Abstracts
Menopausal symptoms in Australian women.
Dennerstein L, Smith AMA, Morse C, Burger H, Green A, Hopper J, Ryan M.
Med J Aust 1993; 159:232-236
Objectives: To describe Australian-born women's experience of symptoms during the natural menopause transition and the relative contribution of menopausal and health status, social factors and lifestyle behaviours.
Design: A community based cross-sectional survey by telephone interview was carried out on a randomly derived sample of Melbourne women.
Participants: The participants were 2000 Australian-born women, aged between 45 and 55 years.
Outcome measures: A list of 22 symptoms was used.
Explanatory variables were: sociodemographic variables; menopausal and health status, lifestyle behaviours; attitudes to ageing and to menopause.
Results: A 70% response rate was achieved for eligible women who could be contacted during the study. Premenopausal women were the least symptomatic and perimenopausal women the most symptomatic. Factor analysis found seven common factors from the 22 symptoms studied. Menopausal status based on menstrual history was significantly related to two groups of symptoms: vasomotor symptoms, which increased through the menopausal transition; and general somatic symptoms which were more frequent in the perimenopause. Analysis of variance of factor scores found fewer symptoms with increasing years of education, better self-rated health, the use of fewer non-prescription medications, the absence of chronic health conditions, a low level of interpersonal stress, the absence of premenstrual complaints, not currently smoking, exercise at least once a week, and positive attitudes to ageing and menopause.
Conclusions: Many factors unrelated to hormonal changes contributed to the symptoms. Longitudinal investigation is needed to determine the relative importance of hormonal, psychosocial and lifestyle variables in the aetiology of midlife symptoms.
The treatment seeking woman at menopause.
Morse CA, Smith AMA, Dennerstein L, Green A, Hopper J, Burger H.
Maturitas 1994;18:161-173
Recent studies suggest that health care utilisation by women during menopause transition in general is highly idiosyncratic, despite the widespread advocation of prophylactic hormone therapy and increased health vigilance. The Melbourne Women's Midlife Health Study, a community-based cross-sectional study of 2001 urban Australian-born women aged 45-55 years, evaluated women's physical and emotional experiences, past and present health status, attitudes and beliefs about menopause, health behaviours and current menopausal status in a 30 min telephone interview. This paper reports on those factors related to help-seeking and health care utilisation. Findings show that treatment utilisers, in contrast to non-utilisers, reported a wider range of general symptoms, but reports on vasomotor symptoms did not contribute to the regression analysis. Treatment utilisers were further identified as problem-related or prevention-related utilisers. In three-way analyses, the past and present social and physical health of the problem-related treatment user was reportedly worse than either the prevention-related utiliser or non-utiliser. These findings suggest that medical and societal views about the health of middle-aged women during menopausal transition are likely to be based on the experiences of a particular segment of the population only. It is proposed that biased views of menopause as a time of considerable distress and ill-health are being perpetuated and over-generalised. This perspective appears to have little relevance for the majority of middle-aged women.
Sexuality and the menopause.
Dennerstein L, Smith AMA, Morse C, Burger HG.
J Psychosom Obstet Gynecol 15 1994; 59-66
Sexual problems are often reported to clinicians by women in the midlife years. Yet few of the epidemiological studies of women in midlife have investigated the relationship of the menopause to sexual functioning. This paper reports the results of a cross-sectional telephone survey of 2001 randomly selected Australian-born women aged between 45 and 55 years. The major outcome variables were questions relating to changes in sexual interest over the prior 12 months, reasons for any changes, occurrence of sexual intercourse, and of unusual pain on intercourse. Logistic regression was used to identify explanatory variables for change in sexual interest. The majority of women (62%) reported no change in sexual interest, although 31% reported a decrease. Decline in sexual interest was significantly and adversely associated with natural menopause (p < 0.01) rather than age, decreased well-being (p < 0.001), decreasing employment (p < 0.01) and symptomatology (vasomotor p < 0.05, cardiopulmonary p < 0.001 and skeletal p < 0.01). Eleven to twelve years of education was associated with a lowered risk of decreased sexual functioning (p < 0.01). Heterogeneous results were reported by users of hormone replacement therapies. Longitudinal studies of large and representative samples are needed to determine the etiology of adverse sexual changes with the menopause and the role of hormone replacement therapies.
Self-rated health: biological continuum or social discontinuity?
Smith AMA,Shelley J, Dennerstein L.
Soc. Sci. Med. 1994;Vol. 39, No. 1, pp. 77-83
Correlates of self-rated health among a randomly selected sample of 1863 Australian-born women 45-55 years of age were examined in two logistic regression analyses: one comparing a self-rated health of worse than one's peers with a self-rated health the same as one's peers; and, one comparing a self-rated health of better than one's peers with a self-rated health the same as one's peers. The final model for worse health was largely a reflection of the physical experience of ill health while that for better health was a more complex construct including not only the absence of illness but also markers of sociodemographic advantage and self-image. The two models had only three variables in common. Notably, the relationship between the outcome measures and one common variable, body mass index, differed markedly. It is suggested that previous analyses of self-rated health have had their power to adequately describe correlates and determinants of health status constrained. By assuming that the various self-rated health states are part of a continuum and employing statistical methods consistent with that assumption, previous studies have been unable to demonstrate the discontinuity among such states. In particular, it is suggested that self-rated health is at least in part a reflection of social role and as there is no basis for assuming that such roles form a continuum as the use of correlation-based analyses imply, then such analyses are inappropriate.
Diagnostic role of follicle-stimulating hormone (FSH) measurements during the menopausal transition-an analysis of FSH, oestradiol and inhibin.
Burger H.
