Menopause and accelerated aortic stiffness.

BACKGROUND: The menopausal transition is widely believed to increase the risk of cardiovascular disease, based on the notion that estrogen is cardioprotective in women. While aortic stiffness is an independent predictor of cardiovascular disease, it has been unclear whether this risk increases during menopause. OBJECTIVE: This study aimed to determine the association between changes in menopausal status and aortic stiffness. MAIN OUTCOME MEASURES: Menopausal status was classified using the Stages of Reproductive Aging in Women criteria in a stratified random sample of Australian women aged 40-80 years, at three time-points over 14 years (n = 469 in 2001-02 and 2005, and n = 323 in 2014). Aortic stiffness was measured non-invasively via carotid-femoral pulse wave velocity at each time point. Mixed modeling was employed to determine the independent associations between menopausal status and aortic stiffness accounting for multiple covariates including age, systolic blood pressure, heart rate, medications, cholesterol, waist circumference, smoking and diabetes status. RESULTS: There was no evidence to support an association between the menopausal transition and an acceleration of aortic stiffness. However, there was an acceleration of aortic stiffness in the late (8+ years) postmenopause phase, after accounting for age and traditional cardiovascular risk factors (0.122 [95%CI: 0.106, 0.139] m/s/year; p < 0.001). CONCLUSIONS: The menopausal transition is not associated with major changes in aortic stiffness beyond normal age-related effects. However, the clinically significant acceleration in aortic stiffness observed in late postmenopause may contribute to greater cardiovascular risk in this later life phase. Study registered in the Australian and New Zealand Clinical Trials Registry, reference ACTRN12618000005257.

Association of change in fat and lean mass with incident cardiovascular events for women in midlife and beyond: A prospective study using dual-energy x-ray absorptiometry (DXA).

OBJECTIVE: To determine whether changes in fat and lean mass over time, quantified using dual-energy x-ray absorptiometry (DXA), are related to incident cardiovascular events. Previous studies using surrogate anthropometric methods have had inconsistent findings. STUDY DESIGN: Prospective, longitudinal observational study of women aged 40 to 80 randomly selected from the electoral roll and stratified into decades: 40-49, 50-59, 60-69 and 70-79 years. MAIN OUTCOME MEASURES: Changes in anthropometric measurements (body mass index and waist-to-hip ratio) and DXA-quantified fat mass and lean mass between the first and fifth years of the study. Incident cardiovascular events recorded from the sixth to the 12th year. RESULTS: In total 449 participants (87.9 %) were analyzed. A 10 % or greater decrease in total fat mass index was associated with a 67 % lower likelihood of any cardiovascular event (OR = 0.33, 95%CI 0.15-0.71); no association was observed for an increase. A 10 % or greater decrease in abdominal fat mass index was associated with a 62 % lower likelihood of incident stroke (OR = 0.38, 95%CI 0.16-0.91); no association was observed for an increase. A 10 % or greater decrease in appendicular lean mass index resulted in increased odds ratio of 2.91 for incident peripheral artery events (OR = 2.91, 95%CI 1.18-7.20). CONCLUSIONS: Reducing fat mass for women in midlife and beyond may decrease the risk of cardiovascular events. An increase in fat mass may not contribute to additional cardiovascular events. A reduction in limb muscle mass may provide an independent marker for cardiometabolic risk and peripheral artery disease. No independent association was found using anthropometric measurements and incident cardiovascular events.

Comparison of obesity and metabolic syndrome prevalence using fat mass index, body mass index and percentage body fat.

