EB Gold NAMS Presentation 10/06/2016 No financial relationships to - PDF document

EB Gold NAMS Presentation 10/06/2016  No financial relationships to disclose Ellen B. Gold, PhD Dept. Of Public Health Sciences University Of California Davis  Vasomotor symptoms (hot flashes/flushes, night sweats) affect 50-80% of women undergoing the menopause transition  Urinary incontinence affects about half of midlife women  Sleep disturbances affect 15-40% of midlife women  All of these affect quality of life in the millions of women annually undergoing the menopause transition and incur in total billions of dollars in health care costs annually 1

EB Gold NAMS Presentation 10/06/2016  20-year longitudinal cohort study of the menopause transition funded by NIA, NINR, ORWH, NCCAM  Objectives  7 sites, each recruited minority sample  Design ◦ Michigan African Americans ◦ MGH - Boston  Methods African Americans ◦ Rush – Chicago African Americans  Results ◦ UCD/Kaiser – Oakland Chinese ◦ Baseline characteristics of study sample ◦ UCLA Japanese ◦ New Jersey Hispanic ◦ Symptoms: Hot flashes and night sweats, Urinary ◦ Pittsburgh African Americans incontinence, Sleep, Vaginal dryness  2 central labs (Michigan, MRL); Coordinating center - Pittsburgh *Funded by NIA, NINR, ORWH, NCCAM; no financial conflicts or other disclosures  Screened 16,025 community-based women for cohort eligibility (age 42-52 years, menstrual period in last 3 months, intact  To identify factors that affect the timing and nature (eg, uterus and >1 ovary, no exogenous hormone use, not endocrine changes, symptoms) of the menopause pregnant) transition and  Annual visits; 3302 at baseline, 2502 at visit 13: ◦ Annual in-person interview, self-administered questionnaire  To identify the characteristics of the transition that are and food frequency questionnaire (baseline, 05, 09) related to long-term disease risk indicators, such as changes in cardiovascular risk markers and bone density. ◦ Fasting blood sample drawn on cycle days 2-5 for serum E2, T, FSH, SHBG, DHEAS, glucose, insulin, clotting factors and lipoprotein levels 2

EB Gold NAMS Presentation 10/06/2016 ◦ Annually measure blood pressure, weight, height and waist and hip circumference ◦ At 5 sites measure bone density annually  Objectives ◦ In subset of 990, one cycle daily urine (urinary E1C, PdG, FSH, LH) and daily symptom diary  Design and Methods  Monthly calendar: menstruation, sx, procedures  Results  Visit 4 cognitive tests began; at visit 12 physical function ◦ Vasomotor symptoms tests began  Longitudinal analyses: Repeated measures, multi-variable analyses to account for multiple observations on the same woman and many confounding variables  Affect the majority of women undergoing menopause transition (Gold Baseline African Cauc. Hisp. Chinese Japanese et al. Amer J PH 2006) Characteristic Amer.  Associated with higher factor VIIc and tPA-ag (Thurston Menop 2011), 46.1 46.1 46.1 46.6 46.7 Median Age CV disease risk (Huang Menop 2009; Roussouw JAMA 2007) and (years) lower bone density (Crandall Menop 2009) % < $50,000 annual hshld 63.1 39.1 91.0 39.2 25.3  Frequency and severity of hot flashes related to quality of life and income sleep (Pinkerton Menop 2016) 24.6 16.6 16.7 1.6 12.9 % Smokers  A chief menopause-related symptom for which US women seek % >6 days HF 14.8 10.2 13.4 6.8 4.3 medical care (Williams Maturitas 2007; Nicholson Am J Obstet in past 2 wks Gynecol 2001), have higher number of outpatient visits (Sarrel Menop % Premenop 49.5 52.3 57.9 61.9 62.2 2015)  Annual direct and indirect costs in hundreds of millions of dollars in US Median BMI 30.2 26.1 28.3 22.4 22.1 3

EB Gold NAMS Presentation 10/06/2016  Assessed VMS for > 6 days in prior 2 weeks (frequent VMS) through follow-up visit 13  Excluded women who reported: ◦ Hysterectomy or oophorectomy during follow-up (n=330) ◦ Initiation of HT before first report of frequent VMS (n=583) ◦ No visits with frequent VMS (n=940)  Assessed persistence of VMS in women with known FMP date who reported frequent VMS at >1 visit after the FMP (n=881) Gold et al, Avis et al, AJPH 2006 JAMA Int Med 2015 4

