An investigation of the metabolic, hormonal and anthropometric characteristics of the menopausal transition in black urban South African women

A thesis submitted to the faculty of health sciences, University of the Witwatersrand in fulfilment of the requirements for the degree of doctor of philosophy Johannesburg, South Africa 2015Background and Objectives: The Study of Women Entering and in Endocrine Transition (SWEET) was developed to examine differences in metabolic, hormonal, and anthropometric parameters in black urban South African women at different stages of the menopause transition (MT). Little data are available on accurate staging of the menopausal transition for sub-Saharan African women. There is a plethora of data on this and related subjects in Western women, but little available research on changes in body composition or risk of metabolic syndrome (MetS) in the MT in midlife black South African women, although obesity is prevalent in this group, and there is a high instance of both diabetes and hypertension. The prevalence of HIV infection is also high in these women but it is not known whether this may affect the symptoms and conditions of the MT, contribute to changes in body composition or increased risk of MetS and cardiovascular disease (CVD). No prior study in sub-Saharan Africa has used the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria to stage reproductive aging or assessed their reliability in classifying ovarian status. The MT is closely associated with changes in body composition including lower bone mineral density, decreased lean muscle mass, increased body mass index (BMI) and adiposity, particularly increased central adiposity. Abdominal obesity is a key risk factor for MetS. This, and the subsequent risk of CVD appear to increase as women transition into menopause. It is unclear if this is due to reproductive or chronological aging, or both combined. Aims: (1) To assess the usefulness of the STRAW + 10 criteria in staging ovarian aging in black South African women. (2) To determine whether there are differences in body adiposity, lean muscle mass, and bone mineral density (BMD) across reproductive groups and ascertain the main correlates of these variables. (3) To determine in this population, if the risk of MetS and the levels of its components and related metabolic factors, differ between women at different stages of the MT and to explore the possible determinants. (4) To investigate whether the high prevalence of HIV infection in these women affects the age at menopause, menopausal symptoms, body composition, and metabolic variables in midlife black South African women. Methods: Participants in this cross-sectional study were 702 black urban African women aged 40 to 60 years. The stages of reproductive aging were categorized using STRAW + 10 criteria. The Menopause Rating Scale was used to measure the prevalence of menopausal symptoms including vasomotor symptoms. Study-specific questionnaires were used to obtain relevant demographic and lifestyle data. Blood levels of follicle stimulating hormone (FSH), estradiol (E2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone (T) and sex hormone blinding globulin (SHBG), insulin, lipids, glucose, leptin and adiponectin were measured. Simple measures of body anthropometry (weight, height, waist and hip circumference) were obtained. Body composition was measured using dual-energy X-ray absorptiometry (DXA) and ultrasonography. Human immunodeficiency virus (HIV) status was assessed using a point-of-care method. Metabolic syndrome and diabetes were diagnosed using internationally recognized criteria. Results: Reported age at final menstrual period (FMP) was higher in subjects interviewed within 4 years of FMP (49.0±3.80) than in subjects interviewed ≥10 years after FMP (42.0±4.06; p<0.0005). Human immunodeficiency virus (HIV) status had no effect on menopause symptoms. A BMI ≥35 kg/m2 was associated with severe vasomotor symptoms. Estradiol (p<0.0005), SHBG (p<0.0005) and DHEAS (p=0007) were significantly lower in post- than premenopausal groups, whilst FSH was higher (p<0.0005). Whole body lean mass (p=0.002) and BMD (p<0.0005) were significantly lower in postmenopausal compared to premenopausal groups. Multivariable linear regression models and ANCOVA demonstrated that the lower lean mass was related to the high postmenopausal FSH levels, whilst the lower BMD was partially explained by the low postmenopausal E2 levels. Use of antiretroviral therapy (ART) correlated negatively with total fat mass (β=-2.92, p=0.008) and total bone mineral content (BMC; β=-78.8, p=0.003). The MetS was highly prevalent (49.6%). Levels of total cholesterol (p<0.0005), LDL (p<0.0005), triglyceride (p=0.01), systolic (p<0.0005) and diastolic (p<0.05) blood pressure were all significantly higher in postmenopausal compared to pre-menopausal groups whilst there was a trend for glucose levels (p=0.05) and MetS prevalence (p=0.05) to also be higher. Multiple regression analyses and ANCOVA showed that the higher levels of cholesterol and LDL were related to higher FSH concentrations whilst elevation in systolic blood pressure was linked to lower estradiol levels. The higher postmenopausal glucose and diastolic blood pressure levels and risk of MetS were related to chronological aging. Adiponectin was strongly correlated with all components of the MetS except for blood pressure. Conclusions: Reporting of age at FMP is unreliable in subjects interviewed ≥ 4 years after the event. The STRAW+10 criteria are accurate in staging reproductive aging, as confirmed by the significant association of FSH and estradiol levels with menopausal transition stage. These guidelines may be appropriate for use in resource-limited settings in the absence of biomarkers. The MT in these women is characterized by lower whole body lean mass and BMD in post- compared to premenopausal subjects but there are negligible differences in fat mass. Lower lean mass and BMD were associated with higher FSH and lower E2 serum levels, respectively. Lower fat mass and BMC were associated with ART use. The lipid profile was more atherogenic and blood pressure was higher in the post- than the premenopausal women. These differences were related to the higher FSH (LDL and total cholesterol) and lower E2 (diastolic blood pressure) levels in the postmenopausal women. These data suggest that the hormonal changes characterizing the menopause may play a role in the etiology of cardiometabolic disease and in the body composition changes that are observed in the MT. The above conclusions should be addressed in longitudinal studies. The terminology of STRAW+10 needs to be simplified and the questions contextualized, and contraceptive use should be specifically addressed in questions on bleeding patterns. In addition there are implications for the use of behavioral interventions in lowering cardio-metabolic risk factors and hence morbidity and mortality in these women. Further research is needed to examine health risks associated with snuff use, and the longterm effects of HIV-infection and different ART regimens. Additional studies should address the poor understanding of menopausal health consequences in this population with appropriate education program

