1 Department of Obstetrics and Gynecology, Lund University Hospital, S-221 85 Sweden, 2 Department of Obstetrics and Gynecology Pramongkutklao Hospital, Bangkok, Thailand, 3 Department of Community Medicine, Lund University Hospital and 4 Department of Endocrinology, University Hospital MAS, Malmö, Sweden
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Abstract |
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Key words: HRT/menopause status/middle-aged women/psycho-somatic symptoms/vasomotor symptoms
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Introduction |
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Other somatic and emotional disturbances occur frequently during women's mid-lives, such as irritation, depressive mood, sleeping problems, fatigue, headache, muscularskeletal pains and joint problems. These problems are considered as atypical because the prevalence of these symptoms is not only limited to women of menopausal age. In addition, the occurrences of these symptoms have no direct relation with hormonal changes (Ballinger et al., 1987). Along with the psycho-physiological alterations, many chronic diseases (cardiovascular diseases, diabetes, osteoporosis, obesity and cancer) increase when women reach their middle age.
The reasons for the high prevalence of health-related problems in middle-aged women are multi-factorial and some issues are still controversial. Existing data on women's health status at mid-life were derived mainly from clinical-based studies. Prospective population-based studies only appeared in the more recent literature (Ledesert et al., 1995; Kuh et al., 1997
; Stadberg et al., 1997
). Nevertheless, the data accumulated so far are insufficient. The aim of the present study was: (i) to investigate the general physical and psychological conditions in middle-aged women; (ii) to evaluate whether the prevalence of symptoms varies by menopausal status as well as by use of hormone replacement therapy (PMT).
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Materials and methods |
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In 1996, all women in the WHILA study were offered a health assessment programme that included a mailed generic selfadministered questionnaire tied to laboratory examinations performed at a screening centre. Women who had findings indicative of disease received appropriate medical attention.
The generic questionnaire contained 104 questions. Most of the questions had been used and validated previously (Li et al., 2000a,b
). After the subjects had filled out the questionnaire, a personal interview was carried out by a specially trained nursemidwife to endorse and correct questionnaire replies. This resulted in one or more corrections in 19% of the questionnaires due mainly to thoughtless mistakes rather than to misunderstanding of the text.
Composition of the generic questionnaire
In the generic questionnaire, the questions detailed by the present study were composed of four parts:
Part I. General background
Questions concerned socio-demographic background, diet, life-style (smoking, alcohol consumption, physical activity), reproductive events, menopausal status, HRT administration, history of previous surgery (hysterectomy and oophorectomy) and chronic disease (hypertension, diabetes, thrombosis, myocardial infarction, stroke and cancer), as well as regular medical surveillance and intake of medication. Measurements of body mass index (BMI) and waist:hip ratio (WHR) were also incorporated.
Part II. Climacteric problems
Women were asked about the occurrence of hot flushes/sweats and vaginal dryness. Symptom severity was graded on a visual analogue scale (010 cm). Absence of a symptom was marked at 0, and scoring 10 indicated a symptom at the highest level. Based on these self-reporting scores, symptom severity was further classified into three degrees, i.e. slight (grade 12), moderate (grade 36), and severe (grade 710).
Part III. Somatic symptoms
This section consisted of 20 questions on several listed symptoms during the preceding 3 months. The answer to each question was `yes' or `no'. According to the sum of the positive response (answer of yes) to each question, the severity of somatic symptoms was categorized into four degrees: absent, slight (16), moderate (712) or severe (1320).
Part IV. Psychological symptoms
There were nine questions concerning this issue. Women were asked whether the symptoms were bothersome or had interfered with their life during the preceding 3 months. The answer to each question was `yes' or `no'. Symptom severity was also based on the sum of the positive answers (answer of yes) distinguished into four degrees: absent, slight (13), moderate (46) and severe (79).
Participants, groups and subgroups
Participants
A total of 6917 women completed the generic questionnaire, which yielded a response rate of 65.1%. The main reasons for no responses were: foreign nationality, moved out of the community prior to the appointment given, refusal and death. The women who responded were then invited to have a physical and laboratory examination as well as a mammography. Up to January 31, 2000, a total of 6200 women had completed the questionnaires as well as the screening procedure. These women constituted the eligible subjects for the present analysis. The rest of women (n = 717) could not be included in this report since they had not yet completed the general screen examination.
Groups
According to the menopause status and HRT use, participants were divided into three groups, i.e. pre-menopause (PM), post-menopause (PMO) and peri- or post-menopausal women with current HRT use (PMT). PM group included the subjects who still had regular menstruation. The subjects whose menstruation had ceased for more than 12 months were grouped as PMO. PMT group comprised the subjects who were using systemic hormone therapy. To identify whether a subject was a current or a past HRT user, an additional specific hormone questionnaire was distributed and collected. Of the total 6200 participants, 4943 (80%) were considered eligible for the present study, and 9% of women (n = 448) with a mean age of 53 ± 1.6 years were classified as pre-menopausal (PM), 52% post-menopausal women (n = 2591) with a mean age of 57 ± 2.9 years (PMO), and 39% current HRT users (n = 1904) with a mean age of 56 ± 2.8 years (PMT). There were 1257 women excluded from this study. The reasons for exclusion were incomplete questionnaires (n = 89), local estrogen administration only (n = 588), lack of information for classification of current HRT use (n = 580) as these women did not respond to the hormone questionnaire.