BACKGROUND: Accurate obesity classification is important so that appropriate intervention can be instituted to modify metabolic risk factors. Commonly utilized body mass index (BMI) and percentage body fat (PBF) are influenced by lean mass whereas fat mass index (FMI) measures only body fat. This study compares the prevalence of obesity and metabolic risk factors with FMI, BMI and PBF using DXA (dual-energy x-ray absorptiometry). METHODS: 489 women randomly recruited from the electoral roll were stratified into 4 age groups; 40-49, 50-59, 60-69 and 70-79 years from 2000 to 2001. Clinical data and DXA body composition were obtained. Statistical analyses were performed using Medcalc v15 (Ostend, Belgium) with significance level at p = 0.05 (two-tailed). RESULTS: There was higher prevalence of obesity using PBF compared to BMI and FMI (p<0.001). This difference was greater from age 50-59 (p<0.05) which may be explained by age-related lean mass loss. PBF over-classified obesity in over 35% of normal and 95% of overweight categories compared to FMI and BMI. BMI has a sensitivity of 78.9% and specificity of 98.3% for obesity using FMI as the standard. BMI under-classified obesity in the overweight category by 14.9% compared to FMI. There was no difference in diabetes, dyslipidemia, hypertension and metabolic syndrome prevalence within the BMI-obesity and FMI-obesity categories (p>0.05). CONCLUSION: PBF classified more obesity than BMI and FMI because of its low pre-determined threshold. The greater difference with PBF compared to BMI and FMI from the 50-59 decade onwards can be attributed to age-related lean mass loss. BMI had the lowest sensitivity for obesity diagnosis. BMI under-classified obesity in the overweight category compared to FMI due to its inability to differentiate lean mass. However, there was no significant difference in the prevalence of metabolic risk factors between BMI and FMI-obesity categories indicating that fat location may influence metabolic dysregulation.

A 5-year longitudinal study of changes in body composition in women in the perimenopause and beyond.

OBJECTIVE: Most studies of the age-related changes in body composition are cross-sectional in design: there have been few longitudinal studies. The aim of this 5-year study was to document body composition changes in perimenopausal and older women. STUDY DESIGN: Prospective, longitudinal observational study. METHODS: 489 women were randomly selected from the electoral roll and stratified into 4 age groups by decade: 40-49, 50-59, 60-69 and 70-79 years. Dual-energy x-ray absorptiometry (DXA) was performed in the first and fifth years of the study. Total body mass (TBM), total fat mass (TFM), total lean mass (TLM), abdominopelvic fat mass, and appendicular fat and lean mass were determined. RESULTS: There were significant increases in TBM (p < 0.001), TFM (p < 0.01), TLM (p < 0.05), arm fat mass (p < 0.05), leg fat mass (p < 0.001) and leg lean mass (p < 0.05) within the 40-49 age decade. TBM, TFM and abdominopelvic fat started to decline from the 50-59 decade. Abdominopelvic fat reduction was significant from the 50-59 decade to the later decades (p = 0.05 to p < 0.001). Arm lean mass showed a significant reduction from the 50-59 decade (p < 0.01). Leg lean mass declined from the 60-69 decade, reaching significance in the 70-79 decade (p = 0.05). CONCLUSION: TFM and abdominopelvic fat declined from the 50-59 age decade, which is earlier than is suggested in the literature. Conversely, the decline in appendicular lean mass with age occurred later, from the 50-59 decade, with earlier and greater loss in the arms, which has implications for exercise strategies to maintain muscle mass from midlife on.

Carotid ultrasound pulsatility indices and cardiovascular risk in Australian women.

INTRODUCTION: Ultrasound-acquired internal carotid arterial (ICA) pulsatility indices (PI) have been demonstrated to be useful measures of cerebrovascular disease. The purpose of this cross-sectional study was to investigate the association between carotid artery PI, cardiovascular risk and ischaemic heart disease in aging women. METHODS: One hundred and fifty-eight female participants of the Longitudinal Assessment of Ageing in Women study, aged 48-85 years, were evaluated. The relationships between common carotid artery (CCA) and ICA Doppler PI to cardiovascular risk factors (age, body mass index, systolic and mean arterial blood pressure, smoking and diabetes), carotid-femoral (femPWV) and carotid-radial (radPWV) pulse wave velocities, and ischaemic heart disease (IHD) were assessed using Spearman's rank correlation (ρ), multiple regression and logistic regression. Dependent variables were Box-Cox transformed to meet linear regression assumptions. RESULTS: CCA and ICA PI were significantly correlated to femPWV (ρ = 0.414 and ρ = 0.544, respectively). Cardiovascular risk factors were significantly predictive of CCA PI (Adj R(2) = 0.176, P < 0.01); however, their relationship to ICA PI (Adj R(2) = 0.508, P < 0.01) was stronger. This result was comparable with the relationship between cardiovascular risk factors and femPWV (Adj R(2) = 0.561, P < 0.01). Age and systolic blood pressure were the dominant risk factors for IHD in this group. CONCLUSION: ICA PI is comparable with femPWV in its association with cardiovascular disease. PI does not improve the prediction of IHD over age and systolic blood pressure.

