Reducing your risk of hormone related cancer , premature death and disability by Optimizing Your Hormone Balance “To encourage and to edify, for “Understanding is a wellspring for LIFE...” Proverbs. 16:22 1. Dysglycemia 2. Impaired Detoxification (Heavy Metals Pb, Hg, Cd) 3. 4. 5. 6. 7. Chronic Inflammation Faulty Methylation Chronic Stress Impaired mitochondria Imbalanced Immune Function (Chronic Infection (Virus, Parasite)) 8. Hormones 9. Digestion 10. Food Sensitivies • Breast cancer has increased from 1 in 10 to 1 in 8 women over the last 50 years • Women’s health initiative study and hormone therapy showed increased risk of breast cancer with Premarin (horse urine) and increased risk of stroke/heart attack with synthetic Progestin (Provera) • Osteoporosis continues to increase at a rapid rate • Women have surpassed men in occurrence rates of cardiovascular disease • Hormonal disorders such as fibroid tumors, severe PMS, infertility, endometriosis, fibrocystic breast disease, and others afflict more women every year • Why the increase? Stress (Cortisol, Toxins. Metabolic Syndrome???) • Prevention is the key (PROACTIVITY!!!) “Strictly speaking, it's possible that we are all -- men, women and children -suffering a little from estrogen dominance, because there is so much of it in our environment.” Dr John Lee © Rakowski, 2004 Estrogen Dominance is a condition where a person’s estrogen can range from less than optimal to excessive estrogen, with less than optimal balancing progesterone. People, (woman as well as males) can have low estrogen levels and still have estrogen dominance symptoms if the body does not produce enough progesterone. Hormones, in balance, are critical to health and disease prevention Hormones, in balance, protect against breast cancer Formby B, & Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Annals of Clin and Lab Science 1998; 28: 360-369. Hormones out of balance, may contribute to an increased risk of breast cancer Synthetic chemical hormones (Prempro, Provera, Estratest, Methyl testosterone) increase the risk of breast cancer Diet and lifestyle are critical to hormone balance and overall health Stress affects hormone balance Acceleration of the aging process Allergies, including asthma, hives, rashes, sinus congestion Autoimmune disorders such as lupus erythematosis and thyroiditis, and possibly Sjoegren's disease Breast cancer Breast tenderness Cervical dysplasia Cold hands and feet as a symptom of thyroid dysfunction Copper excess Decreased sex drive Depression with anxiety or agitation Dry eyes Early onset of menstruation Endometrial (uterine) cancer Fat gain, especially around the abdomen, hips and thighs Fatigue Fibrocystic breasts Foggy thinking Gallbladder disease Hair Loss Headaches Hypoglycemia Increased blood clotting (increasing risk of strokes) Infertility Irregular menstrual periods Irritability Insomnia Magnesium deficiency Memory loss Mood swings Osteoporosis Polycystic ovaries Premenopausal bone loss PMS Prostate cancer (men only) Sluggish metabolism Thyroid dysfunction mimicking hypothyroidism Uterine cancer Uterine fibroids Water retention, bloating Zinc deficiency › Causes: • • • Iodine deficiency Heavy metal toxicity- especially mercury from “silver” fillings Low progesterone, infection, high carbohydrate/caffeine intake › Symptoms: • • • • • • • Weight gain Low basal body temperature (BBT) Fatigue Hair loss Dry skin Brittle nails Depression, bipolar, inability to sweat, and constipation › Diagnosis: • • • • Low Body Temperature TSH > 2 Low to low normal T3/T4 High Reverse T3 › Treatment: • • • • Iodine kelp thyroid support balanced thyroid if all else fails Environmental Estrogens • Organochlorine chemicals such as vinyl chlorides, dioxins, PCBs, and perchloroethylene (~half of “endocrine disrupters” are in this class) • Aromatic hydrocarbons, phthalates and phenols, and some surfactants • Medications such as hormone replacement, oral contraceptives, tamoxifen, and cimetidine • Hormones in animal products consumed by humans Dietary Estrogens32-35 (“Phytoestrogens”) Endogenous Estrogens • Isoflavones (e.g., genistein, daidzein, equol, puerarin, coumestrol, glycitein, biochanins) from soy, beans, peas, clover, alfalfa, and