Duration of vasomotor symptoms in middle-aged women: a longitudinal study.

OBJECTIVE: Vasomotor symptoms adversely affect the quality of life and functional status of most women during the menopausal transition, but little is known about how long these symptoms last. The most effective treatment, hormone therapy (HT), carries risks and benefits that depend on the timing and duration of use. In this study we sought to estimate the duration of vasomotor symptoms in a longitudinal study. METHODS: We reanalyzed primary data from 438 women in the longitudinal cohort of the population-based Melbourne Women's Midlife Health Project. Two hundred and five women who had completed 13 years of follow-up were included in the analyses. The onset and cessation of vasomotor symptoms were reported, stratifying analyses according to ever use of HT. Symptom duration was calculated as the time between the first and last bothersome hot flush reported. RESULTS: The mean (SD) duration of bothersome menopausal symptoms for women who completed 13 years of follow-up and who never used HT was estimated to be 5.2 (3.8) years (median, 4 years). If women who used HT were included, the mean (SD) duration was 5.5 (4.0) years (median, 4 years). The estimated duration of symptoms varied according to the duration of longitudinal follow-up, with a mean estimate of 3.4 years (median, 3 years) when only 8 years of follow-up data were analyzed. The only factor associated with duration of hot flushes was regular exercise-more exercise was associated with shorter symptom duration. CONCLUSIONS: The average duration of vasomotor symptoms in this sample is more than 5 years, substantially longer than had been previously reported.

Sexual function, dysfunction, and sexual distress in a prospective, population-based sample of mid-aged, Australian-born women.

INTRODUCTION: Previous, population-based studies investigating the risk factors for sexual distress have not drawn on longitudinal data. AIMS: Determine the prevalence of sexual distress and dysfunction, explore factors associated with/predictive of sexual distress, and describe changes in sexual function over a decade in a population-based sample of mid-aged women. METHODS: Eleven-year prospective study of Australian-born women, aged 45-55 years, and menstruating at baseline. Short Personal Experiences Questionnaire (SPEQ) was completed in years 1 to 8 and 11 of follow-up. Female Sexual Distress Scale (FSDS) was completed in the 11th year of follow-up. MAIN OUTCOME MEASURES: Validated outcome measures were the SPEQ (total sex score or=15 indicates sexual distress). RESULTS: Two hundred fifty-seven women were interviewed in the 11th year of follow-up. All domains of sexual function declined significantly in the decade studied. Women using hormone therapy in year 11 had significantly greater responsivity and higher frequency of sexual activities than nonusers. Two hundred four women completed both the FSDS and SPEQ questionnaires. One hundred sixty-six (81%) women had an SPEQ score or=15, and were classified as having female sexual dysfunction. The multiple logistic regression analysis found that female sexual distress was concurrently associated with higher depression scores (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.10, 1.56) and more negative feelings for partner (OR 0.49, 95% CI 0.32, 0.76) and predicted by prior negative feelings for partner (OR 0.31, 95% CI 0.14, 0.70), and a greater decline in total sex score (OR 0.77, 95% CI 0.59, 0.99). CONCLUSIONS: By the end of the sixth decade, women have low levels of sexual function. Hormone therapy may help these women maintain sexual function. A minority of these mostly postmenopausal women are significantly distressed about low sexual function. Sexual distress is associated with depression and relationship factors.

New findings from non-linear longitudinal modelling of menopausal hormone changes.

Changes in FSH and estradiol (E2) across the menopausal transition are clearly not linear. The present study utilizes data from 204 women who completed the 13-year prospective Melbourne Women's Midlife Health Project. E2, FSH, symptoms, self-rated health, mood, sexual function and coronary heart disease (CHD) risk were measured longitudinally. We presumed an s-shaped curve for each hormone and estimated five parameters for each hormone curve for each woman: baseline, final value, range, slope at inflexion point and age at inflexion point. These parameters were found to adequately estimate the curve for each hormone. The median age of transition observed for E2 occurs >1 year later than the median age of transition observed for FSH. FSH parameters did not affect any of the health outcomes analysed. Hot flushes, night sweats, sleeping problems, vaginal dryness and to a lesser extent self-rated health were highly significantly associated with E2 range and slope. Sexual response and CHD risk were highly significantly associated with final E2 level (post-menopausally). These findings have clinical relevance in identifying which symptoms will be triggered by steep transitions of E2 such as sudden withdrawal and which health parameters may require a maintenance level of E2.

