Leslie J. Crofford, MD Gloria W. Singletary Professor of Women’s Health Research Director, Center for the Advancement o

1. Healthand the KentuckyWoman Leslie J. Crofford, MDGloria W. Singletary Professor of Women’s Health ResearchDirector, Center for the Advancement of Women’s Health

2. Advancing women’s health throughcomprehensive medical care, education and outreach, and research opportunitieshttp://www.mc.uky.edu/womenshealth/

3. Mission • Createnew knowledge towards the understanding and improvement of women’s health through clinical and basic research initiatives • Train primary care practitioners in gender-specific medicine and sensitize all health practitioners to understand and respond to the health care concerns and needs of women • Providegender-specific diagnostic, treatment and preventive health care services in a coordinated, comprehensive and compassionate manner • Sharewomen's health resources and information with consumers, communities, health care professionals, educators, and policy makers • Enhancethe professional developmentof women at all academic levels within the University of Kentucky Chandler Medical Center, and increase recruitment, retention, promotion and advancement of women faculty

4. Goals for this Presentation • Discuss determinants of health • Review recommendations on how to maintain good health and prevent disease • Review behaviors associated with health • Consider what we can do to promote good health in our families and our community • Introduce the Kentucky Women’s Health Registry http:// www.kywomensregistry

5. Health • Chronic disease prevention • Longevity • Wellness Live well, live long

6. Determinates of Health • Genes • Environment • Behavior • Attitude

7. Single gene disorders Cystic fibrosis, sickle-cell anemia, hemophilia, etc Chromosomal abnormalities Down’s syndrome, etc Complex traits Heart disease, depression, etc Diseases associated with gene mutation Cancer Genes and Health http://www.ygyh.org/

8. http://www.dnaftb.org/ • DNA is the building block for genes • Genes are inherited from parents as discreet units that come in pairs and are carried on chromosomes • Simple genetics can be applied to single-gene traits that are either dominant or recessive • More complex traits and diseases are associated with some genes that are permissive and others that are protective

9. Gene/Environment Interactions • Most chronic diseases are attributable to both genes and environmental exposures • Some exposures cannot be avoided, others are the result of modifiable behaviors • What counts as environment? • Natural environment, e.g. sun • Infectious exposures • Chemical or toxin exposures • Trauma and other physical stressors • Psychological stressors • Dietary exposures

10. Gene/Environment Interactions • Cancer • Metabolic diseases and heart disease • Autoimmunity • Depression • Chronic pain and fatigue

11. Genes, Environment, and Health • Understand your genetic risk factors • Family history • Understand your environmental risk factors • Unavoidable exposures • MODIFYABLE RISKS!! • Know what kinds of preventative steps may be important for you • Screening that works

12. Concept of Preventative Health • Prevention and early detection are essential to good health • Potentially infinite lists of advice and tests • Many have little scientific basis for widespread implementation • Preventative strategies should be evaluated in studies • On what do you base recommendations for screening? • Burden of suffering • Characteristics of screening tests • Effectiveness of early screening in reducing morbidity and mortality

13. Cancer http://www.insidecancer.org/ • Only about 10% of cancer risk can be attributable to inherited genes while the other 90% of cancer is associated with mutations associated with environmental exposures • Genetic mutations accumulate with age and exposures, e.g. • Sun • Diet (saturated fat, fiber) • Chemicals and toxins (tobacco smoke) • Infections (human papillomavirus)

14. Cancer genes are involved in cell growth, and their ability to invade surrounding tissues or metastasize Presence of genes which allow uncontrolled growth Absence of cells which put the brakes on growth Genes that help cancer cells avoid removal Genes that assist cancer cells in spreading Cancer-Associated Genes

15. Lung Cancer Breast Cancer Colon Cancer Cancer in Women: The Big 3

16. Lung Cancer in Women • Lung cancer will kill about 72,130 American women this year • Kentucky leads the nation in lung cancer deaths • With a given smoking exposure, women are more likely to get lung cancer • Women are more likely than men to dieof lung cancer • Kentucky leads the nation in adult smokers • 32.6% (#2 is Alaska at 29.4%) • About 90% of lung cancer deaths in women are related to smoking • Second hand smoke counts • A family history of lung cancer, but not other cancers, increases risk for lung cancer • The risk of inherited lung cancer is greater for women than men • The risk is most easily identified in non-smokers • Those with a family history of lung cancer could be considered high-risk

17. At this time, there is insufficient evidence that screening of asymptomatic persons improves survival High false negatives on chest X-ray High false positives on CT Scan Poor sensitivity when screening sputum for cancer cells Prevention is Essential Lung Cancer Screening?

