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A new methodological approach to the evaluation of quality of life in postmenopausal women
Maturitas, I4 ( 1992) 2 I l-224 Elsevier Scientific Publishers Ireland Ltd.
211
MAT 0067 I
A new methodological approach to the evaluation of quality of life in postmenopausal women I. Wiklund”, J. Holstb, J. Karlberg”, L.-A. Mattssond, G. Samsioee, K. Sandin’, M. Uvebrantd and B. von Schoultzs ‘Department of Medicine, &tra Hospital, GBteborg. hDepartment of Obstetrics and Gynaecology. Umeh Hospital, r/me& ‘Biometric Unit, Department of Anatomy, Giiteborg University, GBteborg, “Department of Obstetrics and Gynaecology. t%tra Hospital, Giiteborg. ‘Department of Obstetrics and Gynaecology, Sahlgrenska Hospital, Gdteborg. JCiba-Geigy Ltd, Medical Department, Viistra Friilunda and RDepartment of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm (Sweden)
(Received October 3 1, 1990; revision received April 18, 1991; accepted April 19, 1991)
An approach employing a range of standardized questionnaires, which included the Nottingham Health Profile (NHP), the Psychological General Well-Being (PGWB) index and the Mood Adjective Check List (MACL), was used to assess health-related quality of life (QoL) in conjunction with a study comparing two doses of transdermal oestrogen (50 or 100 &24 h) combined with an oral progestogen (5 mg medroxyprogesterone acetate for I4 days each cycle). In addition to the QoL measures, climacteric symptoms were self-rated and also summarized by means of the Kupperman index. In all, 59 women, median age 52 (39-71) years, who completed 4 months of therapy were evaluated. The use of a battery of standardized questionnaires enabled a comprehensive evaluation to be made of perceived health, wellbeing and day-to-day functioning. Not only was symptomatic relief, e.g. reduced frequency of sweating episodes, sleep disturbance and hot flushes, observed during treatment, but there were also improvements in terms of sleep, energy and emotions. The frequency of health-related problems associated with paid employment, housework, social life, home life and sex life decreased, indicating enhanced ability to take part in daily activities. The PGWB index showed improvement in the subscales representing well-being, anxiety, depression, vitality, health and self-control, while the mood scales indicated that the women experienced less tension and more satisfaction. Although the results of this study need to be further documented on the basis of a placebo-controlled trial, the findings nevertheless imply that the use of a battery of standardized questionnaires optimizes the possibility of evaluating climacteric complaints reliably before and after treatment. Key words: quality of life; methods; climacteric symptoms; hormone replacement therapy
Introduction
In clinical trials it has become increasingly important to measure the ability of new therapies not only to cure disease and relieve symptoms, but also to improve healthCorrespondence to: I. Wiklund, Department of Medicine, Plan 2 CK, &tra
Sweden. 0378-5122/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
Hospital, S-416 85 Goteborg,
related quality of life (QoL) in individuals receiving medical treatment [ 1,2]. Health, well-being and functional ability to take part in day-to-day activity are important elements in the QoL concept [2-41. Even though the efficacy of oestrogen therapy in relieving vasomotor symptoms is well-documented [5,6-lo], effect variables beyond symptomatic relief and secondary benefits affecting mood have seldom been evaluated. The perceived impact of postmenopausal complaints has primarily been assessed using psychiatric rating scales or non-standardized measures with unknown psychometric properties [5,1 l-141. Where monitoring of subjective responses to treatment has been carried out, it has often been based on the Kupperman index, which is of limited value in that ratings are determined by the clinician rather than the woman concerned [15]. Few attempts have been made to incorporate a battery of standardized psychosocial questionnaires when evaluating the effects of oestrogen replacement therapy on QoL. To obtain a more comprehensive picture of the impact of vasomotor symptoms on health-related QoL, methods designed to address the health status and well-being of a general population must be employed, thus allowing populations and the results of different studies to be compared. The purpose of this study was to try a new approach using a battery of standardized questionnaires and to test its suitability for the evaluation of QoL before and after transdermal oestrogen therapy in postmenopausal women. Subjects and Methods Women whose last menstruation had occurred at least 6 months prior to their first consultation and who were complaining of common climacteric symptoms, such as sweating, hot flushes, insomnia and/or atrophic symptoms, were included in the study. All the patients were volunteers who gave their informed consent to participate. Any previous hormone replacement therapy (HRT) had been discontinued at least 6 weeks before the study was started, and the women concerned experienced withdrawal symptoms. The main exclusion criteria were absolute or relative contraindications for HRT (e.g. diabetes, breast cancer, endometrial hyperplasia, thromboembolism), uncontrolled or beta-blocker/diuretic-treated hypertension for less than 6 months, thyroid diseases, liver disease, undiagnosed enlargement of the uterus, psoriasis, hysterectomy, and digitalis therapy or continuous steroid therapy with medicines other than those administered in the study. Transdermal oestradiol (E2) patches (Estraderm) in two doses (50 and 100 &24 h) were used continuously in combination with an oral progestogen (5 mg oral medroxyprogesterone acetate (MPA) daily for 14 days in each treatment cycle). The rationale for using two different doses was that the primary objective of the study was to compare the metabolic effects and clinical efficacy of the two doses. The study was designed as a randomized, double-blind, cross-over comparison, with treatment cross-overs after 4 months. Since the main reason for including QoL in the trial was to test the usefulness of the measures chosen to evaluate QoL during oestrogen therapy, the QoL assessments were made only at baseline prior to the initiation of active therapy and then after 4 months of therapy during the final days of progestogen suppletion. The questionnaires were self-administered and were completed during the visits to the clinic.