Eur J Endocrinol 1994; 130:38-42
This review examines the role of follicle-stimulating hormone (FSH) measurement in assessing the significance of symptoms and possible continuing fertility during the menopausal transition. Follicle-stimulating hormone measurement is advocated frequently as a useful diagnostic tool in perimenopausal patients. Several investigators have shown that the serum FSH level increases in the early-mid-follicular and early postovulatory phases in women over the age of 40 years who continue to experience regular menstrual cycles. The serum oestradiol level may fall (although this is controversial) and the immunoreactive inhibin level falls, being inversely correlated with the rising FSH level. When alterations in menstrual cyclicity or flow commence, signalling the onset of the menopausal transition, FSH levels may change abruptly, rising into the normal postmenopausal range and falling again into the range normally seen in young fertile women. Oestradiol and inhibin generally fluctuate in parallel with each other but inversely to FSH, although at times oestradiol in particular may be increased markedly. Postmenopausal FSH levels may be followed by endocrine evidence compatible with normal ovulation. After the menopause, FSH levels rise 10-15-fold, with low oestradiol and undetectable inhibin levels. It is concluded that FSH measurement is of little value, if any in the assessment of women during the menopausal transition because it cannot be interpreted reliably and because, apparently, ovulatory (and, presumably, potentially fertile) cycles may occur subsequent to the observation of postmenopausal FSH levels. Both oestradiol and inhibin are important negative feedback regulators of circulating FSH.
Psychological wellbeing, mid-life and the menopause.
Dennerstein L, Smith AMA, Morse C.
Maturitas 1994; 20:1-11
Few studies of women's health in the menopausal years have formally assessed well being. The present study aimed to determine whether well-being during mid-life related to menopausal status, social circumstance, health status, interpersonal stress, attitudes and lifestyle behaviours. A random sample of 2000 Melbourne women aged 45-55 years were sought by random digital telephone dialling. A response rate of 70.6% was achieved. Interviews conducted on the telephone included a well-being scale - the Affectometer 2. The final data set, comprising 1503 individuals, was subjected to analyses of variance. Menopausal status did not significantly affect well-being. Well-being was found to be significantly related to current health status variables of general psychosomatic symptoms, general respiratory symptoms, history of premenstrual complaints, overall health assessment and interpersonal stress. Attitudes to ageing and to menopause were also significantly related to well-being scores. Lifestyle behaviours of smoking, exercise and marital status were also significantly related to well-being. Thus well-being of urban Australian-born, mid-aged women was related to current health status, psychosocial and lifestyle variables rather than to endocrine changes of the menopause.
Physical activity and the menopause experience: a cross-sectional study.
Guthrie J, Smith AMA, Dennerstein L, Morse C.
Maturitas 1995; 20:71-80
A randomly selected community cohort of 2000 Australian born women aged 45 to 55 were interviewed on the telephone and information obtained on their health and well-being. These women were divided into pre-, peri-, natural and surgical menopausal groups on their menstrual history. A physical activity questionnaire was sent to 1181 women in the first three of these groups. These questionnaires were completed and returned by 61.6% of the women. The response rate in all groups was significantly associated with the years of education, employment status, body mass index (BMI) and self-rated health of the participants. The aim of the study was to test the hypothesis that physical activity is a major contributor to health and well-being by establishing the relationships between physical activity and certain health outcomes, such as menopausal symptoms, psychological well-being, self-rated health and BMI in this cohort of mid-life women. The inter-relationship between physical activity and other variables, including menopausal status, interpersonal stress, health related and preventative health behaviours was examined. Levels of physical activity were significantly associated with better self-rated health, lower BMI measurements, moderate alcohol intake and self-breast examination. There was no significant association between levels of physical activity, psychological well-being and women's experience of symptoms during the natural menopause transition.
Hysterectomy experience among mid-aged Australian women.
Dennerstein L, Shelley J, Smith AMA and Ryan M.
Med J Aust 1994; 161:311
Objectives: To determine the rate of oophorectomy in, use of hormone replacement therapy by, and health, social and lifestyle factors of, mid-aged Australian women who have undergone hysterectomy.
Design and participants: A community-based cross-sectional survey by telephone interview of a random sample of 2001 Australian-born Melbourne women aged between 45 and 55 years.
Main outcome measures: The health status, sociodemographic and lifestyle correlates of women who had undergone hysterectomy compared with women in the natural menopause transition.
Results: Twenty-two per cent of the women had undergone hysterectomy. Of these, 21% had had one ovary removed, and 20% both. Mean age at hysterectomy was 40.4 years. There was no trend in the bilateral oophorectomy rate over the last two decades. Current hormone replacement therapy use increased significantly with surgery, from 17% of non-hysterectomised women to 31% of hysterectomised women, and 49% for women who had undergone hysterectomy and bilateral oophorectomy. Hysterectomised women were significantly more likely to he of lower educational level, and to report a history of troublesome premenstrual complaints, more dilatation and curettage procedures and non- gynaecological operations, and use of prescription medications.
Conclusions: Social and pre-existing health problems influence hysterectomy rates. Many women undergo oophorectomy at hysterectomy despite limited evidence of benefit.
Use of hormone replacement therapy by Melbourne women.
Shelley J, Smith A, Dudley E, Dennerstein L.
