EB Gold NAMS Presentation 10/06/2016 · EB Gold NAMS Presentation 10/06/2016 2 Objectives Design Methods Results Baseline characteristics of study sample Symptoms: Hot flashes and

EB Gold NAMS Presentation 10/06/2016

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Ellen B. Gold, PhDDept. Of Public Health Sciences

University Of California Davis

No financial relationships to disclose

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


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Objectives

Design

Methods

Results◦ Baseline characteristics of study sample

◦ Symptoms: Hot flashes and night sweats, Urinary incontinence, Sleep, Vaginal dryness

*Funded by NIA, NINR, ORWH, NCCAM; no financial conflicts or other disclosures

To identify factors that affect the timing and nature (eg, endocrine changes, symptoms) of the menopause transition and

To identify the characteristics of the transition that are related to long-term disease risk indicators, such as changes in cardiovascular risk markers and bone density.

20-year longitudinal cohort study of the menopause transition funded by NIA, NINR, ORWH, NCCAM

7 sites, each recruited minority sample◦ Michigan African Americans◦ MGH - Boston African Americans◦ Rush – Chicago African Americans◦ UCD/Kaiser – Oakland Chinese◦ UCLA Japanese◦ New Jersey Hispanic◦ Pittsburgh African Americans

2 central labs (Michigan, MRL); Coordinating center - Pittsburgh

Screened 16,025 community-based women for cohort eligibility (age 42-52 years, menstrual period in last 3 months, intact uterus and >1 ovary, no exogenous hormone use, not pregnant)

Annual visits; 3302 at baseline, 2502 at visit 13:

◦ Annual in-person interview, self-administered questionnaire and food frequency questionnaire (baseline, 05, 09)

◦ Fasting blood sample drawn on cycle days 2-5 for serum E2, T, FSH, SHBG, DHEAS, glucose, insulin, clotting factors and lipoprotein levels


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◦ Annually measure blood pressure, weight, height and waist and hip circumference ◦ At 5 sites measure bone density annually◦ In subset of 990, one cycle daily urine (urinary E1C,

PdG, FSH, LH) and daily symptom diary

Monthly calendar: menstruation, sx, procedures

Visit 4 cognitive tests began; at visit 12 physical function tests began

Longitudinal analyses: Repeated measures, multi-variable analyses to account for multiple observations on the same woman and many confounding variables

Baseline Characteristic

African Amer.

Cauc. Hisp. Chinese Japanese

Median Age (years)

46.1 46.1 46.1 46.6 46.7

% < $50,000 annual hshldincome

63.1 39.1 91.0 39.2 25.3

% Smokers 24.6 16.6 16.7 1.6 12.9

% >6 days HF in past 2 wks

14.8 10.2 13.4 6.8 4.3

% Premenop 49.5 52.3 57.9 61.9 62.2

Median BMI 30.2 26.1 28.3 22.4 22.1

Objectives

Design and Methods

Results ◦ Vasomotor symptoms

Affect the majority of women undergoing menopause transition (Gold et al. Amer J PH 2006)

Associated with higher factor VIIc and tPA-ag (Thurston Menop 2011), CV disease risk (Huang Menop 2009; Roussouw JAMA 2007) andlower bone density (Crandall Menop 2009)

Frequency and severity of hot flashes related to quality of life and sleep (Pinkerton Menop 2016)

A chief menopause-related symptom for which US women seek medical care (Williams Maturitas 2007; Nicholson Am J Obstet Gynecol 2001), have higher number of outpatient visits (Sarrel Menop 2015)

Annual direct and indirect costs in hundreds of millions of dollars in US


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Gold et al,AJPH 2006

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)

Avis et al, JAMA Int Med 2015


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Duration of Frequent VMS (years)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n o

f W

om

en

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0Premenopausal (N=183)Early perimenopausal (N=700)Late perimenopausal (N=266)Postmenopausal (N=291)All Participants (N=1449)

Total Duration of Frequent VMS by Menopausal Status at First VMS Report


Median 7.4Median 3.4


Total Duration of Frequent VMS by Race/Ethnicity

Duration of Frequent VMS (years)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n o

f W

om

en

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0African American (N=479)White (N=652)Chinese (N=95)Hispanic (N=109)Japanese (N=114)All Participants (N=1449)

Median 10.1

Median 4.8

Post FMP Persistence of Frequent VMS by Menopausal Status at First VMS Report


Post-FMP Persistence of Frequent VMS (years)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n o

f W

om

en

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0Premenopausal (N=72)Early perimenopausal (N=348)Late perimenopausal (N=191)Postmenopausal (N=268)All Participants (N=881)