213
Methodological approach
The evaluation included standardized self-administered questionnaires and assessments of climacteric symptoms by a physician. The approach to the QoL assessment was to use a generic measure as a basis for obtaining a comprehensive evaluation of health-related distress and dysfunction. In view of the variety of psychological complaints usually associated with postmenopausal disorders [13,14,16], measures of well-being and mood were included. In addition, a specific questionnaire focusing on climacteric symptoms was completed by each patient. This meant that both general, problem-oriented aspects and disease-specific aspects of QoL were covered [ 171. The Nottingham Health Profile (NHP)
The NHP is classified as a generic measure for the assessment of health-related QoL [18]. It has been extensively tested in Britain and Sweden with regard to reliability and validity [ 19,201. The NHP comprises two parts. The 38 ‘yes/no items in part I reflect the degree of distress within the sections covering mobility, energy, pain, sleep, emotions and social isolation. The sections on mobility and pain were omitted, since they were considered less relevant to the problems of the present patient population. The NHP answers have been weighted on the basis of several patient and non-patient populations [21]. Weights in each section totalling 100 indicate the presence of all the possible problems, whereas 0 signifies no problems at all. Part II of the NHP contains 7 ‘yes/no’ statements about the frequency of healthrelated problems associated with paid employment, housework, social life, family life, sex life, hobbies and holidays. The Psychological General Well-Being Index (PG WB)
This index comprises 22 questions which cover the six subscales of anxiety (CY= 0.82), depression (a! = 0.89), well-being (a = 0.88), self-control (CX= 0.76) health ((Y= 0.61) and vitality (CY= 0.85) [22]. The scores on the 22 items combine into an overall total (a! = 0.95). The patients rate each question on a six-point scale (with six as the most positive option and one as the most negative). The CYcoefficients were computed using the baseline values and are compatible with the (Yvalues of the original PGWB index [22,23]. The Mood Adjective Check List (MACL)
The MACL contains 38 adjectives which denote positive and negative affects [24]. Three separate dimensions can be formed, viz. activation/deactivation, pleasantness/unpleasantness and tension/calmness. The response format for each item uses four categories. The higher the rating, the more positive is the mood. Reference values are available. Self-rating of postmenopausal symptoms
The patients were asked to rate symptoms, such as hot flushes, sweating, sleep disturbance, nervousness, depression, irritability, vertigo, fatigue, arthralgia, headache, tachycardia and vaginal dryness, using visual analogue scales (VAS) [25]. This method has previously been shown to be a sensitive and clinically valid measure of emotional and symptomatic changes in postmenopausal women [26]. Factor
214
analysis distinguished three factors: vasomotor symptoms’ (hot flushes, sweating), emotions (sleep disturbance, nervousness, depression, irritability, headache), and other symptoms (tachycardia, vaginal dryness) [26]. Similar symptom clusters have been derived elsewhere in menopause research [27]. In addition to the postmenopausal symptoms, a single item covering ‘general complaints’ was assessed. The women also recorded hot flushes and sweating by number and intensity (O-3) for 3 consecutive days prior to every visit. The Kupperman Index The physician’s assessment of climacteric symptoms, summarized in a menopausal index which was a slight modification of Kupperman’s, was based on the most common complaints (hot flushes, sweating, sleep disturbance, nervousness, depression, vertigo, fatigue, arthralgia, headache, tachycardia and vaginal dryness) [9]. The symptom findings were converted into a summary numerical figure based on severity (graded O-3). The severity score for sweating, sleep disturbance and nervousness was multiplied by 2 and that for hot flushes by 4, so that the highest possible score was 5 1. Even though the reproducibility of the Kupperman index is open to question it is still the predominant method used in Sweden to quantify the severity of climacteric complaints in clinical trials. Before the start of the trial a physical and gynaecological examination was carried out which included the measurement of blood pressure, weight and height. Basic demographic data and information on concomitant medication as well as the severity and duration of postmenopausal complaints were recorded. The study was approved by the ethical committees at the local participating institutions. Statistics The mean individual differences in QoL and self-rated postmenopausal symptoms prior to and after therapy were tested using the t-test for paired samples. The same procedure was followed to test the differences in QoL scores between the two dosage regimens. Only two-tailed tests were used, and the underlying distributions were all close to the Gaussian (without bimodal or skewed patterns). The primary statistical analysis was conducted on the overall scores. In cases where the differences were statistically significant (P < O.Ol), a secondary analysis was performed in a similar fashion using the questionnaire subscales/dimensions. Because of the multiplicity of tests, only P values < 0.01 were considered. Change score correlations were computed between the different measures using Pearson’s correlation coefficient in order to test the clinical validity of the QoL measures [28,29]. Results Out of 70 women, 59 completed the first 4 months of the study on which the QoL evaluation was based; their median age was 52 (range 39-71 years). The reasons for drop-out were poor compliance (two cases), poor efficacy (one), skin irritation (four), skin irritation and vaginal bleeding (one), vaginal bleeding (two), and breast tenderness (one). The majority of the women (76%) were married or cohabiting. Sixty-nine percent
215
TABLE
I
MORBIDITY Morbidity
AND MEDICATION
AT BASELINE
and medication
(n = 59)
W) I 5
Angina pectoris Arthralgia Other unspecified morbidity Allergy, nervous complaints Previous hormone therapy Antihypertensives
17 0 71 12
Analgesics Psychoactive drugs Other medication
IO 8 17
sew life
House work
Paid empkymenf
Hobbies
Family life
Social life
Fig. 1. Mean values (out of 100) for the Nottingham Health Profile (Part I) before and after transdermal oestrogen therapy (n = 59). These means are compared with those for ‘normal’ females (n = 200) [22].
216
were non-smokers, while 2% smoked l-4 cigarettes per day, 16% 5-14 and 14% more than 15 cigarettes per day. As regards alcohol consumption, 33% were teetotallers, 57% had a very modest and 5% a modest intake, whereas 5% admitted drinking every day. Clinical data, morbidity and medication The mean weight of the 59 women was 68.5 kg (S.D. 11.3 kg), the mean height 164.5 cm (S.D. 6.2 cm), the mean systolic blood pressure 133.6 mmHg (S.D. 15.4 mmHg) and the mean diastolic blood pressure 82.1 mmHg (S.D. 7.3 mmHg). The median duration of climacteric complaints was 48 months (range 4-384 months). Descriptive statistics of morbidity and medication at baseline are presented in Table I.
Energy
Emotions
Social isolation
Fig. 2. Percentages of health-related problems in the Nottingham Health Profile (Part II) before and after transdermal oestrogen therapy (n = 59). These values are compared with those for ‘normal’ females (n = 200) [22].
217
Confounding variables
In view of the variation in age and duration of climacteric complaints, it was checked whether these factors influenced the responses to the QoL questionnaires. Similarly, because of the high proportion of women who had received previous hormonal therapy, the influence of this source of potential bias was tested. Neither age nor duration of climacteric complaints was found to have any significant effect on QoL scores. Only in the energy section of the NHP did women who had previously had hormonal therapy score higher (P = 0.05). However, women in whom the duration of climacteric complaints was above the median, i.e. 2.5 years, had higher Kupperman index values (P = 0.05). The Kupperman index scores were also higher among women who had had previous therapy (X = 27.6 versus .W= 22.0; P = 0.01) than among those previously untreated. TABLE
II
NOTTINGHAM BEING (PGWB)
HEALTH INDEX,
PROFILE (NHP), PART I, PSYCHOLOGICAL MOOD ADJECTIVE CHECK LIST (MACL)
POSTMENOPAUSAL SYMPTOMS OESTRADIOL THERAPY (n = 59) Dimension
Before therapy
Sleep Emotions Isolation PGWB, total score Anxiety Depression Well-being Health Vitality Self-control MACL Tension Deactivation Unpleasantness VAS, total score Vasomotor Emotions Other Kupperman
Index
BEFORE
After 4 months
Mean NHP, total score Energy
(VAS)
S.D.
Mean
AND
GENERAL WELLAND SELF-RATED
AFTER
TRANSDERMAL
Individual difference (after-before) S.D.
Mean
P-value*
S.D.