Aust J Public Health 1995;19:387-92
Hormone replacement therapy (HRT) is used for relief of symptoms related to the menopause and for the prevention of postmenopausal osteoporosis and cardiovascular disease. Patterns of use of HRT are thought to be changing rapidly, but little is known about who is using the therapy, for what purpose or for what period of time. Telephone interviews were conducted in May 1991 with a randomly selected sample of 2001 Australian born women aged 45 to 55 years living in Melbourne, as part of the Melbourne Women's Midlife Health Project. Questions related to use of HRT, health status, use of health services, sexual functioning, attitudes to menopause and aging, and sociodemographic characteristics. 21% of the sample were using HRT. Use was more prevalent among women 50 years and over (28%) than those under 50 (15%). 17% of non-hysterectomised women; 31% of hysterectomised women and 49% of women who had undergone hysterectomy and bilateral oophorectomy were current users. Almost 60% had been using the therapy for 2 years or less, and 34% for one year or less. Just over half reported control of hot flushes as a benefit, and 10% mentioned prevention of bone loss as a benefit. Logistic regression analysis identified differences between users and nonusers in experience of hot flushes, health status, use of preventive and treatment services, sexual functioning, wellbeing, attitudes to menopause and aging, and sociodemographic characteristics. These differences may relate to risk of later cardiovascular disease.
The endocrinology of the menopausal transition: A cross-sectional study of population based sample.
Burger H, Dudley E, Hopper J, Shelley J, Green A, Smith A, Dennerstein L, Morse C.
J Clin Endocrinol Metab 1995; 80:3537-3545.
In a study of the endocrinology of the perimenopausal Years, levels of serum FSH, estradiol (E2), immunoreactive inhibin (INH), testosterone, and sex hormone-binding globulin were measured in a population-based sample of 380 women (mean age, 49.4 yr: range, 45.6- 56.9 yr). Subjects were divided into women who reported continuing regular menstrual cycles (27%: group I), a change in menstrual flow without a change in frequency ( 23%: group II), a change in frequency but no change in flow (9%: group III), changes in both frequency and flow (28%; group IV), and at least 3 months since their last menstrual period (131%: group V). After adjusting for age and body mass index, the geometric mean FSH increased across menstrual groups and, compared with group I, was 53% higher in group IV (P < 0.0005) and 253% higher in group V (P < 0.0001). Age and body mass index-adjusted geometric means for E2 and INH in group V were 54% and 53% of those in group I, respectively (P < 0.005, P < 0.0001). Women in group V who did not have a menstrual period in the next year had higher FSH and lower E2 and INH levels than those who subsequently went on to have at least one more menstrual period (P < 0.05). FSH was negatively correlated with E2 (r = -0.30) and INH (r = -0.39), whereas INH was positively correlated with E2 (r = 0.45). We conclude that an increase in serum FSH and decreases in E2 and INH are the major endocrine changes associated cross-sectionally with the menopausal transition.
Role of lifestyle approaches in the management of the menopause.
Guthrie, J.
Journal of the British Menopause Society, March 1999
The lifestyle variables - physical activity, dietary intakes and smoking - are considered in relation to menopausal symptoms, skeletal and cardiovascular health in women experiencing the menopausal transition and in the postmenopausal years. Aerobic physical activity is recommended to reduce risk factors for coronary heart disease. Site specific high-resistance exercise maintains bone density in postmenopausal women but customary physical activity has not been proven to be effective, particularly during the perimenopause and in the early postmenopausal years. Calcium intakes greater than 1000 mg per day have a beneficial effect on bone density in postmenopausal women, but not during the menopausal transition. Cessation of smoking is advantageous to both cardiovascular and bone health. The weight gain and an increase in abdominal fat which occurs during midlife is detrimental on cardiovascular risk factors. Reduction in calorific intake and an increase in physical activity can diminish these changes. Dietary intakes of phytoestrogens are reported to reduce menopausal symptoms, improve serum lipid profiles and reduce bone loss. Further research is needed to elucidate the role of phytoestrogens and to prescribe the style of diet to prevent cardiovascular disease, osteoporosis and reduce menopausal symptoms.
Relationships between premenstrual complaints and perimenopausal experiences.
Morse CA, Dudley E. Guthrie J. Dennerstein L.
J. Psychosom Obstet Gynecol 1998; 19:182-191
This study evaluates whether a history of menstrually-related problems, termed premenstrual complaints (PMCs), is a significant predictive marker for a more symptomatic perimenopausal experience. Two hundred and ninety-one randomly selected urban women, aged between 45 and 55 years were interviewed yearly for three consecutive years to record their individual experiences and changes as they progressed through the menopause transition. Repeated measures were obtained on a range of physical, psychological and social indicators. The experiences of women who reported a self-defined history of premenstrual complaints (n = 104) were compared with those women with no prior premenstrual problems (n = 187) and predictors of perimenopausal symptoms were assessed. Relationships were found between a prior history of both physical and psychological premenstrual complaints and a more symptomatic perimenopause characterised by dysphoria, skeletal, digestive and respiratory symptoms (all ps < 0.05). The more symptomatic women also reported pronounced interpersonal stress (p < 0. 001), significant 'hassles', current smoking and low exercise (ps 0.05). The findings support predictive relationships between a prior history of premenstrual problems and a more problematic menopause transition. The issues of vulnerability and help-seeking behaviours are discussed.
Menopausal status: subjectively and objectively defined.
Garamszegi C, Dennerstein L, Dudley E, Ryan M, and Burger H.
J. Psychosom Obstet Gynecol 1998; 19:165-173
This study aims to assess the relationship between self-rated and menstrually defined menopausal status, assesses criteria women use in perceiving their own menopausal status and compares symptom reporting and hormonal levels for self- rated and menstrually defined menopausal status. Women in the third year of the longitudinal phase of the Melbourne Women's Midlife Health Project (n = 332) were asked to assess their own menopausal status and the basis for this assessment. They were also specifically questioned on current menstrual cycle characteristics and levels of follicle-stimulating hormone (FSH), estradiol and inhibin were measured. For 67% of the women, the two definitions of menopausal status were in agreement. In women menstrually defined as premenopausal, self-rated menopausal status of peri- or postmenopausal appeared to be based on the occurrence of symptoms. In women menstrually defined as postmenopausal, persistence of hot flushes was taken to mean that 'the menopause was still in progress' despite absence of menses for more than 12 months. In women menstrually defined as perimenopausal yet who self-rated as premenopausal, FSH was lower (p < 0.01) and inhibin higher (p = 0.05) than women who self-rated as peri- or postmenopausal. Women's perceptions of the menopause are based on symptoms. Self-rated menopausal status appears to relate more closely to a woman's endocrine status than definitions based on purely menstrual cycle characteristics.
