Logistic regression was used to determine predictors of symptoms in late perimenopause. Women who reported symptoms in early perimenopause were excluded. Explanatory variables associated with developing symptoms at the P = .10 level of significance were retained for model building. A backward stepwise elimination method based on the likelihood ratio test and the significance level of P = .05 was used to determine a parsimonious model. Levels of follicle-stimulating hormone and E2 were log-transformed to reduce the influence of extreme points. Breast soreness-tenderness was not included because it was not introduced until the third year of follow-up.
The proportion of women who reported a particular symptom as bothersome in the previous 2 weeks for each category of menopausal status is given in Table 2.
By postmenopause, almost all women were reporting at least one symptom, and most were reporting five or more. The average total number of symptoms increased by 17%, from 4.2 to 4.9 (P < .001).
Figure 1 summarizes changes; 0 indicates no change. Severity scores for breast soreness were reduced in late perimenopause and postmenopause compared with breast soreness scores before and in early perimenopause (P < .001). Symptom severity of trouble sleeping (P < .05), vaginal dryness (P < .001), night sweats (P < .01), and hot flushes (P < .001) were all increased in late perimenopause and postmenopause. No other symptom showed any significant change with menopausal status at P < .05.
Sample proportions of symptom reporting were calculated for each of the six categories of menopausal status (Table 2). The magnitude between categories was assessed. The transition of most change was clearly between early and late perimenopause for hot flushes (+27%), night sweats (+17%), vaginal dryness (+17%), and breast soreness-tenderness (−21%). The symptom of trouble sleeping appears to follow a more gradual increase across menopausal categories (+6% between early and late perimenopause).
The number of women who reported five or more symptoms increased by 14% between early and late perimenopause (P < .05). Table 3 lists variables related to hot flushes, night sweats, vaginal dryness and trouble sleeping in late perimenopause in women free of those symptoms in early perimenopause.
The findings of the present study were consistent with those of previous studies that middle-aged women were very symptomatic according to a checklist. Vasomotor symptoms were not the most frequently reported until 3 years after final menstrual periods. Our findings were similar to those of Avis et al,1 who reported the percentages of Massachusetts women who had five or more core symptoms as 23% for premenopausal women, 35% for perimenopausal women, and 32% for naturally postmenopausal women. Our figures for the same groups using the same set of symptoms were 22%, 22%, and 36%, respectively. In this Australian study, only a few women reported no or only one symptom, and that declined as women went through the transition, whereas the number of symptoms reported increased by 17%.
There were some limitations in our study design, which might have caused underestimation of symptom prevalence for this population. Volunteers for the longitudinal phase of the study differed at baseline from nonparticipants in certain variables (self-rated health, education level, work, exercise participation) that were shown in our own baseline cross-sectional analysis to be related to symptom reporting.2 During the longitudinal study, there also was attrition related to women taking HRT. In the second year of follow-up, we asked about reasons for HRT use among 108 of 438 women who began the longitudinal study, who were then current users of HRT. The most common reasons were hot flushes, sweats (45%); moods, depression, anxiety (16%); headaches (4%); prevention of osteoporosis and heart disease (22%), bleeding problems (7%); no reason or non-classified reason (6%). Thus, most who took HRT did so because of bothersome symptoms, which would be expected to lower the point prevalence of symptoms, but should not affect the aim of this paper, which was to measure change in symptoms during the natural menopausal transition.
The prevalence of symptom reporting might be related to the order in which symptoms were presented in the checklist. Four of nine symptoms reported as bothersome by 30% or more of women were among the first nine symptoms presented in the checklist, and their high prevalence might indicate early position on the checklist, which should be considered when comparing prevalence rates from different studies. The position of all symptoms except lack of energy was held constant during the baseline and 7 subsequent years, so we were able to detect reliably change in prevalence of symptom reporting, our aim.
