| Summary: | 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 2015 === Background 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 programs
|
|---|
