Of the women in the initial MWMHP longitudinal cohort, 291 participants remained after 13 years of follow-up (FU), giving a retention rate of 67% (). The majority of women who were lost to FU had refused further participation in the study and the most common reason given was that they were “too busy with other things”. In comparison to the women who dropped out of the study, those who remained until year 13 were better educated (Χ2
=31.9, df=l, p<0.001), had less negative attitudes towards the menopause (Χ2
=51.1, df=l, p<0.001), had better self-rated health (Χ2
=31.9, df=l, p<0.001) and were more likely to undertake physical activities (x2
=6.7, df=l, p=0.01). However they were also more likely to be either overweight or obese (Χ2
=16.9, df=2, p=0.002) and to drink larger quantities of alcohol (Χ2
=18.5, df=l, p<0.001).
Flow of participants from recruitment in the longitudinal cohort to analysis in this current study
For the present analysis, women who had bled within the last 12 months and thus were not postmenopausal, were excluded (n=19)39
, as were current users of HT (n=49), women who were not assessed for depressive symptoms in year 11 or 13 (n=21) and those women who did not provide blood samples for hormone measurements in both years (n=64). This analysis is therefore based on a sub-sample of 138 postmenopausal women. In a number of respects these women were significantly different from the women who were selectively excluded from this analysis.
Compared to the analysed sample, women not included in this analysis were more likely to have a lower educational level (Χ2=45.1, df=l, p<0.001), to be current smokers (Χ2=8.1, df=l, p=0.005), have poorer self-rated health (Χ2=29.1, df=l, p<0.001) and more negative attitudes towards the menopause (Χ2=72.2, df=l, p<0.001). The participants in this analysis however were more likely to consume larger quantities of alcohol (Χ2=16.7, df=l, p<0.001), have no daily physical activity (Χ2=10.4, df=l, p=0.001), to experience bothersome physical symptoms (Χ2=14.5, df=l, p<0.001), and daily hassles (Χ2=8.3, df=l, p=0.004) and to be either overweight or obese (Χ2=18.6, df=l, p<0.001). There were no significant differences in depression status, hormone levels or in terms of the other variables, between women included in this analysis and those who were not.
In year 11 of the study, the mean age of the women was 60.1, ranging from 55.9 to 66.8 years. Less than half of these women had a tertiary education, and there were few current smokers. The majority of women participated in regular physical activity and over a third claimed they were in good health. After the 2-year follow-up period, the prevalence of depression symptoms among these women was 25%. The year 11 socio-demographic, health and lifestyle characteristics of these women are summarised in . Women with depressive symptoms were significantly more likely to be younger or closer to the menopause, and were less likely to have participated in regular physical activity. They also differed in respect to other health-related factors such as their experience of hot flushes/night sweats or their number of daily hassles. These associations are in accordance with previous analysis based on the women recruited from the MWMHP 12
Socio-demographic, health and lifestyle characteristics of the participants according to their depression status in year 13.
The hormone levels of the women overall and according to their depression status are shown in . From year 11 to year 13, all women had an increase in FSH levels, with a median of increase of 8.3 IU/1. In year 11, 39.1% of women had the minimal detectable levels of estradiol and this increased to 51.5% at follow-up. Overall, 39.9% of the women had a decline in estradiol levels across the 2-year follow-up period, with a median change of 0pmol/l. In unadjusted analysis depressive symptoms were associated with higher levels of total estradiol in year 11, and there was a similar difference in free estradiol levels between depressed and non-depressed women, although this did not reach significance (). There were a higher percentage of depressed women who experienced a decline in estradiol levels over the 2-year period, and a large increase in FSH levels was significantly associated with depressive symptoms. There was no indication that the serum levels of either testosterone, FAI or SHBG were associated with depressive symptoms at follow-up (p>0.20) and thus they were not considered further in the analysis.
Serum hormone levels according to depression status in year 13.
Hormone levels and depressive symptoms in year 13
shows the results of the logistic regression analysis to determine whether levels of estradiol or FSH were associated with depressive symptoms over the 2-year follow-up. Initial analysis adjusting for only baseline depression score (model 1) suggested that a change in total estradiol or FSH levels was associated with the risk of depressive symptoms and there was also a trend for an association between depression and higher estradiol levels in year 11. Logistic models were then generated taking into account the covariates that a priori could potentially confound the association between depressive symptoms and hormone levels. Successive adjustment for age and BMI (model 2), and then with further inclusion of high alcohol consumption, number of years since menopause and hot flushes or night sweats (model 3), did not have a substantially effect on the results. After this multivariate adjustment, a 2-year decline in estradiol levels remained the strongest risk factor for depressive symptoms. Women whose estradiol levels dropped between year 11 and 13, had a 3.5-fold increased risk of having depressive symptoms in year 13. Likewise, changes in FSH levels also appeared to be associated with depression. The results suggest that women whose FSH levels increased by 9 IU/1, had more than 2-times the risk of depressive symptoms. The variables for the decline in estradiol, or the large increase in FSH were not associated with one another (Χ2=0.2, d.f=l, p=0.65), and therefore, an association with one of these measures, did not necessarily imply an association with the other.
Adjusted Logistic Regression models for depression in year 13.
Using these models as a basis, adjustment was made for the other covariates which were found to be associated with depression status in year 11 at the 20% significance level (). After the addition of living alone, physical activity, more negative attitudes towards the menopause or a higher number of daily hassles, to model 3, a decline in estradiol or a large increase in FSH levels, were still significantly associated with depressive symptoms (data not shown). On the other hand, we did not find a significant association between depression and absolute levels of FSH or estradiol, in year 11 or 13.
The same hormone variables were examined in secondary analysis, to determine whether absolute or changing hormone levels predicted incident cases of depression, among women without depressive symptoms in year 11 (CES-D<10). Similar results were obtained to those described above (data not shown). Once again, even after multivariate analysis, a decrease in estradiol levels over the follow-up period was significantly associated with incident depression (adjusted OR=3.80, 95%CI: 1.15–12.5, Χ2=4.8, df=l, p=0.03) and there was a trend for increased depression risk with a large increase in FSH levels (adjusted OR=3.21, 95%CI: 0.97–10.8, Χ2=3.6, df=l, p=0.06).