A Prospective Study of Bone Loss in Menopausal Australian-Born Women.
Guthrie J, Ebeling P, Hopper J, Barrett-Connor E, Dennerstein L, Dudley E, Burger H, and Wark J.
Osteoporos Int 1998; 8:282-290
Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46-59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14-41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n = 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of - 0.9% (0.4%) at the lumbar spine and - 0.7% (0.6%) at the femoral neck (both p < 0.05 compared with women who remained premenopausal). In the women who became postmenopausal (n = 42) the mean annual changes in BMD were -2.5% (0.2%) at the lumbar spine and -1.7% (0.2%) at the femoral neck (both p0.0005), and in the women who remained post- menopausal (n = 60) they were -0.7% (0.2%) per year and 0.5%(0.3%) per year respectively (both p < 0.05), compared with women who remained premenopausal. In the 1-3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p < 0.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n = 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p<0.005). in the women who remained postmenopausal there was an association between baseline body mass index (bmi) and percentage change per year in femoral neck bmd (p< 0.05), such that women with higher bmi had less bone loss. in conclusion, during the time of transition from peri- to postmenopause, women had accelerated bmd loss at both the hip and spine.
Bone mineral density and hormone levels in menopausal Australian women.
Guthrie J, Ebeling P, Hopper J, Dennerstein L, Wark J and Burger H.
Gynecol. Endocrinol. 1996; 10:199-205
To assess the relationships between bone mineral density (BMD) at the lumbar spine and femoral neck and menopausal status, age, physical variables, and lifestyle and gynecological factors, BMD and follicle-stimulating hormone (FSH), estradiol and inhibin levels were measured in 167 women born in Australia, aged 46-57 years, who had no record of receiving hormone replacement therapy. Using the premenopausal group as a baseline, the FSH level was higher in peri- and postmenopausal subjects (p < 0.0005), and estradiol and inhibin levels in the postmenopausal women were lower (p < 0. 0005). Mean (±SE) lumbar spine and femoral neck BMD were 15 ± 3 % and 10 ± 3 % lower, respectively, in post-menopausal than in premenopausal women. Lumbar spine BMD decreased with increasing age in peri-menopausal women only (p < 0. 005), and femoral neck BMD decreased with increasing age in the pre-, peri- (p < 0. 05) and postmenopausal women. The difference between femoral neck BMD in the pre- and post- menopausal women was explained by the difference in age between these groups, whereas for lumbar spine BMD the menopausal status was an additional determining factor. There was a negative effect of smoking on femoral neck BMD (p < 0.05) in postmenopausal women. In the perimenopausal decade the femoral neck BMD is primarily dependent on age, whereas lumbar spine BMD is dependent on both age and menopausal status.
Determinants of self rated menopause status.
Taffe J, Garamszegi C, Dudley E, and Dennerstein L.
Maturitas 1997; 27:223-229.
This study, based on a population survey, examines the self ratings of progress through the menopausal transition of women in natural menopause, women using hormone therapy and women who have undergone hysterectomy. The latter two groups are usually excluded from discussions of menopausal transition, since the accepted menstrually defined criteria do not apply to them. Hysterectomised women do not differ in their self rating profile from non-hysterectomised women, after hormone therapy status is taken into account. This is surprising, since they may have been expected to see themselves as in the main postmenopausal. Use of hormone therapy is tantamount to self perception as at least perimenopausal. Among women in natural menopause there is 29% disagreement between self ratings and menstrually defined categories. On the basis of these observations it is hypothesised that experience of symptoms associated with menopause is important in determining self ratings. The good fit of logistic regression predictions of self ratings from hysterectomy status, hormone therapy status and experience of hot flushes is consistent with this hypothesis. This research indicates that it is important to take women's subjective evaluations into account in assessing progress through the menopausal transition.
Using longitudinal data to define the perimenopause by menstrual cycle characteristics.
Dudley, E. Hopper, J. Taffe, J. Guthrie, R. Burger, H. and Dennerstein, L.
Climacteric 1998; 1:18-25.
Objectives: To determine which aspects of menstrual change best predict time to postmenopause.
Methods: A total of 250 Australian-horn women aged 45-55 years were divided into five menstrual status categories: Group I reported no change in menstrual flow or frequency; Group II reported change in flow; Group III reported change in frequency; Group IV reported change in both frequency and flow; and Group V reported between 3 and 11 months of amenorrhoea. Menstrual status groups were compared on baseline data for age, hormone levels, hot flushes and self-rated menopausal status. The proportion of women moving to postmenopause in subsequent years was compared using 4 years of follow-up data.
Results: Women in Group V were older, had lower estradiol and inhibin levels, higher follicle stimulating hormone levels, and were more likely to report hot flushes, and to self-rate themselves as having started the menopausal transition, compared with the women who had menstruated in the last 3 months (Groups I-IV). Groups I and 11 were similar in age and hormonal status, as were Groups III and IV. The proportion of women who had moved to postmenopausal status in the 4 years after baseline were 12%, 14%, 58%, 53% and 94% for Groups I-V, respectively.
