Janet R. Guthrie

Objective: The objective of this study was to investigate hormonal and other factors associated with mammographic density during the menopausal transition and in postmenopause. Design: Mammograms were obtained from 252 participants in the Melbourne Women's Midlife Health Project-a longitudinal population-based study that included annual interviews, blood collection, and physical measurements; 869 original films of the right craniocaudal view were digitized. Total area of the breast and the area of dense tissue were measured, and the percentage of mammographically dense tissue (PMD) was calculated. Data were analyzed using time-series regression models. Results: Of the 252 women, 87% had more than one mammogram, and the mean age was 56.0 (SD 3.6) years (range 45-67); 129 women who had never used hormone therapy were included in the analyses. The mean nondense breast tissue area increased through the menopausal transition (P for trend = 0.01), there was no significant trend in the mean dense breast tissue area, and mean PMD decreased (P for trend = 0.004). Multivariate analysis showed that increasing age (P < 0.005) and body mass index (BMI) (P < 0.05), having had children (P < 0.05), and higher than average free testosterone levels (P < 0.05) (or lower than average sex hormone-binding globulin levels) were associated with increased area of nondense tissue. Increasing age (P < 0.05) and BMI (P < 0.05) were associated with decreased PMD. There was a tendency for higher than average free testosterone levels (P < 0.07) and having had children (P = 0.07) to be associated with lower PMD. After controlling for age, there were no significant associations with the area of dense tissue. Conclusions: This longitudinal observational study has shown that after controlling for age, there was no apparent effect of menopausal change on the area of dense breast tissue. Aging and increasing BMI through the menopausal transition were associated with increased nondense breast tissue and explain a small, but statistically significant, portion of the variation in PMD tissue.

To determine the effect of weight and physical activity on the prevalence of radiological knee osteoarthritis (OA) in a cohort of middle-aged women. The longitudinal phase of the Melbourne Women's Mid-life Health Project is a population-based prospective study of 438 Australian-born women who have been followed annually over 11 years. Of these women, 257 (59%) remained in longitudinal assessment at eleventh year of followup, and 224 of these women agreed to undergo radiographs of their knees. Radiographs were scored for features of OA [osteophytes and joint space narrowing (JSN)] using a validated scale, by 2 investigators who were blinded to questionnaire results. Data were obtained by both self-administered and face-to-face interview questionnaires. The average weight increase over the study period of 11 years was 4 kg (range -14 to 25 kg). Of the 224 women evaluated, 65 (29%) had knee joint osteophytes and 95 (42%) had evidence of knee JSN. Current weight and weight at baseline were independent factors associated with a higher prevalence of both osteophytes and JSN in all compartments of the knee. The average amount of physical activity over the 11 years of followup was a significant factor independently associated with an increased prevalence of patellofemoral JSN and approached significance for tibiofemoral osteophytes and total knee JSN. Our study supports a longterm detrimental effect of weight on the knee joint and suggests the importance of longterm weight maintenance programs in preventing knee OA. The average amount of physical activity was associated with an increased prevalence of some features of knee OA.

To investigate factors associated with the presence, severity, and frequency of hot flushes. A 9-year prospective study of 438 Australian-born women, aged 45 to 55 years and menstruating at baseline. Annual fasting blood collection, physical measurements, and interviews including questions about bothersome hot flushes in previous 2 weeks were performed. A “hot flush index” score was calculated from the product of the severity and frequency data. Data were analyzed using random-effects time-series regression models. A total of 381 women supplied complete data over the follow-up years. A total of 350 women experienced the menopause transition, of whom 60 (17%) never reported bothersome hot flushes. At baseline, women who reported hot flushes were significantly more likely to have higher negative moods, not be in full- or part-time paid work, smoke, and not report exercising every day. Over the 9-year period of the study, variables significantly associated with reporting bothersome hot flushes were relatively young age (P < 0.001), low exercise levels (P < 0.05), low estradiol levels (P < 0.001), high follicle-stimulating hormone (FSH) levels (P < 0.001), smoking (P < 0.01), being in the late menopause transition (P < 0.001), or being postmenopausal (P < 0.001). In women reporting hot flushes, the hot flush index score increased as their FSH levels increased (P < 0.01), as they entered the late stage of the menopause transition (P < 0.001), and as they became postmenopausal (P < 0.05), and decreased with as their age (P < 0.001) and exercise level (P < 0.05) increased. Between-women analyses found that the hot flush index score was greater in women with higher average FSH levels over time (P < 0.05). Menopause status, FSH and estradiol levels, age, exercise level, and smoking status all contributed to the experience of bothersome hot flushes.