93.8 zt 27.6 f
86.4 35.7
42.4 f II.8 zt
62.5 27.9
-51.4 -15.8
f f
54.1 24.8
0.0001 0.0001
37.7 f 19.9 f II.5 zt
28.5 26.2 18.1
17.9 f 7.9 f 3.9 zt
25.9 15.9 10.6
-19.8 -12.0 -1.6
zt 23.4 zt 18.4 f 17.5
0.0001 0.0001 0.002
94.2 21.9 14.2 15.1
f f f f
18.2 4.6 3.1 3.8
12.6 f 14.9 f 14.1 f
2.8 4.2 3.4
14.0 ?? 18.2 f 15.7 f
2.7 3.0 1.8
+ +z f f f zt f
13.6 3.8 2.7 3.1 2.6 3.5 3.0
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0003
0.7 0.7 0.6
3.1 f 3.3 f 3.2 f
0.5 0.5 0.5
0.4 f 0.3 f 0.2 ??
0.5 0.4 0.4
0.0001 0.0001 0.0005
2.1 f 2.9 zt 3.0 f
430.9 zt 172.8 110.4 ?? 47.4 174.9 f 100.9 54.9 + 43.8 25.9 +
8.4
107.2 24.8 16.1 17.6
151.9 19.1 64.4 23.1
f f zt zt
II.4 3.2 1.9 2.8
13.0 2.9 1.9 2.5 1.4 3.2 I.5
f f f f
110.3 34.5 58.5 24.8
-279.0 -91.3 -110.5 -31.8
f f f f
169.8 49.1 88.5 42.1
0.0001 0.ooo1 0.0001 0.0001
1.7 f
15.9
-18.2
+
8.0
0.0001
*Paired r-test with an expected value of zero was applied to the mean of the individual score); P-values are shown in the table. VAS = visual analogue scales.
differences
(change
218
Quality of life
Thirty-two of the women received transdermal oestrogen at a dose of 50 pg/24 h and 27 at a dose of 100 &24 h. No statistically significant (P < 0.01) dose-related differences in QoL were observed. The results will therefore be presented for the total population, irrespective of dose. The Nottingham Health Profile
As shown in Figs. 1 and 2, climacteric complaints had a considerable impact on health-related QoL as compared with that in an age-matched Swedish female reference group (n = 200) derived from a WHO screening project in Gothenburg [26]. In particular, sleep and energy were impaired. After treatment, all dimensions of health-related QoL had improved significantly (Table II). The frequency of health-related problems showed the same pattern, with improvements in the cases of paid employment in women below 65 years of age (P = O.OOl), housework (P = O.Ol), social life (P = 0.006), family life (P = 0.006), hobbies (P = 0.03) and sex life (P < 0.0001). Comparison with the reference group showed that after 4 months of treatment the women had achieved a similar level of health-related QoL (Figs. 1 and 2). The Psychological General Well-Being Index
The mean total PGWB index score (Sz = 94) indicates that well-being was considerably affected for the worse compared with population-based reference values, where the mean was 105 [22]. The value was normalized after treatment (Table II). Well-being improved similarly within all subscales (Table II). The Mood Adjective Check List
Comparison with the mean values in a Swedish population (tension, X = 3.0; unpleasantness, X = 3.1; activation, X = 3.1) indicates that the postmenopausal women expressed more tension and dissatisfaction. Improvements were observed after treatment, denoting that the women were less tense, more satisfied and felt more active (Table II). Self-rating of postmenopausal symptoms
The most frequent complaints were sweating, sleep disturbance and hot flushes, which decreased considerably after treatment (Fig. 3). Significant differences were observed after treatment in the total score as well as in the emotions, vasomotor, and other climacteric symptoms dimensions (Table II). The number of hot flushes and sweating episodes was 6.7 and 8.3 respectively prior to therapy, and 0.9 and 0.4 after therapy (P < 0.0001). The intensity of hot flushes fell from 2.1 to 0.3 and that of sweating from 2.4 to 0.4 after treatment (P < 0.0001). Kupperman Index
As shown in Table III, the distribution of patients by severity indicates that the majority of the women had moderately severe complaints before treatment, whereas over 90% were classified as having no or only mild complaints after therapy. The
219
Symptom Sweats
Sleep disturbance
u
12.8
Hot flu&s
Fatigue
Vaginal dryness
Depression
Headache
Irritability
Arthralgia
u
18.1 25.7
Nervousness
Palpitations
Vertigo
General comlaints
1 I
1 28.1 10
Fig. 3. Means for self-rated climacteric oestrogen therapy (n = 59).
20
symptoms
30
40
(visual analogue
5p
60
70
scales) before and after transdermal
220 TABLE III KUPPERMAN INDEX BEFORE AND AFTER THERAPY CLIMACTERIC COMPLAINTS (n = 59) Severity
ACCORDING
TO SEVERITY OF
Kupperman Index
Absent or mild (< 18) Slight (18-22) Moderate (23-37) Severe (2 38)
Before therapy (“/)
After 4 months of therapy (u/o)
16.1 14.3 62.5 7.1
92.9 1.8 5.4 0
TABLE IV CORRELATIONS BETWEEN QoL MEASURES AND KUPPERMAN AND DURING TREATMENT Subjective measure (change score) VAS, total score Emotions Vasomotor Other PGWB, total score Vitality Depression Anxiety Well-being Health Self-control
Before
INDEX BEFORE, AFTER
Change score
After
r value
P value
r value
P value
r value
P value
0.67 0.56 0.56 0.24
0.0001 0.0001 0.0001 NS
0.75 0.66 0.68 0.22
0.0001 0.0001 0.0001 NS
0.64 0.61 0.59 0.19
0.0001 0.0001 0.0001 NS
-0.42 -0.44 -0.34 -0.30 -0.37 -0.15 -0.29
0.003 0.0008 0.01 0.02 0.008 NS 0.03
-0.51 -0.45 -0.37 -0.25 -0.36 -0.41 -0.13
0.0001 0.0005 0.005 0.05 0.008 0.001 NS
-0.38 -0.48 -0.40 -0.37 -0.34 -0.22 -0.17
0.007 0.0002 0.003 0.005 0.01 NS NS
NHP, total score Sleep Emotions Social isolation Energy
0.46 0.51 0.33 0.33 0.32
0.0005 0.0001 0.01 0.01 0.02
0.37 0.40 0.29 0.18 0.21
MACL Unpleasantness Tension Deactivation
0.34 -0.31 -0.52
0.01 0.03 0.0001
-0.27 -0.15 -0.18
0.004 0.002 0.03 NS NS
0.40 0.50 0.32 0.23 0.15
0.003 0.0001 NS NS NS
0.05 NS NS
-0.46 -0.4.1 -0.33
0.0008 0.003 NS
VAS, visual analogue scales for self-rated postmenopausal symptoms; PGWB, Psychological General Well-being Index; NHP, Nottingham Health Profile; MACL, Mood Adjective Check List.
