrogen Botanical supplements for menopause Suzanne B. Bartlett, M.D.

supplements through the Mercy Integrative Medicine Center Natural Estrogens in the Body Estrogen Natural Estrogens To Remember: Different estrogens have different origins: Estrone, E1

1 Overview NON-HORMONAL MANAGEMENT OF MENOPAUSE IPAS APRIL 20, 2015 A whole new look at estrogen Promoting healthy forms of estrogen Botanical supplements for menopause Suzanne B. Bartlett, M.D., FACOG, ABOIM Disclosure Hormones of interest I have no relationship with any companies manufacturing any of the products or supplements discussed I derive no benefit from the sale of any supplements through the Mercy Integrative Medicine Center Natural Estrogens in the Body Estrogen Natural Estrogens To Remember: Different estrogens have different origins: Estrone, E1 Estradiol, 17β- estradiol, E2 Estriol, E3 one = 1 ( bad ) Di = 2 ( medium ) Tri = 3 ( best ) E1 (estrone) from adipose (fat) tissue E2 (estradiol) from the ovary E3 (estriol) from the placenta during pregnancy 1

2 Estrone (E1) Estrone (E1) The main estrogen the body makes after menopause High levels stimulate breast & uterine tissue Before menopause: Made in ovaries, adrenals, liver, fat cells; converted to E2 in ovaries After menopause: made in fat cells, liver, adrenal; little conversion to E2 Estrone (E1) Estrone (E1) Obesity: increased E1:E2 ratio > Alcohol consumption shifts production to E1 Activates estrogen receptor sites that increase cell proliferation; has greatest risk of stimulating breast cancer Estradiol (E2) Estradiol (17β-estradiol; E2) Strongest estrogen n 12x stronger than E1 n 80x stronger than E3 Predominant estrogen before menopause High levels associated with increased risk breast & uterine cancer Estriol (E3) Estriol (E3) Least stimulating effect on breast and endometrium Shown not to promote breast cancer Evidence indicates protective effect against breast cancer by blocking estrone in estrogen receptor sites on breast cells Asian & vegetarian women have higher levels of E3, much lower rates of breast cancer Important Estrogen Metabolites Estrogen Metabolites Estrone ( pathways: ) breaks down via three competing Estrone Estradiol (aka 17- β Estradiol ) 2-hydroxyestrone 16-hydroxyestrone 4-hydroxyestrone 4-Hydroxyestrone Minor pathway Cancerstimulating 2-Hydroxyestrone Anticancerous 16 α-hydroxyestrone Cancer-stimulating Benefit: Osteoporosis prevention Estriol 2

Important Estrogen Metabolites Important Estrogen Metabolite 2-Hydroxyestrone Good estrogen Does not stimulate cell division May inhibit other estrogen products from binding to receptors Felt to be

estrogens) Important Estrogen Metabolites Our GOAL: 4-Hydroxyestrone pathway Minor pathway May enhance cancer development Higher in patients deficient in folic acid and methionine Increased levels

3 Important Estrogen Metabolites Important Estrogen Metabolite 2-Hydroxyestrone Good estrogen Does not stimulate cell division May inhibit other estrogen products from binding to receptors Felt to be anti-cancerous 16-Hydroxyestrone Bad estrogen Highly active Strong stimulatory effect on cell division Associated with increased risk of breast cancer Permanently binds to receptors (unlike other estrogens) Important Estrogen Metabolites Our GOAL: 4-Hydroxyestrone pathway Minor pathway May enhance cancer development Higher in patients deficient in folic acid and methionine Increased levels noted in patients with uterine fibroids Equine estrogens (e.g. Premarin) increase metabolism to 4- hydroxyestrones Studies show equine estrogen causes cancerous change 5x more rapidly than natural forms of 4-hydroxyestrone Increase 2:16 Hydroxyestrone ratio : Because... 2:16 Hydroxyestrone ratio : Low 2:16 Hydroxyestrone ratio associated with higher breast cancer risk Breast cancer survival rate is greater in women with higher ratios Dietary Factors Omega 3 Fatty Acids n Plant sources n Fish sources Soy (organic, whole food sources, fermented (miso, tempeh)) Kudzu (source of isoflavones) Rosemary, turmeric 3

Dietary Factors, continued Vitamins B6, B12 and Folate SAM-e Cruciferous vegetables n Indole-3-carbinol n

n Kale n Cabbage n Broccoli n Cauliflower n Brussels sprouts n Radish n Wasabi n Horseradish n Turnips n

catecholamine production by decreasing stress n Mind-body modalities 16-hydroxyestrone production is

Stress-induced catecholamines How can we naturally raise progesterone levels?

