Mrrrurirr/.v. 14 (1992) 127-141 Elsevier Sctentilic Publishers Ireland
Ltd.
MAT 00663
Influences of natural menopause on health complaints: A prospective study of healthy Norwegian women Arne Holte Department
of Behavioural
Sciences in Medicine,
University of Oslo, Oslo (Norway)
As a continuation of a cross-sectional study in 1981 involving a representative sample of 1886 women between 45 and 55 years of age, 200 pre-menopausal subjects were selected randomly to take part in a follow-up study. Eighty-seven single measures covering 26 areas of health complaints which have been associated with the menopause in medical textbooks were investigated. A tentative method for relating health complaints at several time points to menopausal status is proposed. A significant number of women reported an increase in vasomotor complaints, vaginal dryness, heart palpitations and social dysfunction following the menopause, although many reported no change or even a reduction in these complaints. On the other hand, a decrease in headache and breast tenderness was noted. No significant differences were observed between the numbers of women reporting an increase or a decrease respectively on any of the other 69 measures (20 complaints), which included anxiety, depression and irritability. Further analyses indicated that the increase in social dysfunction was caused by hot flushes and sweating. This paper raises a number of issues regarding the methodology of longitudinal studies. Key words: menopause;
health
complaints:
prospective
study
Introduction To what extent the decline in reproduction hormones associated with the menopause affects health complaints is still a controversial question. This controversy stems partly from methodological issues and partly from the fact that opinions about the effects of menopause are still mainly influenced by studies of self-selected clinical samples. Findings from such biased groups may not apply to the general population. Among the general-population-based studies that have been carried out common weaknesses have been the use of age as a proxy for menopausal status or failure to control for the influence of age and life events, thus confounding the effects of hormonal status, age and life events. Furthermore, where relationships between menopause and psychological complaints have been detected, several studies have omitted to control for the effects of vasomotor complaints, thus confounding the direct and indirect effects of hormonal change. Nearly all population-based studies Correspondence to; A. Holte, Department of Behavioural Box I I I I, Blindern, N-0317 Oslo 3, Norway. 0378-5122/92/$05.00 0 1992 Elsevier Scientific Printed and Published in Ireland
Publishers
Sciences in Medicine,
Ireland
Ltd
University
of Oslo. P.O.
have failed to control for the effect of previous premenopausal complaints. As they have mostly been restricted to cross-sectional designs they have not provided any opportunity to analyze predictive relationships. Recently, a few follow-up studies of non-clinical populations have been reported [l-4]. Even though most of the above problems have been overcome in these studies, they still have limitations because of their small number of time points for measurements [2,3] and short follow-up periods [l-4]. Most of them also used a possibly insensitive criterion for the menopause, namely 12 months of amenorrhoea [l-4]. In some studies data were collected only via telephone interviews [ 11. Although data on important factors (e.g. menopausal status) may be collected reliably and validly by telephone [5], it is doubtful whether telephone interviews can replace standard methods and face-to-face interviews when investigating emotionally sensitive areas of life. In some cases the representative nature of the sample may be questioned because the source from which the sample was drawn already had a selection bias (American census lists, driving licence lists, general practitioners’ lists, telephone directories, etc.). Finally, longitudinal studies are frequently weakened by attrition and contamination of data over time; this is because artificial menopause and hormonal treatment are distributed unevenly in the population (selection effect). These weaknesses in no way imply that the few available prospective studies of healthy populations are inconclusive. They do, however, indicate that further prospective investigations using alternative approaches are necessary. Most longitudinal menopause research is also faced with the problem of circumventing statistical problems associated with the measurement of change. When two groups are being compared within a cross-sectional design, a common method of analysis is to apply separate two-sample tests (viz. t-tests or Mann Whitney Utest) to assess the differences between groups. This method cannot be used to test differences between measurements in the same subjects at different time points in a longitudinal study. There are several reasons for this. (a) Successive observations on a given subject are likely to be correlated. Hence, the value at one time point cannot be treated statistically as though it was independent from the value at an earlier time point. (b) It is inherent in the longitudinal design that the main interest lies in the way individual subjects respond over time. When data are analyzed as if they belonged to different cross-sectional studies, as was done by Kaufert [4], no account is taken of the fact that measurements at different time points are from the same subjects. (c) The curve joining the group means may hide important variations in the shapes and locations of curves for different subjects and will thus not represent the typical curve for an individual [6]. In order to circumvent some of these problems, researchers [3] have used repeated-measures analysis of variance (ANOVA), but this approach has been criticized on statistical grounds [7-91. McKinlay et al. [ 1) used discriminant analysis and other multivariate techniques applicable to their data, but these methods impose requirements on the data which cannot always be met. Hunter [2] used paired r-tests to compare measurements before and after the menopause. This strategy, however, does not allow analysis of time-series, as it is restricted to comparison of two time points only.
One of the main objectives of this paper is to address some of the methodological problems raised above. In particular, a tentative method which has not been used previously in menopause research for relating health complaints at several time points to menopausal status is proposed. This makes it possible to determine which among 87 measures of the 26 ordinary health complaints most frequently cited in medical textbooks as being associated with the menopause are really affected by the menopause.
Subjects and Methods Subjects The subjects were drawn from a representative sample of 1886 Norwegian women who were 45-55 years of age in 198 1 when they participated in a cross-sectional survey of menopausal complaints [ 10-121. The subjects in the latter survey were randomly selected from the Community Register of the City of Oslo by the Norwegian Central Bureau of Statistics. After excluding those who had had a hysterectomy and/or oophorectomy, had never menstruated, or had received hormone replacement therapy (HRT) or other relevant endocrinological treatment, the sample was reduced to 1,668. Of these, 200 pre-menopausal women were randomly selected to take part in a 5-year prospective longitudinal study which ran from 1982 to 1986. Data collection At intervals of 12 months, all the subjects went through a 3-4-h semi-structured personal interview with fixed response categories, psychological testing and gynaecological examination. Interviewing and testing took place in the subjects’ homes and at the Department of Behavioural Sciences in Medicine, University of Oslo, while the gynaecological examinations were carried out in the Department of Gynaecology and Obstetrics at the National Hospital, Oslo. The interview covered information about work, linance, education, marriage, family, husband, household, home, children, life events, medical treatment, menstruation, menopause, quality of life, sexuality, social network, intimacy and communication, general health, somatic and psychological complaints. The standard psychological tests used were Torgersen’s Basic Character Inventory (personality) [ 131, Plutchic and Kellerman’s defence-mechanism test (psychological defence) [ 141, Bern’s Sex-role Inventory (sex-role identification) [ 151, Spanier’s Dyadic Adjustment Scale (marital adjustment) [16], a revised version of Jourard and Secord’s Body Cathexis method (satisfaction with body appearance, self-esteem) [17] and selected measures of quality of life [18.19]. The gynaecological examination includccl cytology and measurement of blood pressure. Blood samples were collected and frozen for future analyses. Two psychologically trained sociologists conducted all interviews and tests, while two gynaecologists carried out all the medical examinations. As a rule, each subject saw the same interviewer and the same gynaecologist at all observation time points during the course of the study. The interviewers and gynaecologists were females of approximately the same age as the subjects themselves.
Health complaints This paper presents results only on subjective health complaints. In all, 87 single measures covering the 26 health complaints cited most frequently in the literature as being affected by the menopause, and which had been included previously in the Oslo Menopausal Survey [ lo-121 and the Drammen Menopausal Survey [20,21], were examined. Questions were taken from Goldberg’s General Health Questionnaire (GHQ) [22] and adapted for use in personal interviews by the author. When an area was not covered sufficiently by the GHQ (e.g. vasomotor complaints), questions that had been used by the research team in previous studies were added. Table I lists the areas of complaints investigated and the number and types of measures used in each case. Within each area the subjects were usually asked (a)
TABLE
I
AREAS OF HEALTH COMPLAINTS INVESTIGATED MEASURES USED WITHIN EACH AREA Area of complaints
Number
General health (GHQ) Headaches (GHQ) Dizziness Forgetfulness Heart palpitations Shortness of breath
5 3 3 2 3 3
(currentd) (current, (current. (current, (current, (current.