18. Breast Cancer • Breast cancer is the second leading cause of cancer deaths in all women, and the leading cause in young women • 1 in 8.2 women will develop breast cancer in their lifetime • 1 in 30 women will die from breast cancer • Risks • Genes • Mutations in BRCA1 and BRCA2, cancer suppressing genes, are associated with breast, ovarian, and prostate cancer • Environmental Risks • Estrogen • Early menarche, late menopause, nulliparity • Hormone replacement therapy (2002 WHI study and 2006 NHS) • 24% increased risk after 5 years for combination estrogen-progestin • Significant risk for estrogen only after 15-20 years (42% after 20 years) • Especially significant risk for thin women • High-dose radiation, obesity, heavy alcohol use • Protection from risk • Exercise, diet

19. Breast Cancer Screening • Screening mammography should be performed every 1-2 years for women aged 40 and older • Little evidence separating 12-33 month intervals • With or without clinical breast exam • Insufficient evidence for breast self-exam • Evidence that digital mammography superior to traditional mammography • Effectiveness of early detection • Strongest for women aged 50-69 • Most, but not all studies, show reduction in mortality for women 40-49 • One study demonstrating reduced mortality for women 65-74

20. Colon Cancer • Colorectal cancer effects women and men equally and is the 3rd leading cause of cancer death in women • 60% of patients with colorectal cancer have regional or distant metastases at the time of diagnosis • 5-year survival • 91% for localized disease • 60% for regional disease • 6% for distant metastatic disease

21. Risk Factors for Colon Cancer • Family history • Familial syndromes account for 6% of colorectal cancers • Family history increases the risk by up to 4x in those 40-60 • Prior diagnosis of endometrial, breast or ovarian cancer • Personal history of polyps • Diets high in fat, low in fiber

22. Colon Cancer Screening • Should begin at age 50 • Yearly test for blood in the stool • Flexible sigmoidoscopy • Colonoscopy • Especially important for women as cancers tend to be in the proximal colon 64.8% of the time • Screen earlier in high-risk patients

23. Diabetes, Hypertension, Hyperlipidemia, and Heart Disease • Genes and exposures control risks for metabolic diseases • Metabolic diseases (and smoking) are the most important risks for heart disease • Heart disease is the #1 killer of women • Preventing these chronic diseases is essential for health, wellness and longevity • Behavioral factors are critical for preventing these diseases

24. Preventing Metabolic and Heart Diseases • Know your family history • Maintain a normal body weight • Exercise regularly • Eat healthy foods • Control blood pressure, blood sugar and cholesterol • Use medications if needed • Don’t smoke • More than ½ of heart attacks in women under 50 are related to smoking

25. Screening for Metabolic Diseases Associated with Heart Disease • Diabetes • Screen for type 2 diabetes in adults with hypertension or hyperlipidemia • Yearly fasting glucose for all starting at 45 years of age and younger for those with risk factors • Family history of type 2 diabetes, overweight, and hypertension • Hypertension • Screen in adults aged 18 or older • Weight reduction, exercise and reduced salt intake helpful • Early treatment and good follow-up reduces all cause mortality 17% • Hyperlipidemia • Women should be screened starting at age 45 (men at age 30) • Screen earlier if other risk factors for heart disease present • Women age 20 or higher • Measure total cholesterol LDL (bad) and HDL (good) cholesterol • Diet can lower cholesterol, but drug treatment lowers risk of death • Treat to LDL <100 (<70 if other risk factors) • Routine screening for coronary artery disease in asymptomatic women is not recommended

