Menopausal Symptoms, Menopausal Stage and Cognitive Functioning in Black Urban African Women NICOLE G JAFF, PHD, NCMP DEPARTMENT OF CHEMICAL PATHOLOGY, UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG, SOUTH AFRICA LEAH H RUBIN, PHD DEPARTMENT OF PSYCHIATRY, UNIVERSITY OF ILLINOIS AT CHICAGO, CHICAGO, IL, DEPARTMENTS OF NEUROLOGY, PSYCHIATRY, AND EPIDEMIOLOGY, JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD NIGEL J CROWTHER, PHD DEPARTMENT OF CHEMICAL PATHOLOGY, NHLS AND UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG, SOUTH AFRICA SHANE A NORRIS, PHD SAMRC/DEVELOPMENTAL PATHWAYS FOR HEALTH RESEARCH UNIT, UNIVERSITY OF THE WITWATERSRAND, CHRIS HANI BARAGWANATH HOSPITAL, JOHANNESBURG, SOUTH AFRICA PAULINE M MAKI, PHD DEPARTMENTS OF PSYCHIATRY, PSYCHOLOGY AND OB/GYN, UNIVERSITY OF ILLINOIS AT CHICAGO, CHICAGO, IL.
Disclosures None: I disclose that I have no relevant financial relationships with any commercial interests .
Background • North American and European studies show cognitive function is influenced by menopausal symptoms and menopausal stage 1 • These associations are understudied in sub- Saharan African women • Defining a uniform experience of menopause in women of different cultures is challenging 2 • Standardized tools accounting for cultural and ethnic specifics of menopausal symptoms should be used 1. Greendale GA, et al. Am J Epidemi ol 2010;171:1214 – 24 2; 2. Parsons MA, & Obermeyer CM Menopause 2007;14:760 – 8
Aims and Hypotheses AIM: • Evaluate the association of cognitive function with menopausal symptoms and stage HYPOTHESES: • Premenopausal women will show better cognitive performance than those women later in the transition • Menopausal symptoms will be inversely related to cognition
Methods Participants • Enrolled in the Study of Women Entering and in Endocrine Transition (SWEET) 1 – Mothers and caregivers of children participating in the longitudinal Birth to Twenty cohort (BT20) 2 – After 21 years, 2200 of these women were in contact with the researcher teams – During the SWEET 3-year recruitment period , 902 of these 2200 women were randomly selected for SWEET • Entry criteria: – Black urban South African women between 40 to 60 years – Within 10 years of menopause • Sample size: n=702 1. Jaff NG, et al. Menopause 2014;21:1225 – 33 2. Richter L, et al. Int J Epidemiol 2007;36:504 – 11
Methods Methods • Design - Cross sectional • Menopause Stage - STRAW+10 criteria 1 • Menopause Symptoms - Menopause Rating Scale (MRS) 2 • Cognitive Function - Symbol Digit Modalities Test (SDMT), a measure processing speed and incidental recall 3 FILL IN 1. Harlow SD, et al. Menopause ; 2012;19(4):387-95. 230. 2. Heinemann LA, et al. Health Qual Life Outcomes . 2003;1:1 – 4 3. Smith A, Symbol Digit Modalities Test . Los Angeles, CA: Western Psychological Service; 1982
Methods cont. • Questionnaires - menstrual history, general and reproductive health, educational level, smoking and snuff use • Body anthropometry - Blood pressure, height, weight, waist, hip circumference • HIV serostatus - voluntary HIV antibody test • Hormone assays - Follicle-stimulating hormone (FSH) and estradiol (E2) levels as supportive criteria for staging 1 • Statistical methods: ANOVA, chi-squared tests, multivariable linear regression analyses 1. Randolph JF Jr & Zheng H. JCEM . 2011;96:746-541
Table 1. Characteristics of the study sample by menopausal stage. Menopausal stages (from STRAW+10) Menopausal Early Late Variables Late reprodutíve transition postmenopause postmenopause p-value -3b & -3a -2 & -1 +1a to +1c +2 (n=192) (n=121) (n=147) (n=130) Age (years) 45.2 ± 3.30 48.2 ± 3.73 51.6 ± 3.85 55.2 ± 3.50 <0.001 No HS education 118 (62) 65 (54) 85 (58) 81 (62) 0.45 Employed 125 (65) 61 (50) 79 (54) 70 (54) 0.04 BMI (kg/m 2 ) 33.6 ± 7.61 34.3 ± 7.96 33.3 ± 7.28 32.1 ± 6.26 0.12 HIV-serostatus: Unknown 84 (44) 56 (46) 69 (47) 42 (32) 0.07 Negative 77 (40) 49 (40) 65 (44) 75 (58) Positive, no ARV 13 (7) 8 (7) 5 (3) 4 (3) Positive, ARV 18 (9) 8 (7) 8 (6) 9 (7) Estradiol 5.69 ± 0.98 4.90 ± 1.31 4.06 ± 1.11 3.64 ± 0.73 <0.001 FSH 0.88 ± 0.40 1.35 ± 0.50 1.68 ± 0.36 1.79 ± 0.19 <0.001 Data given as mean ± SD or n (%); HS=high school
Table 2. Severe menopausal symptoms and cognitive performance on the Symbol Digit Modalities Test (SDMT) by menopausal stage. Menopausal stages (from STRAW+10) Variables Late Menopausal Early Late reproductive transition postmenopause postmenopause p-value (n=192) (n=121) (n=147) (n=130) Severe symptoms: Exhaustion 36 (19) 20 (17) 30 (20) 42 (32) 0.008 Anxiety 19 (10) 20 (17) 22 (17) 23 (18) 0.19 Irritability 47 (25) 34 (28) 30 (20) 39 (30) 0.29 Mood 36 (19) 27 (22) 32 (22) 32 (25) 0.65 Sleep disturbance 39 (20) 24 (20) 37 (25) 31 (24) 0.64 Hot flushes 32 (17) 32 (26) 40 (27) 33 (25) 0.08 Cognition (SDMT): Processing speed 31.0 ± 10.8 30.0 ± 11.5 26.4 ± 11.1 23.7 ± 9.84 <0.001 Incidental recall 5.05 ± 3.86 4.97 ± 3.65 4.14 ± 3.31 4.27 ± 3.37 0.05 Data given as mean ± SD and n (%); SDMT = Symbol digit modalities test.