Subgroups
According to the years of menopause, the subjects in the PMO group were categorized into five subgroups, i.e. being post-menopausal 1, 2, 3, 45 and 610 years. Based on the duration of HRT use, the HRTU subjects were placed in five subgroups, i.e. 02, 23, 34, 46 and
610 years.
Statistical approach
Statistical analyses were carried out by SAS version 6.12 statistical package (SAS, Inc., Cary, NC, USA). The baseline characteristics and the prevalence of symptoms between the groups were compared by using 2-test and t-test. In order to investigate whether the incidence of symptoms had an increasing or decreasing tendency associated with menopausal status or with the duration of HRT application, we used logistic regression models to analyse the symptom tendency. The models were adjusted for age. P-Value was tested by Bonferroni correction for multiple comparisons. P
0.05 was considered statistical significant.
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Results |
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Vaginal dryness
The prevalence of vaginal atrophy was also significantly correlated to menopausal status. In the pre-menopausal phase, only 11% of women suffered from such symptoms. The frequency and severity of symptoms increased gradually with time after menopause. The highest rate of symptoms (22%) was found in the late post-menopause. This increasing tendency was not influenced by adjustment of age (P < 0.001).
The frequency of vaginal dryness was higher (24%) in the PMT group than that in the PM (11%) and PMO (20%) groups, but the symptom tendency declined significantly along with the duration of HRT use, i.e. from 27% during the first year of treatment to 21% after more than 610 years of treatment (P = 0.03). Age had no impact on the symptom tendency.
Somatic symptoms in middle-aged women
Somatic symptoms were very common. Approximately one-quarter of women had more than seven different somatic complaints. The most common symptoms were pain (headache, back and/or leg pain) and joint problems that were independent of hormonal status. However, the general somatic condition worsened progressively from the groups of PM to PMO to PMT, i.e. the mean percentage of the total symptoms was 25% in the PM group, 27% in PMO group and 29% in the PMT group. In Table III, only the significant symptoms were presented.
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Except for sweats, the frequencies of the majority of somatic symptoms were higher in the PMT group than in the PMO group. Statistically significant differences were found for headache, joint problems, feeling cold and breast tenderness. In addition, a group of gastrointestinal disorders, such as abdominal pain, constipation, diarrhoea and nausea, was also significantly more frequent in the PMT group.
From the stage of pre-menopause to post-menopause, the trend of somatic symptoms indicated that only the symptoms of headache (P = 0.008) and feeling cold (P < 0.001) decreased significantly while leg/back ache and joint problems increased (P < 0.001). Sweats, headache and feeling cold were also inclined to decrease with post-menopausal age.
In the PMT group, the symptoms of sweats and nausea revealed a decreasing tendency in line with the increasing duration of HRT consumption (P = 0.02, 0.004 respectively).
Psychological symptoms in middle-aged women
Eighty-five per cent of all women complained of psychological problems and nearly half experienced at least four listed emotional problems. More than 50% of the women had a feeling of fatigue and depression, irrespective of hormonal status. More than 40% of the women considered that their life was too stressful to cope with (Table IV).
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The symptom tendency analysis indicated that the majority of psychological symptoms had no relation with menopausal status. One exception was feeling overstressed. This problem had a significant declining trend from the stages of pre-menopause to post-menopause (P = 0.05). Crying spells and nervousness tended to be significantly lower with longer duration of HRT use (P = 0.03, 0.04 respectively).
The severity of both somatic and psychological symptoms in PM, PMO and PMT groups based on the sum of positive answers reported by the subjects is set out in Table V.
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Discussion |
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Menopausal status and women's health
In this study, the prevalence of several health problems differed significantly between pre- and post-menopausal women, particularly pertaining to the typical menopausal symptoms (hot flushes/sweats and vaginal dryness), muscleskeletaljoint problems, headache and sleeping complaints, though the mean age between two groups of women was close. Moreover, the frequencies of vasomotor symptoms (hot flushes/sweats), unstable mood disturbances (irritation), sleeping and concentration problems peaked in the first year after menopause, but waned subsequently. These findings are in agreement with the reports in other population-based surveys (Hunter et al., 1986; Hunter, 1992
; Kuh et al., 1997
).
Vasomotor symptoms
Women with hormonal intervention were not included in our analysis of hot flushes. Hence the prevalence of hot flushes in this study was determined in pre- and post-menopausal women only, which differed from other population-based studies in which the prevalence of hot flushes was observed on the basis of all subjects. Hot flushes and sweats were the predominant complaints of the women studied and prevalence was clearly associated with menopausal status. Although the aetiology of menopausal-related hot flushes is still a matter of debate, the changes of hormonal milieu, especially variations of estrogen concentrations rather than the level of estrogen per se, are considered relevant to the occurrence of hot flushes. The findings of this study further underline this assumption.