221
correlations between the Kupperman index and the intensity of hot flushes and sweating were 0.61 and 0.52, respectively, before and 0.65 and 0.72 after therapy. Change score correlations
The changes in the Kupperman Index were correlated with the changes in the subjective measures during treatment (Table IV). As expected, the highest correlations were observed between changes in the Kupperman Index and changes in climacteric symptoms and sleep disturbance, which supports the clinical validity of these selfassessment measures. The correlations between changes in climacteric symptoms and changes in mood states such as anxiety, tension and depression were also comparatively high. Discussion Many previous studies have used ad hoc and psychometrically undocumented measures, making comparisons between different populations and/or studies difficult or, at worst, impossible. In clinical trials the ability of a measure to detect treatment-induced changes over time is a particular concern, and the only way in which this can be tested is within the framework of an actual clinical trial [30]. Generally, specific measures are more responsive to change [17,31]. Since no single validated questionnaire appears to encompass the range of features requiring evaluation whilst also being responsive to the magnitude of the changes anticipated, the use of a battery consitutes an interesting approach. If a battery that includes both specific and generic measures is used, both scope and responsiveness are achieved [31]. However, QoL data can only provide valuable supplementary information if the methods are well-documented in terms of reliability, validity and responsiveness. Both reliability and validity were satisfactory for all the measures, as was their ability to detect treatment-induced changes over time, these being findings that have also been reported elsewhere [26]. The most typical symptoms prior to and around the menopause are hot flushes and sweating. Even though these symptoms are most pronounced during the first few postmenopausal years, as many as 50% of women suffer for up to 5 years, and 10% for 10 years or more [32,33]. Hence, around one-third of a woman’s life can be expected to be spent in the postmenopausal state. In view of this prospect, it is of the utmost importance to take QoL during these years into account. Although far from all postmenopausal women require HRT, the contrast between the prevalence of vasomotor complaints and the comparatively small number of women receiving treatment is striking [34,35]. It is therefore essential to use methods that allow comprehensive exploration of all the potential benefits of HRT, including its effect on QoL. The open, non-comparative study design for the QoL data used in this investigation represents a limitation. However, the positive effect of oestrogen replacement therapy on vasomotor symptoms has been demonstrated in controlled clinical trials [8,9,14,36]. Since the primary aim of this report was to study the suitability of the questionnaires chosen to evaluate the effect of oestrogen therapy on health-related QoL, the open study design, although a drawback, was considered to be of less importance at this stage.
222
While age did not affect the responses to the QoL questionnaires, vasomotor symptoms were, as expected, more pronounced with increasing duration of climacteric complaints and in women who had had previous HRT. The approach used for the assessment of QoL made it possible to gain a comprehensive picture of the full impact of climacteric complaints not only on vasomotor symptoms but also on mood and day-to-day activity before and after transdermal oestrogen therapy. VA scales consitute a simple means of evaluating the frequency of self-reported postmenopausal symptoms. Our results were similar to those of other authors [37]. The symptomatic decrease was most pronounced in terms of alleviation of vasomotor symptoms, which was also in agreement with previous studies [ 11,14,38]. Even though the reproducibility of assessments made by different physicians as regards the Kupperman Index is open to question, potential bias was avoided in the present study, since the same gynaecologist always rated the same individuals before and after treatment. There was also close agreement between the Kupperman index and the individual records of severity of hot flushes and sweating. The severity of climacteric complaints before and after therapy according to the Kupperman index was similar to that reported in another study [39]. It has been postulated that symptoms such as fatigue, headache and irritability are psychosomatic manifestations due to the disturbed balance between the neurovegetative and endocrine systems [40]. Some studies show that the prevalence of minor psychosomatic symptoms increases prior to the menopause [40,41], while others claim that no such differences have been observed [ 131. Vasomotor symptoms may induce distress and discomfort, and a high incidence of psychosomatic symptoms could be interpreted as a secondary reaction. Sleep disturbances represented an obvious problem, as can be seen in the sleep section of the NHP and in the VA scales, In the present study, improved sleep was correlated with alleviation of hot flushes and sweating, which occur more frequently during the night and disrupt sleep. It has been shown previously that improvement in sleep quality after oestrogen replacement therapy is secondary to amelioration of physical symptoms [ 12,14,42]. The choice of measures designed for use in a general population enabled comparisons to be made with other populations. It was possible to estimate the extent of distress and dysfunction in our population of climacteric women compared with a general sample of women in a corresponding age range. Comparison with a general American population sample [22], as well as hypertensive patients [23], indicated that well-being was lower among the postmenopausal women before treatment. The differences between the postmenopausal women before treatment and the reference group as regards well-being, sleep disturbance, fatigue and the frequency of problems associated with day-to-day activities show that satisfactory QoL in the postmenopausal years should not be taken for granted. The women reported less impairment of well-being after oestrogen therapy, which is consistent with previous reports [5,43]. Similarly, improvement in headache, arthralgia, and insomnia has also been documented [14,44]. No relationship between cause and effect has been established, but the interpretation that the alleviation of other subjective complaints, e.g. mood, was brought about by the relief of vasomotor symptoms cannot be excluded [40].
223
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44
Dupuy HJ. The Psychological General Well-Being (PGWB) Index. In: Wenger NK, Masson ME, Furberg CD, Elinson J, eds. Assessment of quality of life in clinical trials of cardiovascular therapies. USA: Le Jacq Pub1 Inc. 1984; 170-183. Croog SH, Levine S, Testa MA, Brown B, Bulpitt CJ, Jenkins CD, Klerman GL, Williams GH. The effects of antihypertensive therapy on the quality of life. N Engl J Med 1986; 314: 1657-1664. Sjiiberg L, Svensson E, Persson L-O. The measurement of mood. Stand J Psycho1 1979; 20: I-18. Aitken RC. Measurement of feelings using visual analogue scales. Proc R Sot Med 1969; 2: 989-993. Wiklund 1, Karlberg J. Evaluating quality of life in clinical trials: selection of quality of life measures. Contr Clin Trials 1991; 12 (Suppl.): 2045-2165. Greene JG. The social and psychological origins of the climacteric syndrome. Glasgow: Gower Press, 1984. Kirschner B, Guyatt G. A methodologic framework for assessing health indexes. J Chron Dis 1985; 38: 27-36. Jaeschke R, Singer J, Guyatt G. A comparison of seven-point and visual analogue scales. Contr Clin Trials 1990; II: 43-51. Guyatt G, Bombardier C, Tugwell PX. Measuring disease-specific quality of life in clinical trials. Can Med Assoc J 1986; 154: 889-895. Wiklund I, Dimenls E, Wahl M. Factors of importance when evaluating quality of life in clinical trials. Contr Clin Trials 1990; 1I: 169- 179. McKinlay JB, McKinlay SM, Brambilla D. The relative contribution of endocrine changes and social circumstances in mid-aged women. J Health Sot Behav 1987; 28: 345-363. McKinlay JB, McKinlay SM, Brambilla DJ. Health status and utilization behavior associated with menopause. Am J Epidemiol 1987; 125: 110-121. Brenner PF. The menopause syndrome. Obstet Gynecol 1988; 72 (Suppl): 6%1 IS. Pedersen SH, Jeune B. Prevalence of hormone replacement therapy in a sample of middle-aged women. Maturitas 1988; 9: 339-345. Dennerstein L, Burrows GD. A review of studies of the psychological symptoms found at the menopause. Maturitas 1978; I: 55-64. Andersson E, Hamburger S, Liu SH, Reber RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 1987; 156: 428-433. Hunt K. Perceived value of treatment among a group of long-term users of hormone replacement therapy. J R Coll Gen Pratt 1988; 38: 398-401. Keller PJ. Die perkutane Gstrogentherapie in der Postmenopause. Schweiz med Wschr 1989; 119: 999- 1004. Jaszmann L. Epidemiology of climacteric and post-climacteric complaints. Front Hormone Res 1973; 2: 22-34. Bungay GT, Vessey MP, McPherson CK. Study of symptoms in middle life with special reference to the menopause. Br Med J 1980; 281: 181-183. Erlik Y, Tataran IV, Meldrum DR, Lomax P, Bajorch JG, Judd HL. Association of waking episodes with postmenopausal hot flushes. J Am Med Assoc 1981; 245: 1741-1744. Padwick ML, Siddle NC, Lane G, Endacott JA, Cooper H, Pryse-Davies J, Whitehead MI. Oestriol with oestradiol versus oestradiol alone: a comparison of endometrial, symptomatic and psychological effects. Br J Obstet Gynaecol 1986; 93: 606-612. Chakravarti S, Collins WP, Thorn MH, Studd JWW. Relation between plasma hormone profiles. symptoms, and response to oestrogen treatment in women approaching menopause. Br Med J 1979: 1: 983-985.
