Managing a Healthy Menopause Transition Priorities for Consideration - PDF document

10/17/2019 Managing a Healthy Menopause Transition Health Considerations for all • Menopausal Women Managing a Healthy Menopause “The menopause transition, a portal Transition: Portal to the Second Half of Life to the second half of life, provides a critical window to:  Reassess lifestyle  Recognize ongoing and Cynthia A. Stuenkel, MD potential health concerns Clinical Professor of Medicine, Department of Medicine  Encourage a proactive approach Division of Endocrinology and Metabolism to future well ‐ being” University of California, San Diego, School of Medicine Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, Santen RJ.. J Clin Endocrinol Metab 2015;100:3975 ‐ 4011. Managing a Healthy Menopause Transition Priorities for Consideration  Cardiovascular (and brain) health  Cancer prevention  Bone health Brown HL, Warner JJ, et al. Circulation 2018;137:e843 ‐ e852. 1

10/17/2019 Preventive Strategies for Optimizing A Wider “CV Window” of Opportunity? Cardiovascular Health in Women  Routinely screen for CVD risk every 4 to 6 years in women starting >20 years Risk evaluation  Consider compelling factors Standardized risk assessment tools ‐ Pregnancy Imaging to improve risk stratification Emerging risks in women ‐ Breast cancer Review risk management ‐ Menopause Lifestyle  Ask retrospectively at midlife Control of hypertension, diabetes, dyslipidemia  Better to engage in primary prevention early Nabel EG. Circulation 2015; 132:989 ‐ 991; Brown HL, Warner JJ, et al. Circulation 2018;137:e843 ‐ e852. . Women’s Healthy Lifestyle Project Women’s Healthy Lifestyle Project  Randomized clinical trial With premenopausal diet and exercise intervention,  275 control and 260 lifestyle participants mean age 47 yr women transitioning through menopause were able to:  Mean body index at baseline 25 kg/m 2  Stave off midlife weight gain ( ‐ .2 lb vs +5.2 lb)  Intervention: reduced saturated fat and cholesterol intake  Reduce waist circumference ( ‐ 2.9 cm vs 0.5 cm)  Prevent weight gain by decreased caloric and fat intake and  Reduce anticipated increase in LDL, TG, glucose increased physical activity  Reduce progression of subclinical atherosclerosis on  By 54 months, 35% were postmenopausal carotid intima ‐ media thickness 2 Kuller LH, Circulation , 2001;103:32 ‐ 37; Wildman RP, J Am Coll Cardiol 2004;44:579 ‐ 585. Kuller LH, Circulation , 2001;103:32 ‐ 37; 2. Wildman RP, J Am Coll Cardiol 2004;44:579 ‐ 585. 2

10/17/2019 Modest Caloric Reduction Improves Cardiometabolic Health  RCT of 218 nonobese adults ages 21 ‐ 50  Targeted 25% fewer calories/day  After 2 years:  Achieved 12% fewer calories ( ‐ 279 cal/d)  Lost 16.5 lb or 10% of body weight  All cardiometabolic risk factors improved  How? Just do not eat after dinner Rubin R. JAMA 2019; August 28; Krauss W, Lancet Diabetes and Endocrinology , 2019 Li Y, et al. Circulation 2018;137: April 30 Estimated Life Expectancy at age 50 Estimated Life Expectancy at age 50 According to Number of Low ‐ Risk Factors According to Number of Low ‐ Risk Factors During 34 y of follow ‐ up, the multivariate adjusted Low ‐ Risk Lifestyle Factors HR for mortality in adults with 5 compared with  Never smoking zero low ‐ risk lifestyle factors were:  BMI 18.5 ‐ 24.9 kg/m 2 All ‐ cause Cancer CVD  > 30 min/d moderate to vigorous physical activity 0.26 0.35 0.18  Moderate alcohol intake (0.22 ‐ 0.31) (0.27 ‐ 0.45) (0.12 ‐ 0.26)  High diet quality score Li Y, et al. Circulation 2018;137: April 30 Li Y, et al. Circulation 2018;137: April 30 3

10/17/2019 Estimated Life Expectancy at age 50 According to Number of Low ‐ Risk Factors Menopause Transition: Cognition/Memory Li Y, et al. Circulation 2018;137: April 30 Maki PM and Henderson VW. Menopause 2016;23:803 ‐ 805. Want to prevent dementia? Menopause Transition: Cognition/Memory Improve everyday health habits  World Health Organization Risk Reduction of Cognitive Decline  If the history and PE do not raise new concerns of a  Recommends regular exercise, maintaining a healthy weight, neurologic disorder, assure the patient that cognitive symptoms are: regulating blood sugar levels, and keeping cholesterol within  Common recommended limits  Usually self ‐ limited  Give up unhealthy habits: drinking and smoking 1  Not known to lead to dementia later in life  In UK Biobank study, favorable lifestyle was associated with a  Emphasize that brain health is promoted by factors that lower dementia risk, even in adults with a high genetic risk 2 maximize cardiovascular health  ‘Strategies that are good for your heart and overall health are  Check and treat risk factors; improve lifestyle good for your brain’ 3 1.WHO Guidelines; Geneva, 2019; 2. Lourida I, et al. JAMA 2019 July 14; 3. Harvard Women’s Health Watch , Vol. 26: Number 12, August 2019 Maki PM and Henderson VW. Menopause 2016;23:803 ‐ 805 4