The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Stress and midlife women’s health

Abstract Stress is ubiquitous in everyday life, and chronic stress can have negative consequences for health and social welfare. Although a growing body of research addresses the relationships between stress, health, and quality of life, there is a gap in the literature with regard to the effects of stress among women at midlife. The purpose of this commentary is to provide a brief history of stress research, including various methods for measuring stress; discuss the physiological effects of stress; and review relevant studies about women at midlife in order to identify unanswered questions about stress. This commentary also serves as an introduction to a thematic series on stress and women’s midlife health where stress is examined in relation to a wide range of symptom experiences, in the context of family and negative life events, as associated with women’s work, and correlated with the challenges of violence and discrimination. The goal of this commentary and thematic series is to extend the conversation about stress to include women at midlife, and to examine where we are, and where we are going, in order to direct future research and provide relevant care for this growing population

Metabolic and Body Composition Risk Factors Associated with Metabolic Syndrome in a Cohort of Women with a High Prevalence of Cardiometabolic Disease - Fig 1

<p>Risk of metabolic syndrome across hexiles/quintiles of: A. trunk fat-free, soft-tissue mass, B. abdominal subcutaneous fat thickness, C. HOMA, D. adiponectin and E. age. Lighter bars represent unadjusted odds ratios whilst darker bars represent odds ratios with adjustment for smoking and all 4 of the other variables shown in this figure; *p<0.05, **p<0.005, ***p<0.0005 vs hexile 1.</p

Logistic regression model showing significant risk factors for the individual components of the metabolic syndrome.

<p>Logistic regression model showing significant risk factors for the individual components of the metabolic syndrome.</p

Anthropometric and metabolic variables in women with and without metabolic syndrome^a.

<p>Anthropometric and metabolic variables in women with and without metabolic syndrome<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162247#t001fn001" target="_blank">^a</a>.</p

Demographic, socio-economic and behavioural correlates of BMI in middle-aged black men and women from urban Johannesburg, South Africa

Background: There is a high and increasing prevalence of overweight and obesity in South Africans of all ages. Risk factors associated with overweight and obesity must be identified to provide targets for intervention. Objective: To identify the demographic, socio-economic and behavioural factors associated with body mass index (BMI) in middle-aged black South African men and women. Methods: Data on demographic and socio-economic factors were collected via questionnaire on 1027 men and 1008 women from Soweto Johannesburg, South Africa. Weight and height were measured and BMI was determined. Behavioural factors included tobacco use and consumption of alcohol, and physical activity data were collected using the Global Physical Activity Questionnaire. Menopausal status was determined for the women, and HIV status was available for 93.6% of the men and 39.9% of the women. Results: Significantly more women were overweight or obese than men (87.9 vs. 44.9%). Smoking prevalence (current or former) and minutes spent in moderate to vigorous intensity physical activity was significantly different between the sexes (both p < 0.0001). In the final hierarchical model, marital status (+ married/cohabiting), household asset score (+), current smoking (-), moderate to vigorous physical activity (-) and HIV status (- HIV infected) significantly contributed to 26% of the variance in BMI in the men. In the women, home language (Tswana-speaking compared to Zulu-speaking), marital status (+ unmarried/cohabiting), education (-), current smoking (-) and HIV status (- HIV infected) significantly contributed to 14% of the variance in BMI. Conclusions: The sex difference in BMI and the prevalence of overweight and obesity between black South African men and women from Soweto, as well as the sex-specific associations with various demographic, socio-economic and behavioural factors, highlight the need for more tailored interventions to slow down the obesity epidemic