4 Dietary Factors, continued Vitamins B6, B12 and Folate SAM-e Cruciferous vegetables n Indole-3-carbinol n Diindolymethane (DIM) n Sulforaphane glucosinolate Cruciferous vegetables: ½ cup per day! n Kale n Cabbage n Broccoli n Cauliflower n Brussels sprouts n Radish n Wasabi n Horseradish n Turnips n Collard greens Factors that lower the 2:16 ratio Lifestyle Factors Exercise Weight loss Reducing catecholamine production by decreasing stress n Mind-body modalities 16-hydroxyestrone production is stimulated by: Obesity Hypothyroidism Pesticide toxicity Omega-6 fatty acids Inflammatory cytokines Stress-induced catecholamines How can we naturally raise progesterone levels? USP Progesterone (yam-derived) Premenopausal women should have one week break at menses How can we more naturally address vaginal dryness? Vegetable Oil as lubricant Vitamin E intravaginally DHEA intravaginally 5 mg vaginally each night x 2 weeks, then MWF Alternate Estrace cream and Testosterone 2% (natural, not synthetic methyl-testosterone) cream (by prescription) applied to outer vulva every other day 4

Black Cohosh (Cimicifuga racemosa) Benefits n One of the most studied herbal supplements for menopause n Acts as a selective estrogen-receptor modulator on the central nervous system and on bone

Studies n A strong study done in 2003 showed that Black Cohosh: n Similar effectiveness to estrogen in treating menopausal symptoms (Menopause Rating Scale) n Both (Black Cohosh & estrogen)

5 Black Cohosh (Cimicifuga racemosa) Benefits n One of the most studied herbal supplements for menopause n Acts as a selective estrogen-receptor modulator on the central nervous system and on bone tissue n May prevent loss of bone density that occurs with menopause (Li et al., 1996) Black Cohosh (Cimicifuga racemosa), cont. Studies n A strong study done in 2003 showed that Black Cohosh: n Similar effectiveness to estrogen in treating menopausal symptoms (Menopause Rating Scale) n Both (Black Cohosh & estrogen) significantly more effective than placebo n Did not negatively affect lining of the uterus, as did estrogen Black Cohosh (Cimicifuga racemosa), cont. Studies, cont. n Combination Black Cohosh & St. John s Wort (Uelbelhack, 2006) n Menopause Rating Scale (MRS) decreased by: n 50% treatment group n 19.6% placebo group n Combination or SJW responsible? Dose n mg/day of Black Cohosh extract Red Clover (Trifolium pratense) Shown in 3 out of 6 clinical trials to improve vasomotor symptoms Found to increase arterial elasticity 28% more than placebo (e.g. may reduce heart disease risk) (Nestel, 1999) Dose: Standardized extract of 40 mg total isoflavones taken 1-2 times/day Chaste Berry (Vitex agnus castus) Uses n Shown to be effective for PMS n Approved by German Commission E for irregular menses and PMS n In perimenopausal women, can be useful for managing dysfunctional uterine bleeding associated with irregular ovulation Chaste Berry, continued Study n 16-week trial n Combination of St. John's Wort and Vitex n Found to relieve PMS-type symptoms in perimenopausal women; improved menopause-related symptoms such as hot flashes and night sweats (van Die, 2009) Dose n 500 mg per day taken continuously throughout the month n If using an extract (strength of 12-16:1), the dose is generally mg per day 5

Maca (Lepidium peruvianum) 2000 mg/day shown to reduce hot flashes, improve insomnia, depression, memory, energy, and concentration, reduce vaginal dryness, as well as to improve lipids, blood

At least 28 studies have looked at Maca s benefit for libido (note: most of the studies were in men!