Modeling women's health during the menopausal transition: a longitudinal analysis.

OBJECTIVE: There has been controversy about the relative effects on various health outcomes of hormonal, psychosocial, and lifestyle changes during the menopausal transition. In previous studies the risk factors for one particular health endpoint have been analyzed separately. Separate analyses do not provide an overall view of the relationships between all the variables or the relative importance of different factors. Thus, the objective of this study was to provide an overall analysis of the influence of hormonal changes during the menopausal transition on a range of health outcomes while simultaneously considering all the available predictors and all the endpoints and to test the hypothesis that prior health status predicts current health status. DESIGN: This was a 9-year prospective observational study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews were conducted and fasting blood and physical measurements were performed annually. RESULTS: Main outcome measures were hormone levels, sociodemographic variables, attitudes and lifestyle variables, self-rated health and well-being, bothersome symptoms, coronary heart disease risk, bone mineral density, and sexuality. Data from 336 women, 77% of the original sample, were analyzed. Statistical modeling using structural equations showed that for all health endpoints, the prior level of that variable was the most important predictor. Declining levels of estradiol during the menopausal transition affected certain health outcomes: bone mineral density, coronary heart disease risk, vasomotor symptoms, vaginal dryness, and sexual response. Well-being is negatively affected by symptoms, hassles, and stress. Exercise has beneficial effects on hot flushes, well-being, body mass index, and coronary heart disease risk. Relationship factors and mood affect sexual response. CONCLUSIONS: This observational study provides a conceptual data-based framework for understanding changes in women's health during the natural menopausal transition.

Mammographic densities during the menopausal transition: a longitudinal study of Australian-born women.

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.

Hot flushes during the menopause transition: a longitudinal study in Australian-born women.

OBJECTIVE: To investigate factors associated with the presence, severity, and frequency of hot flushes. DESIGN: 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. RESULTS: 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). CONCLUSION: Menopause status, FSH and estradiol levels, age, exercise level, and smoking status all contributed to the experience of bothersome hot flushes.

Hyperhomocysteinemia is associated with lower performance on memory tasks in post-menopausal women.

Increased levels of total homocysteine (tHcy) have been associated with lower performance on tests of cognitive function, and may be a potential preclinical marker for Alzheimer's disease. Most reports have focused on older cohorts, but raised tHcy levels, in association with cognitive changes may be occurring in earlier years. Scores for verbal and working memory were compared to plasma homocysteine levels for 200 healthy women aged 56--67 (mean=60). Smoking, hormone therapy and age were significantly associated with increased levels of tHcy, whilst vitamin B or folate supplements were significantly associated with lower tHcy levels. Hyperhomocysteinemia (>13 micromol/l) was significantly associated with poor performance for combined verbal and working memory, and there was a trend for hyperhomocysteinemia to be associated with the learning trials for 2 word lists, but not for the delayed trial. As hyperhomocysteinemia is associated with memory changes in women aged 56--67, it may be playing a role in the early dementia processes.

A population-based study of depressed mood in middle-aged, Australian-born women.

OBJECTIVE: There has been controversy about the relationship between menopause and depression. This study utilizes a unique prospective population-based data set of middle-aged, Australian-born women to identify determinants of depressed mood. DESIGN: The Melbourne Women's Midlife Health Project sample consisted of 438 women aged 45 to 55 at baseline; they were followed annually for 11 years. Of this group, 314 (72%) completed the Center for Epidemiologic Studies Depression Scale (CES-D) scale in year 11 to measure depressed mood. Variables measured at baseline and annually included negative mood (measured with Affectometer) and psychosocial, hormonal, health, and lifestyle factors. RESULTS: Women who had the highest CES-D scores were those who by year 11 were still in the menopause transition stage (had not reached final menstrual period) or had experienced surgical menopause. CES-D correlated with negative mood measured concurrently (r = 0.63) and baseline negative mood (r = 0.37). There was a significant reduction in negative mood for all menopause status groups, but those who experienced surgical menopause showed less reduction than other women. Ever-use or number of years of use of hormone therapy made no difference to CES-D outcome. CES-D was associated with baseline negative attitudes toward aging, mood, and premenstrual complaint experience and annual mood, poor self-rated health, number of bothersome symptoms, and daily hassles. CONCLUSIONS: Women most likely to have higher depressed mood in the age group 57 to 67 are those who have undergone surgical menopause or have menstruated within the last 12 months. Prior negative mood, history of premenstrual complaints, negative attitudes toward aging or menopause, poor health, and daily hassles predict depressed mood.