Conclusions: Amenorrhoea is the best predictor of future menopause followed by changes in menstrual frequency. Change in flow only was not predictive of future menopause. A two-stage classification scheme is suggested for defining the perimenopause. 'Early perimenopause' is defined as the self-reporting of changes in menstrual frequency over the last year, and 'late perimenopause' is defined as the self-report of 3-11 months of amenorrhoea.
Wellbeing, symptoms and the menopausal transition.
Dennerstein L.
Maturitas 1996; 23:147-157
Objectives: This paper reviews the knowledge accumulated from published population studies of health and ill-health experiences during the menopausal transition.
Results:
Well-being: mid-aged women are more likely to report positive moods than negative moods. Well-being is not associated with menopausal status but is associated with current health status, psychosocial and lifestyle variables.
Symptoms: Symptoms vary greatly across cultures, with North American and European samples reporting higher rates of symptoms than Asian women. The most symptomatic women in the North American samples and Australian studies are those whose menstrual cycles have changed. Vasomotor symptoms increase through the menopausal transition. Other variables such as socio-demographic, health status, stress, premenstrual complaints, attitudes to ageing and menopause, and health behaviours are associated with the occurrence of symptoms.
Psychological complaints: There is no increase in the incidence of major depression with the menopause. Negative moods are not associated with the natural menopausal transition. Factors associated with negative moods include surgical menopause, prior depression, health status, menstrual problems, social and family stressors and negative attitudes to menopause.
Sexuality: Several studies suggest a decline in sexual functioning associated with menopausal status rather than ageing. Social factors and health status factors are also associated with sexual outcomes.
Recommendations: Future research should bring together biomedical and sociological aspects. Positive aspects of health should be assessed as well as troubling symptoms. Longitudinal studies are needed with measures of hormonal change. Promoting positive attitudes to ageing and menopause, health lifestyles and stress reduction can be used as community interventions and as part of individual care.
Osteoporotic fractures: background and prevention strategies.
Wark JD.
Maturitas 1996; 23:193-207.
Objectives: To review current knowledge of the epidemiology, pathogenesis, prevention and treatment of osteoporosis, with particular reference to issues related to the menopause.
Methods: Peer-reviewed publications were assessed.
Results: Much international variation exists in the prevalence of osteoporosis and the incidence of fracture. Risk fractures for osteoporosis are numerous. The menopause, and other causes of hypogonadism in both women and men strongly predispose to osteoporosis. Various endocrinopathies, especially glucocorticoid excess, also are important. The contribution of family history may be explained by one or more genetic markers. Poor vitamin D and calcium nutrition, smoking, high alcohol consumption and inactivity increase risk. Reduced bone mass is a major risk factor for fracture, although the magnitude of that risk may vary between populations. In addition, bone fragility, length of the femoral neck (for hip fracture), history of prior fracture (for vertebral fracture) and falls affect fracture risk. Useful methods for measuring bone density are available for both epidemiologic surveillance and for clinical practice. Dual energy x-ray absorptiometry is the most desirable method in clinical care settings. Some risk factors can be modified for prevention of osteoporosis. Postmenopausal bone loss can be inhibited with estrogen or estrogen plus progestin therapy. Bone loss in the elderly may be moderated with calcium and vitamin D supplementation. Maintenance of muscle tone and strength through exercise may reduce falls.
Conclusions: Osteoporosis is a large and growing health problem in many countries. Prevention of osteoporosis is a high priority, especially because treatment of the established disease remains sub-optimal. Prevention requires immediate, intermediate-term and long-term strategies. First line therapy for established osteoporosis in women in many countries is estrogen or estrogen plus progestin, calcium and vitamin D. Prospects for improved prevention of osteoporotic fractures are encouraging.
Hot flushes, menstrual status, and hormone levels in a population-based sample of midlife women.
Guthrie J, Dennerstein L, Hopper J, Burger H.
Obstet Gynecol 1996; 88:437-42
Objective: To determine the frequency of hot flushes in a population sample of 453 pre-, peri-, and postmenopausal women (aged 48-59 years), and to investigate the relationship of hot-flush reporting with menstrual status, serum levels of estradiol (E2), inhibin, and FSH, history of premenstrual complaints, and physical and life-style factors.
Methods: We used a population-based sample. Interviews were conducted in the women's homes.
Results: Frequency of hot-flush reporting was associated with menstrual status (P < .001). Twenty-nine percent of women who had more than 3 and less than 12 months of amenorrhoea, and 37% of postmenopausal women experienced hot flushes several times a day. In total, 13% of premenopausal women, 37% of perimenopausal women, 62% of postmenopausal women, and 15% of women on hormone therapy reported having had at least one hot flush in the previous 2 weeks. Follicle-stimulating hormone levels were higher in women who experienced hot flushes at least once a day or more (P < .001); E2 levels were higher in women experiencing one or no hot flushes per week (P < .001). The women in the perimenopausal group who experienced hot flushes had higher FSH levels (P = .008) and were more likely to have reported premenstrual complaints at the first interview 3 years earlier (P = .03). In the postmenopausal group, there was no significant difference with any of the variables studied between the women who were experiencing hot flushes and those who were not.
Conclusion: Reporting of hot flushes is greatest 3 months or more after the final menstrual period. The frequency of hot flushes is associated with increasing FSH, decreasing E2, and a history of premenstrual complaints.
Bone turnover markers and bone density across the menopausal transition.
Ebelling P, Atley L, Guthrie J, Burger H, Dennerstein L, Hopper J, and Wark J.