Table 3. Association between menopausal symptoms and cognitive performance on the Symbol Digit Modalities Test (SDMT). SDMT scores Symptoms Processing Speed p-value Incidental Recall p-value Exhaustion: Severe (n=128) 25.7 ± 11.8 0.008 4.07 ± 3.63 0.04 Not severe (n=460) 28.6 ± 10.9 4.79 ± 3.63 Anxiety: Severe (n=84) 25.1 ± 12.3 0.009 4.13 ± 3.33 0.17 Not severe (n=499) 28.5 ± 11.0 4.72 ± 3.65 Irritability: Severe (n=150) 26.8 ± 10.9 4.26 ± 3.45 0.14 0.15 Not severe (n=438) 28.4 ± 11.3 4.75 ± 3.64 Mood: Severe (n=127) 27.2 ± 11.3 0.34 3.87 ± 3.24 0.007 Not severe (n=463) 28.3 ± 11.1 4.84 ± 3.66 Sleep disturbance: Severe (n=131) 27.1 ± 12.2 0.28 4.33 ± 3.78 0.26 Not severe (n=458) 28.3 ± 10.9 4.73 ± 3.54 Hot flushes: Severe (n=137) 25.1 ± 11.6 <0.001 4.31 ± 3.62 0.23 Not severe (n=452) 29.0 ± 10.9 4.73 ± 3.59 Data given as mean ± SD
Table 4. Multivariable model predicting cognitive performance on the Symbol Digit Modalities Test (SDMT). SDMT Variables Processing speed (n=578) Incidental recall (n=586) β -coefficient β -coefficient Age -0.24*** -0.12 † -0.08 † Snuff user (vs. not) -0.04 No high school (vs. high school) -0.12** -0.06 -0.08 † Unemployed (vs. employed) -0.21*** BMI 0.02 0.02 HIV status (vs. HIV-uninfected): HIV-infected no ARV -0.05 -0.02 HIV-infected ARV -0.04 0.00 Unknown Status -0.06 0.03 Menopausal Stage (vs. late reproductive): Menopausal transition 0.05 0.02 Early postmenopausal -0.01 -0.03 Late postmenopausal -0.04 0.02 Severe hot flushes (vs. not) -0.11** - Severe mood symptoms (vs. not) - -0.11** -0.07 † Severe fearfulness (vs. not) - ***p<0.001; **p<0.01; *p<0.05; † p>0.05 and p<0.09 .
Limitations/Strengths Limitations: • Cross-sectional study limited sensitivity - possible effects of menopausal stages • Unable to assess verbal memory performance due to language – 11 different languages in South Africa • No formal tool to measure anxiety • Assessment of HIV serostatus voluntary so status of all participants not determined - may explain the lack of association between HIV serostatus and processing speed Strengths: • Open and close-ended questions asked by a single interviewer in a well-suited approach to self reported VMS in cultural diverse groups 1,2 • The MRS symptom list is cross-culturally applicable - internationally validated, and translated into nine different languages 3 1. Parsons MA & Obermeyer CM. Menopause 2007;14:760 – 8; 2. Crawford SL. Menopause 2007;14:725 – 33 3. Heinemann LA, et al Health Qual Life Outcomes 2003;1:1 – 4
Conclusions • No association between menopause stage and SDMT performance • Menopausal symptoms are associated with processing speed • Anxiety and hot flashes are significantly associated with decreased psychomotor speed • Severe mood symptoms are a significant predictor of incidental recall • A common underlying neurological substrate is reflected in the associations between menopausal symptoms and cognitive performance and is not related to cultural understanding and expectations of the menopause
Acknowledgements • The mothers and caregivers of the BT20 study • SWEET team members – Thozile Lephato, Thabile Sibya, S’mangele Sigasa • Grants - Medical Research Council of South Africa (MRC), National Health laboratory Service (NHLS) and the Iris Ellen Hodges Cardio-vascular Research Trust
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