Insomnia (GHQ) Tiredness Loss of feeling Numbness and stiffness
6 3 3 I
Muscle and joint pain Breast tenderness Digestive problems Vaginal dryness
7 3 5 3 5 5 3 3 3 3 3 3 3 I 3 2
Other gynaecological complaints Urinary problems Hot flushes, sweating Night sweats Cold shivers (GHQ) Anxiety (GHQ) Weepiness Social dysfunction (GHQ) Depression (GHQ) Suicidal thoughts (GHQ) Loneliness Weight gain “Visual analogue scale (IO points) bAdditive index: 8 items (yes/no). CAdditive index: 7 items (yes/no). dAdditive index: 4 items (yes/no). eAdditive index: 8 items (yes/no).
AND
NUMBER
TYPES
and types of measures
frequency, frequency, distress) frequency, frequency,
distress) distress)
(current, (current, (current, (current)
frequency, frequency, frequency.
distress) distress) distress)
(current, (current, (current, (current, (current, (current, (current, (current, (current, (currentb, (current, (current’, (currentd, (currente, (current, (current,
frequency, frequency, frequency, frequency, frequency. frequency, frequency, frequency, frequency, frequency, frequency, frequency. frequency, frequency, frequency, distress)
distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress)
and 4 questions
AND
from General
distress) distress)
Health
Questionnaire
(GHQ)
OF
I .i I
whether or not they were experiencing the complaint now (current: yes/no), (b) how frequently they had experienced the complaint during the past 12 months (7-point scale) and (c) how much distress the complaint caused them at the time they were experiencing it, irrespective of its frequency (4-point scale). General subjective health was measured by means of a visual analogue scale and 4 questions (yes/no) from the GHQ. Current experience of anxiety, social dysfunction, depression, and suicidal thoughts was measured using additive indices adopted from the GHQ. Frequency of experiencing forgetfulness, numbness and stiffness, weight gain and the degree of distress caused by numbness and stiffness, were not assessed. Menopause The menopause was defined as the date of the last menstrual mediately before the start of at least 6 months of amenorrhoea.
period
(LMP)
im-
Analyses Matthews et al. [6] recently discussed a way of overcoming some of the problems associated with the measurement of change, namely the summary measurement procedure. Although it cannot replace multivariate techniques, this simple method has the advantage of considering the individual as the basic unit of analysis. The responses for each individual subject are used to construct a single number (e.g. mean, mean rank, slope) which summarizes some aspect of that subject’s response curve over a time-period (e.g. pre-menopausal phase and post-menopausal phase). Once the appropriate summary measures have been calculated for each subject, their values can be treated as raw data for an appropriate statistical analysis. To be applicable for detecting effects of the menopause in studies such as the present one, the method requires (a) that the exact time point of the natural menopause can be decided for each subject, (b) that measurements are available both before and after the menopause, (c) that measurements are available for all the time points investigated, and (d) that the measurements of complaints are not contaminated by artificial influences, such as HRT, oophorectomy, etc. Having excluded those women for whom these requirements could not be met, the exact date of the menopause was determined for each of the remaining subjects. Summary measurements of each subject’s level of complaint before at least a 6-month period of amenorrhoea (the 6-month criterion) were calculated, as were summary measurements of each subject’s level of complaint after the 6-month criterion was passed (Fig. 1). This was done for each of the 87 measures. Finally, the differences between the summary measurements before and after the 6-month criterion were tested. The r-test for paired samples was used for differences with normal distributions (means). Wilcoxon’s matched-pairs signed-rank test was used for distributions with bimodal or skewed patterns (mean ranks). Effects of age To check whether a significant difference between the measurements before and after the menopause could have been caused by age, several procedures were applied. Firstly, one-way ANOVA was used, with the frequency of experiencing the complaint concerned as the dependent variable and chronological age as the independent
132
Level of complaint I-
L
L ___---_
premenopausal
P
mean
1 1. 0
postmenopausal mean )’
--..--------+--
??
I
L
1962
1964
1963
1966
1966
Level of complain t
postmenopausal mean
0 c-----
____*
k I 1902
1 1963
premenopausal
mean
1 1984
1966
1986
Fig. 1. Summary measurements. Two examples of individual scores for a complaint plotted against time. Case A illustrates a decrease in complaints after the menopause. Case B illustrates an increase. Circles mark the levels of complaints at each measurement point before a period of at least 6 months of amenorrhoea. Squares mark the levels of complaints at each measurement point after this period. The dotted lines illustrate 6-month
the mean levels of complaints before and after this 6-month criterion. Case A reached criterion between 1983 and 1984. Case B reached it between 1984 and 1985.
the
variable. Secondly, the frequency of reporting the complaint was regressed on chronological age. Menopausal status was kept constant in these analyses by conducting them first on the 1982 data, when all subjects were still premenopausal, and then on the 1986 data, when all the subjects had become post-menopausal. Thirdly, the post-menopausal frequency of reporting the complaint was regressed on age controlled for the pre-menopausal frequency of reporting the complaint (multiple regression). Finally, the difference between the mean frequencies of complaints before and after the 6-month criterion was regressed on chronological age.
Effects of vasomotor complaints To check whether a significant change in psychological complaints after menopause could have been caused indirectly by an increase in hot flushes and sweating and hence whether these complaints were less likely to be affected directly by hormonal changes, three strategies were adopted. Firstly, the mean postmenopausal frequency of the psychological complaint concerned was regressed on the mean post-menopausal frequency of vasomotor complaints, controlled for the mean pre-menopausal frequency of the psychological complaint (multiple regression). Secondly, the difference in the mean frequency of the psychological complaint before and after the 6-month criterion was regressed on the corresponding difference for vasomotor complaints. Thirdly, the difference in the mean frequency of the psychological complaint before and after the 6-month criterion was included as the dependent variable in a multiple regression analysis, with the difference in vasomotor complaints before and after the 6-month criterion and chronological age as the independent variables. Results Subjects Altogether, 193 (96.5%) of the women accepted our invitation to participate. Out of these, 177 (9 1.7%) completed all parts of the study. In all, 118 (66.7%) of the subjects did not meet all the criteria for inclusion in the summary measurement procedure. Premenopausal measurements were lacking for 7 (4”/u) of the subjects because they had already become post-menopausal by the start of the study (mean age = 50.9, SD. = 2.4 years) and one of them had also received HRT. Postmenopausal measurements were lacking for 41 (23%) of the subjects because they did not reach the menopause during the course of the study (mean age = 49.0, S.D. = 1.9 years). Post-menopausal measurements were also lacking for 3 1 (18%) of the subjects because of HRT (mean age = 49.5, S.D. = 2.1 years). The postmenopausal measurements were contaminated in the case of 12 (7%) of the subjects who after at least a 6-month period of amenorrhoea experienced one or more episodes of bleeding because of HRT (mean age = 52.0, S.D. = 2.1 years). For 2 subjects the exact point of menopause could not be decided because after 6 months of amenorrhoea they experienced further bleeding even though they did not receive HRT. Three (2%) of the subjects were hysterectomized (mean age = 48.5), one of .whom also received HRT. Only one subject had a bilateral oophorectomy. Another 21 subjects received HRT for different reasons, so that of those who were not suitable for inclusion in the summary measurement procedure a total of 69 had received some form of local or general hormone treatment over the full course of the study. The final sample which could be subjected to the summary measurement procedure consisted of 59 women. Age and menopause The mean age of the final sample at the start of the longitudinal study (1982) was 51.1 (S.D. = 2.0, range 47.3-55.8 years). This was significantly higher (P < 0.00) than the mean age of those who were not suitable for inclusion in the summary
134
measurement procedure (mean age = 49.8, S.D. = 2.1 years). Mean age at menopause in the final sample was 52.9 (S.D. = 2.1, range 40.3-58.7 years) with a close to normal distribution. Out of the 69 subjects who did not receive any kind of hormone treatment or have a surgical menopause, and who experienced 6 months of amenorrhoea between the end of the cross-sectional study in 1981 and that of the longitudinal study in 1986, 97% (63) never menstruated again during the course of the study.