26. What about Body Weight? Underweight is associated with smoking and osteoporosis; overweight with diabetes, hypertension, and heart disease N Engl J Med. 2006 Aug 24;355(8):763-78

27. Obesity Trends* Among U.S. AdultsBRFSS,1990, 1995, 2005 (*BMI 30, or about 30 lbs overweight for 5’4” person) 1990 1995 2005 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

28. Why this Epidemic? http://www.cdc.gov • Overweight and obesity result from an energy imbalance. This involves eating too many calories and not getting enough physical activity.  • Body weight is the result of genes, metabolism, behavior, environment, culture, and socioeconomic status.  • Behavior and environment play a large role causing people to be overweight and obese. These are the greatest areas for prevention and treatment actions. • “Despite obesity having strong genetic determinants, the genetic composition of the population does not change rapidly. Therefore, the large increase in . . . [obesity] must reflect major changes in non-genetic factors.”

29. Obesity in Kentucky • The epidemic in Kentucky • 63% of adults in Kentucky are obese or overweight • 30% of Kentucky high school children are overweight or at risk of becoming overweight • 35%of lower-income children between the ages of 2 and 5 are overweight or at risk of becoming overweight • Kentucky nutrition and physical activity plan • New standards for nutrition and physical activity in schools through legislation (Senate Bill 172) passed in March 2005, the state’s first public policy created in direct response to the obesity epidemic

30. Impacting Obesity

31. Aspirin? • Aspirin thins the blood to reduce blood clots that can cause heart attack and stroke • The benefits of low-dose aspirin differ in men and women • In women aged 40-65, aspirin did NOT reduce the risk of a first heart attack, but did reduce the risk of stroke (more common in women) • After age 65, aspirin use decreased the risk of heart attack by 34% • Remember that aspirin can cause ulcers and bleeding, a side effect that increases with age and with the use of other non-steroidal drugs (ibuprofen, naproxen)

32. Other Issues of Preventative Health • Osteoporosis • Risk factors • Female, advanced age, Caucasian race, low-body weight, surgical removal of ovaries before menopause, smoking, alcohol use, glucocorticoid use • 50% of post-menopausal women will develop a spontaneous fracture • 15% of women will sustain a hip fracture • Screening • All women aged 65 and older should be screened • Women with risk factors should be screened at age 60 • Prevention • Calcium and vitamin D – lifelong!! • Weight-bearing exercise • Estrogen – increased bone density and reduces fractures

33. Hormone Replacement Therapy • Benefits and Harms • Benefits • Reduced osteoporosis and fractures • Reduced colon cancer • Harms • Breast cancer • Contraindications • Absolute • Undiagnosed vaginal bleeding, breast or endometrial cancer, recent blood clot • Relative • Liver disease, melanoma, gallstones, increased triglycerides, endometriosis, fibroids, history of blood clots

34. Vitamins and Supplements • Eating a wide variety of foods, including fruits, vegetables, whole grains, legumes and lean meats • Vitamin and mineral supplements may be needed if: • Poor dietary habits • Less than 1,200 calories a day • Problems with absorption • Folic Acid • All women during reproductive years • Multivitamin or breakfast cereal • Calcium and Vitamin D • Iron • If heavy menstrual bleeding • Pregnant or trying to become pregnant • Other vitamins, minerals or supplements? • Omega-3 Fatty Acids • Fish or supplements • Reduces inflammation and heart disease • Fiber • Promotes healthy bowel function, reduces colon cancer, and may decrease risk of health disease

35. Vaccinations • Influenza A: Yearly • For those at risk or who care for those at risk • Adverse effects rare • Pneumococcal: Every 5 years • Elderly (>65), chronically ill or immunocompromised • Tetanus and diptheria: Every 10 years • Measles, mumps, rubella: One time • Hepatitis B: One time • All under 18 and high risk groups • Meningiococcal • High risk groups (including residents of dormitories) • Human papilloma virus? • Example of policy issue • Detectable in 75-95% of cervical cancer