To investigate the association of hormone levels at menopause, lifestyle variables, and body composition with the predicted 10-year risk of a coronary event, calculated using the PROCAM scoring system, in a population-based sample of Australian-born, middle-aged women. A 9-year prospective study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews, fasting blood, and physical measurements were taken annually. The risk of an acute coronary event was calculated using the PROCAM scoring system (includes: age, low-density lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides). Retention rate after 8 years of follow-up was 88% (n = 387). In women not using hormone therapy (HT): higher than average body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than average estradiol levels (P < 0.005), estradiol levels that decreased (P < 0.001), and high free testosterone levels (P < 0.05) were associated with increased risk of a coronary event. There was a trend for high exercise frequency to be associated with a decreased risk (P < 0.07). After BMI and lifestyle variables were taken into account, use of HT did not have a significant effect on risk of a coronary event. In this longitudinal observational study of middle-aged Australian-born women, high BMI, an increase in BMI, high free testosterone, low estradiol, and a decrease in estradiol levels were the main determinants of increased risk of an acute coronary event, based on the PROCAM scoring system calculation. More frequent exercise tended to lower the risk.

Normative data for tests of working memory and executive function (a term adopted to cover a range of cognitive skills) are primarily based on the U.S. population and are not always specific for gender or education levels. The diagnosis of, and research into, cognitive diseases rely on the use of relevant normative data. This study presents normative data for an ageing, female, Australian‐born population, and an analysis of the factors that contribute to variation in performance. Three tasks of executive function: Trail Making Test, Part B (Trails‐B); Tower of London, and the oral version of the Symbol Digit Modalities Test (SDMT), and a working memory task (Letter‐Number Sequencing, LNS) were administered as part of a 14‐item neuropsychological battery to 257 participants (M age=60 years, range=56–67 years), who have been participating in the Melbourne Women's Midlife Health Project. The Center for Epidemiological Studies Depression Scale (CES‐D) was also administered. A regression analysis incorporating age, years of education, CES‐D score, current use of hormone therapy and menopausal status as independent variables demonstrated that education and age contributed to the variation in SDMT and the LNS but not in the Tower of London. Education alone contributed to variation in Trails‐B, although there was a trend for performance to decrease with age. Mood, hormone therapy use, and menopausal status were unrelated to test scores. Tables of mean scores were constructed for age ranges and level of education, for each of the tests except the Tower of London, which was presented as education groups only. Partial correlations between test performances demonstrated significant correlations between all the major components of the tests. This study provides education‐ and age‐based normative data for tests of executive function for the ageing female, Australian‐born population.

The aims of this study were: 1) to describe, in relation to the date of final menses, the average hormone levels of women in the years before and after this date and to determine the extent to which these average levels were dependent on age and body mass index (BMI); and 2) to determine the degree of tracking in residual hormone levels[ i.e., the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses]. Serial levels of serum FSH, circulating estradiol (E2), and the dimeric inhibins (INH) A and B were measured annually in 150 women who experienced a natural menopause during 6 years of follow-up. Means of the log-transformed hormonal levels were analyzed as a double-logistic function of time relative to FMP, as well as age and BMI and correlations between repeated hormonal levels, were measured. Mean FSH levels started to increase from about 2 years before the FMP, increased most rapidly about 10 months before the FMP, and had virtually plateaued by 2 years after the FMP. FSH levels were, on average, 3% greater for each year of age and 2% lower for each kg/m2 of BMI. After adjusting for time relative to the FMP, logFSH showed modest tracking. Age-adjusted values of logFSH were moderately correlated across time, and much of this tracking was explained by the actual timing of a woman’s FMP. Mean E2 levels started to decrease about 2 years before the FMP, decreased most rapidly around the time of the FMP, and had virtually plateaued by 2 years after the FMP. E2 levels were lower, on average, by about 9% per year of age, and residual values showed weak tracking. Levels of both INHA and INHB decreased, on average, in the years before the FMP and were undetectable (INHA, <10 pg/mL; INHB, < 25 pg/mL) in the majority of women by the time of the FMP and in almost all women by 4 years post-FMP. Significant negative correlations between log serum FSH and log E2 (r = −0.73) and log INHA (r = −0.41) and log INHB (r = −0.36) were observed. It is concluded that substantial changes in reproductive hormone levels occur within 1–2 yr on each side of the FMP, that falling concentrations of E2 and the INH contribute to the rising concentrations of FSH, and that there is no single reliable hormonal marker of menopausal status for an individual woman.