Post FMP Persistence of Frequent VMS by Race/Ethnicity

Post-FMP Persistence of Frequent VMS (years)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n o

f W

om

en

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0African American (N=310)White (N=380)Chinese (N=65)Hispanic (N=50)Japanese (N=76)All Participants (N=881)


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Factor Cessation over Total Duration Post FMP Cessation

HR (95% CI) Median Years HR (95% CI) Median Years

Age at onset, years

45-49.950-54.9>55

2.43 (1.30-4.51)2.71 (1.44-5.09)3.60 (1.78-7.29)

9.347.736.42

Ref1.16 (0.84-1.60)1.53 (1.05-2.24)

6.765.724.48

> College 1.25 (1.03-1.52) 7.66 1.40 (1.13-1.74) 4.54

Sx sens. V1lowmoderatehigh

0.77 (0.58-1.00)0.85 (0.64-1.13)0.64 (0.46-0.89)

9.578.22

10.81

0.76 (0.56-1.04)0.78 (0.57-1.07)0.58 (0.39-0.85)

5.485.458.47

Someperceived stress

0.75 (0.58-0.96) 10.78 0.70 (0.54-0.91) 8.13


aHR=hazard ratio for VMS cessation

Melbourne Women’s Midlife Health (Col et al 2009): shortertotal duration (5.2 years) for bothersome VMS (mostly white, excluded those with VMS at baseline, VMS at last visit considered no VMS)

Penn Ovarian Aging: longer total duration, 10.2 years, and similar post-FMP duration, 4.6 years, (Freeman et al 2014) for moderate to severe hot flashes (VMS in past year, 13-year follow-up, age 35-47 years at entry),

◦ Also, longer duration with onset of hot flashes early in the menopause transition or at younger age

Factor Total Cauc. Afr. Amer.

Hisp. Chin. Japan.

Age

(per year)

1.17** 1.16** 1.18** 1.04 1.29** 1.30**

BMI

(per unit)

1.03** 1.03 1.02 1.03 1.03 1.05

Smoking 1.63** 1.14 1.98** 3.09** 2.97 1.49

Baseline anxiety score

3.10** 2.59** 3.65** 1.64 17.3** 3.36+

*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


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Longitudinal analyses of women who did not report any VMS at baseline, n=1546

Examined incidence of any and frequent VMS (>6 days in past 2 weeks)

◦ Concurrent BMI (waist)

◦ Change in weight (waist) from baseline

◦ Change in weight (waist) from prior visit

Determined if relationships varied by menopausal status

Gold et al. Menopause 2016 in press

(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

p=0.0003

p=0.053

0

5

10

15

20

25

30

35

40

<25 25-29.9 30+

Pe

rce

nt

Inc

ide

nc

e

Concurrent BMI

Pre-/early peri

Late peri/post

P for interaction by menopause stage <0.0001

0

2

4

6

8

10

12

14

16

18

<25 25-29.9 30+

Pe

rce

nt

Inc

ide

nc

e

Concurrent BMI

Pre & Early Peri

Late Peri & Post

P for interaction by menopause stage = 0.03

P = 0.10

P = 0.34


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0

5

10

15

20

25

30

35

40

45

Lost >5% Lost 1-5%

Stable Gained 1-5%

Gained 5-10%

Gained>10%

Pe

rce

nt

Inc

ide

nc

e

% Weight Change Since Baseline

Pre & Early Peri

Late Peri and Post

P = 0.08

P = 0.39

0

2

4

6

8

10

12

14

16

18

20

Lost >5% Lost 1-5%

Stable Gained 1-5%

Gained 5-10%

Gained>5%

Pe

rce

nt

Inc

ide

nc

e

Percent Weight Change Since Baseline

Pre & Early Peri

Late Peri & Post


P = 0.004

P = 0.07

For a given concurrent BMI, incidence of VMS not affected by weight change; weight changes did not add predictive power; also, adjusting for weight change did not affect relation of concurrent BMI to incident VMS.

Women who gained the most or the least since baseline had greater incident frequent VMS in the early stage but lower incidence in the late stage; may be chance associations as no U‐shaped relations for any VMS in early or late stage.

Results may reflect that most percent weight changes were relatively small absolute changes and do not rule out that large absolute changes may be needed to change VMS risk.

Interactions with menopause status: concurrent BMI positivelyassociated with any VMS in the early stage and negatively associated in the late stage; trends not always monotonic or significant for frequent VMS (small numbers)

Consistent with Galicchio et al’s (2014) longitudinal study of midlife women showing change in BMI and weight over 1‐5 years of follow‐up not related to hot flashes in two racial groups; shorter follow‐up and shorter‐term change examined

Differed from WHI: postmenopausal women with VMS at baseline who lost 10+ pounds or 10% or more of their baseline body weight in one year were more likely to “eliminate” VMS (Kroenke et al 2012).