Health complaints The summary measurement procedure yielded significant differences before and after the 6-month criterion in 14 single measures within 6 areas of complaints (Fig. 2). No effects of the menopause were detected in the 69 measures of the remaining 20 health complaints. All results which were significant when subjected to Wilcoxon’s test were also significant (P < 0.05) when subjected to pairwise t-tests, but the distribution tended to be skewed. Headache and breast tenderness decreased after the 6-month criterion was passed, while vasomotor complaints, vaginal dryness, heart palpitations measures and social dysfunction increased. However, in all measures yielding significant differences, an increase was observed after a 6-month criterion in some subjects, while a decrease was observed in others. For example, although 58% showed more frequent vasomotor complaints after the 6-month criterion, 20% showed less frequent complaints and 22% no change. Similarly, although 47% indicated a greater amount of distress due to social dysfunction after the 6-month criterion, 24% indicated less and 29% no change (Fig. 2). The menopause had significant effects on current experience of most complaints, the frequency with which they had been experienced during the past 12 months, and the amount of distress they caused, irrespective of their frequency. There were a few exceptions to this rule; the reduction in the amount of distress due to headache was not significant. The reduction in current experience of headache (P < 0.1) and the increased amount of distress due to vaginal dryness (P < 0.07) were only marginally significant. No bivariate relationship with age was found for any of the measures affected by the menopause, with one exception. Simple regression yielded a significant relationship between the frequency of vasomotor complaints and age, both when all subjects were pre-menopausal (I = 0.27, P < 0.05) and when all had become post-menopausal (r = -0.30, P < 0.05).
Social dysfunction A significant relationship before and after the 6-month in vasomotor complaints (r effect of age was controlled adjusted R* = 0.11, P < = 0.36, P < 0.01; beta for
was found when the difference in social dysfunction criterion was regressed on the corresponding difference = 0.37, P < 0.01). This result did not change when the for in a multiple regression analysis (multiple R = 0.37, 0.01; beta for the difference in vasomotor complaints chronological age = -0.05, NS).
% women
Distress
Frequency
Current
(566t-d 59)
Headache
m
*
Palpitations
dn
17
33
50
Decrease (post < pre)
*
12
41
20
2g
51
Increase (post > pre)
ILL
20
54
58
& 16
22
22
4539
0
??
Social dysfunction
No change (post = pre)
Tenderness in breasts
Vaginal dryness
Vasomotor complaints
d/L
24
l/dl_Ld
47
m
136
The aim of this study was to investigate the effect of the menopause on ordinary health complaints in healthy women. The approach was to employ standard measures of health complaints in a prospective investigation of randomly selected pre-menopausal subjects, representative of the general population. As a tentative way of surmounting some of the difficulties involved in the analysis of serial measurements, a simple procedure was proposed combining summary measurements before and after 6 months of amenorrhoea and paired statistical tests. Health complaints
The results showed that hot flushes, sweating, vaginal dryness and heart palpitations - but none of the psychological complaints - were influenced negatively and directly by the climacteric transition. This is consistent with the findings of some other recent studies of healthy women [l-4, lo- 12,20,2 1,23-251. Our approach also led to several important developments in our knowledge. Few methodologically sound population studies have found evidence of a direct association between menopause and psychological complaints (anxiety, depression, irritability) [23,25]. This study was no exception in this respect. However, a signiticant decrease in social dysfunction after the menopause was detected. Some might suggest that the questions in the additive index used to measure social dysfunction (Table II) really measure depression. Factor analytic studies constituting the basis for Goldberg’s General Health Questionnaire indicate, however, that although correlated, social dysfunction and depression should be regarded as different dimensions [22]. Furthermore, the regression analyses showed that the decreased social function after menopause could be caused by an increase in vasomotor complaints. This supports the ‘domino-hypothesis’ [26], which regards some psychological complaints as a secondary effect of the menopause and not as being caused directly by the hormonal changes associated with the menopause. This study, therefore, lends no support to the view that social dysfunction is an indication for HRT. Vasomotor complaints leading to social dysfunction may, however, be so indicative.
TABLE
II
QUESTIONS
USED TO MEASURE
CURRENT
SOCIAL
DYSFUNCTION
Have you recently: been managing to keep yourself busy and occupied? I. been taking longer over the things you do? 2. felt on the whole you were doing things well? 3. been satisfied with the way you have carried out your task? 4. felt that you are playing a useful part in things? 5. felt capable of taking decisions about things? 6. been able to enjoy your normal day-to-day activities? I.
Ii7
Heart palpitations In previous studies palpitation of the heart has mainly been associated with vague somatic complaints and not with the menopause [ 11,241. From a biological point of view the lack of association is unexpected. This situation is most likely due to the difficulties involved in obtaining reliable subjective measures of heart palpitations when data have been collected cross-sectionally by means of postal questionnaires or telephone interviews. Consequently, it is no surprise that, in the present study, heart palpitations showed a pattern similar to that of the other vasomotor complaints. However, this finding must still be treated with caution, since it deviates from all previous factor analytic studies [ 11,231. Relief from health complaints Few studies have yet examined the extent to which the climacteric transition is accompanied by relief of health complaints. It should therefore be noted that, depending on the measure chosen, 40-51X had fewer headaches and 46-48X had less breast tenderness after the menopause. These changes were mainly due to relief from premenstrual and menstrual complaints. Although a significant increase was found in vasomotor complaints, vaginal dryness, palpitations and social dysfunction, it is pointed out that, depending on the measure chosen, 16-24(1/o and fewer vasomotor complaints after the menopause, 16-20X had less dryness of the vagina, 15- 19% had less frequent palpitations and 22-24X had less social dysfunction. This shows that the widely accepted perception of menopause as an event followed by a uniformly negative change in health complaints is erroneous. The reality is far more complicated and involves large individual variation. Unlike several others, this study used standard methods to a large extent and several indicators to measure each complaint. With a few exceptions (in particular headache), the results showed that if one indicator of a complaint (e.g. frequent) produced a significant effect, then the others (e.g. current, distress) did so also. If one indicator showed no effect, neither did the remaining indicators within that area. This supports the construct validity of our measurements. Confounding factors At an individual level, the effects of the menopause may easily be confounded with age, life events occurring at this stage of life [26], increased rapport with the interviewer over time, or the sheer fact that time has passed. How then do we know that the differences in the level of complaints before and after the menopause really were caused by the climacteric transition? By combining summary measures and pairwise tests of significance in a random sample within a prospective design, each subject acted as her own control, while age at the menopause was randomly and almost normally distributed. Therefore, in order to hypothesize that the change in health complaints was due to variables other than the menopause, it has to be assumed that these variables are highly correlated with the timing of the menopause. Such correlations have not been documented in any study and seem theoretically far-fetched, except in the case of age [28,29]. However, the regression analyses showed no relationship between age and menopausal complaints, except for the vasomotor types. When the subjects were still pre-menopausal being older increased the