Normative verbal and non-verbal memory test scores for Australian women aged 56-67.

OBJECTIVE: To establish normative data for tests of verbal and non-verbal memory for midlife Australian-born women, and in so doing investigate factors which contribute to variation in test performance. METHOD: Two hundred and fifty-seven healthy women aged 56-67 years (mean age 60), who are participating in the Melbourne Women's Midlife Longitudinal Health Project, were administered two word list learning tasks, a story recall task (the East Boston Memory Test) and the Faces subtest from the Wechsler Memory Scale III as part of a larger neuropsychological battery. Word list learning tasks consisted of either 16 semantically related words, derived from the California Verbal Learning Test II, or a list of 10 unrelated words. Mood was assessed by the Center for Epidemiological Studies Depression questionnaire. RESULTS: Education was significantly related to memory performance and there was a non-significant trend for test scores to decline with age. Mood was unrelated to test performance. A confirmatory factor analysis indicated a clear distinction between verbal and non-verbal memory performances. Mean scores were stratified by education (less than 12 years vs. 12 or more years) and age (56-59 vs. 60-67 years), and scaled normative data were constructed for all the tests. CONCLUSION: This study provides education-based normative data for tests of verbal and non-verbal memory for midlife Australian women. The establishment of population-based normative data will facilitate future investigations of ageing and dementia in Australian women.

Childhood abuse and its association with mid-aged women's sexual functioning.

The aim of this study was to investigate the association of recalled childhood sexual and physical abuse with current sexual functioning in mid-life. The sample was participants in the longitudinal population-based cohort of mid-aged women, The Melbourne Women's Midlife Health Project. Three hundred sixty two of the women (92% of the available cohort) were administered the Violence Questionnaire in the sixth year of follow-up. This included questions on physical abuse and sexual abuse experienced in childhood. We used the Short Personal Experiences Questionnaire (Dennerstein, Anderson-Hunt, & Dudley, 2002) to assess current sexual functioning. Forty eight percent of the women had no experience of childhood sexual abuse, 42% had experienced noncontact sexual abuse, 36% had experienced contact sexual abuse, and 7% had experienced penetrative sexual abuse. Nine percent of the women had experienced physical abuse in childhood. Women who had experienced penetrative childhood sexual abuse were significantly more likely to have fewer children (median 2) than women who had not experienced penetrative childhood sexual abuse (median 3) (P < 0.05). The only area of sexual or relational functioning significantly affected by childhood sexual abuse was that of feelings for partner (P < 0.05). Those who experienced penetrative childhood sexual abuse had, on average, significantly shorter current relationships (P < 0.05). Women who had experienced both childhood sexual and physical abuse reported a lower frequency of current sexual activities (P < 0.05). This study of mid-aged women found that the major impact of childhood sexual abuse is on the quality of relationship with the partner.

Association between hormonal changes at menopause and the risk of a coronary event: a longitudinal study.

OBJECTIVE: 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. DESIGN: 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). RESULTS: 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. CONCLUSION: 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.

The relative effect of endogenous estradiol and androgens on menopausal bone loss: a longitudinal study.

OBJECTIVE: The aim of this study was to assess the relative strength of the association of endogenous estradiol and androgens with bone loss at the lumbar spine and femoral neck during the menopausal transition. DESIGN: A longitudinal study of a population-based cohort of 159 Australian-born women who at baseline had a mean age of 50.0 years (SD=2.4) and had menstruated in the prior 3 months. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck on up to three occasions. RESULTS: Of the 159 participants, 50 had two BMD measurements and 109 had a third measure. The mean time between the first and final measures for the whole group was 39 months and at the time of the final measures 49% of the participants had become postmenopausal. The mean percentage change/year in lumbar spine BMD was -0.9% (95% CI, -1.1 to -0.6) and at the femoral neck, -0.5% (95% CI, -0.7 to -0.2). A highly significant association with estradiol at the final time point was found, whereas the contribution of estradiol at baseline was negligible. The variance explained by estradiol levels was 19% and 11% for change in BMD at the LS and FN, respectively. Excluding baseline estradiol values and using the average of change in BMD at the LS and FN, the final regression equation estimated that an estradiol level of 330 pmol/l (95% CI, 274 to 386) and 245 pmol/l (95% CI, 194 to 296) is required for preservation of LS and FN BMD, respectively. A stepwise linear regression model was used to assess the effect of age, BMI, estradiol, testosterone, DHEAS, SHBG, and free testosterone index on changes in BMD and found that only the final estradiol level had a significant association with change in BMD. CONCLUSION: Endogenous estradiol was the only hormone among those investigated to have a significant effect on bone mineral density during the menopausal transition.