Flat Ownership Act and Cadastr of real estate

Developing countries are disproportionately affected by hypertension, with Black women being at greater risk, possibly due to differences in body fat distribution. The objectives of this study were: (1) To examine how different measures of body composition are associated with blood pressure (BP) and incident hypertension; (2) to determine the association between baseline or change in body composition, and hypertension; and (3) to determine which body composition measure best predicts hypertension in Black South African women. The sample comprised 478 non-hypertensive women, aged 29-53 years. Body fat and BP were assessed at baseline and 8.3 years later. Body composition was assessed using dual-energy X-ray absorptiometry (DXA) (n = 273) and anthropometry. Hypertension was diagnosed based on a systolic/diastolic BP ≥140/90 mmHg, or medication use at follow-up. All body composition measures increased (p<0.0001) between baseline and follow-up. SBP and DBP increased by ≥20%, resulting in a 57.1% cumulative incidence of hypertension. Both DXA- and anthropometric-derived measures of body composition were significantly associated with BP, explaining 3-5% of the variance. Baseline BP was the most important predictor of hypertension (adjusted OR: 98-123%). Measures of central adiposity were associated with greater odds (50-65%) of hypertension than total adiposity (44-45%). Only change in anthropometric-derived central fat mass predicted hypertension (adjusted OR: 32-40%). This study highlights that body composition is not a major determinant of hypertension in the sample of black African women. DXA measures of body composition do not add to hypertension prediction beyond anthropometry, which is especially relevant for African populations globally, taking into account the severely resource limited setting found in these communities

Menopause is associated with bone loss, particularly at the distal radius, in black South African women: Findings from the Study of Women Entering and in Endocrine Transition (SWEET)

Menopause transition is associated with accelerated bone loss, though data are limited from sub-Saharan African (SSA). Our objective was to describe bone density, geometry and estimated strength in women by menopause status and to explore whether patterns differed within those living with HIV.Methods: radius and tibia peripheral QCT data were collected for Black South African women (n = 430) aged 40-61 years with verified menopause and HIV status. pQCT outcomes were distal 4 % radius and tibia total cross-sectional area (CSA), total volumetric bone mineral density (vBMD), and compressive bone strength (BSIc); proximal 66 % radius and 38 % tibia cortical vBMD, total CSA, cortical thickness, and Stress-strain Index (SSI). Linear regression assessed associations between pre, peri-, and postmenopausal groups and pQCT outcomes adjusting for age, height, and weight, and then stratified by HIV status. Mean [95%CI] and tests for trend (p-trend) across menopausal groups are presented.Results: women were mean (SD) age 49.2 (5.3) years, with a body mass index (BMI) of 32.4 (6.3) m/kg2, and 18 % were living with HIV. After adjustment, later menopause stage was associated with lower 4 % radius total mean [95%CIs] vBMD (premenopause: 345.7 [335.8,355.5] vs. postmenopause: 330.1 [322.7,337.6] mg/cm3, p-trend = 0.017) and BSIc (premenopause: 0.39 [0.37,0.41] vs. postmenopause: 0.36 [0.35,0.37] g2/cm4; p-trend = 0.012). Similar trends were observed at the 66 % radius for cortical vBMD (premenopause: 1146.8 [1138.9,1154.6] vs. postmenopause: 1136.1 [1130.1,1142.0] mg/cm3; p-trend = 0.028) and cortical thickness (premenopause: 2.01 [1.95,2.06] vs. postmenopause: 1.93 [1.89,1.98] mm; p-trend = 0.036). After stratification by HIV status a similar patten was observed in women with HIV (cortical vBMD premenopause: 1152.9 [1128.5,1177.2] mg/cm3 vs. postmenopause: 1123.6 [1106.0,1141.2] mg/cm3, p-trend = 0.048). Total CSA varied little by menopause or HIV status at either radius sites; few differences were found at the tibia.Conclusion: in black South African women, menopause is associated with lower bone density and strength at the distal radius, a common site of osteoporotic fracture, in addition to lower cortical density and thickness at the proximal radius. Although the sample size was small, following stratification by HIV, women living with HIV had evidence of lower cortical density across menopause stages, unlike those without HIV. These findings raise concern for the incidence of Colles' fractures in postmenopausal women in South Africa; longitudinal studies of fracture incidence and implications of living with HIV are required.</p

The impact of human immunodeficiency virus and menopause on bone mineral density: a longitudinal study of urban-dwelling South African women

An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34/205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 [95% confidence interval -0.026, -0.001] g/cm2 , p = 0.040) and gained more weight 1.96 [0.32, 3.60] kg; p = 0.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (-0.092 [-0.042, -0.142] g/cm2 ; p = 0.001) than without HIV (-0.038 [-0.016, -0.060] g/cm2 , p = 0.001; interaction p = 0.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (-0.070 [-0.031, -0.108], p = 0.001) than women without HIV (-0.036 [-0.015, -0.057], p = 0.001, interaction p = 0.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</p