Muscle and joint problems
The second most common cluster of physical symptoms found in this cohort were those from muscles and joints, affecting more than 40% of post-menopausal women including HRT users. Joint problems and leg pain also showed an increasing trend from pre-menopause to post-menopause, independent of age.
It has been indicated that the majority of women with self-reported physician-diagnosed arthritis have osteoarthritis (OA) (Verbrugge et al., 1991; Verbrugge, 1995
). Observational studies have demonstrated that the prevalence of OA not only increases with age, but also is higher in women than in age-matched men, especially after women's menopause (Tsai and Liu, 1992
; Verbrugge, 1995
); these observations are in line with the findings of this study.
It is known that overweight women have a higher risk of developing OA due to increasing mechanical stress on joints (Hartz et al., 1986). In this cohort, the fact that overweight and obesity were more common in post-menopausal than in pre-menopausal women may be one of the reasons for the difference of symptom prevalence. However, the interaction of estrogen deficiency and genesis of osteoarthritis is not clear. Even the therapeutic effect of estogen therapy on osteoarthritis remains unclear.
Psychological conditions
Women also complained of abundant psychological symptoms. We did not find a correlation between menopause status and mood disturbances, in keeping with several previous cross-sectional and longitudinal studies (Matthews et al., 1990; Dennerstein et al., 1994
; Porter et al., 1996
) except that women 1 year after menopause experienced more frequent mood swings and sleep problems, again consistent with findings by others (O'Connor et al., 1994
; Kuh et al., 1997
).
The drop in estrogen has a direct impact on neurotransmitters in the brain, which, in turn, may lead to mood instability. However, this bio-hormonal interaction has been demonstrated mainly in studies on surgical menopause rather than in the natural situation (Sherwin and Gelfand, 1985). It is conceivable that some women who are more susceptible to the biological hormone changes may experience temporary mood swings during their menopause transition.
The higher rate of mood instability and sleeping problems during the first year after menopause may also be attributed to the domino effect of estrogen deficiency via the effect of night sweats on sleep patterns causing irritation, fatigue, and even depressed mood during the day. When controlling for vasomotor symptoms, one study revealed that the significant correlation between depressed mood and menopausal status disappeared (Collins and Landgren, 1994).
Hormonal intervention and women's health
Women of climacteric age often use HRT to relieve their symptoms. In this cohort, ~40% of women used HRT. Previous observations indicated that HRT users were generally healthier than non-users (Matthews et al., 1996; Collins and Landgren, 1997
). However, this did not seem to hold true in the present cohort. In fact, one of the prominent findings in this study was that the health status of HRT users was not superior to that of non-users. HRT users had more complaints of various symptoms than pre- and post-menopausal women. The reasons for the poor health profile among HRT users could be explained by several factors including: (i) prior depressed mood, (ii) clinical depression, or (iii) adverse effects of HRT.
Prior depressive mood
A prior depressive mood seems to be a major predictive factor for recurrence of depression during menopause (Avis et al., 1994). Women with a high psychological stress around the menopause often have past histories of pre-menstrual syndrome (PMS) and post-partum depression (Stewart and Boydell, 1993
) and we have reported that HRT users in our cohort had a higher rate of previous psychological problems than non-users (Li et al., 2000a
). These observations imply that some women are more vulnerable to hormone fluctuations and hence may be more inclined to use hormone treatment during their menopausal years.
Clinical depression
It has been reported that 50% of patients attending gynaecology clinics have significant emotional disturbance (Byrne, 1984) and that 45% met the criteria for either a major or a minor depression (Hay et al., 1994
). In this study, more than 50% of HRT users complained of depressed mood and 20% had experienced at least seven to nine of the listed psychological symptoms. Some of these women may well have reached the clinical major or minor depression levels and this is not expected to be improved by using conventional doses of HRT.
Adverse effects of HRT
Adverse effects of HRT may also be considered as one of the reasons for the higher symptomatology among HRT users. We found that several somatic symptoms, such as headache, chest pain, a cluster of gastrointestinal disorders, as well as psychological complaints, were more prevalent in HRT users than in non-users. This phenomenon could be a consequence of possible untoward effects by HRT, as most of these symptoms were reported also as negative effects by HRT in our previous report (Li et al., 2000a) and others have also observed gastrointestinal complaints to rise in peri- and post-menopausal women, particularly in HRT users (Triadafilopoulos et al., 1998
). Apart from being side-effects of HRT, the high frequency of gastrointestinal symptoms among HRT users may also be related to women's individual personality and psychological condition since these may affect such symptoms (Addolorato et al., 1998
; Ali et al., 2000
).
In conclusion, middle-aged women experience several physical and emotional symptoms, which may follow from interactions between biological changes and psycho-social life events. Ageing, alteration of the hormonal milieu and women's personality were the major contributors in this respect.
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Acknowledgements |
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Notes |
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References |
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Submitted on January 1, 2001; resubmitted on November 9, 2001; accepted on December 29, 2001.