kudzu • Lignans (e.g., matairesinol, pinoresinol, secoisolariciresinol) especially from flaxseed, rye, wheat, and sea vegetables • Certain flavonoids (e.g., rutin, naringenin, luteolin, resveratrol, quercetin) especially from citrus and grapes • • • • Estradiol Estrone Estriol Hydroxylated estrogen metabolites • Methoxylated estrogen metabolites • Other estrogen metabolites A xenohormone is a foreign, manmade hormone that has toxic effects on the human body. Xenohormones are most commonly found in plastics, pesticides on foods, acetones (e.g. nail polish remover), and in industrial pollutants such as PCBs. Because they are a foreign substance and the body doesn't know how to get rid of them, xenohormones tend to accumulate in the body over time. Xenohormones can be particularly damaging to a developing fetus, and xenoestrogens in particular may increase a woman's risk of breast cancer. The vast majority of these xenohormones are manmade petrochemical (fat soluble) products used in pesticides, cleaning agents, solvents, adhesives, emulsifiers, plastics and many other chemicals used in manufacturing and industry. They are also found in (non-organic) food from crops sprayed with pesticides, hormones in (non-organic) meat/poultry, in the out-gassing of the materials we build our homes and offices with, in cosmetics, coloring agents, in the various sprays we use to kill insects on our pets, in our homes and gardens, and in the weed killers and fungicides we use on our lawns and gardens. The class of “exoginous hormones are very toxic and are also called Endocrine Distrupers in that they alter or reduce the optimal function of other major hormone secreting glands such as the pituitary (the master gland) the adrenal (stress gland), the thyroid (control caloric burn rate), the testicles the ovaries, and the pancreas (which produces insulin). Pituitary Hypothalamus TSH LH/FSH ACTH Thyroid T3 T4 Adrenal DHEA Cortisol Aldosterone Ovaries Glucose (Sugar) Insulin Mineral/Water metabolism Estradiol Estrone Progesterone Testosterone Estriol Phthalates: most commonly in plastics that foods are wrapped in. Alkylphenols and nonylphenols: most commonly found in detergents, shampoos, cosmetics, spermicidal lubricants, pesticides, and clear plastics… also found in tap water Bisphenol A (BPA): mostly found in hard plastics like water bottles and in dental sealants most of Europe has already banned this Increase the risk of breast cancer Increase the risk of heart disease › Coronary vasoconstrictor › Negate the beneficial effects of estrogen Fluid retention and edema Increase incidence of blood clots › Venous thrombosis › Pulmonary embolism › Stroke Cause weight gain Estrogens Have Been Reported to Increase the Risk of Endometrial Cancer Three independent, case-controlled studies have reported an increased risk of endometrial cancer in post-menopausal women exposed to exogenous estrogens for more than 1 year… The three case-controlled studies reported that the risk of endometrial cancer in estrogen users was about 4.5 to 13.9 times greater than in nonusers. • Are there other beneficial effects of tamoxifen? • While tamoxifen acts against the effects of estrogen in breast tissue, it acts like estrogen in other tissue. This means that women who take tamoxifen may derive many of the beneficial effects of menopausal estrogen replacement therapy, such as lower blood cholesterol and slower bone loss (osteoporosis). • Does tamoxifen cause cancers of the uterus? • Tamoxifen increases the risk of two types of cancer that can develop in the uterus: endometrial cancer, which arises in the lining of the uterus, and uterine sarcoma, which arises in the muscular wall of the uterus. Like all cancers, endometrial cancer and uterine sarcoma are potentially lifethreatening. 