likelihood of vasomotor complaints 0. = 0.27) and when they had become postmenopausal it reduced it (Y = -0.30). However, assuming that these correlations reflect an effect by age as such and not hormonal changes associated with menopause, one would expect them to be positive not only when all subjects were pre-menopausal but also when all subjects were post-menopausal. It might be objected that menopausal status was kept constant in terms of conducting the analyses when all subjects were still pre-menopausal and also when they had become post-menopausal. This does not, however, preclude the possibility that a positive correlation with age when the subjects were pre-menopausal may reflect an ongoing hormonal change which leads to more frequent vasomotor complaints in the oldest women, but which has not yet manifested itself as 6 months of amenorrhoea. This most likely interpretation is supported by Holte and Mikkelsen’s finding that 8% and 7% of pre-menopausal women aged 45-55 ‘often’ suffer from hot [ lo]. flushes and excessive sweating, respectively Age and menopause Mean age at menopause in this study was about 1 year later than that usually suggested for Caucasians in Northern Europe and America [28,29]. This most likely reflects the fact that subjects not meeting the criteria for the summary measurement procedure were treated more frequently for pathological processes associated with an early natural menopause; such subjects are also more frequently smokers [30,31]. Thus, the high mean age at menopause most probably indicates that age at menopause among healthy women is higher than that in the general population. Accordingly, use of the mean age at menopause in the general population as a basis for informing healthy, non-smoking women about when they should expect menopause is very likely to be misleading. Further prospective studies are needed in order to specify more precisely the expected age at menopause for different groups in the population and factors affecting this. Only 2 out of 69 women menstruated after a period of more than 6 months of amenorrhoea. In a sample similar to ours Kaufert [32] reported that this occurred in 9% of the subjects. These findings indicate that among untreated, healthy, premenopausal women aged over 47 years, more than 6 months of amenorrhoea is a very reliable indicator that menopause has been reached. This should be preferred to the less sensitive and more frequently used I%-month criterion. Further investigation is, however, necessary to determine whether more than 6 months of amenorrhoea is valid in younger women and if an even shorter period would be appropriate for older women. Attrition rate Only 16 (8.3’S) out of 193 subjects dropped out at one or more data-collection points. However, a large number were excluded because they did not satisfy the strict requirements for conducting summary measures analyses. The main reasons were that they had not become post-menopausal or that they were receiving hormone treatment at one time point at least during the course of the study. Because the subjects receiving treatment were not the same each year, the sum total of subjects treated at least once during the 5 years became high. This does not reflect an ag-
gressive treatment philosophy among Norwegian gynaecologists, but illustrates an ethical dilemma in pursuing longitudinal research aims in a clinical context. Treatment was offered to symptomatic subjects who would not otherwise have visited a gynaecologist had they not participated in a scientific study. We do not know how this may ultimately have affected the results. There are, however, several indications that the effects of this possible sample bias were minor. For example, the percentage of subjects experiencing vasomotor complaints for the first time after menopause (45%) was almost identical to the prevalence of hot flushes reported among women who were l-3 years post-menopausal in the general population of Oslo. Furthermore, the proportions of subjects with signs of depressed mood in the final sample and the original sample were very similar at all time points (approx. 20%) and this was also the case for other complaints [ 101. The summary measurement
procedure
Although simple to use and less prone to the problems associated with other methods of analyzing serial measurements [6-91, the summary measurement procedure has not been used previously in menopause research. The high degree of agreement with previous findings, however, indicates that the procedure may be a simple and useful means of circumventing some of the problems involved in the analysis of serial measurements in menopause research. Nevertheless, one should be aware that, like most others, the method as applied here has its limitations. The most obvious ones are that (a) menopausal status was treated as a discrete variable and not as a continuous development, (b) our approach cannot take the place of multivariate techniques in controlling for effects of variables that are highly correlated with the timing of the menopause (e.g. age), and (c) summary measures (e.g. means, mean ranks) may hide variation in the curves for different subjects and thus not represent the typical curve for an individual. It is unlikely, however, that our conclusions would have been different if methods free from these limitations had been available. Acknowledgements
The Norwegian Menopause Project is supported by the Norwegian Research Council for Science and the Humanities and by the Anders Jahre’s Foundation (Mag. art. medical sociology). Aslaug Mikkelsen assisted in designing the study. Professor Julie Skjae&en and Dr Mette Moen carried out the gynaecological examinations. Ellen Sandberg and Eva Marie Solheim conducted the interviews and the psychological testing. Research Fellow Ragna Holter assisted in assessing the subjects’ menopausal status. Manager of Computer services Nils Eivind Naas and Research Fellow Louise Nicol Smith provided data and technical assistance and Professor Petter Laake provided valuable advice regarding statistics. Their contributions are much appreciated. References 1
McKinlay JB, McKinlay SM, Brambilla DJ. Health status and utilization menopause. Am J Epidemiol 1987; 125: 110-121.
behaviour
associated
with
2
4
6
8 9 IO
11 12 13 14 15 16 17 18 19 20
Hunter M. Somatic experience of the menopause: A prospective study. Psychosom Med 1990; 52: 357-367. Mathews KA, Wing RR, Kuller LH, Meilahn EN, Kelsey SF. Costello JE. Caggiula A. Influences of natural menopause on psychological characteristics and symptoms of middle-aged healthy women. J Consult Clin Psycho1 1990; 58: 345-351. Kaufert PA, Gilbert P, Hassard T. Researching the symptoms of menopause: An exercise in methodology. Maturitas 1988; 10: 117-131. Brambilla DJ, McKinlay SM. Comparison of responses to mailed questionnaires and telephone interviews in a mixed mode health survey. Am J Epidemiol 1987: 126: 962-971. Matthews JNS, Altman DC, Campbell MJ, Royston P. Analysis of serial measurement in medical research. Br Med J 1990; 300: 230-235. Hertzog C. Rovine M. Repeated-measures analysis of variance in development research: Selected issues. Child Dev 1985; 56: 787-800. Editorial. Repeated warnings re repeated measures. Aust NZ J Med 1986: 16; 637-638. Ekstrom D, Quade D, Golden RN. Statistical analysis of repeated measures in psychiatric research. Arch Gen Psychiatry 1990; 47: 770-772. Holtc A. Prevalence of climacteric complaints m a representative sample of middle-aged women in Oslo. Norway. J Psychosom Obstet Gynaecol 199 I: 12: in press. Holte A, Mikkelsen A. The menopausal syndrome: A factor analytic replication. Maturitas 1991; 13: 193-203. Holte A, Mikkelsen A. Psychosocial determinants of climacteric complaints. Maturitas 1991; 13: 205-215. Torgersen S. Hereditary-environmental differentiation of general neurotic, obsessive, and impulsive hysterical personality traits. Acta Genet Med Gamellol 1980; 29: 193-207. Plutchic R, Kellerman H. Manual for the emotions profile index. Los Angeles: Western Psychological Services, 1974. Bern S. The measurement of psychological androgyny. J Consult Clin Psycho1 1974; 42: 155-162. Spanier GB. Measuring dyadic adjustment: New scales for assessing the quality of marriage and similar dyads. J Marriage Family 1976; 38: 15-28. Journard SM, Secord PF. Body-Cathexis and the ideal female figure. J Abnorm SOC Psycho1 1955; 50: 243-246. Mourn T. The role of values and life goals in quality of life: On measuring and predicting subjective well-being. UNESCO report. Division of Socioeconomic Analysis, 1980. Atkinson T. The stability and validity of quality of life measure. Sot Indicators Res 1982; 10: 113-132. Holte A, Mikkelsen A. Menstrual coping style, social background and climacteric symptoms.
22
Psychiatry Sot Sci 1982; 2: 41-45. Mikkelsen A, Holte A. A factor analytic study of climacteric symptoms. Psychiatry Sot Sci 1982; 2: 35-39. Goldberg DP, Hillier VF. A scaled version of the General Health Questionnarie. Psycho1 Med 1979;
23
9: 139- 145. Greene JG. The social and psychological
24
1984. Hunter
21
25 26 27 28
M. Battersby
R. Whitehead
origins
of the climacteric
M. Relationships
between
complaints and menopausal status. Maturitas 1986; 8: 217-228. Hunter MS. Emotional well-being, sexual behaviour and hormone 1990: 12: 299-314. Campbell S, Whitehead M. Oestrogen therapy and the menopausal
syndrome.
psychological replacement syndrome.
Aldershot:
Cower,
symptoms,
somatic
therapy.
Maturitas
Clin Obstet Gynecol
1977: 4: 31-47. Greene JG. Cooke DJ. Life stress and symptoms at the climacteric. Br J Psychiatry 1980; 136: 486-491. Brand C. Age at menopause: An investigation into the median age at menopause in Ede, the Netherlands, and into the possible influence of certain environmental variables upon this age. Doctoral dissertation. University of Leiden. 1978.
29 30 31 32
Brambilla DJ, McKinlay SM. A prospective study of factors affecting age at menopause. J Clin Epidemiol 1989; 42: 1031- 1039. Lindquist 0, Bengtsson C. The effect of smoking on menopausal age. Maturitas 1979: I : I7 I - 173. McKinlay SM, Bifano NL, McKinlay JB. Smoking and age at menopause in women. Ann Intern Med 1985: 103; 350-356. Kaufert PA, Gilbert P, Tate R. Defining menopausal status: The impact of longitudinal data. Maturitas
1987; 9: 217-226.