Towards validation of use of an Australian reference database for the diagnosis of osteoporosis with DXA.

INTRODUCTION: Bone densitometry in Australia uses the data from the Geelong Osteoporosis Study for conversion of bone mineral density (BMD) to T-scores to diagnose osteoporosis based on the World Health Organization (WHO) classification criteria. An underlying assumption is that the bone status of women in Geelong city is representative of the rest of Australia. The aim of this study is to compare the prevalence of normal BMD, osteopenia and osteoporosis of sample Brisbane women to Geelong, and to assess the validity of the Geelong reference database for Australia-wide application. METHODS: The subjects were recruited as part of a longitudinal assessment of age-related changes in a random sample of women from Brisbane. The sample consisted of 503 women, aged between 40 and 79 years. Each subject had BMD measured at the lumbar spine and femoral neck. RESULTS: Using the WHO osteoporosis classification criteria based on T-scores, and the BMD cut-offs from the Geelong Study, the prevalence of normal BMD, osteopenia and osteoporosis was determined for the following age groupings, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69 and 70-79, to match the Geelong Study for comparison. There were no systematic differences in the prevalence of normal BMD, osteopenia and osteoporosis in the Brisbane subjects compared to the Geelong Study. CONCLUSION: This finding supports the use of the Geelong data as the reference for the generation of T-scores for bone densitometry assessment for osteoporosis using dual-energy X-ray absorptiometry in Australia.

Age-related changes in heart function by serial echocardiography in women aged 40-80 years.

AIM: To determine if a defined set of echocardiographic parameters at entry and exit of a longitudinal study over 5 years showed changes with aging. METHODS: The cohort consisted of 484 randomly recruited women aged 40-80. They were examined by two echocardiography cardiologists, independent of the medical information for these women. RESULTS: Across the age decades (40-49, 50-59, 60-69, 70-79 years), body weight and body surface area (BSA) did not vary, and diastolic blood pressure (DBP) was stable; systolic blood pressure (SBP) progressively increased. There was gradual decline in left ventricular (LV) diastolic function, increase in LV muscle mass, and decrease in LV end-diastolic volume (LVEDV). The serial decrease in rate of change over 5 years in ejection fraction (ET) was small but significant across the four age decades. CONCLUSIONS: As expected, there were age-related changes in cardiac structure and function over time in women who showed no apparent cardiovascular disease (CVD) at entry to the study. The direction of these serial changes was toward the development of LV stiffness and likelihood of subsequent heart failure. The clinical significance of the decrease in rate of change in EF remains unclear.

Psychometric properties and health correlates of the Geriatric Anxiety Inventory in Australian community-residing older women.

OBJECTIVE: To assess the psychometric properties and health correlates of the Geriatric Anxiety Inventory (GAI) in a cohort of Australian community-residing older women. METHOD: Cross-sectional study of a population-based cohort of women aged 60 years and over (N = 286). RESULTS: The GAI exhibited sound internal consistency and demonstrated good concurrent validity against the state half of the Spielberger State Trait Anxiety Inventory and the neuroticism domain of the NEO five-factor inventory. GAI score was significantly associated with self-reported sleep difficulties and perceived memory impairment, but not with age or cognitive function. Women with current DSM-IV Generalized Anxiety Disorder (GAD) had significantly higher GAI scores than women without such a history. In this cohort, the optimal cut-point to detect current GAD was 8/9. Although the GAI was designed to have few somatic items, women with a greater number of general medical problems or who rated their general health as worse had higher GAI scores. CONCLUSION: The GAI is a new scale designed specifically to measure anxiety in older people. In this Australian cohort of older women, the instrument had sound psychometric properties.

Persistence and malignant sequelae of gestational trophoblastic disease: Clinical presentation, diagnosis, treatment and outcome.