41% increase in strokes 29% increase in heart attacks 26% increase in breast cancer Twice the rate of blood clots Possible contributor to Alzheimer's •Increase coronary heart disease risk •Increase stroke risk 29 percent 41 percent •Reduces colon cancer risk Reduces fractures by 37 percent 24 percent •Increase invasive breast cancer risk 26 percent “Results On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits.” © Rakowski, 2004 Epidemiological and animal studies have identified estrogen exposure as a risk factor for several cancers, namely breast, endometrium, ovary, prostate, testis, and thyroid. Much of the evidence comes from the observation that cancer risk increases with increased exposure to endogenous or exogenous estrogens, and the positive relationship observed between blood levels of estrogens and cancer risk. Prolonged estrogen exposure can cause direct genotoxic effects by inducing cell proliferation in estrogen-dependent target cells (increasing the opportunity for the accumulation of random genetic errors), affecting cellular differentiation, and altering gene expression. Additionally, there is increasing evidence for indirect genotoxic effects of estrogens as well. The relative importance of each mechanism is likely a function of the specific estrogen, as well as the exposed tissue or cell type and its metabolic state. “ABSTRACT - Large study reported in AMA Journal finds that hormone treatment doubles risk of Alzheimer's disease and other forms of dementia in women who began treatment at age 65 or older; latest bad news about hormone therapy comes from four-year experiment involving 4,532 women at 39 medical centers, half taking placebos and half Prempro, estrogen-progestin combination that is most widely prescribed form of therapy; 40 cases of dementia developed after four years in hormone group and 21 in placebo group;” New York Times: NATIONAL DESK | May 28, 2003, Wednesday Hormone Use Found to Raise Dementia Risk By DENISE GRADY Obesity increases endogenous estrogen production by fat tissue, where the enzyme aromatase converts androgens into estrogen. Excess insulin in the bloodstream prompts the ovaries to secrete excess testosterone and reduces SHBG levels, thus increasing levels of free estrogen and testosterone. (PCOS) (Hirsutism) Alcohol consumption increases estrogen levels, and epidemiological studies suggest that moderate alcohol consumption increases the risk of breast cancer, an effect that may be synergistically enhanced when combined with estrogen replacement therapy Excessive estrogen exposure from both endogenous and exogenous sources is a causal factor in the development of cancer in hormone-dependent tissues, such as the breast, endometrium, ovary, uterus, and prostate Hormonal imbalances between progesterone, testosterone, and estrogen can lead to symptoms and conditions of estrogen dominance. The metabolism of estrogen takes place primarily in the liver through Phase I (hydroxylation) Phase II (methylation, glucuronidation, and sulfation) pathways with final excretion in the urine and feces The 2-OH metabolite confers very weak estrogenic activity, and is generally termed the “good” estrogen. In contrast, the 16a-OH and 4-OH metabolites show persistent estrogenic activity and promote tissue proliferation. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the C16a hydroxylation pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the C-2 pathway. It is theorized that shifting estrogen balance toward a less estrogenic state through promotion of the C-2 pathway may prove beneficial for a variety of conditions related to estrogen dominance or imbalance.- 16a-OH and 4-OH are the primary estrogen metabolites that have been associated with direct genotoxic effects and carcinogenicity. The researchers found that premenopausal women who developed breast cancer had a decreased 2-OH:16a-OH ratio and a higher percentage of 16a-OH than 2-OH. Dietary interventions such as increased consumption of cruciferous vegetables (e.g., broccoli and cabbage) and phytoestrogenrich foods such as soy and flaxseeds can significantly promote C-2 hydroxylation and increase the 2-OH:16a-OH ratio. The oxidation of catechol estrogens (2-OH and 4-OH) yields reactive molecules called quinones. Quinones are thought to play a role in carcinogenesis by inducing DNA damage directly or as a result of redox cycling between the quinones and their semiquinone radicals, which generates ROS. Supplementation with antioxidant nutrients can reduce the oxidation of the catechols and promote greater excretion of these metabolites through the methylation pathway. National Health