Ltd.
MAT 00663
Influences of natural menopause on health complaints: A prospective study of healthy Norwegian women Arne Holte Department
of Behavioural
Sciences in Medicine,
University of Oslo, Oslo (Norway)
As a continuation of a cross-sectional study in 1981 involving a representative sample of 1886 women between 45 and 55 years of age, 200 pre-menopausal subjects were selected randomly to take part in a follow-up study. Eighty-seven single measures covering 26 areas of health complaints which have been associated with the menopause in medical textbooks were investigated. A tentative method for relating health complaints at several time points to menopausal status is proposed. A significant number of women reported an increase in vasomotor complaints, vaginal dryness, heart palpitations and social dysfunction following the menopause, although many reported no change or even a reduction in these complaints. On the other hand, a decrease in headache and breast tenderness was noted. No significant differences were observed between the numbers of women reporting an increase or a decrease respectively on any of the other 69 measures (20 complaints), which included anxiety, depression and irritability. Further analyses indicated that the increase in social dysfunction was caused by hot flushes and sweating. This paper raises a number of issues regarding the methodology of longitudinal studies. Key words: menopause;
health
complaints:
prospective
study
Introduction To what extent the decline in reproduction hormones associated with the menopause affects health complaints is still a controversial question. This controversy stems partly from methodological issues and partly from the fact that opinions about the effects of menopause are still mainly influenced by studies of self-selected clinical samples. Findings from such biased groups may not apply to the general population. Among the general-population-based studies that have been carried out common weaknesses have been the use of age as a proxy for menopausal status or failure to control for the influence of age and life events, thus confounding the effects of hormonal status, age and life events. Furthermore, where relationships between menopause and psychological complaints have been detected, several studies have omitted to control for the effects of vasomotor complaints, thus confounding the direct and indirect effects of hormonal change. Nearly all population-based studies Correspondence to; A. Holte, Department of Behavioural Box I I I I, Blindern, N-0317 Oslo 3, Norway. 0378-5122/92/$05.00 0 1992 Elsevier Scientific Printed and Published in Ireland
Publishers
Sciences in Medicine,
Ireland
Ltd
University
of Oslo. P.O.
have failed to control for the effect of previous premenopausal complaints. As they have mostly been restricted to cross-sectional designs they have not provided any opportunity to analyze predictive relationships. Recently, a few follow-up studies of non-clinical populations have been reported [l-4]. Even though most of the above problems have been overcome in these studies, they still have limitations because of their small number of time points for measurements [2,3] and short follow-up periods [l-4]. Most of them also used a possibly insensitive criterion for the menopause, namely 12 months of amenorrhoea [l-4]. In some studies data were collected only via telephone interviews [ 11. Although data on important factors (e.g. menopausal status) may be collected reliably and validly by telephone [5], it is doubtful whether telephone interviews can replace standard methods and face-to-face interviews when investigating emotionally sensitive areas of life. In some cases the representative nature of the sample may be questioned because the source from which the sample was drawn already had a selection bias (American census lists, driving licence lists, general practitioners’ lists, telephone directories, etc.). Finally, longitudinal studies are frequently weakened by attrition and contamination of data over time; this is because artificial menopause and hormonal treatment are distributed unevenly in the population (selection effect). These weaknesses in no way imply that the few available prospective studies of healthy populations are inconclusive. They do, however, indicate that further prospective investigations using alternative approaches are necessary. Most longitudinal menopause research is also faced with the problem of circumventing statistical problems associated with the measurement of change. When two groups are being compared within a cross-sectional design, a common method of analysis is to apply separate two-sample tests (viz. t-tests or Mann Whitney Utest) to assess the differences between groups. This method cannot be used to test differences between measurements in the same subjects at different time points in a longitudinal study. There are several reasons for this. (a) Successive observations on a given subject are likely to be correlated. Hence, the value at one time point cannot be treated statistically as though it was independent from the value at an earlier time point. (b) It is inherent in the longitudinal design that the main interest lies in the way individual subjects respond over time. When data are analyzed as if they belonged to different cross-sectional studies, as was done by Kaufert [4], no account is taken of the fact that measurements at different time points are from the same subjects. (c) The curve joining the group means may hide important variations in the shapes and locations of curves for different subjects and will thus not represent the typical curve for an individual [6]. In order to circumvent some of these problems, researchers [3] have used repeated-measures analysis of variance (ANOVA), but this approach has been criticized on statistical grounds [7-91. McKinlay et al. [ 1) used discriminant analysis and other multivariate techniques applicable to their data, but these methods impose requirements on the data which cannot always be met. Hunter [2] used paired r-tests to compare measurements before and after the menopause. This strategy, however, does not allow analysis of time-series, as it is restricted to comparison of two time points only.
One of the main objectives of this paper is to address some of the methodological problems raised above. In particular, a tentative method which has not been used previously in menopause research for relating health complaints at several time points to menopausal status is proposed. This makes it possible to determine which among 87 measures of the 26 ordinary health complaints most frequently cited in medical textbooks as being associated with the menopause are really affected by the menopause.
Subjects and Methods Subjects The subjects were drawn from a representative sample of 1886 Norwegian women who were 45-55 years of age in 198 1 when they participated in a cross-sectional survey of menopausal complaints [ 10-121. The subjects in the latter survey were randomly selected from the Community Register of the City of Oslo by the Norwegian Central Bureau of Statistics. After excluding those who had had a hysterectomy and/or oophorectomy, had never menstruated, or had received hormone replacement therapy (HRT) or other relevant endocrinological treatment, the sample was reduced to 1,668. Of these, 200 pre-menopausal women were randomly selected to take part in a 5-year prospective longitudinal study which ran from 1982 to 1986. Data collection At intervals of 12 months, all the subjects went through a 3-4-h semi-structured personal interview with fixed response categories, psychological testing and gynaecological examination. Interviewing and testing took place in the subjects’ homes and at the Department of Behavioural Sciences in Medicine, University of Oslo, while the gynaecological examinations were carried out in the Department of Gynaecology and Obstetrics at the National Hospital, Oslo. The interview covered information about work, linance, education, marriage, family, husband, household, home, children, life events, medical treatment, menstruation, menopause, quality of life, sexuality, social network, intimacy and communication, general health, somatic and psychological complaints. The standard psychological tests used were Torgersen’s Basic Character Inventory (personality) [ 131, Plutchic and Kellerman’s defence-mechanism test (psychological defence) [ 141, Bern’s Sex-role Inventory (sex-role identification) [ 151, Spanier’s Dyadic Adjustment Scale (marital adjustment) [16], a revised version of Jourard and Secord’s Body Cathexis method (satisfaction with body appearance, self-esteem) [17] and selected measures of quality of life [18.19]. The gynaecological examination includccl cytology and measurement of blood pressure. Blood samples were collected and frozen for future analyses. Two psychologically trained sociologists conducted all interviews and tests, while two gynaecologists carried out all the medical examinations. As a rule, each subject saw the same interviewer and the same gynaecologist at all observation time points during the course of the study. The interviewers and gynaecologists were females of approximately the same age as the subjects themselves.
Health complaints This paper presents results only on subjective health complaints. In all, 87 single measures covering the 26 health complaints cited most frequently in the literature as being affected by the menopause, and which had been included previously in the Oslo Menopausal Survey [ lo-121 and the Drammen Menopausal Survey [20,21], were examined. Questions were taken from Goldberg’s General Health Questionnaire (GHQ) [22] and adapted for use in personal interviews by the author. When an area was not covered sufficiently by the GHQ (e.g. vasomotor complaints), questions that had been used by the research team in previous studies were added. Table I lists the areas of complaints investigated and the number and types of measures used in each case. Within each area the subjects were usually asked (a)
TABLE
I
AREAS OF HEALTH COMPLAINTS INVESTIGATED MEASURES USED WITHIN EACH AREA Area of complaints
Number
General health (GHQ) Headaches (GHQ) Dizziness Forgetfulness Heart palpitations Shortness of breath
5 3 3 2 3 3
(currentd) (current, (current. (current, (current, (current.