EB Gold NAMS Presentation 10/06/2016 Total Duration of Frequent VMS by Menopausal Post FMP Persistence of Frequent VMS by Status at First VMS Report Menopausal Status at First VMS Report Premenopausal (N=183) 1.0 Early perimenopausal (N=700) 1.0 Late perimenopausal (N=266) Premenopausal (N=72) 0.9 Postmenopausal (N=291) Early perimenopausal (N=348) All Participants (N=1449) 0.9 Late perimenopausal (N=191) 0.8 Postmenopausal (N=268) 0.8 Proportion of Women All Participants (N=881) 0.7 Proportion of Women 0.7 0.6 0.6 0.5 0.5 Median 3.4 0.4 Median 7.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Duration of Frequent VMS (years) Post-FMP Persistence of Frequent VMS (years) Avis et al, Avis et al, JAMA Int Med 2015 JAMA Int Med 2015 Post FMP Persistence of Frequent VMS by Total Duration of Frequent VMS by Race/Ethnicity Race/Ethnicity African American (N=479) 1.0 White (N=652) 1.0 African American (N=310) Chinese (N=95) 0.9 Hispanic (N=109) White (N=380) 0.9 Chinese (N=65) Japanese (N=114) 0.8 Hispanic (N=50) All Participants (N=1449) 0.8 Japanese (N=76) Proportion of Women Proportion of Women All Participants (N=881) 0.7 0.7 0.6 Median 10.1 0.6 0.5 0.5 0.4 Median 4.8 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Duration of Frequent VMS (years) Post-FMP Persistence of Frequent VMS (years) Avis et al, Avis et al, JAMA Int Med 2015 JAMA Int Med 2015 5

EB Gold NAMS Presentation 10/06/2016 Factor Cessation over Total Duration Post FMP Cessation HR (95% CI) Median Years HR (95% CI) Median Years Age at onset, years 45-49.9 2.43 (1.30-4.51) 9.34 Ref 6.76 50-54.9 2.71 (1.44-5.09) 7.73 1.16 (0.84-1.60) 5.72 >55 3.60 (1.78-7.29) 6.42 1.53 (1.05-2.24) 4.48 > College 1.25 (1.03-1.52) 7.66 1.40 (1.13-1.74) 4.54 Sx sens. V1 low 0.77 (0.58-1.00) 9.57 0.76 (0.56-1.04) 5.48 moderate 0.85 (0.64-1.13) 8.22 0.78 (0.57-1.07) 5.45 high 0.64 (0.46-0.89) 10.81 0.58 (0.39-0.85) 8.47 Some perceived 0.75 (0.58-0.96) 10.78 0.70 (0.54-0.91) 8.13 stress a HR=hazard ratio for VMS cessation Avis et al, JAMA Int Med 2015 Factor Total Cauc. Afr. Hisp. Chin. Japan Amer. .  Melbourne Women’s Midlife Health (Col et al 2009) : shorter total duration (5.2 years) for bothersome VMS (mostly white, Age 1.17** 1.16** 1.18** 1.04 1.29** 1.30** excluded those with VMS at baseline, VMS at last visit (per year) considered no VMS) BMI 1.03** 1.03 1.02 1.03 1.03 1.05  Penn Ovarian Aging : longer total duration, 10.2 years, and (per unit) similar post-FMP duration, 4.6 years, (Freeman et al 2014) Smoking 1.63** 1.14 1.98** 3.09** 2.97 1.49 for moderate to severe hot flashes (VMS in past year, 13-year follow-up, age 35-47 years at entry), 3.36 + Baseline anxiety 3.10** 2.59** 3.65** 1.64 17.3** score ◦ Also, longer duration with onset of hot flashes early in the menopause transition or at younger age *Each factor adjusted for others, menopausal status, education, hx premens sx, sx sensitivity and depressive sx score; ** p<0.01; + p<0.05 Gold et al, Am J Public Health 2006 6

EB Gold NAMS Presentation 10/06/2016 18  Longitudinal analyses of women who did not report any 16 VMS at baseline, n=1546 14 P = 0.10 P for interaction Percent Incidence by menopause 12 stage = 0.03  Examined incidence of any and frequent VMS (>6 days 10 in past 2 weeks) Pre & Early Peri 8 ◦ Concurrent BMI (waist) Late Peri & Post 6 P = 0.34 ◦ Change in weight (waist) from baseline 4 2 ◦ Change in weight (waist) from prior visit 0 <25 25-29.9 30+  Determined if relationships varied by menopausal status Concurrent BMI Gold et al. Menopause 2016 in press 40 35 P for interaction by menopause p=0.0003 30 stage <0.0001 Percent Incidence 25 20 p=0.053 Pre-/early peri Late peri/post 15 10 5 0 <25 25-29.9 30+ Concurrent BMI (a) Adjusted: Time ‐ invariant ‐ baseline age, race/ethnicity, site, V01 symptom sensitivity, baseline CES ‐ D depression, history of PMS, and education; Time ‐ varying – smoking, number very upsetting life events Gold et al Menop 2016 in press 7