Organizations recommended Therapeutic Lifestyle Changes (TLC) as a “first line” treatment National Health Orgs. National Institutes of Health Am. Heart, Blood & Lung Institute Am. Diabetes Association Am. Heart Association Am. Association Clinical Endocrinologists Arthritis Foundation North American Menopause Society Many others Conditions High Cholesterol High Blood Pressure High Blood Sugar and/or Diabetes Heart Disease Osteoarthritis Osteoporosis Metabolic Syndrome Many others Improving estrogen metabolism can be of benefit in women with various conditions and family histories, including family history of: Breast cancer Uterine cancer ovarian cancer endometriosis premenstrual syndrome uterine fibroid tumors fibrocystic or painful breasts, cervical dysplasia, systemic lupus erythematosis Multiple dietary and nutritional factors have the ability to influence estrogen synthesis and receptor activity, as well as the detoxification pathways through which estrogens are metabolized Dietary Fiber Dietary fiber, especially lignin, can bind unconjugated estrogens in the digestive tract, which are then excreted in the feces. Second, dietary fiber can beneficially affect the composition of intestinal bacteria and reduce intestinal b-glucuronidase activity, resulting in a lowered deconjugation of estrogen and reduced reabsorption. Dietary fiber intake also increases serum concentrations of SHBG, thus reducing levels of free estradiol. Carbohydrates/Fats/Protein Excess consumption of simple carbohydrates raises blood glucose and insulin levels, resulting in adverse influences on sex hormone balance. Conversely, complex carbohydrates attenuate glycemic and insulinemic responses. Inadequate dietary protein may lead to decreases in overall cytochrome P450 activity. Rice fortified with lysine and threonine is a source of protein frequently used to nutritionally support hepatic detoxification function “Nearly 10 percent of all women have some form of androgen or “male” hormone imbalance.” Symptoms include: › › › › › › › › › › Irregular periods, Infertility, Unexplained weight gain, “Apple” body shape, Fluid retention, Fatigue, Mood swings, Acne, Hair loss, Unwanted hair growth. I can take it anymore! I’ve got extreme PMS, I’m losing my hair, growing a mustache, gaining weight, and breaking out with zits. “Nearly 10 percent of all women have some form of androgen or “male” hormone imbalance.” Symptoms include: Irregular periods, Infertility, Unexplained weight gain, “Apple” body shape, Fluid retention, Fatigue, Mood swings, Acne, Hair loss, Bland, New Approaches to Anti-Aging: 2001, page 71 Unwanted hair growth.© Rakowski, 2004 They have a similar structure to estradiol and can bind to the ER, they increase plasma SHBG levels, they decrease aromatase activity,46 and 4.) they shift estrogen metabolism away from the C-16a pathway to the C-2 pathway. two Recent studies found that increased isoflavone consumption decreased urinary excretion of the genotoxic estrogen metabolites16a-OH and 4-OH, indicative of their decreased formation, and significantly increased the 2-OH:16a-OH ratio in both preand postmenopausal women Higher intakes of soy products and other Isoflavones, such as consumed in traditional Japanese diets, are associated with low rates of hormone-dependent cancers. The average daily isoflavone intake of Japanese women is to 80 mg, while that of American women is 1 to 3 mg. Magnesium optimizes the methylation and excretion of catechol estrogens which promotes estrogen detoxification. Ovarian hormones influence magnesium levels, triggering decreases at certain times during the menstrual cycle. These cyclical changes can produce many of the well-known symptoms of PMS in women who are deficient in magnesium and/or calcium. Indole-3-Carbinol (I3C) is a naturally occurring compound derived from cruciferous Vegetables that actively promotes the breakdown of estrogen to the beneficial metabolite, 2-OH. Therefore, I3C is protective to estrogen-sensitiv tissues and may be beneficial to those with health issues related to estrogen dominance thereby decreasing carcinogenic 4-OH formation. B Vitamins such as B6, B12, and folate, function as important cofactors for enzymes involved in estrogen