Insomnia (GHQ) Tiredness Loss of feeling Numbness and stiffness
6 3 3 I
Muscle and joint pain Breast tenderness Digestive problems Vaginal dryness
7 3 5 3 5 5 3 3 3 3 3 3 3 I 3 2
Other gynaecological complaints Urinary problems Hot flushes, sweating Night sweats Cold shivers (GHQ) Anxiety (GHQ) Weepiness Social dysfunction (GHQ) Depression (GHQ) Suicidal thoughts (GHQ) Loneliness Weight gain “Visual analogue scale (IO points) bAdditive index: 8 items (yes/no). CAdditive index: 7 items (yes/no). dAdditive index: 4 items (yes/no). eAdditive index: 8 items (yes/no).
AND
NUMBER
TYPES
and types of measures
frequency, frequency, distress) frequency, frequency,
distress) distress)
(current, (current, (current, (current)
frequency, frequency, frequency.
distress) distress) distress)
(current, (current, (current, (current, (current, (current, (current, (current, (current, (currentb, (current, (current’, (currentd, (currente, (current, (current,
frequency, frequency, frequency, frequency, frequency. frequency, frequency, frequency, frequency, frequency, frequency, frequency. frequency, frequency, frequency, distress)
distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress) distress)
and 4 questions
AND
from General
distress) distress)
Health
Questionnaire
(GHQ)
OF
I .i I
whether or not they were experiencing the complaint now (current: yes/no), (b) how frequently they had experienced the complaint during the past 12 months (7-point scale) and (c) how much distress the complaint caused them at the time they were experiencing it, irrespective of its frequency (4-point scale). General subjective health was measured by means of a visual analogue scale and 4 questions (yes/no) from the GHQ. Current experience of anxiety, social dysfunction, depression, and suicidal thoughts was measured using additive indices adopted from the GHQ. Frequency of experiencing forgetfulness, numbness and stiffness, weight gain and the degree of distress caused by numbness and stiffness, were not assessed. Menopause The menopause was defined as the date of the last menstrual mediately before the start of at least 6 months of amenorrhoea.
period
(LMP)
im-
Analyses Matthews et al. [6] recently discussed a way of overcoming some of the problems associated with the measurement of change, namely the summary measurement procedure. Although it cannot replace multivariate techniques, this simple method has the advantage of considering the individual as the basic unit of analysis. The responses for each individual subject are used to construct a single number (e.g. mean, mean rank, slope) which summarizes some aspect of that subject’s response curve over a time-period (e.g. pre-menopausal phase and post-menopausal phase). Once the appropriate summary measures have been calculated for each subject, their values can be treated as raw data for an appropriate statistical analysis. To be applicable for detecting effects of the menopause in studies such as the present one, the method requires (a) that the exact time point of the natural menopause can be decided for each subject, (b) that measurements are available both before and after the menopause, (c) that measurements are available for all the time points investigated, and (d) that the measurements of complaints are not contaminated by artificial influences, such as HRT, oophorectomy, etc. Having excluded those women for whom these requirements could not be met, the exact date of the menopause was determined for each of the remaining subjects. Summary measurements of each subject’s level of complaint before at least a 6-month period of amenorrhoea (the 6-month criterion) were calculated, as were summary measurements of each subject’s level of complaint after the 6-month criterion was passed (Fig. 1). This was done for each of the 87 measures. Finally, the differences between the summary measurements before and after the 6-month criterion were tested. The r-test for paired samples was used for differences with normal distributions (means). Wilcoxon’s matched-pairs signed-rank test was used for distributions with bimodal or skewed patterns (mean ranks). Effects of age To check whether a significant difference between the measurements before and after the menopause could have been caused by age, several procedures were applied. Firstly, one-way ANOVA was used, with the frequency of experiencing the complaint concerned as the dependent variable and chronological age as the independent
132
Level of complaint I-
L
L ___---_
premenopausal
P
mean
1 1. 0
postmenopausal mean )’
--..--------+--
??
I
L
1962
1964
1963
1966
1966
Level of complain t
postmenopausal mean
0 c-----
____*
k I 1902
1 1963
premenopausal
mean
1 1984
1966
1986
Fig. 1. Summary measurements. Two examples of individual scores for a complaint plotted against time. Case A illustrates a decrease in complaints after the menopause. Case B illustrates an increase. Circles mark the levels of complaints at each measurement point before a period of at least 6 months of amenorrhoea. Squares mark the levels of complaints at each measurement point after this period. The dotted lines illustrate 6-month
the mean levels of complaints before and after this 6-month criterion. Case A reached criterion between 1983 and 1984. Case B reached it between 1984 and 1985.
the
variable. Secondly, the frequency of reporting the complaint was regressed on chronological age. Menopausal status was kept constant in these analyses by conducting them first on the 1982 data, when all subjects were still premenopausal, and then on the 1986 data, when all the subjects had become post-menopausal. Thirdly, the post-menopausal frequency of reporting the complaint was regressed on age controlled for the pre-menopausal frequency of reporting the complaint (multiple regression). Finally, the difference between the mean frequencies of complaints before and after the 6-month criterion was regressed on chronological age.
Effects of vasomotor complaints To check whether a significant change in psychological complaints after menopause could have been caused indirectly by an increase in hot flushes and sweating and hence whether these complaints were less likely to be affected directly by hormonal changes, three strategies were adopted. Firstly, the mean postmenopausal frequency of the psychological complaint concerned was regressed on the mean post-menopausal frequency of vasomotor complaints, controlled for the mean pre-menopausal frequency of the psychological complaint (multiple regression). Secondly, the difference in the mean frequency of the psychological complaint before and after the 6-month criterion was regressed on the corresponding difference for vasomotor complaints. Thirdly, the difference in the mean frequency of the psychological complaint before and after the 6-month criterion was included as the dependent variable in a multiple regression analysis, with the difference in vasomotor complaints before and after the 6-month criterion and chronological age as the independent variables. Results Subjects Altogether, 193 (96.5%) of the women accepted our invitation to participate. Out of these, 177 (9 1.7%) completed all parts of the study. In all, 118 (66.7%) of the subjects did not meet all the criteria for inclusion in the summary measurement procedure. Premenopausal measurements were lacking for 7 (4”/u) of the subjects because they had already become post-menopausal by the start of the study (mean age = 50.9, SD. = 2.4 years) and one of them had also received HRT. Postmenopausal measurements were lacking for 41 (23%) of the subjects because they did not reach the menopause during the course of the study (mean age = 49.0, S.D. = 1.9 years). Post-menopausal measurements were also lacking for 3 1 (18%) of the subjects because of HRT (mean age = 49.5, S.D. = 2.1 years). The postmenopausal measurements were contaminated in the case of 12 (7%) of the subjects who after at least a 6-month period of amenorrhoea experienced one or more episodes of bleeding because of HRT (mean age = 52.0, S.D. = 2.1 years). For 2 subjects the exact point of menopause could not be decided because after 6 months of amenorrhoea they experienced further bleeding even though they did not receive HRT. Three (2%) of the subjects were hysterectomized (mean age = 48.5), one of .whom also received HRT. Only one subject had a bilateral oophorectomy. Another 21 subjects received HRT for different reasons, so that of those who were not suitable for inclusion in the summary measurement procedure a total of 69 had received some form of local or general hormone treatment over the full course of the study. The final sample which could be subjected to the summary measurement procedure consisted of 59 women. Age and menopause The mean age of the final sample at the start of the longitudinal study (1982) was 51.1 (S.D. = 2.0, range 47.3-55.8 years). This was significantly higher (P < 0.00) than the mean age of those who were not suitable for inclusion in the summary
134
measurement procedure (mean age = 49.8, S.D. = 2.1 years). Mean age at menopause in the final sample was 52.9 (S.D. = 2.1, range 40.3-58.7 years) with a close to normal distribution. Out of the 69 subjects who did not receive any kind of hormone treatment or have a surgical menopause, and who experienced 6 months of amenorrhoea between the end of the cross-sectional study in 1981 and that of the longitudinal study in 1986, 97% (63) never menstruated again during the course of the study.