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MAT 0067 I
A new methodological approach to the evaluation of quality of life in postmenopausal women I. Wiklund”, J. Holstb, J. Karlberg”, L.-A. Mattssond, G. Samsioee, K. Sandin’, M. Uvebrantd and B. von Schoultzs ‘Department of Medicine, &tra Hospital, GBteborg. hDepartment of Obstetrics and Gynaecology. Umeh Hospital, r/me& ‘Biometric Unit, Department of Anatomy, Giiteborg University, GBteborg, “Department of Obstetrics and Gynaecology. t%tra Hospital, Giiteborg. ‘Department of Obstetrics and Gynaecology, Sahlgrenska Hospital, Gdteborg. JCiba-Geigy Ltd, Medical Department, Viistra Friilunda and RDepartment of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm (Sweden)
(Received October 3 1, 1990; revision received April 18, 1991; accepted April 19, 1991)
An approach employing a range of standardized questionnaires, which included the Nottingham Health Profile (NHP), the Psychological General Well-Being (PGWB) index and the Mood Adjective Check List (MACL), was used to assess health-related quality of life (QoL) in conjunction with a study comparing two doses of transdermal oestrogen (50 or 100 &24 h) combined with an oral progestogen (5 mg medroxyprogesterone acetate for I4 days each cycle). In addition to the QoL measures, climacteric symptoms were self-rated and also summarized by means of the Kupperman index. In all, 59 women, median age 52 (39-71) years, who completed 4 months of therapy were evaluated. The use of a battery of standardized questionnaires enabled a comprehensive evaluation to be made of perceived health, wellbeing and day-to-day functioning. Not only was symptomatic relief, e.g. reduced frequency of sweating episodes, sleep disturbance and hot flushes, observed during treatment, but there were also improvements in terms of sleep, energy and emotions. The frequency of health-related problems associated with paid employment, housework, social life, home life and sex life decreased, indicating enhanced ability to take part in daily activities. The PGWB index showed improvement in the subscales representing well-being, anxiety, depression, vitality, health and self-control, while the mood scales indicated that the women experienced less tension and more satisfaction. Although the results of this study need to be further documented on the basis of a placebo-controlled trial, the findings nevertheless imply that the use of a battery of standardized questionnaires optimizes the possibility of evaluating climacteric complaints reliably before and after treatment. Key words: quality of life; methods; climacteric symptoms; hormone replacement therapy
Introduction
In clinical trials it has become increasingly important to measure the ability of new therapies not only to cure disease and relieve symptoms, but also to improve healthCorrespondence to: I. Wiklund, Department of Medicine, Plan 2 CK, &tra
Sweden. 0378-5122/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
Hospital, S-416 85 Goteborg,
related quality of life (QoL) in individuals receiving medical treatment [ 1,2]. Health, well-being and functional ability to take part in day-to-day activity are important elements in the QoL concept [2-41. Even though the efficacy of oestrogen therapy in relieving vasomotor symptoms is well-documented [5,6-lo], effect variables beyond symptomatic relief and secondary benefits affecting mood have seldom been evaluated. The perceived impact of postmenopausal complaints has primarily been assessed using psychiatric rating scales or non-standardized measures with unknown psychometric properties [5,1 l-141. Where monitoring of subjective responses to treatment has been carried out, it has often been based on the Kupperman index, which is of limited value in that ratings are determined by the clinician rather than the woman concerned [15]. Few attempts have been made to incorporate a battery of standardized psychosocial questionnaires when evaluating the effects of oestrogen replacement therapy on QoL. To obtain a more comprehensive picture of the impact of vasomotor symptoms on health-related QoL, methods designed to address the health status and well-being of a general population must be employed, thus allowing populations and the results of different studies to be compared. The purpose of this study was to try a new approach using a battery of standardized questionnaires and to test its suitability for the evaluation of QoL before and after transdermal oestrogen therapy in postmenopausal women. Subjects and Methods Women whose last menstruation had occurred at least 6 months prior to their first consultation and who were complaining of common climacteric symptoms, such as sweating, hot flushes, insomnia and/or atrophic symptoms, were included in the study. All the patients were volunteers who gave their informed consent to participate. Any previous hormone replacement therapy (HRT) had been discontinued at least 6 weeks before the study was started, and the women concerned experienced withdrawal symptoms. The main exclusion criteria were absolute or relative contraindications for HRT (e.g. diabetes, breast cancer, endometrial hyperplasia, thromboembolism), uncontrolled or beta-blocker/diuretic-treated hypertension for less than 6 months, thyroid diseases, liver disease, undiagnosed enlargement of the uterus, psoriasis, hysterectomy, and digitalis therapy or continuous steroid therapy with medicines other than those administered in the study. Transdermal oestradiol (E2) patches (Estraderm) in two doses (50 and 100 &24 h) were used continuously in combination with an oral progestogen (5 mg oral medroxyprogesterone acetate (MPA) daily for 14 days in each treatment cycle). The rationale for using two different doses was that the primary objective of the study was to compare the metabolic effects and clinical efficacy of the two doses. The study was designed as a randomized, double-blind, cross-over comparison, with treatment cross-overs after 4 months. Since the main reason for including QoL in the trial was to test the usefulness of the measures chosen to evaluate QoL during oestrogen therapy, the QoL assessments were made only at baseline prior to the initiation of active therapy and then after 4 months of therapy during the final days of progestogen suppletion. The questionnaires were self-administered and were completed during the visits to the clinic.