One hundred seventy-two women (all premenopausal at baseline) contributed to the analysis, but not all supplied data points for each menopausal phase, as shown in Table 2. That does not indicate subject attrition but does show that it can take many years to observe women through menopausal transition.
In the current study, fieldworkers verified women's self-reports of 3 months' or more amenorrhea or of having reached final menstrual period against menstrual calendars recorded daily. Late perimenopause and date of final menstrual period from which postmenopause was calculated were ratified objectively. There was no such ratification of women's reports of whether or not there had been changes in their menstrual frequency over the prior 12 months. Our earlier21 and current results suggest that premenopause and early perimenopause can be combined.
Regarding which symptoms truly relate to endocrine change rather than aging, this study found that only vasomotor symptoms, breast tenderness, and vaginal dryness changed significantly with menopause. Many studies also noted a marked temporal relationship between vasomotor symptoms and menopause.23 We confirmed other studies that found vasomotor symptoms significantly elevated in late perimenopause and remained elevated for some years.11,24–26 Several studies, including our earlier factor analysis,2 found an association between hot flushes and night sweats,27 and some an association between those vasomotor symptoms and insomnia.28
The present study confirmed that hot flushes contribute to reported trouble sleeping, which appeared to be related to depression (low well-being) or busy lifestyle. The pattern of change seen for trouble sleeping was different from other symptoms that changed with menopause, showing a small, gradual change rather than a large incremental one. This suggesting that the change in trouble sleeping was not a direct effect of hormonal changes of menopause.
We found a five-fold increase in the prevalence of vaginal dryness as women advanced through menopause (see also Oldenhave and Jaszmann25). Despite that, most observational studies neglected to include that symptom in their checklists. Breast soreness-tenderness (mastalgia), the prevalence of which we found decreased by more than half, was also absent from most checklists in population-based studies of menopause. It is not clear why those two important symptoms were omitted because both have been known for many years to be related to menopause (Neugarten and Kraines29) and in clinical trials were related to estrogen-progestin levels.5,30 We suggest those symptoms should be included in future studies.
Population-based studies have been less consistent on the relationship of psychologic symptoms to menopause. Some cross-sectional studies24,25 reported small but transient increases in non–vasomotor symptoms in perimenopause. We found increased symptoms such as nervous tension and sadness in late perimenopause, but the increase was not statistically significant. When validated mood scales were used in longitudinal studies,7,19 no significant increase in depression or negative moods was directly associated with menopause.
On the effect of physical, psychosocial, and lifestyle factors in those symptoms related to menopause, cross-sectional studies explored associations between symptom experience and a wide range of other factors. Cross-sectional studies that incorporated hormone levels found vasomotor symptoms associated with decreased E231,21 and increased follicle-stimulating hormone.31
Longitudinal population-based studies are best able to establish likely relationships between symptoms and physical, psychosocial, and lifestyle factors. The present study is one of few longitudinal population-based studies to include hormone levels. We found that E2 was the best predictor for vasomotor symptoms. The development of hot flushes in late perimenopause was increased for lower levels of E2. A particularly high odds ratio (OR) (20.5) was observed for the middle E2 category, 30–100 pmol/L; however, the OR was not significantly greater than the last category, less than 30 pmol/L. One interpretation is that hot flushes are precipitated by falling levels of E2, so are closely related to the phase of late perimenopause when E2 levels are changing. Length of smoking (in pack-years) contributed to vasomotor symptoms of hot flushes, and smoking has adverse effects on ovarian function.33 Although increased vaginal dryness was associated with menopause, logistic regression did not find a relationship between it and hormone levels, and it showed a different pattern in relation to menopause. Vaginal dryness was the only symptom that appeared to increase exponentially with time from the late perimenopause, indicating that it was a later consequence of hormonal changes during menopause. Women with tertiary education were less likely to report that symptom, suggesting that increased knowledge might be related to factors that helped women with it maintain sexual function.
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