BACKGROUND: The major concern in gestational trophoblastic disease is management of persistent disease and malignant sequelae. However, prediction of response to treatment is difficult and methods used controversial. AIM AND METHODS: To evaluate the usefulness of clinical presentation, methods of diagnosis and categorisation of risk in determining clinical outcomes, by analysis of a database of 705 registered patients collected over 30 years. RESULTS: From the database, there were 97 patients who developed persistent disease and malignant sequelae on the basis of defined criteria - 80.4% had molar pregnancy and 19.6% non-molar pregnancy. Vaginal bleeding was not a common presentation; 59.8% had no clinical symptoms. According to protocol, monitoring by serial human chorion gonadotrophin (HCG) levels followed by imaging screen was used in all patients; histology was also available in 41.2% from hysterectomy and curettage specimens. There were 16 of 76 patients with persisting disease who had metastases (21.1%), and 2 of 20 patients with choriocarcinoma who had an antecedent molar pregnancy (10.0%). Based on five risk factors, 25 patients were categorised as 'high risk' and assigned to receive multi-drug chemotherapy. There were two deaths (2.1% for all malignant sequelae); both were from molar pregnancies. One patient failed to respond and the other suffered a complication of intensive chemotherapy. CONCLUSION: Serial HCG levels remain the best monitor to determine therapeutic response. Categorisation of 'high risk' by five factors is useful in treatment. Albeit a small series, clinical outcome is favourable with a five-year survival of 89.7%.

Effect of lifestyle factors and hormone therapy on heart function by serial echocardiography in postmenopausal women.

BACKGROUND: There is conflicting information on the effects of oestrogen on the heart in women, especially those using postmenopausal hormone therapy. Whilst some studies reported a beneficial effect, others showed adverse outcomes. The interplay of lifestyle factors and type/timing of therapy remains to be clarified. AIM: The aim of this study was to determine the effects of lifestyle and hormone therapy on heart function and structure in postmenopausal women. METHOD: As part of a large longitudinal study of women randomly recruited from an urban population, the study assessed 410 suitable women by echocardiography in Year 1 and Year 5 of the study by two independent cardiologists. RESULTS: In lifestyle characteristics, the difference in age and body mass (as markers of cardiovascular risk) was in favour of never-users versus hormone therapy-users. Using an arbitrary cut-off > or =15% change for an effect, we found lifestyle factors had minimal effect on the two measured parameters - ejection fraction, left ventricular mass. Effects of hormone therapy were variable and mixed; greatest effect was found for an 'early start' of hormone therapy with oestrogen-only preparation - the risk of reduced ejection fraction was decreased [hazard ratio (HR) 0.42, confidence interval = 0.17-1.03, P = 0.06] and risk of increased left ventricular mass was increased (HR 2.21, 1.09-4.49, P = 0.03). CONCLUSION: Our findings add to the evidence that oestrogen given to postmenopausal women has a mixed effect on the heart, with effect best shown when started early.

The obstructed hemivagina, ipsilateral renal anomaly, uterus didelphys triad.

The triad of obstructed hemivagina, renal anomaly and uterus didelphys is an uncommon cause of abdominal pain and menstrual discomfort in adolescent girls. Accurate diagnosis and surgical treatment can be delayed for several months or even years. Adolescent girls presenting with these symptoms should have a baseline pelvic ultrasound scan to establish uterine anatomy. In those with ultrasound findings of Müllerian anomalies appropriate follow up would include a magnetic resonance imaging, preferably at a tertiary centre with expertise in interpretation of Müllerian anatomy, as well as early consultation and referral to a centre with experience in the management of these rare conditions. Appropriate surgery would be a single stage procedure to either excise or completely divide the obstructing septum. There is currently no consensus on concurrent laparoscopy. We present a case series of four patients with the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis managed between 2005-2009 at a tertiary centre for paediatric and adolescent gynaecology.

Analysis of risk factors for persistent gestational trophoblastic disease.