Health complaints The summary measurement procedure yielded significant differences before and after the 6-month criterion in 14 single measures within 6 areas of complaints (Fig. 2). No effects of the menopause were detected in the 69 measures of the remaining 20 health complaints. All results which were significant when subjected to Wilcoxon’s test were also significant (P < 0.05) when subjected to pairwise t-tests, but the distribution tended to be skewed. Headache and breast tenderness decreased after the 6-month criterion was passed, while vasomotor complaints, vaginal dryness, heart palpitations measures and social dysfunction increased. However, in all measures yielding significant differences, an increase was observed after a 6-month criterion in some subjects, while a decrease was observed in others. For example, although 58% showed more frequent vasomotor complaints after the 6-month criterion, 20% showed less frequent complaints and 22% no change. Similarly, although 47% indicated a greater amount of distress due to social dysfunction after the 6-month criterion, 24% indicated less and 29% no change (Fig. 2). The menopause had significant effects on current experience of most complaints, the frequency with which they had been experienced during the past 12 months, and the amount of distress they caused, irrespective of their frequency. There were a few exceptions to this rule; the reduction in the amount of distress due to headache was not significant. The reduction in current experience of headache (P < 0.1) and the increased amount of distress due to vaginal dryness (P < 0.07) were only marginally significant. No bivariate relationship with age was found for any of the measures affected by the menopause, with one exception. Simple regression yielded a significant relationship between the frequency of vasomotor complaints and age, both when all subjects were pre-menopausal (I = 0.27, P < 0.05) and when all had become post-menopausal (r = -0.30, P < 0.05).
Social dysfunction A significant relationship before and after the 6-month in vasomotor complaints (r effect of age was controlled adjusted R* = 0.11, P < = 0.36, P < 0.01; beta for
was found when the difference in social dysfunction criterion was regressed on the corresponding difference = 0.37, P < 0.01). This result did not change when the for in a multiple regression analysis (multiple R = 0.37, 0.01; beta for the difference in vasomotor complaints chronological age = -0.05, NS).
% women
Distress
Frequency
Current
(566t-d 59)
Headache
m
*
Palpitations
dn
17
33
50
Decrease (post < pre)
*
12
41
20
2g
51
Increase (post > pre)
ILL
20
54
58
& 16
22
22
4539
0
??
Social dysfunction
No change (post = pre)
Tenderness in breasts
Vaginal dryness
Vasomotor complaints
d/L
24
l/dl_Ld
47
m
136
The aim of this study was to investigate the effect of the menopause on ordinary health complaints in healthy women. The approach was to employ standard measures of health complaints in a prospective investigation of randomly selected pre-menopausal subjects, representative of the general population. As a tentative way of surmounting some of the difficulties involved in the analysis of serial measurements, a simple procedure was proposed combining summary measurements before and after 6 months of amenorrhoea and paired statistical tests. Health complaints
The results showed that hot flushes, sweating, vaginal dryness and heart palpitations - but none of the psychological complaints - were influenced negatively and directly by the climacteric transition. This is consistent with the findings of some other recent studies of healthy women [l-4, lo- 12,20,2 1,23-251. Our approach also led to several important developments in our knowledge. Few methodologically sound population studies have found evidence of a direct association between menopause and psychological complaints (anxiety, depression, irritability) [23,25]. This study was no exception in this respect. However, a signiticant decrease in social dysfunction after the menopause was detected. Some might suggest that the questions in the additive index used to measure social dysfunction (Table II) really measure depression. Factor analytic studies constituting the basis for Goldberg’s General Health Questionnaire indicate, however, that although correlated, social dysfunction and depression should be regarded as different dimensions [22]. Furthermore, the regression analyses showed that the decreased social function after menopause could be caused by an increase in vasomotor complaints. This supports the ‘domino-hypothesis’ [26], which regards some psychological complaints as a secondary effect of the menopause and not as being caused directly by the hormonal changes associated with the menopause. This study, therefore, lends no support to the view that social dysfunction is an indication for HRT. Vasomotor complaints leading to social dysfunction may, however, be so indicative.
TABLE
II
QUESTIONS
USED TO MEASURE
CURRENT
SOCIAL
DYSFUNCTION
Have you recently: been managing to keep yourself busy and occupied? I. been taking longer over the things you do? 2. felt on the whole you were doing things well? 3. been satisfied with the way you have carried out your task? 4. felt that you are playing a useful part in things? 5. felt capable of taking decisions about things? 6. been able to enjoy your normal day-to-day activities? I.
Ii7
Heart palpitations In previous studies palpitation of the heart has mainly been associated with vague somatic complaints and not with the menopause [ 11,241. From a biological point of view the lack of association is unexpected. This situation is most likely due to the difficulties involved in obtaining reliable subjective measures of heart palpitations when data have been collected cross-sectionally by means of postal questionnaires or telephone interviews. Consequently, it is no surprise that, in the present study, heart palpitations showed a pattern similar to that of the other vasomotor complaints. However, this finding must still be treated with caution, since it deviates from all previous factor analytic studies [ 11,231. Relief from health complaints Few studies have yet examined the extent to which the climacteric transition is accompanied by relief of health complaints. It should therefore be noted that, depending on the measure chosen, 40-51X had fewer headaches and 46-48X had less breast tenderness after the menopause. These changes were mainly due to relief from premenstrual and menstrual complaints. Although a significant increase was found in vasomotor complaints, vaginal dryness, palpitations and social dysfunction, it is pointed out that, depending on the measure chosen, 16-24(1/o and fewer vasomotor complaints after the menopause, 16-20X had less dryness of the vagina, 15- 19% had less frequent palpitations and 22-24X had less social dysfunction. This shows that the widely accepted perception of menopause as an event followed by a uniformly negative change in health complaints is erroneous. The reality is far more complicated and involves large individual variation. Unlike several others, this study used standard methods to a large extent and several indicators to measure each complaint. With a few exceptions (in particular headache), the results showed that if one indicator of a complaint (e.g. frequent) produced a significant effect, then the others (e.g. current, distress) did so also. If one indicator showed no effect, neither did the remaining indicators within that area. This supports the construct validity of our measurements. Confounding factors At an individual level, the effects of the menopause may easily be confounded with age, life events occurring at this stage of life [26], increased rapport with the interviewer over time, or the sheer fact that time has passed. How then do we know that the differences in the level of complaints before and after the menopause really were caused by the climacteric transition? By combining summary measures and pairwise tests of significance in a random sample within a prospective design, each subject acted as her own control, while age at the menopause was randomly and almost normally distributed. Therefore, in order to hypothesize that the change in health complaints was due to variables other than the menopause, it has to be assumed that these variables are highly correlated with the timing of the menopause. Such correlations have not been documented in any study and seem theoretically far-fetched, except in the case of age [28,29]. However, the regression analyses showed no relationship between age and menopausal complaints, except for the vasomotor types. When the subjects were still pre-menopausal being older increased the