J Clin Endocrinol Metab 1996; 81:3366-3371
We measured lumbar spine and femoral neck bone mineral density (BMD); urine markers of bone resorption; serum markers of bone formation; and serum gonadotrophin, estradiol and inhibin concentrations in a population-based cohort of 281 women aged 45-57 yr. Women were classified into pre-, peri-, and postmenopausal groups, depending on menstrual bleeding patterns. Compared with premenopausal women, BMD was lower only in postmenopausal women but not in women currently using hormone replacement therapy (HRT). BMD decreased with age in the perimenopausal group. Compared with premenopausal women, perimenopausal women had 20% greater urine N-telopeptide excretion (P < 0.05) and a doubling of gonadotrophin levels (P < 0.01), whereas serum estradiol and bone formation marker concentrations were no different. Postmenopausal women had greater levels of bone turnover markers (P < 0.0001), except free deoxypyridinoline and type 1 procollagen propeptide. Among postmenopausal women, bone resorption markers were lower in those using HRT. Levels of nearly all bone turnover markers were positively related to serum FSH concentrations (P < 0.0001). Overall, the major independent predictors of BMD were age, urine N-telopeptide, serum bone alkaline phosphatase, and serum FSI-I, whereas urine free deoxypyridinoline was positively related to BMD in pre- and perimenopausal women. In conclusion, the perimenopause is associated with elevated bone resorption rates and declining BMD, and factors in addition to estrogen deficiency may also contribute to the pathogenesis of postmenopausal osteoporosis.
Menopausal experiences of Thai women. Part 1: Symptoms and their correlates.
Punyahotra S, Dennerstein L, Lehert P.
Maturitas 1997; 26:1-7
This study was a cross-sectional survey of mid-aged Thai women with the following aims: to describe their experience of symptoms and attitudes to menopause and to examine the relationships between symptoms, attitudes to menopause, sociodemographic variables and menopausal status. The sample was 268 women aged between 40 and 59 y who had accompanied patients to the outpatients department of the Royal Irrigation Hospital. Mean age at menopause was 50.13 (SD 4.67) y. Fifty-one percent were premenopausal, 9% perimenopausal and 40% post- menopausal. The symptoms which showed strongest association (p< 0.001) with menopausal status were: joint aches/n, hot flushes, depression and insomnia. women most likely to experience symptoms were: older than 50 years of age, had more children, peri- or post-menopausal, of little education, housewives or landowners and reported their health was not so good and required treatment. (p < 0.001).
Menopausal experiences of Thai women. Part 2: The cultural context.
Punyahotra S, Dennerstein L.
Maturitas 1997; 26:9-14
This paper describes the cultural context of middle-aged Thai women who took part in a survey of symptoms and attitudes to menopause. The women lived in Nonthaburi province, adjacent to Bangkok, which has undergone a transition from rural to urban. Household structure often includes three generations. There have been changing opportunities for women in areas of education, occupation and family size and women's power increases with age. Thai women perceive menstruation as an indicator of health and take special care during menstruation. There is a special idiom in Thai 'leod cha pai - lom cha ma' (the blood will go - the wind will come) used to describe changes in a woman's behaviour, emotions and well-being during the menopause. These changes are expected to happen occasionally, not in every woman. Some women looked forward to menopause, while others were found to be ambivalent towards it.
Sexuallity, Hormones and the menopausal transition.
Dennerstein L, Dudley E, Hopper J, Burger H.
Maturitas 1997; 26:83-93
Objectives: To assess the validity and reliability of a sexuality questionnaire, and to assess the relationship of sexual functioning to age, menopausal status and hormone levels.
Methods: Cross-sectional analysis of a population-based cohort of 201 women aged 48-58 years in the fourth year of a longitudinal study. Sexual functioning was measured by self-completed questionnaire. E2, FSH, Inhibin, total T and SHBG were sampled on cycle days 4-8 or after 3 months of amenorrhoea.
Results: Internal consistency, as measured by Cronbach's alpha, was 0.71. Six factors were found on principal components factor analysis: (1) Feelings for Partner, (2) Sexual Responsivity, (3) Sexual Frequency, (4) Libido, (5) Partner Problems and (6) Vaginal Dryness/Dyspareunia. Sexual Responsivity decreased with age (ß=-0.060, P =0.05), and Vaginal Dryness/Dyspareunia decreased with log E2 (ß=-0.181, P < 0.00 1). Testosterone was not associated with the aspects of female sexual functioning measured in this study.
Conclusions: This longitudinal study found that most aspects of female sexual functioning were not affected by age, menopausal functioning or hormone levels.
Wellbeing, Hormones and the menopausal transition.
Dennerstein L, Dudley E, Burger H.
J Psychosom Obstet Gynecaol 1997; 18:95-101
This paper examines the relationship between well-being, age, menopausal status, hormone levels and hot -flashes. Data from the first 4 years of longitudinal observations from the Melbourne Women's Midlife Health project ipas utilized. This study involved a population-based sample of 405 women interviewed annually. Blood was taken during the follicular phase (if still menstruating) for estradiol, sex hormone binding globulin, follicle stimulating hormone and testosterone. A validated well-being scale was used. Positive affect increased with age while negative affect decreased with age but only in the postmenopausal category. Positive affect was significantly lower in the 2 years postmenopausal group but this effect of menopausal status did not remain when hot flashes were included in the analysis. Negative affect was highest in the 1-2 years postmenopausal group. Although hot flashes adversely affected negative moods, a significant effect of menopausal status remained. No direct association between any of the hormone levels and positive or negative affect scores was evident. In conclusion, this study found that well-being was decreased in the-first 2 years after the first menstrual period but began to improve spontaneously after this time.
Changes in physical a activity and health outcomes in a population-based cohort of mid-lilfe Australian-born women.
Guthrie J, Dudley E and Dennerstein L.