conjugation and methylation. B6 can attenuate the biological effects of estrogen. Mechanism of Action Nutrient Promote C-2 hydroxylation over C-4 and/or C-16a hydroxylation of estrogens Cruciferous vegetables, indole-3-carbinol, rosemary, isoflavones (soy, kudzu, clover) Reduce the oxidation of catechol estrogens (2-OH and 4-OH) Vitamins A, E, & C, N-acetylcysteine, turmeric, green tea, lycopene, a-lipoic acid, flavonoids Promote the methylation of catechol estrogens (2-OH and 4-OH) Folate, vitamins B2, B6, & B12, trimethylglycine, magnesium Increase circulating concentrations of SHBG, thus reducing levels of unbound, active estrogens Fiber, lignans (flaxseed), isoflavones (soy, kudzu, clover) Inhibit the activity of aromatase, which converts into estrogens Lignans (flaxseed), flavonoids (chrysin) Promote the detoxification of estrogens by upregulating Phase I and Phase II enzymes Turmeric (curcumin), D-limonene, magnesium, vitamins B2, B6, & B12, flavonoids Inhibit the activity of b-glucuronidase, which deconjugates estrogens in the large intestine, allowing them to be reabsorbed and re-metabolized Fiber, probiotics (acidophilus, bifidobacteria), calcium D-glucarate Modify estrogen receptor activity Isoflavones (soy, kudzu), lignans (flaxseed), We will all have expensive urine… But…We get to choose how we spend the money!!! Ovarian Estrogens © Rakowski, 2004 Adrenal Estrogens In a well-nourished, vibrant woman, the adrenals and other glands pick up the job of estrogen secretion to keep her active and attractive after menopause. In fact, this phenomenon increases with aging as nature compensates for menopause..... and it is even so in women who have had a hysterectomy. http://www.healthyhealing.com/W MN-MenoNaturalWay.html Stress Reduction Get rid of chemicals, pesticides etc. Improved diet, reduce carbohydrates, whole foods › Lower insulin levels Exercise Fiber / supplements / flaxseed Balanced hormone therapy* › Bio identical Testosterone › Bio identical Progesterone (NOT progestins) *When needed • Identify root cause of illness • Commit to diet and exercise FIRST • Detoxify the body and maintain adequate elimination • Test for hormone imbalances • Work with a practitioner who understands the interplay of all the hormones Heart disease: 652,091 Cancer: 559,312 Stroke (cerebrovascular diseases): 143,579 Chronic lower respiratory diseases: 130,933 Accidents (unintentional injuries): 117,809 Diabetes: 75,119 Alzheimer's disease: 71,599 Influenza/Pneumonia: 63,001 Nephritis, nephrotic syndrome, and nephrosis: 43,901 Septicemia: 34,136 Source: Center for Disease Control (CDC). According to the study, bad eating habits and lack of exercise cause about 400,000 people to die prematurally in the United States in 2000. Tobacco use, currently the leading cause of preventable death in the U.S., killed 435,000 people. SLOW SUICIDE "Americans need to understand that overweight and obesity are literally killing us," said Secretary of the U.S. Department of Health and Human Services Tommy Thompson. In adults the numbers for obesity are higher. According to the Health and Human Services Department, about 64 percent of Americans -- an estimated 129.6 million people -- are overweight or obese. People with a BMI of 25 percent to 29.9 percent are overweight, according to the CDC. Those with a BMI of 30 percent or more are obese. A HIGH BMI STRESSES THE BODY'S HEART, BONES AND LUNGS AND INCREASES THE RISK OF DISEASES SUCH AS: TYPE 2 DIABETES, HEART DISEASE AND EVEN SOME FORMS OF CANCER. Scientific studies have shown a strong correlation between steroid hormone levels in saliva and the amount of hormone in the blood that is active or "bioavailable." It is this fraction of total hormone that is free to enter the target tissues in the brain, uterus, skin, and breasts. Estrogens circulate in the body bound mainly to the sex hormone binding globulin (SHBG); however, only unbound estrogens can enter target-tissue cells and induce biological activity. Its Never Wrong to do Right and its Never Right to Do wrong!!! “Information without implementation is of NO Value!!!” “…he who does not use his endeavors to heal himself is brother to him who commits suicide. “ King Solomon Prov 18:9 Amp