Update in Women’s Health

1. Update in Women’s Health Amparo Villablanca, MD Professor, Cardiovascular Medicine Frances Lazda Endowed Chair, Women’s Cardiovascular Med. University of California, Davis Judith Walsh, MD, MPH, FACP Professor of Medicine Women’s Health Center of Excellence University of California, San Francisco

2. OVERVIEW CVD Prevention in Women Angina With Normal Coronary Arteries Menopause and Hormone Therapy Osteoporosis Vitamin D Cancer Screening

3. CVD PREVENTION IN WOMEN

4. Clinical Case A 58 yo woman presents for cardiovascular risk assessment. She has a BP of 148/80, TG of 170, FBS of 100, and is a non-smoker. She does not exercise regularly and eats ‘whatever tastes good’. Her Echo shows LVH. What do you tell her about her CV risk?

5. CLINICAL QUESTIONS How are the CVD risk categories defined? How do you calculate CVD risk? Does the Framingham risk calculator still have a role?

6. BACKGROUND CVD is the leading cause of death in women Women are under-treated and lifetime risk is often underestimated Prior use of just Framingham risk score alone led to too narrow of a focus on short-term 10 year risk Too many women were incorrectly categorized as low risk ‘At risk’ category now greatly expanded, and ‘lower risk’ category has narrow definition

7. What is this woman’s CVD risk? Lower Risk At Risk High Risk

8. CVD RISK CATEGORIES High Risk: Established CVD/PVD CVD risk equivalent (DM) CRI Framingham risk >20% Lower Risk: No CVD risk factor AND Healthy Lifestyle (Diet + Exercise) At Risk: Major CVD risk factor(s) Evidence of Subclinical Disease Family Hx; Limited exercise capacity

9. PREVENTIVE INTERVENTIONS Effective preventive interventions: 1. Therapeutic lifestyle changes: implement in all women 2. Management of major CVD risk factor(s): follow established guidelines (e.g. Lipids- ATPIII; HTN- JNCVII) 3. Drug therapy (ACEI, BB, Aldactone if EF <40% or MI) 3. Additional preventive interventions: Depression screening, cardiac rehab, omega 3 fish oil- all high risk women Caveats re. ASA: All high risk women women age >65 for CVA prevention some intermediate risk women Contraindicated interventions: Antioxidants, MHT

10. IMPACT FOR PRACTICE Gender-specific guidelines for heart disease prevention in women published & updated A woman’s lifetime risk of CVD is high Level of aggressiveness in prevention and treatment needs to match lifetime risk level ASA should not be used in all women Exercise capacity is a determinant of risk Very few women will fall into the lower risk category

11. KEY ARTICLES Evidence-Based Guidelines for Heart Disease Prevention in Women: 2007 Update AHA (Mosca, L.), Circulation 2007 AHA (Mosca, L.), Circulation 2004

12. ANGINA WITH NORMAL CORONARY ARTERIES

13. CLINICAL CASE A 58 yo postmenopausal woman returns to you for follow up after undergoing cardiac cath due to persistent chest pain (intense ‘constricting’ pain, persisting >30 min, radiating to sub-mammary areas, variable threshold with physical activity, some association with emotional stress/palpitations). She had a nuclear medicine myocardial perfusion study that was positive for ischemia, but cardiac cath showed normal coronary arteries. She wonders if her heart is ‘fine’. What do you advise her?

14. What do you tell her about her symptoms? Her nuclear medicine study was likely a false positive Her symptoms are likely not cardiac Her symptoms may be due to GERD or anxiety She needs further management

15. CLINICAL QUESTIONS What is the pathogenesis of angina with normal coronary arteries? What is the clinical outcome for this group of patients? Is reassurance alone the most appropriate course of action?

16. BACKGROUND 55% of women with CAD present with angina. Approximately 58% of women undergoing cardiac cath for angina will have normal cors or non flow-limiting disease. A significant proportion of these patients have abnormalities of vascular function (endothelial dysfunction), coronary flow reserve (microvascular disease), or both. Prinzmetal’s angina (coronary vasospasm) is a rare syndrome. High health care costs & re-admissions rates due to persistence of sx are associated with non treatment.

17. MANAGEMENT ACEI Beta blocker Statin Exercise training L-Arginine Imipramine Ranexa Calcium channel blockers not effective

18. IMPACT FOR PRACTICE Systematic complete evaluation first for CAD Ischemic syndromes with normal cors are common Prognosis not as benign as previously thought Reassurance alone is not appropriate Relatively high rates of progression to obstructive CAD Higher rate of adverse cardiac events (MI, CVA, CHF, sudden death): 14% 2-yr, 30% 10-yr event rate --It is important to treat the ischemia to control sx--

19. KEY ARTICLES Women’s Ischemic Syndrome Evaluation Study (WISE) WISE, Circulation 2004 WISE, Johnson, 2003 Bugiardini, Circulation 2004

20. VASOMOTOR SYMPTOMS

21. Vasomotor Symptoms Minnie Pause is a 53 year old woman who had her last menstrual period 18 months ago. She is still having hot flashes and awakens at least twice a night with them. She is considering taking estrogen but wants to know how much longer this will last. What do you tell her?