SETTING: Persistent disease is a serious consequence of molar pregnancies. Its early detection is critical to effective chemotherapy. Therefore, determination of risk becomes an important clinical decision. OBJECTIVES: To determine the relative risk of persistent disease in a cohort of patients with partial and complete molar pregnancies by analysis of five factors derived from a database using multivariate analysis. RESULTS: Of 686 patients, 78 developed persistent disease which required treatment (rate of 11.3%). Risk was markedly increased when serum human chorionic gonadotrophin (HCG) failed to reach negative by 12 weeks after evacuation [hazard ratio (HR) = 120.78, P < 0.001]. Risk was markedly decreased when the interval from last pregnancy exceeded 12 months (HR = 0.24, P = 0.005). Other factors such as patient's age, stage of gestation and serum HCG level at presentation were not found to be strongly associated with risk of persistent disease. CONCLUSION: These findings support the application of the following two factors in risk prediction for molar pregnancies: > 12 weeks to become HCG negative and interval from last pregnancy < 12 months. They will contribute to a greater awareness of persistent disease and assist in early detection and effective chemotherapy.

Age-related changes relevant to health in women: design, recruitment, and retention strategies for the Longitudinal Assessment of Women (LAW) study.

OBJECTIVES: The primary aim was to assess the age-related changes that occur in older women. This paper describes the study rationale and methods, recruitment, and retention strategies. METHODS: The Longitudinal Assessment of Women (LAW) Study was a longitudinal, observational, and multidisciplinary evaluation of a population-based cohort of urban-living women, aged between 40 and 80 years at recruitment and randomly invited from a district in Brisbane (a city in Australia) via the electoral roll. Five hundred eleven women were recruited and stratified into four age groups (40-49, 50-59, 60-69, 70-79 years) and were assessed on three or four occasions each year, using interviews and diagnostic instruments (echocardiography, applination tonometry, dual-energy x-ray absorptiometry [DEXA]) Retention strategies included flexibility, accessibility, personalized attention, and feedback. RESULTS: From a sample frame of 1598 names, there were 1082 respondents, of whom 511 (47%) were successfully recruited from those eligible to participate. Recruitment was quickest for the oldest age group, 70-79 years, and slowest for the age group 40-49 years; all age groups achieved their required quota. A scheduling program was developed to minimize the number of visits and maximize the use of allocated time. The largest dropout was seen in year 1 of the study, with very few thereafter. Of the 9 deaths, cancer was the cause in 7. The retention rate after 5 years was 95.5%. CONCLUSIONS: The design of the present study, with careful attention to coordination and a personal approach, facilitated the completion of a 5-year study, enabling a collection of a set of wide-ranging data from almost all the women recruited. The information thus collected will form the basis of cross-linking analysis of the risk factors associated with health problems in aging women.

Hormones down under: hormone therapy use after the Women's Health Initiative.

AIMS: The primary objective was to describe the usage pattern of hormone therapy (HT) in a sample of urban Australian women in 2001 and to assess the characteristics of users vs. non-users. The second objective was to determine whether there had been any change in usage since the publication of the results of the combined oestrogen plus progestagen arm of the Women's Health Initiative (WHI) in 2002. METHODS: A cohort of 374 postmenopausal women aged 50-80 years participated in this substudy of the LAW (Longitudinal Assessment of Ageing in Women) project: a 5-year multidisciplinary, observational study. Participants completed an annual medical assessment including details of the use of HT and the reasons for use, as well as demographic and psychosocial data. RESULTS: In December 2001, 30.8% of the participants were using HT, whereas 55.4% were ever users. The management of vasomotor symptoms and mood disturbance were the primary reasons for use. Of those who had been using HT in December 2001 (24.4%) women ceased using HT in the 3 months following publication of the WHI results. The percentage of women using HT in December 2003 (13.9%) was less than half of that of December 2001. CONCLUSION: The rate of HT use and the reasons for use, in 2001 in Brisbane was similar to that of other Australian regions. Usage of HT decreased since the publication of the WHI results in 2002 which may reflect changing attitudes by patients and practitioners regarding HT.

A medical management of interstitial ectopic pregnancy: a 5-year clinical study.