likelihood of vasomotor complaints 0. = 0.27) and when they had become postmenopausal it reduced it (Y = -0.30). However, assuming that these correlations reflect an effect by age as such and not hormonal changes associated with menopause, one would expect them to be positive not only when all subjects were pre-menopausal but also when all subjects were post-menopausal. It might be objected that menopausal status was kept constant in terms of conducting the analyses when all subjects were still pre-menopausal and also when they had become post-menopausal. This does not, however, preclude the possibility that a positive correlation with age when the subjects were pre-menopausal may reflect an ongoing hormonal change which leads to more frequent vasomotor complaints in the oldest women, but which has not yet manifested itself as 6 months of amenorrhoea. This most likely interpretation is supported by Holte and Mikkelsen’s finding that 8% and 7% of pre-menopausal women aged 45-55 ‘often’ suffer from hot [ lo]. flushes and excessive sweating, respectively Age and menopause Mean age at menopause in this study was about 1 year later than that usually suggested for Caucasians in Northern Europe and America [28,29]. This most likely reflects the fact that subjects not meeting the criteria for the summary measurement procedure were treated more frequently for pathological processes associated with an early natural menopause; such subjects are also more frequently smokers [30,31]. Thus, the high mean age at menopause most probably indicates that age at menopause among healthy women is higher than that in the general population. Accordingly, use of the mean age at menopause in the general population as a basis for informing healthy, non-smoking women about when they should expect menopause is very likely to be misleading. Further prospective studies are needed in order to specify more precisely the expected age at menopause for different groups in the population and factors affecting this. Only 2 out of 69 women menstruated after a period of more than 6 months of amenorrhoea. In a sample similar to ours Kaufert [32] reported that this occurred in 9% of the subjects. These findings indicate that among untreated, healthy, premenopausal women aged over 47 years, more than 6 months of amenorrhoea is a very reliable indicator that menopause has been reached. This should be preferred to the less sensitive and more frequently used I%-month criterion. Further investigation is, however, necessary to determine whether more than 6 months of amenorrhoea is valid in younger women and if an even shorter period would be appropriate for older women. Attrition rate Only 16 (8.3’S) out of 193 subjects dropped out at one or more data-collection points. However, a large number were excluded because they did not satisfy the strict requirements for conducting summary measures analyses. The main reasons were that they had not become post-menopausal or that they were receiving hormone treatment at one time point at least during the course of the study. Because the subjects receiving treatment were not the same each year, the sum total of subjects treated at least once during the 5 years became high. This does not reflect an ag-
gressive treatment philosophy among Norwegian gynaecologists, but illustrates an ethical dilemma in pursuing longitudinal research aims in a clinical context. Treatment was offered to symptomatic subjects who would not otherwise have visited a gynaecologist had they not participated in a scientific study. We do not know how this may ultimately have affected the results. There are, however, several indications that the effects of this possible sample bias were minor. For example, the percentage of subjects experiencing vasomotor complaints for the first time after menopause (45%) was almost identical to the prevalence of hot flushes reported among women who were l-3 years post-menopausal in the general population of Oslo. Furthermore, the proportions of subjects with signs of depressed mood in the final sample and the original sample were very similar at all time points (approx. 20%) and this was also the case for other complaints [ 101. The summary measurement
procedure
Although simple to use and less prone to the problems associated with other methods of analyzing serial measurements [6-91, the summary measurement procedure has not been used previously in menopause research. The high degree of agreement with previous findings, however, indicates that the procedure may be a simple and useful means of circumventing some of the problems involved in the analysis of serial measurements in menopause research. Nevertheless, one should be aware that, like most others, the method as applied here has its limitations. The most obvious ones are that (a) menopausal status was treated as a discrete variable and not as a continuous development, (b) our approach cannot take the place of multivariate techniques in controlling for effects of variables that are highly correlated with the timing of the menopause (e.g. age), and (c) summary measures (e.g. means, mean ranks) may hide variation in the curves for different subjects and thus not represent the typical curve for an individual. It is unlikely, however, that our conclusions would have been different if methods free from these limitations had been available. Acknowledgements
The Norwegian Menopause Project is supported by the Norwegian Research Council for Science and the Humanities and by the Anders Jahre’s Foundation (Mag. art. medical sociology). Aslaug Mikkelsen assisted in designing the study. Professor Julie Skjae&en and Dr Mette Moen carried out the gynaecological examinations. Ellen Sandberg and Eva Marie Solheim conducted the interviews and the psychological testing. Research Fellow Ragna Holter assisted in assessing the subjects’ menopausal status. Manager of Computer services Nils Eivind Naas and Research Fellow Louise Nicol Smith provided data and technical assistance and Professor Petter Laake provided valuable advice regarding statistics. Their contributions are much appreciated. References 1
McKinlay JB, McKinlay SM, Brambilla DJ. Health status and utilization menopause. Am J Epidemiol 1987; 125: 110-121.
behaviour
associated
with
2
4
6
8 9 IO
11 12 13 14 15 16 17 18 19 20
Hunter M. Somatic experience of the menopause: A prospective study. Psychosom Med 1990; 52: 357-367. Mathews KA, Wing RR, Kuller LH, Meilahn EN, Kelsey SF. Costello JE. Caggiula A. Influences of natural menopause on psychological characteristics and symptoms of middle-aged healthy women. J Consult Clin Psycho1 1990; 58: 345-351. Kaufert PA, Gilbert P, Hassard T. Researching the symptoms of menopause: An exercise in methodology. Maturitas 1988; 10: 117-131. Brambilla DJ, McKinlay SM. Comparison of responses to mailed questionnaires and telephone interviews in a mixed mode health survey. Am J Epidemiol 1987: 126: 962-971. Matthews JNS, Altman DC, Campbell MJ, Royston P. Analysis of serial measurement in medical research. Br Med J 1990; 300: 230-235. Hertzog C. Rovine M. Repeated-measures analysis of variance in development research: Selected issues. Child Dev 1985; 56: 787-800. Editorial. Repeated warnings re repeated measures. Aust NZ J Med 1986: 16; 637-638. Ekstrom D, Quade D, Golden RN. Statistical analysis of repeated measures in psychiatric research. Arch Gen Psychiatry 1990; 47: 770-772. Holtc A. Prevalence of climacteric complaints m a representative sample of middle-aged women in Oslo. Norway. J Psychosom Obstet Gynaecol 199 I: 12: in press. Holte A, Mikkelsen A. The menopausal syndrome: A factor analytic replication. Maturitas 1991; 13: 193-203. Holte A, Mikkelsen A. Psychosocial determinants of climacteric complaints. Maturitas 1991; 13: 205-215. Torgersen S. Hereditary-environmental differentiation of general neurotic, obsessive, and impulsive hysterical personality traits. Acta Genet Med Gamellol 1980; 29: 193-207. Plutchic R, Kellerman H. Manual for the emotions profile index. Los Angeles: Western Psychological Services, 1974. Bern S. The measurement of psychological androgyny. J Consult Clin Psycho1 1974; 42: 155-162. Spanier GB. Measuring dyadic adjustment: New scales for assessing the quality of marriage and similar dyads. J Marriage Family 1976; 38: 15-28. Journard SM, Secord PF. Body-Cathexis and the ideal female figure. J Abnorm SOC Psycho1 1955; 50: 243-246. Mourn T. The role of values and life goals in quality of life: On measuring and predicting subjective well-being. UNESCO report. Division of Socioeconomic Analysis, 1980. Atkinson T. The stability and validity of quality of life measure. Sot Indicators Res 1982; 10: 113-132. Holte A, Mikkelsen A. Menstrual coping style, social background and climacteric symptoms.
22
Psychiatry Sot Sci 1982; 2: 41-45. Mikkelsen A, Holte A. A factor analytic study of climacteric symptoms. Psychiatry Sot Sci 1982; 2: 35-39. Goldberg DP, Hillier VF. A scaled version of the General Health Questionnarie. Psycho1 Med 1979;
23
9: 139- 145. Greene JG. The social and psychological
24
1984. Hunter
21
25 26 27 28
M. Battersby
R. Whitehead
origins
of the climacteric
M. Relationships
between
complaints and menopausal status. Maturitas 1986; 8: 217-228. Hunter MS. Emotional well-being, sexual behaviour and hormone 1990: 12: 299-314. Campbell S, Whitehead M. Oestrogen therapy and the menopausal
syndrome.
psychological replacement syndrome.
Aldershot:
Cower,
symptoms,
somatic
therapy.
Maturitas
Clin Obstet Gynecol
1977: 4: 31-47. Greene JG. Cooke DJ. Life stress and symptoms at the climacteric. Br J Psychiatry 1980; 136: 486-491. Brand C. Age at menopause: An investigation into the median age at menopause in Ede, the Netherlands, and into the possible influence of certain environmental variables upon this age. Doctoral dissertation. University of Leiden. 1978.
29 30 31 32
Brambilla DJ, McKinlay SM. A prospective study of factors affecting age at menopause. J Clin Epidemiol 1989; 42: 1031- 1039. Lindquist 0, Bengtsson C. The effect of smoking on menopausal age. Maturitas 1979: I : I7 I - 173. McKinlay SM, Bifano NL, McKinlay JB. Smoking and age at menopause in women. Ann Intern Med 1985: 103; 350-356. Kaufert PA, Gilbert P, Tate R. Defining menopausal status: The impact of longitudinal data. Maturitas
1987; 9: 217-226.