10/17/2019 CVD and Breast Cancer Shared Risk Factors Mehta LS, et al. Circulation 2018;137:e30 ‐ e66. Mehta LS, et al. Circulation 2018;137:e30 ‐ e66. Postmenopausal Women with ‘Normal’ Insulin Resistance and Cancer ‐ Specific and BMI may be Overweight or Obese All ‐ Cause Mortality: The WHI WHI RCT and Observational Study  22,837 participants aged 50 ‐ 79 y  N=156,624  Baseline fasting glucose and insulin levels (HOMA ‐ IR)  BMI < 30 kg/m2  18.9 years follow ‐ up  Waist circumference > 88 cm  Higher HOMA ‐ IR quartile (even in women with BMI < 25)  2.6% of study population Elevated risk: associated with higher:  All ‐ cause mortality HR 1.31  Cancer ‐ specific mortality HR 1.26 p=.003  CVD 1.24  All ‐ cause mortality HR 1.63 p<.001  Cancer mortality 1.20 Pan K, et al. J Natl Cancer Inst 2019 Apr 26; HOMA ‐ IR, homeostasis model assessment of insulin resistance Rubin R. JAMA 2018;319:1185 ‐ 1187; Sun Y et al. JAMA Network Open 2019; July 3. 5

10/17/2019 Studies Linking Healthy Lifestyle Cancer Overtakes CVD as Leading with Lower Cancer Risks Cause of Death in Wealthy Nations  A healthy ‘lifestyle index’ was associated with a  Worldwide, CVD remains the leading cause of lower risk of endometrial cancer; HR 0.61 (.51 ‐ .72) 1 mortality  Postmenopausal women who lose weight have  In High Income Countries lower breast cancer risk; HR 0.88 (.78 ‐ .98); p=.02 2  Cancer mortality 1.7 deaths/ 1000 person ‐ yr  In women assigned to a low ‐ fat dietary pattern, a  Death from CVD 0.6 deaths/ 1000 person ‐ yr reduction in deaths after breast cancer resulted; HR 0.65 (.45 ‐ .94); p=.02 3 1. Arthur R, et al . Am J Epidemiol 2019; 188:261 ‐ 273. HLI : diet, alcohol, physical activity, BMI, smoking; Dagenais GR, et al . Lancet 2019; Sept 3 2. Chlebowski RT, et al. Cancer 2019; 125:205 ‐ 212; 3.Chlebowski RT, et al. JNCI Cancer Spectr 2019 Jan 7 Fracture Risk and the Menopausal Transition Early Intervention to Prevent Osteoporosis  Between ages 42 and 58 y, 1 in 6 women in SWAN fractured Lifestyle modification  Predicted by:  Physical activity in midlife  Low BMD  Indices of femoral neck composite strength  Associated with larger femoral neck composite strength indices  High levels of U ‐ NTX  Healthy diet  Additional factors:  Adequate calcium intake  Low education in nonwhite women  Diabetes  Maintain serum 25 ‐ OH Vit D > 20 ng/mL  Chronic inflammation: C ‐ reactive protein > 3 mg/L  Lower levels associated with 85% higher fracture risk  Plasma triglycerides > 300 mg/dL  Obesity: greater impact forces in a fall  Smoking cessation, temper alcohol, review medications Karlamangla AS, et al. Obstet Gynecol Clin N Am 2018;45:695 ‐ 708. Karlamangla AS, et al. Obstet Gynecol Clin N Am 2018;45:695 ‐ 708. 6

10/17/2019 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Part 1, Lifestyle and Behavioral Factors  Team ‐ based care is an effective approach  Incorporate social determinants of health into plan  Healthy diet: vegetables, fruits, nuts, whole grains, fish  > 150 minutes/wk of moderate intensity physical activity (or 75 min/wk of vigorous ‐ intensity  Achieve and maintain weight loss if overweight/obese  Strongly advise to quit tobacco use (at every visit) Arnett DK, et al. JAMA Cardiology 2019; July 31 Arnett DK, et al. JAMA Cardiology 2019; July 31; Arnett DK, et al. Circulation 2019;140:Sept 10 Managing a Healthy Gretchen Reynolds Tuesday, September 24, 2019 Menopause Transition Summary and Conclusions  Healthy lifestyle contributes to longevity and quality of life  Improvements achieved in cardiovascular, cognitive, and bone health with reduced malignancy and mortality risk  Small steps may accrue large benefits “Interestingly, while both groups included men and women, the latecomers featured a much larger percentage of women.” 7