38. Risk Behaviors are Established Early in Life • Smoking • More than 1 in 5 high school students are current smokers • Unhealthy dietary behaviors • Almost 80% of high school students do not eat the recommended 5 servings of fruits and vegetables • Inadequate physical activity • Nearly 1 and 3 children and adolescents are overweight or at risk of becoming overweight • Alcohol an other drug use • Sexual behaviors that may results in HIV infection, other sexually transmitted diseases, unintended pregnancy • Every year, more than 870,000 adolescents become pregnant and over 3 million become infected with a sexually transmitted disease • Behaviors that contribute to unintentional injuries and violence • Not wearing seat belts, riding with a driver drinking alcohol, carrying a weapon

39. Incorporates concepts of being physically and mentally healthy Exclusive of specific disease Includes some components of functional capacity or activity Adds positive psychological constructs of happiness and life satisfaction Concept of “Wellness” in Health

40. Health-Related Quality of Life • Americans said they feel unhealthy (physically or mentally) about 6 days per month • Americans said they feel "healthy and full of energy" about 19 days per month • Nearly one-third of Americans say they suffer from some mental or emotional problem every month—including 10 percent who said their mental health was not good for 14 or more days a month • Younger American adults, aged 18–24 years, suffered the most mental health distress • Older adults suffered the most poor physical health and activity limitation • Adults with the lowest income or education reported more unhealthy days than did those with higher income or education • Americans with chronic diseases or disabilities reported high levels of unhealthy days

41. Mean Number of Unhealthy Days by State: Kentucky Leads the Nation

42. Depression/anxiety/ emotional problems Cancer Diabetes Stoke High blood pressure Back or neck problems Heart problems Lung/breathing problems Walking problem Fracture/joint injury Arthritis/rheumatism Eye/vision problem Hearing problem Main Factors Associated with Health and Activity Limitations

44. What Kinds of Things Cause Stress? Then And Now • Predators • Escaping • Surviving attack • Weather extremes • Drought • Heat • Cold • Starvation • Parasites • Deadlines • Too much to do; to little time • Conflicts at home • Divorce • Illness • Worries about children • Discord at work • Interpersonal conflicts • Lack of respect/control • Money worries • Daily hassles • Traffic, rude behavior

45. Coping Style Life Experience Learning Genetics Context Stress and Adaptation Individual Response Stressor Allostasis

46. Hypothalamus Slow wave sleep Determinants of the Stress Response Circadian Rhythm Stress • Genetics • Early life experiences • Childhood maltreatment • Deprivation • Family stress • Chronic stress • Social hierarchy • Instability • Coping • Glass half full/empty: Optimism • Locus of control • Learned helplessness CRH Pituitary ACTH Cortisol Adrenal Cortex 20 Cortisol mg/dL 10 0 700 1300 1900 100 700 Time

47. Exposure to violence is an important cause of physical and mental health problems • 12-14% prevalence in Emergency Rooms • 21-37% prevalence in primary care settings • Associated with stress-associated disorders • Continues during pregnancy • Important cause of injury and death during and after pregnancy • Mental health conditions associated with interpersonal victimization • Depression, anxiety, post-traumatic stress disorder, suicidality, hopelessness and low self-esteem

48. 75% reported multiple forms of IVP 74% injured and 69% more than one type of injury 44% report children present during abuse 40% of perpetrators use children to threaten 39% abuse increased throughout relationship 20% abused during pregnancy 15% perpetrator harmed a pet 5% perpetrator killed a pet Exposure to Intimate Partner Violence in Kentucky

49. Myth Health inevitably declines as we get older Reality People of any age can improve their health by adopting healthy behaviors Healthy Aging

50. Insights from Centenarians: “the older you get, the healthier you’ve been”Thomas Perls, MD, MPH • Genetics is important • Absence of disease-causing genes and presence of longevity-enabling genes • Siblings live longer • Children have lower mortality • Lower prevalence of age-related chronic disease • Lower body mass index • Healthy cognitive functioning is a better predictor of independence than physical health • Some people markedly delay or escape age-associated brain diseases • Impact of chronic diseases important • Diabetes, heart disease, cancer, etc • 20% completely escape chronic disease • 40% have marked delay until after age 85 • 40% develop diseases before 65, but survive long after diagnosis