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Women’s Health in Lund Area (WHLA) study and Australian Longitudinal Study on Women’s Health (ALSWH) results differed: VMS reported more by women who gained weight but not significantly less in those who lost weight

WHLA (Li et al 2003) was cross‐sectional, asked weight gain in last 5 years, did not report time over which VMS reported nor racial/ethnic composition, sample aged 51‐61 years

ALSWH (Herber‐Gast et al 2013) was longitudinal over 15 years, asked about VMS in last 12 months in 10,454 women aged 45‐50 years at baseline; race/ethnicity was not reported

Objectives

Design and Methods

Results

◦ Vasomotor symptoms

◦ Urinary symptoms

00.20.40.60.8

11.21.41.61.8

2

Ad

just

ed*

Od

ds

Rat

io

Stress UI Urge UI

Type of Incontinence

Cauc

Afr Amer

Chinese

Japanese

Hispanic

**

**

**

**

*Adj. for social support, BMI, parity; ** significant compared to Cauc

Waetjen LE, et al, Amer J Epidemiol 2007

** **

Incidence Of Any, Stress, And Urge Urinary Incontinence Per 100 Woman‐years By

Menopausal Status, Baseline ‐ Visit 06 , SWAN

Waetjen et al. Obstet Gynecol 2009


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Waetjen, et al. Obstet Gynecol 2009

Hazard Ratio

a b

aAdj. for anxiety change, BMI, education, basics, race/ethnicity, parity, weight change;bAdj. for BMI, race/ethnicity, weight changes; cAdj. for anxiety change, education, basics, race/ethnicity, HBP, change in life stressors

*

*

*

*

*

*95% CI Excludes1.0c

At baseline 46.7% had UI, 15.3% several days/week

Over first 6 years of SWAN, 14.7% worsened, 32.4% improved, 52.9% reported no change in frequency

Change in menopausal status was not associated with worsening

Each pound of weight gain significantly increased odds of worsening and reduced odds of improving

Odds of improving did not vary by race/ethnicity

Waetjen LE, et al, ObGyn 2008

Objectives

Design and Methods

Results



◦ Difficulty sleeping

Kravitz et al, Sleep 2008


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Adjusted*Odds Ratio

*Adj. for age, race/ethnicity, site, depr. & anxiety sx, get up to urinate, pain, lifeevents, psychotropic & sleep meds; **sig. different from premenopause


**

**

**

**** **

** **

****

For all 3 types of sleep difficulties, a significant dose-response relationship was observed with number of days of reporting VMS, similar to Penn Ovarian Aging study (Pien et al 2008; Freeman et al 2015).

Decreases in annual E2 levels were significantly associated with trouble falling asleep and waking up several times.

Increases in annual FSH levels were significantly associated with waking up several times.

Significantly more Caucasian women reported waking up several times and awaking early than other racial/ethnic groups.


Objectives

Design and Methods

Results



◦ Difficulty sleeping

◦ Vaginal dryness

Adj

uste

d O

dds

Rat

io

a Adjusted for age, race/ethnicity, education, employment, maritalstatus, parity, BMI, smoking, physical activity

Gold et al Am J Epidemiol 2000

Menopausal Status


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0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Race/ethnicity

Afr. Am*

Hispanic*

White

ChineseJapaneseA

djus

ted

Odd

s R

atio

aAdjusted for age, menopause status, education, parity employment, marital status, parity, BMI, smoking, physical activity

Gold et al Am J Epidemiol 2000

Virtually all symptoms differed by race/ethnicity, adjusted for differences in socioeconomic and lifestyle factors, suggests symptom risks differ by race/ethnicity

Vasomotor sx increased most in association with progression through the menopause transition, followed by sleep difficulties

Changes in UI largely not related to the menopause transition

BMI related to many outcomes, except vaginal dryness:◦ Concurrent BMI, not weight change, most related to VMS◦ Weight control should be addressed in a culturally

appropriate manner

The Study of Women‘s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women‘s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553,U01AG012554, U01AG012495). The content of this presentation is solely the responsibility of the authors and does not necessarily reflect the official views of the NIA, NINR, ORWH, or the NIH.

We wish to express our appreciation too for the women who have participated in SWAN for over 15 years and given of their time and information for the

benefit of future generations of midlife women!

Documents

EB Gold NAMS Presentation 10/06/2016 · EB Gold NAMS Presentation 10/06/2016 2 Objectives Design Methods Results Baseline characteristics of study sample Symptoms: Hot flashes and