BACKGROUND: Medical treatment of the rare interstitial ectopic pregnancy with methotrexate has been considered an alternative to surgical resection. AIM: To determine the treatment success rate with a single-dose intravenous methotrexate/folinic acid regimen and to identify predictors of treatment outcome. METHODS: A 5-year audit (April 2000-August 2005) was carried out, collecting clinical imaging data and serum beta-human chorionic gonadotrophin (beta-hCG). Time taken for complete beta-hCG resolution was recorded, and a negative beta-hCG result was used as an endpoint of successful outcome. RESULTS: Of the 13 cases, two required urgent surgery for rupture on presentation. In the remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic acid rescue (15 mg x 4 doses). There were no side-effects. Complete beta-hCG resolution was achieved in 10 of the 11 medically treated cases (91% success rate), requiring 21-129 days. Successful outcome was seen with initial beta-hCG level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live fetus. CONCLUSION: The methotrexate/folinic acid regimen used as a one-dose treatment is safe and effective for unruptured interstitial pregnancy, with no side-effects and the advantage of avoiding invasive surgery. Subsequent tubal patency and reproductive function are yet to be ascertained.

The influence of postmenopausal hormone replacement therapy on cognitive functioning: results from an observational study.

OBJECTIVES: The aim of this study was to evaluate the impact of hormone replacement therapy (HRT) upon memory deficit in a group of urban Australian women. PARTICIPANTS AND SETTING: A cohort of 493 women aged 40-80 years was tested as part of the Longitudinal Study of Ageing in Women (LAW study) at the Royal Brisbane and Women's Hospital, Brisbane, Australia. MAIN OUTCOME MEASURES: The current memory functioning of participants was evaluated using the Wechsler Memory Scale - version three (WMS-III) while pre-morbid cognitive functioning was estimated from scores on the National Adult Reading Test (NART). Memory deficit was estimated by comparing NART scores with the age-corrected scale scores of the WMS-III. RESULTS: Overall, NART scores correlated with WMS-III scores, consistent with the expected relationship between pre-morbid functioning and current functioning. For the sample as a whole, memory deficit was evident but mostly, age appropriate. There was considerable variation as to the extent of memory deficit within the sample. When memory functioning for women with a history of five or more years of combined oestrogen plus progestogen HRT or oestrogen replacement therapy (ERT) was compared with that of women who had never used HRT or ERT there was no evidence of any effect for either HRT or ERT on memory deficit. CONCLUSIONS: The use of HRT or ERT had neither a protective nor an adverse effect on memory deficit.

Clinical aspects of gestational trophoblastic disease: a review based partly on 25-year experience of a statewide registry.

BACKGROUND: Gestational trophoblastic disease is a fascinating group of pregnancy disorders characterised by abnormal proliferation of trophoblast, ranging from benign to malignant. Because the disease is uncommon, there is a need to formulate management with the assistance of collective information. METHODOLOGY: A review of available information from English written literature was undertaken, especially data reported by registries around the world (Charing Cross Hospital in England, the North-western University and the New England area in the USA as well as our own experience in Queensland, Australia). Where possible, collated data from relevant studies were analysed to answer some of the questions posed in clinical practice, with reference to metastatic disease to liver and brain, twinning of molar gestation and coexisting fetus, and placental-site tumour. RESULTS: We found that molar gestation can be classified according to its clinical presentation which influences the time taken to reach human chorionic gonadotropin (HCG) 'negativity' and the risk of persisting disease. Categorisation of risk is the basis for choice of chemotherapy to achieve good outcomes. Metastases to liver and brain remain problems in management; the development of 'new' metastases during chemotherapy is a very poor prognostic factor. In the variant of twinning with molar gestation and coexisting fetus, it is important to elucidate the fetal karyotype in planning management: a 69XXX fetus is not salvageable but a normal 46XX or 46XY fetus faces the prospect of early preterm delivery. The placental-site tumour is very rare; localised disease is curable by surgery; chemotherapy is less effective in disseminated disease. From collated worldwide data, the recurrence rate after one mole is 1.3% and after two or more is 20%. Reproductive outcome in subsequent pregnancies, even after multidrug chemotherapy, is not different from the general population. Because of the increased risk long-term of second tumours after multidrug chemotherapy a closer surveillance of these patients is necessary. CONCLUSION: In general, the disease in its persisting or malignant form is 'a cancer model par excellence' because of an identifiable precursor condition, a reliable HCG marker, and sensitivity of the disease to cytotoxic drugs. With current management, retention of fertility is possible and normal reproductive outcome assured.