213
Methodological approach
The evaluation included standardized self-administered questionnaires and assessments of climacteric symptoms by a physician. The approach to the QoL assessment was to use a generic measure as a basis for obtaining a comprehensive evaluation of health-related distress and dysfunction. In view of the variety of psychological complaints usually associated with postmenopausal disorders [13,14,16], measures of well-being and mood were included. In addition, a specific questionnaire focusing on climacteric symptoms was completed by each patient. This meant that both general, problem-oriented aspects and disease-specific aspects of QoL were covered [ 171. The Nottingham Health Profile (NHP)
The NHP is classified as a generic measure for the assessment of health-related QoL [18]. It has been extensively tested in Britain and Sweden with regard to reliability and validity [ 19,201. The NHP comprises two parts. The 38 ‘yes/no items in part I reflect the degree of distress within the sections covering mobility, energy, pain, sleep, emotions and social isolation. The sections on mobility and pain were omitted, since they were considered less relevant to the problems of the present patient population. The NHP answers have been weighted on the basis of several patient and non-patient populations [21]. Weights in each section totalling 100 indicate the presence of all the possible problems, whereas 0 signifies no problems at all. Part II of the NHP contains 7 ‘yes/no’ statements about the frequency of healthrelated problems associated with paid employment, housework, social life, family life, sex life, hobbies and holidays. The Psychological General Well-Being Index (PG WB)
This index comprises 22 questions which cover the six subscales of anxiety (CY= 0.82), depression (a! = 0.89), well-being (a = 0.88), self-control (CX= 0.76) health ((Y= 0.61) and vitality (CY= 0.85) [22]. The scores on the 22 items combine into an overall total (a! = 0.95). The patients rate each question on a six-point scale (with six as the most positive option and one as the most negative). The CYcoefficients were computed using the baseline values and are compatible with the (Yvalues of the original PGWB index [22,23]. The Mood Adjective Check List (MACL)
The MACL contains 38 adjectives which denote positive and negative affects [24]. Three separate dimensions can be formed, viz. activation/deactivation, pleasantness/unpleasantness and tension/calmness. The response format for each item uses four categories. The higher the rating, the more positive is the mood. Reference values are available. Self-rating of postmenopausal symptoms
The patients were asked to rate symptoms, such as hot flushes, sweating, sleep disturbance, nervousness, depression, irritability, vertigo, fatigue, arthralgia, headache, tachycardia and vaginal dryness, using visual analogue scales (VAS) [25]. This method has previously been shown to be a sensitive and clinically valid measure of emotional and symptomatic changes in postmenopausal women [26]. Factor
214
analysis distinguished three factors: vasomotor symptoms’ (hot flushes, sweating), emotions (sleep disturbance, nervousness, depression, irritability, headache), and other symptoms (tachycardia, vaginal dryness) [26]. Similar symptom clusters have been derived elsewhere in menopause research [27]. In addition to the postmenopausal symptoms, a single item covering ‘general complaints’ was assessed. The women also recorded hot flushes and sweating by number and intensity (O-3) for 3 consecutive days prior to every visit. The Kupperman Index The physician’s assessment of climacteric symptoms, summarized in a menopausal index which was a slight modification of Kupperman’s, was based on the most common complaints (hot flushes, sweating, sleep disturbance, nervousness, depression, vertigo, fatigue, arthralgia, headache, tachycardia and vaginal dryness) [9]. The symptom findings were converted into a summary numerical figure based on severity (graded O-3). The severity score for sweating, sleep disturbance and nervousness was multiplied by 2 and that for hot flushes by 4, so that the highest possible score was 5 1. Even though the reproducibility of the Kupperman index is open to question it is still the predominant method used in Sweden to quantify the severity of climacteric complaints in clinical trials. Before the start of the trial a physical and gynaecological examination was carried out which included the measurement of blood pressure, weight and height. Basic demographic data and information on concomitant medication as well as the severity and duration of postmenopausal complaints were recorded. The study was approved by the ethical committees at the local participating institutions. Statistics The mean individual differences in QoL and self-rated postmenopausal symptoms prior to and after therapy were tested using the t-test for paired samples. The same procedure was followed to test the differences in QoL scores between the two dosage regimens. Only two-tailed tests were used, and the underlying distributions were all close to the Gaussian (without bimodal or skewed patterns). The primary statistical analysis was conducted on the overall scores. In cases where the differences were statistically significant (P < O.Ol), a secondary analysis was performed in a similar fashion using the questionnaire subscales/dimensions. Because of the multiplicity of tests, only P values < 0.01 were considered. Change score correlations were computed between the different measures using Pearson’s correlation coefficient in order to test the clinical validity of the QoL measures [28,29]. Results Out of 70 women, 59 completed the first 4 months of the study on which the QoL evaluation was based; their median age was 52 (range 39-71 years). The reasons for drop-out were poor compliance (two cases), poor efficacy (one), skin irritation (four), skin irritation and vaginal bleeding (one), vaginal bleeding (two), and breast tenderness (one). The majority of the women (76%) were married or cohabiting. Sixty-nine percent
215
TABLE
I
MORBIDITY Morbidity
AND MEDICATION
AT BASELINE
and medication
(n = 59)
W) I 5
Angina pectoris Arthralgia Other unspecified morbidity Allergy, nervous complaints Previous hormone therapy Antihypertensives
17 0 71 12
Analgesics Psychoactive drugs Other medication
IO 8 17
sew life
House work
Paid empkymenf
Hobbies
Family life
Social life
Fig. 1. Mean values (out of 100) for the Nottingham Health Profile (Part I) before and after transdermal oestrogen therapy (n = 59). These means are compared with those for ‘normal’ females (n = 200) [22].
216
were non-smokers, while 2% smoked l-4 cigarettes per day, 16% 5-14 and 14% more than 15 cigarettes per day. As regards alcohol consumption, 33% were teetotallers, 57% had a very modest and 5% a modest intake, whereas 5% admitted drinking every day. Clinical data, morbidity and medication The mean weight of the 59 women was 68.5 kg (S.D. 11.3 kg), the mean height 164.5 cm (S.D. 6.2 cm), the mean systolic blood pressure 133.6 mmHg (S.D. 15.4 mmHg) and the mean diastolic blood pressure 82.1 mmHg (S.D. 7.3 mmHg). The median duration of climacteric complaints was 48 months (range 4-384 months). Descriptive statistics of morbidity and medication at baseline are presented in Table I.
Energy
Emotions
Social isolation
Fig. 2. Percentages of health-related problems in the Nottingham Health Profile (Part II) before and after transdermal oestrogen therapy (n = 59). These values are compared with those for ‘normal’ females (n = 200) [22].