Aust N ZJ Public Health 1 997; 21:682-7
Cross-sectional studies and intervention programs have suggested that physical activity is a potential contributor to the health and wellbeing of mid-life and older women. This prospective longitudinal study investigates whether natural changes in physical activity are associated with changes in health outcomes in a population-based cohort of Australian-born women aged 45-55 years living in Melbourne. Of the 352 women from the Melbourne Women's Midlife Health Project who filled in a base-line physical activity questionnaire, 292 (83 per cent) were evaluated around three years later with regard to physical activity, psychological wellbeing, self-rated health, symptoms experienced, body mass index (BMI), blood pressure and serum lipids. Mean (SD) physical activity measured at baseline was 5.9 (5.7) hours/week, or 1496 (1449) kcal/week; mean (SD) change in physical activity per week was 0.05 (5.24) hours, or 44 (1347) kcal, indicating that although mean change was small there was substantial variation in change. There were significant increases in BMI (P< 0.001), wellbeing (P <0.05), the number of reported menopause-related symptoms, and high-density lipoprotein cholesterol (hdl- c) levels (p<0.001), and a decrease in low-density lipoprotein cholesterol (ldl-c) levels (p <0.05). change in level of physical activity was positively associated with change in hdl-c (p<0.01) and change in wellbeing (p="0.08)" and negatively associated with change in coronary heart disease risk score. by increasing physical activity in mid-life, women may reduce at least one risk factor (hdl-c) associated with coronary heart disease. p <0.05).
Relationship of endogenour sex hormones to lipids and blood pressure in mid-aged women.
Shelley J, Green A, Smith A, Dudley E, Dennerstein L. Hopper J, and Burger H.
Ann Epidemiol 1998; 8:39-45.
The relationship between endogenous sex hormones and blood lipids was examined in a representative sample of 438 Australian-born women 45 to 56 years of age taking part in a longitudinal study of the menopausal transition. Data from 363 women who were taking neither exogenous hormones nor lipid-altering medications, were not diabetic, and who had provided blood samples were available for analysis.
METHODS: Multiple linear regression was used to examine the relationship between sex hormones and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides, and diastolic blood pressure (DBP), taking account of the effects of age, body mass index (BMI), smoking, alcohol intake, and exercise.
RESULTS: There was no significant relationship between estradiol and HDL, LDL, triglyceride, or DBP levels. Free androgen index was positively associated with LDL. However, BMI was an important predictor of all three lipid measures and DBP. HDL was positively associated with age and was highest among women with lowest BMI, high alcohol intake, and in nonsmokers. LDL increased with BMI, free androgen index, and age, but was lower amongst women who exercised more than two or three times per week. Triglyceride also increased with BMI, and was higher among smokers. DBP increased with BMI only.
CONCLUSIONS: The results do not support the view that endogenous sex hormones are strongly associated with cardiovascular risk factors around the time of menopause.
Serum inhibins A and B fall differentially as FSH rises in perimenopausal women.
Burger H, Cahir N, Robertson D, Groome N, Dudley E, Green A and Dennerstein L.
Clinical Endocrinology 1998; 48:809-813
BACKGROUND: Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to the postmenopausal state. The contributions of decreasing levels of inhibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclear, as there are no reports of dimeric INH levels in relation to menopausal status. The present study was undertaken in order to provide preliminary data on relationships amongst the dimeric inhibins, oestradiol (E2) and FSH in normal subjects of defined menopausal status.
METHODS: Single serum samples were obtained between cycle days 3 and 8 in regularly cycling women, or at random in those with irregular cycles or amenorrhoea, in 110 women, aged 48-59 years, in the third year of a prospective longitudinal study of the menopausal transition, 'The Melbourne Women's Midlife Health Project'. Samples were assayed for FSH, E2, INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were analysed following logarithmic transformation. Undetectable values were assigned the limit of sensitivity of the respective assays. The relationships between hormones were evaluated as a function of menopausal stage. The latter was assigned as Stage 1, premenopausal (no reported change in menstrual cycle pattern), Stage 2, early peri-menopausal (reported change in menstrual cycle frequency in the preceding year with a bleed in the preceding 3 months). Stage 3, late peri-menopausal (no menses in the preceding 3-1 1 months) and Stage 4, postmenopausal (no menses in the preceding 12 months).
RESULTS: The hormone concentrations in premenopausal subjects (geometric means, FSH 13.5 IU/I, E2 306pmol/l, IR-INH 217U/I, INH-A 96 ng/l, and INH-B 48 ng/l) were used as reference points for the other stages of menopausal status. Early peri-menopausal subjects had significantly lower levels of IR-INH (147U/I) and INH-B (13.5 ng/l) in the presence of a small, statistically non-significant rise in FSH (to 21.4 U/I) and no significant change in E2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76U/I, INH-A fell to 4.2 ng/l, whilst INH-B was not significantly different at 14 ng/l. FSH had risen significantly to 72-2IU/I. Oestradiol also fell significantly to 89 pmol/l. In the postmenopausal subjects there were no further significant changes in the peptide hormones or FSH, but E2 fell further to 41 pmol/l. There was a significant (P<0.05) inverse correlation between fsh and e2 (r="-0.78)," fsh and ir-inh (r="-0.66)," fsh and inh-a (r="-" 0.53), fsh and inh-b (r="-" 0.29) while ir-inh and either inh-a or inh-b were positively correlated (r="+0.57" and +0.35, respectively). the data are consistent with negative feedback roles for both dimeric inhibins and e2 as contributors to the regulation of fsh secretion as menopausal status changes.
CONCLUDSIONS: The major significant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-b with no significant change in inhibin-a or oestradiol. progression to late peri-menopausal status is accompanied by a marked fall in inhibin-a and oestradiol and a rise in fsh without further change in inhibin-b. lnhibin-b, a marker of follicle number, is a significant factor in the endocrinology of the menopausal transition.(p <0.05)
The endocrinology of the menoapuse.
Burger H.