22. What do you tell her about when they will go away? Average duration is about 2 years and so they should be gone in about 6 months. Average duration is about 4 years They will never go away

23. BACKGROUND Treatment for menopausal symptoms is based on their transitory nature Many clinical guidelines suggest that symptom duration is approximately 2 years Many studies do not follow women more than 2 years Risks and benefits of hormone therapy depend on duration of use “Use lowest dose for shortest duration”

24. CLINICAL QUESTIONS What is the natural progression of vasomotor symptoms during the menopause transition? How long is it safe to use hormone therapy?

25. DURATION OF VASOMOTOR SYMPTOMS Politi MC et al. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. JGIM 2008:23: 1507-13 Objective: to estimate the natural progression of menopausal symptoms

26. Vasomotor symptoms Rigorous meta-analysis included 10 studies with over 35,000 participants Clear definition of vasomotor symptoms Assessed prevalence of symptoms and “bothersome symptoms”

27. Results Percent of women with symptoms increased in the two years before the final menstrual period (FMP) , peaked one year after the FMP and did not return to premenopausal levels until 8 years after the FMP 50% of women had symptoms during the 4 years after FMP 10% of women had symptoms up to 12 years after FMP

28. Results: Bothersome Symptoms

29. Impact for practice Menopausal symptoms last about 4 years Risks and benefits of hormone therapy must be considered within the longer period of use

30. Key articles Evidence based guidelines for the use of hormone therapy Risk defined as “possibility or chance of harm” Put level of risk in perspective HT should not be used as an anti-depressant No data to support any particular route of administration or dosing regimen Use greater caution in women over 60 NAMS, Menopause, 2008

31. OSTEOPOROSIS

32. Question Bonnie Bony is a 71 year old woman who you started on a weekly bisphosphonate a year ago for a hip BMD score of -2.8. She comes in today wondering when she should have her next bone density. When would you recommend that she have her next bone density test?

33. Question Now Next year In two more years Never

34. BMD Monitoring Bell K et al. Value of routine bone mineral density monitoring after starting bisphosphonate treatment: a secondary analysis of trial data. BMJ 2009: 338: B2266 AIM: To evaluate the usefulness of routine monitoring of BMD among women on bisphosphonate treatment

35. MONITORING TREATMENT Recent analysis of data from the FIT study Over 3 year follow-up, comparison of between person variation (treatment) with within person variation (measurement) Within person variation was greater than between person variation 97.5% of individuals gained BMD with alendronate treatment Routine monitoring in the first 3 years of bisphosphonate treatment is unnecessary

36. MONITORING TREATMENT? Treatment should be continued in patients who lose BMD initially Patients who have the largest increases during the first year are more likely to lose or have modest gains during the second year If most women will gain BMD with treatment and since resistance to osteoporosis drugs has not been documented, there may not be value in monitoring BMD during treatment Will monitoring reinforce adherence?

37. Follow-up Bonnie Bony calls your office several weeks later to inform you that she has stopped her bisphosphonate because she has been reading about an increased risk of fractures in women who take these medications. What are you going to advise her?

38. Femoral Shaft Fractures Black DM et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. NEJM 2010:362:1761-71 AIM: To determine the incidence of femoral shaft fractures in patients in bisphosphonate RCTs

39. Background Several case series have described an increased risk of atypical femoral shaft fractures in bisphosphonate users Subtrochanteric fracture makes up 2-4% of all hip fractures No estimate of population prevalence In population based registries, fracture rates higher in alendronate users Increased alendronate use in high risk individuals

40. RESULTS 284 hip or femur fractures in 14,195 women in 3 randomized trials 12 were subtrochanteric or diaphyseal Relative hazards RH 1.03 (95% C.I. 0.06, 16.46) for alendronate use in FIT RH 1.50 (95% C.I. 0.25, 9.00) for zoledronic acid use in HORIZON-PFT RH 1.33 (95% C.I. 0.12, 14.67) for continued alendronate use in FLEX

41. CONCLUSIONS Fracture of subtrochanteric or diaphyseal femur was very rare even in women on bisphosphonates for up to 10 years There was no significant increase in risk but confidence intervals were wide Small number of events

42. IMPACT Even if there is a small risk of atypical fracture associated with bisphosphonate use, this must be weighed against the population benefits associated with an overall reduction in hip fractures with bisphosphonates in women with osteoporosis

43. VITAMIN D

44. Case Violet D. is a 69 year old woman who comes in for a health care maintenance exam. You order a bone mineral density. She tells you she also wants a Vitamin D level checked. What do you do?

45. Question: Vitamin D Order a Vitamin D level Don’t order a Vitamin D level because you are not sure to do with the results Don’t order it but start her on a calcium/Vitamin D supplement

46. BACKGROUND Vitamin D deficiency is common in older adults, homebound individuals and women admitted with hip fracture Association between Vitamin D level and fracture risk is inconsistent Association could be influenced by renal function, muscle strength and estrogen receptors

47. CLINICAL QUESTIONS What is the association between Vitamin D level and fracture? Does Vitamin D prevent fracture? When should Vitamin D levels be checked? When and how should Vitamin D supplementation be given?

48. VITAMIN D AND HIP FRACTURE RISK

49. Vitamin D and Fracture Linear association suggests dose-response effect No difference by age or geographic region Low serum 25 (OH) vitamin D concentrations can help identify women at high risk for hip fracture Does Vitamin D supplementation prevent fracture?

50. Vitamin D and Fractures Bischoff-Ferrari HA, Willett WC, Wong JB et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: meta-analysis of randomized controlled trials. Arch Intern Med 2009: 169: 551-61 AIM: To determine whether oral Vitamin D can prevent non-vertebral and hip fractures