217
Confounding variables
In view of the variation in age and duration of climacteric complaints, it was checked whether these factors influenced the responses to the QoL questionnaires. Similarly, because of the high proportion of women who had received previous hormonal therapy, the influence of this source of potential bias was tested. Neither age nor duration of climacteric complaints was found to have any significant effect on QoL scores. Only in the energy section of the NHP did women who had previously had hormonal therapy score higher (P = 0.05). However, women in whom the duration of climacteric complaints was above the median, i.e. 2.5 years, had higher Kupperman index values (P = 0.05). The Kupperman index scores were also higher among women who had had previous therapy (X = 27.6 versus .W= 22.0; P = 0.01) than among those previously untreated. TABLE
II
NOTTINGHAM BEING (PGWB)
HEALTH INDEX,
PROFILE (NHP), PART I, PSYCHOLOGICAL MOOD ADJECTIVE CHECK LIST (MACL)
POSTMENOPAUSAL SYMPTOMS OESTRADIOL THERAPY (n = 59) Dimension
Before therapy
Sleep Emotions Isolation PGWB, total score Anxiety Depression Well-being Health Vitality Self-control MACL Tension Deactivation Unpleasantness VAS, total score Vasomotor Emotions Other Kupperman
Index
BEFORE
After 4 months
Mean NHP, total score Energy
(VAS)
S.D.
Mean
AND
GENERAL WELLAND SELF-RATED
AFTER
TRANSDERMAL
Individual difference (after-before) S.D.
Mean
P-value*
S.D.
93.8 zt 27.6 f
86.4 35.7
42.4 f II.8 zt
62.5 27.9
-51.4 -15.8
f f
54.1 24.8
0.0001 0.0001
37.7 f 19.9 f II.5 zt
28.5 26.2 18.1
17.9 f 7.9 f 3.9 zt
25.9 15.9 10.6
-19.8 -12.0 -1.6
zt 23.4 zt 18.4 f 17.5
0.0001 0.0001 0.002
94.2 21.9 14.2 15.1
f f f f
18.2 4.6 3.1 3.8
12.6 f 14.9 f 14.1 f
2.8 4.2 3.4
14.0 ?? 18.2 f 15.7 f
2.7 3.0 1.8
+ +z f f f zt f
13.6 3.8 2.7 3.1 2.6 3.5 3.0
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0003
0.7 0.7 0.6
3.1 f 3.3 f 3.2 f
0.5 0.5 0.5
0.4 f 0.3 f 0.2 ??
0.5 0.4 0.4
0.0001 0.0001 0.0005
2.1 f 2.9 zt 3.0 f
430.9 zt 172.8 110.4 ?? 47.4 174.9 f 100.9 54.9 + 43.8 25.9 +
8.4
107.2 24.8 16.1 17.6
151.9 19.1 64.4 23.1
f f zt zt
II.4 3.2 1.9 2.8
13.0 2.9 1.9 2.5 1.4 3.2 I.5
f f f f
110.3 34.5 58.5 24.8
-279.0 -91.3 -110.5 -31.8
f f f f
169.8 49.1 88.5 42.1
0.0001 0.ooo1 0.0001 0.0001
1.7 f
15.9
-18.2
+
8.0
0.0001
*Paired r-test with an expected value of zero was applied to the mean of the individual score); P-values are shown in the table. VAS = visual analogue scales.
differences
(change
218
Quality of life
Thirty-two of the women received transdermal oestrogen at a dose of 50 pg/24 h and 27 at a dose of 100 &24 h. No statistically significant (P < 0.01) dose-related differences in QoL were observed. The results will therefore be presented for the total population, irrespective of dose. The Nottingham Health Profile
As shown in Figs. 1 and 2, climacteric complaints had a considerable impact on health-related QoL as compared with that in an age-matched Swedish female reference group (n = 200) derived from a WHO screening project in Gothenburg [26]. In particular, sleep and energy were impaired. After treatment, all dimensions of health-related QoL had improved significantly (Table II). The frequency of health-related problems showed the same pattern, with improvements in the cases of paid employment in women below 65 years of age (P = O.OOl), housework (P = O.Ol), social life (P = 0.006), family life (P = 0.006), hobbies (P = 0.03) and sex life (P < 0.0001). Comparison with the reference group showed that after 4 months of treatment the women had achieved a similar level of health-related QoL (Figs. 1 and 2). The Psychological General Well-Being Index
The mean total PGWB index score (Sz = 94) indicates that well-being was considerably affected for the worse compared with population-based reference values, where the mean was 105 [22]. The value was normalized after treatment (Table II). Well-being improved similarly within all subscales (Table II). The Mood Adjective Check List
Comparison with the mean values in a Swedish population (tension, X = 3.0; unpleasantness, X = 3.1; activation, X = 3.1) indicates that the postmenopausal women expressed more tension and dissatisfaction. Improvements were observed after treatment, denoting that the women were less tense, more satisfied and felt more active (Table II). Self-rating of postmenopausal symptoms
The most frequent complaints were sweating, sleep disturbance and hot flushes, which decreased considerably after treatment (Fig. 3). Significant differences were observed after treatment in the total score as well as in the emotions, vasomotor, and other climacteric symptoms dimensions (Table II). The number of hot flushes and sweating episodes was 6.7 and 8.3 respectively prior to therapy, and 0.9 and 0.4 after therapy (P < 0.0001). The intensity of hot flushes fell from 2.1 to 0.3 and that of sweating from 2.4 to 0.4 after treatment (P < 0.0001). Kupperman Index
As shown in Table III, the distribution of patients by severity indicates that the majority of the women had moderately severe complaints before treatment, whereas over 90% were classified as having no or only mild complaints after therapy. The
219
Symptom Sweats
Sleep disturbance
u
12.8
Hot flu&s
Fatigue
Vaginal dryness
Depression
Headache
Irritability
Arthralgia
u
18.1 25.7
Nervousness
Palpitations
Vertigo
General comlaints
1 I
1 28.1 10
Fig. 3. Means for self-rated climacteric oestrogen therapy (n = 59).