1999) In a study of 384 women, hot flashes and night sweats were not found to be improved (Wiklun et al.

at least 20 centuries to strengthen the heart, lung, and liver meridians Most recent studies have not found it to be helpful for relief of hot flashes (Hirata, 1997; Haines, 2008) Tendency to

Melatonin The more common, higher dosages less effective; peak sooner than natural for circadian rhythm taken at dusk or about two hours before bedtime Dose: 1 to 2 mg, sustained release

6 Maca (Lepidium peruvianum) 2000 mg/day shown to reduce hot flashes, improve insomnia, depression, memory, energy, and concentration, reduce vaginal dryness, as well as to improve lipids, blood pressure, body mass index, and bone density (Meisner, et. al, 2006) It has been found to improve low libido caused by anti-depressant medications such as SSRIs. At least 28 studies have looked at Maca s benefit for libido (note: most of the studies were in men!) Safe supplement; very few side effects/drug interactions Ginseng (Panax ginseng) mg ginseng extract increases energy and improves insomnia and depression (Tode et al. 1999) In a study of 384 women, hot flashes and night sweats were not found to be improved (Wiklun et al. 1999) Ginseng helps with adaptation to physical and mental stressors as an adrenal support (Bobardelli, 1980) Dong Quai (Angelica Sinensis) Has been used in traditional Chinese Medicine (TCM) for at least 20 centuries to strengthen the heart, lung, and liver meridians Most recent studies have not found it to be helpful for relief of hot flashes (Hirata, 1997; Haines, 2008) Tendency to increase menstrual flow and aggravate menopausal flooding--caution is advised Interacts with warfarin, other medications used to prevent clots Dose is typically 3-6 grams per day Sleep Supplements Melatonin The more common, higher dosages less effective; peak sooner than natural for circadian rhythm taken at dusk or about two hours before bedtime Dose: 1 to 2 mg, sustained release formulation Sleep Supplements, cont. Valerian root (Valeriana officinalis) Taken regularly for 2-4 weeks, shown to promote and restore natural sleep Often found in herbal teas Dose: 2-3 grams of the dried herb one or more times daily Sleep Supplements, cont. Hops (Humulus lupulus) Shown to improve restlessness, anxiety and sleep disturbances Study found hops (orally) and vitamin E (vaginally) to be of benefit for vaginal dryness Dose: 0.5 mg of dried herb 6

energy, weight management n Chaste berry relief of menstrual symptoms n Rhodiola concentration, mental alertness, endurance PM n Black Cohosh night sweats, mood swings n Valerian, Hops, L-Theanine

n Valerian, Hops, L-Theanine insomnia Key Points Lifestyle factors determine whether dangerous forms of estrogen are converted to healthy forms If lifestyle/diet inadequately control menopausal

7 Sleep Supplements, cont. L-Theanine Amino acid found in green tea and in mushrooms Antioxidant and relaxant effects The recommended dose for rest and relaxation is 100 mg Proprietary Blends AM/PM Perimenopause AM n Green tea energy, weight management n Chaste berry relief of menstrual symptoms n Rhodiola concentration, mental alertness, endurance PM n Black Cohosh night sweats, mood swings n Valerian, Hops, L-Theanine insomnia Proprietary Blends AM/PM Menopause AM n Green tea energy, weight management n Ginseng energy n Black Cohosh hot flashes, irritability PM n Black Cohosh hot flashes, night sweats, mood swings n Valerian, Hops, L-Theanine insomnia Key Points Lifestyle factors determine whether dangerous forms of estrogen are converted to healthy forms If lifestyle/diet inadequately control menopausal symptoms, consider botanical remedies If hormones are needed, consider bio-identical forms of therapy Come see us! Contact me Current workshops on: Introduction to Integrative Medicine Stress Sleep Menopause Supplements Cancer Chronic pain All include presentations by: Myself Mary McInnis Meyer, MS, yoga teacher 500 RYT Luke Hansen, PsyD, Clinical Psychologist Cindy Corwin, Certified Clinical Aromatherapist Terri Clark, Registered Dietitian Nancy Lorenzini, M.D., Acupuncturist Suzanne Bartlett, MD, FACOG, ABOIM Mercy Integrative Medicine Mercy Medical Center th Street, SE Cedar Rapids, IA (319) sbartlett@mercycare.org Register online at 7

What is the menopause?

What is the menopause? Information for you Alternatives to hormone replacement therapy for symptoms of the menopause Published in December 2011 This information is for you if you are considering alternatives to hormone replacement