Central abdominal fat and endogenous hormones during the menopausal transition.

OBJECTIVE: To investigate the effect of endogenous hormone levels on central abdominal fat during the menopausal transition in a population-based cohort of Australian-born women. DESIGN: Prospective observational study. SETTING: Population-based sample. Body composition was assessed in the Royal Melbourne Hospital, and interviews were conducted at the patient's home. SUBJECT(S): One hundred two women from the Melbourne Women's Midlife Health Project. Data, physical measures, and blood were obtained by interview when the longitudinal study commenced (baseline) and at the time of the total body scan approximately 5 years later. Body composition was measured using dual-energy X-ray absorptiometry. INTERVENTION(S): None. MAIN OUTCOME MEASURES: Total body fat and central abdominal fat. RESULT(S): The 102 women were either premenopausal or in the early menopausal transition at baseline. At the time of their dual-energy X-ray absorptiometry scan, 31 were in the early menopausal transition, 22 were in the late menopausal transition, and 49 were postmenopausal. Multiple regression analysis found that total percentage of body fat was associated with weight measures, whereas central abdominal fat was also positively associated with baseline free T index (FTI) and with the increase in FTI since baseline. CONCLUSION(S): The major hormonal change associated with central adiposity during the menopausal transition is the increase in the FTI. This effect is significant even after allowing for baseline and final weight.

Predictors of declining self-rated health during the transition to menopause.

OBJECTIVE: To determine factors associated with declining self-rated health as measured annually for 8 years in a prospective population-based cohort of middle-aged Australian-born women. In particular, to investigate the potential role of the menopausal transition in changing self-rated health. METHODS: A total of 262 women from the Melbourne Women's Midlife Health Project were asked to rate their present health compared with other women about the same age as worse than, the same as or better than most. RESULTS: Women reporting their health to be "better than most" decreased from 51.2% at Year 1 to 41.3% at Year 8. In the year prior to the late menopausal transition, women reporting their health to be 'better than most' declined by 5%. Comparing women who experienced the menopausal transition with women whose menopausal status did not change, there was no significant difference in changes in self-rated health. Change in body mass index (OR = 1.53; 95% CI = 1.13 to 2.06) and change in feelings for partner (OR = 0.38; 95% CI = 0.17 to 0.86) predicted a change in self-rated health from a baseline status of 'better than most.' Having an operation or procedure in the last year (OR = 8.63; 95% CI = 1.84 to 40.4) and an increase in the number of symptoms (OR = 1.32; 95% CI = 1.01 to 1.72) predicted a decline in self-rated health from baseline status of 'same as others.' CONCLUSION: This prospective study found a small decline in self-rated health with age but no significant effect of the menopausal transition. Different factors relate to differing self-rated health groupings. Further studies involving other ethnic groups and larger sample sizes are needed.

Physical activity: measurement in mid-life women.

OBJECTIVES: To review methods of assessing physical activity, and to compare two different questionnaires that were administered in the Melbourne Women's Midlife Health Project (MWMHP). METHODS: Cross-sectional and subsequent longitudinal population-based study of Australian-born women who were aged 45-55 at baseline. Self-administered modified form of the Minnesota Leisure-Time Physical Activity questionnaire and interviewer-administered short physical activity question. RESULTS: Two hundred and ninety-two women completed the Minnesota Leisure-Time Physical Activity questionnaire at both cross-sectional and 3rd year of follow-up (L3) and there was no difference in the total mean time spent exercising at both phases [5.9 (SD, 5.7) and 5.8 (SD, 5.0) hours per week, respectively]. The responses to the two questionnaires were significantly associated (beta = -0.89, SE 0.17, p < 0.0005). Using the Minnesota Leisure-Time Physical Activity questionnaire between the cross-sectional and L3 phases, 10% of the women increased the time they spent exercising by 5 h per week and 10% decreased it by the same amount. Using the short exercise question, 12% of women decreased their participation by two or more sessions per week and 14% increased their participation by this amount between the cross-sectional and L3 phases. CONCLUSION: In this cohort of mid-life women the short exercise question was comparable in terms of measuring participation and change in physical activity with the more complex Minnesota Leisure-Time Physical Activity questionnaire.