20
symptoms
30
40
(visual analogue
5p
60
70
scales) before and after transdermal
220 TABLE III KUPPERMAN INDEX BEFORE AND AFTER THERAPY CLIMACTERIC COMPLAINTS (n = 59) Severity
ACCORDING
TO SEVERITY OF
Kupperman Index
Absent or mild (< 18) Slight (18-22) Moderate (23-37) Severe (2 38)
Before therapy (“/)
After 4 months of therapy (u/o)
16.1 14.3 62.5 7.1
92.9 1.8 5.4 0
TABLE IV CORRELATIONS BETWEEN QoL MEASURES AND KUPPERMAN AND DURING TREATMENT Subjective measure (change score) VAS, total score Emotions Vasomotor Other PGWB, total score Vitality Depression Anxiety Well-being Health Self-control
Before
INDEX BEFORE, AFTER
Change score
After
r value
P value
r value
P value
r value
P value
0.67 0.56 0.56 0.24
0.0001 0.0001 0.0001 NS
0.75 0.66 0.68 0.22
0.0001 0.0001 0.0001 NS
0.64 0.61 0.59 0.19
0.0001 0.0001 0.0001 NS
-0.42 -0.44 -0.34 -0.30 -0.37 -0.15 -0.29
0.003 0.0008 0.01 0.02 0.008 NS 0.03
-0.51 -0.45 -0.37 -0.25 -0.36 -0.41 -0.13
0.0001 0.0005 0.005 0.05 0.008 0.001 NS
-0.38 -0.48 -0.40 -0.37 -0.34 -0.22 -0.17
0.007 0.0002 0.003 0.005 0.01 NS NS
NHP, total score Sleep Emotions Social isolation Energy
0.46 0.51 0.33 0.33 0.32
0.0005 0.0001 0.01 0.01 0.02
0.37 0.40 0.29 0.18 0.21
MACL Unpleasantness Tension Deactivation
0.34 -0.31 -0.52
0.01 0.03 0.0001
-0.27 -0.15 -0.18
0.004 0.002 0.03 NS NS
0.40 0.50 0.32 0.23 0.15
0.003 0.0001 NS NS NS
0.05 NS NS
-0.46 -0.4.1 -0.33
0.0008 0.003 NS
VAS, visual analogue scales for self-rated postmenopausal symptoms; PGWB, Psychological General Well-being Index; NHP, Nottingham Health Profile; MACL, Mood Adjective Check List.
221
correlations between the Kupperman index and the intensity of hot flushes and sweating were 0.61 and 0.52, respectively, before and 0.65 and 0.72 after therapy. Change score correlations
The changes in the Kupperman Index were correlated with the changes in the subjective measures during treatment (Table IV). As expected, the highest correlations were observed between changes in the Kupperman Index and changes in climacteric symptoms and sleep disturbance, which supports the clinical validity of these selfassessment measures. The correlations between changes in climacteric symptoms and changes in mood states such as anxiety, tension and depression were also comparatively high. Discussion Many previous studies have used ad hoc and psychometrically undocumented measures, making comparisons between different populations and/or studies difficult or, at worst, impossible. In clinical trials the ability of a measure to detect treatment-induced changes over time is a particular concern, and the only way in which this can be tested is within the framework of an actual clinical trial [30]. Generally, specific measures are more responsive to change [17,31]. Since no single validated questionnaire appears to encompass the range of features requiring evaluation whilst also being responsive to the magnitude of the changes anticipated, the use of a battery consitutes an interesting approach. If a battery that includes both specific and generic measures is used, both scope and responsiveness are achieved [31]. However, QoL data can only provide valuable supplementary information if the methods are well-documented in terms of reliability, validity and responsiveness. Both reliability and validity were satisfactory for all the measures, as was their ability to detect treatment-induced changes over time, these being findings that have also been reported elsewhere [26]. The most typical symptoms prior to and around the menopause are hot flushes and sweating. Even though these symptoms are most pronounced during the first few postmenopausal years, as many as 50% of women suffer for up to 5 years, and 10% for 10 years or more [32,33]. Hence, around one-third of a woman’s life can be expected to be spent in the postmenopausal state. In view of this prospect, it is of the utmost importance to take QoL during these years into account. Although far from all postmenopausal women require HRT, the contrast between the prevalence of vasomotor complaints and the comparatively small number of women receiving treatment is striking [34,35]. It is therefore essential to use methods that allow comprehensive exploration of all the potential benefits of HRT, including its effect on QoL. The open, non-comparative study design for the QoL data used in this investigation represents a limitation. However, the positive effect of oestrogen replacement therapy on vasomotor symptoms has been demonstrated in controlled clinical trials [8,9,14,36]. Since the primary aim of this report was to study the suitability of the questionnaires chosen to evaluate the effect of oestrogen therapy on health-related QoL, the open study design, although a drawback, was considered to be of less importance at this stage.
222
While age did not affect the responses to the QoL questionnaires, vasomotor symptoms were, as expected, more pronounced with increasing duration of climacteric complaints and in women who had had previous HRT. The approach used for the assessment of QoL made it possible to gain a comprehensive picture of the full impact of climacteric complaints not only on vasomotor symptoms but also on mood and day-to-day activity before and after transdermal oestrogen therapy. VA scales consitute a simple means of evaluating the frequency of self-reported postmenopausal symptoms. Our results were similar to those of other authors [37]. The symptomatic decrease was most pronounced in terms of alleviation of vasomotor symptoms, which was also in agreement with previous studies [ 11,14,38]. Even though the reproducibility of assessments made by different physicians as regards the Kupperman Index is open to question, potential bias was avoided in the present study, since the same gynaecologist always rated the same individuals before and after treatment. There was also close agreement between the Kupperman index and the individual records of severity of hot flushes and sweating. The severity of climacteric complaints before and after therapy according to the Kupperman index was similar to that reported in another study [39]. It has been postulated that symptoms such as fatigue, headache and irritability are psychosomatic manifestations due to the disturbed balance between the neurovegetative and endocrine systems [40]. Some studies show that the prevalence of minor psychosomatic symptoms increases prior to the menopause [40,41], while others claim that no such differences have been observed [ 131. Vasomotor symptoms may induce distress and discomfort, and a high incidence of psychosomatic symptoms could be interpreted as a secondary reaction. Sleep disturbances represented an obvious problem, as can be seen in the sleep section of the NHP and in the VA scales, In the present study, improved sleep was correlated with alleviation of hot flushes and sweating, which occur more frequently during the night and disrupt sleep. It has been shown previously that improvement in sleep quality after oestrogen replacement therapy is secondary to amelioration of physical symptoms [ 12,14,42]. The choice of measures designed for use in a general population enabled comparisons to be made with other populations. It was possible to estimate the extent of distress and dysfunction in our population of climacteric women compared with a general sample of women in a corresponding age range. Comparison with a general American population sample [22], as well as hypertensive patients [23], indicated that well-being was lower among the postmenopausal women before treatment. The differences between the postmenopausal women before treatment and the reference group as regards well-being, sleep disturbance, fatigue and the frequency of problems associated with day-to-day activities show that satisfactory QoL in the postmenopausal years should not be taken for granted. The women reported less impairment of well-being after oestrogen therapy, which is consistent with previous reports [5,43]. Similarly, improvement in headache, arthralgia, and insomnia has also been documented [14,44]. No relationship between cause and effect has been established, but the interpretation that the alleviation of other subjective complaints, e.g. mood, was brought about by the relief of vasomotor symptoms cannot be excluded [40].
223
Even though the most pronounced changes that were observed concerned the alleviation of vasomotor symptoms, the present methodology made it possible to assess other functional changes that were secondary to the symptomatic improvement. It was concluded that the combination of carefully selected standardized measures, ranging from the general to the disease-specific, provided highly relevant information in assessing the impact of climacteric complaints in postmenopausal women before and after treatment. References I
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