Journal of Steroid Biochemistry and Molecular Biology 1999; 69:31-35
Menopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Ovarian primordial follicle numbers decrease with increasing age up to about age 38 following which there is a much steeper decline in the last 12 or so years of reproductive life. At the time of the menopause itself, few follicles remain within the ovary. The recent availability of assays specific for the dimeric inhibins A and B has permitted clarification of the endocrine events leading up to and occurring around the time of final menses. Those women who show clear elevations in serum FSH above age 40, while continuing to cycle regularly have significantly lower inhibin B levels than those whose FSH levels remain in the range seen earlier in reproductive life. Early in the menopause transition, when cycle irregularity is first observed, the initial event is a decline in circulating inhibin B levels in the early follicular phase. In the late perimenopause, levels of estradiol and inhibin A also fall, inhibin B levels remain low and FSH is markedly elevated. The variability of hormone levels in women in their 40s, even in those who are continuing to cycle regularly makes FSH and estradiol unreliable markers of menopausal status. Serum androgen levels appear to fall with age rather than having any clear cut relationship to the menopause transition or menopause. The endocrine changes which occur during the menopausal transition and early postmenopausal period have clinical consequences in terms of symptoms and changes in bone mass.
Mood and the menopausal transition.
Dennerstein L, Lehert P, Burger H, and Dudley E.
J Nerv Ment Dis 1999; 187:685-691
This study determined which variables affect women's mood state during the menopausal transition by using six prospective annual assessments of a community-based sample of 354 Australian mid-aged women. Repeated measures multivariate analysis of covariance found that negative mood scores decreased significantly over time and were not related to natural menopausal transition, follicle-stimulating hormone, estradiol, inhibin, age, or education. The magnitude of negative mood was significantly predicted by baseline reporting of premenstrual complaints, negative attitudes to ageing and menopause, and parity of one. During follow-up, the magnitude of negative mood was significantly adversely affected by: prior experience of negative mood, experience of bothersome symptoms, poor self-rated health, negative feelings for partner, no partner, current smoking, low exercise, daily hassles, and high stress. Negative mood was reduced by decreasing symptoms, improving health, positive feelings for partner, gaining a partner, and reducing stress. The menopausal transition had an indirect effect in amplifying the effect of reducing paid work, poor health, and daily hassles.
Hormone therapy use in Australian-born women: a longitudinal study.
Guthrie J, Garamszegi C, Dudley E, Dennerstein L, Green A, MacLennan A and Burger H
MJA 1999; 171:358-361
Objectives: To describe the pattern of use of hormone therapy (HT) among Australian women, and its side-effects and benefits, and to compare baseline characteristics of HT users with never users.
Design: Longitudinal community-based study with annual interviews.
Setting: Melbourne, May 1991-October 1997
Participants: 357 Australian-born women aged 45-55 years who were pre- or peri- menopausal and not using HT at baseline.
Main outcome measures: Rates of HT use; baseline characteristics of users and non-users; side effects and benefits of HT use.
Results: 151 women (42%) used HT over the six years and 93 (26%) were current users at six-year follow-up. HT users did not differ significantly from non-users in lifestyle, sociodemographic and cardiovascular risk factors or in most health status factors at baseline. However, HT users were significantly more likely to have had a breast examination by a health professional (odds ratio [OR], 2.60; 95% Cl, 1.62-4.17), to have had a tubal ligation (OR, 1.73; 95% Cl, 1.09@-2.74), to report a history of premenstrual complaints (OR, 1.72; 95% Cl, 1.08-2.74), to agree that women "regret when their period stops for the last time' (OR, 1.69; 95% 01, 1.04-2.74), and to report that they took non-prescription medications (OR, 1.62; 95% 01, 1.02-2.59). Most (84%) HT users described benefits (most commonly relief of hot flushes and improved wellbeing), while 53% complained of side effects (most commonly weight gain and breast tenderness).
Conclusions: HT users did not differ significantly from non-users at baseline, in most characteristics. Long-term follow-up of this cohort is now required to assess any difference in cardiovascular events or other health outcomes between HT users and non-users.
Weight gain and the menopause: a 5 year prospective study of a population based cohort.
Guthrie J, Dennerstein L, and Dudley E.
Climacteric 1999; 2:205-211
Objective: To investigate prospectively changes in weight, skin-fold measurements, waist circumference and waist/hip ratio in relation to changes in menopausal status, hormone therapy use and life-style factors.
Method: The study was a 5-year follow-up of volunteers from a population-based cohort of Australian-horn women aged 46-57 years at baseline: 106 premenopausal, 106 perimenopausal and 21 hormone therapy users.
Results: Mean (SD) weight gain of the entire cohort over 5 years was 2.1 (5.1) kg. Baseline age was negatively associated with weight change (regression coefficient = A.4, SE 0.1, p < 0.05). After 5 years, 20 women remained premenopausal, 80 were perimenopausal, 112 had become naturally postmenopausal and 21 remained on hormone therapy. Changes in weight were greater than zero (p < 0.05) in all groups except for the women who remained on hormone therapy. There was no significant difference in weight gain between women who remained premenopausal and those who had a natural menopause. Increases in suprailiac skin-fold measurements (p < 0.05) and in waist circumference and waist/hip ratio occurred in women who experienced the menopausal transition but not in those who took hormone therapy continuously. There was no association between weight change and baseline weight, exercise, alcohol intake or smoking.
Conclusion: Weight gain was not related to change in menopausal status nor to any life-style factors measured. Women who were older at baseline gained less weight than the younger members. Suprailiac skin-fold measurements, waist circumference and waist/hip ratio all increased during the menopausal transition. Continuous hormone therapy users showed no gain in mean weight, suprailiac skin-fold measurements or waist measurements over the follow-up period.