In this randomized controlled trial of an intensive behavioral weight loss intervention vs a structured health education program in women who were overweight or obese and had urinary incontinence, women with bothersome hot flushes who were randomized to the intensive intervention reported significantly greater improvement in flushing bothersomeness after 6 months compared with controls. Improvements in weight, BMI, and abdominal circumference (but not self-reported physical activity, calorie intake, overall physical and mental functioning, or measured blood pressure) were associated with improvement in bothersome hot flushes in this population. The effect of the intensive intervention on bothersome hot flushes was partly but not completely explained by improvements in weight, BMI, and abdominal circumference.
Multiple observational studies have documented that women with a higher BMI report more frequent or severe hot flushes during menopause, but the mechanisms underlying this association are poorly understood. Women who are overweight or obese are known to have higher circulating estrogen levels as a result of adipocyte-based aromatization of estrone and conversion of androstenedione to estrone, which might be expected to decrease rather than increase the severity of their menopausal symptoms. Recently proposed explanations for the observed association between BMI and hot flushes have included greater insulation against heat loss owing to increased peripheral fat,23
abnormal sympathetic neural activity associated with increased visceral fat,24
and alterations in leptin and other cytokines expressed by adipocytes that affect thermoregulatory function.25
Alternatively, women who are overweight or obese may differ in psychological or social factors that affect their subjective experience of and willingness to report symptoms such as hot flushes.
Our findings indicate that women who are overweight or obese and experience bothersome hot flushes may also experience improvement in these symptoms after pursuing behavioral weight loss strategies; however, improvements in weight or body composition may not be the only mediators of this effect. Given that the behavioral intervention in PRIDE could not be masked, 1 possible explanation for the apparent incomplete mediation of the intervention effect by weight loss is that participants’ reporting of their symptoms at 6 months was influenced by knowledge of their treatment assignment. It is notable, however, that women randomized to the intensive intervention did not report greater improvement in other quality-of-life outcomes, such as physical or mental functioning as measured by the SF-36, compared with controls, even though these were also self-reported outcomes with the potential to be influenced by knowledge of treatment assignment. Furthermore, because the primary outcome of the PRIDE trial was change in frequency of urinary incontinence rather than improvement in menopausal symptoms, participants were given no special counseling about hot flushes and had no particular reason to expect that their flushing symptoms would be influenced by the study intervention.
Several previous studies of physical activity interventions have reported conflicting effects on menopausal symptoms, with one nonrandomized trial suggesting that physical activity is protective against hot flushes,26
another randomized trial suggesting that physical activity may worsen hot flushes,10
and other studies reporting no effect on flushing.27–29
Prior interventional studies were not confined to women with hot flushes at baseline, however, and detection of intervention effects tended to be limited by the low prevalence of baseline symptoms. In our study, we did not find that increased self-reported physical activity was associated with either improvement or worsening in bothersome flushing among women who were symptomatic at baseline, and change in physical activity did not explain intervention effects. Physical activity may be overestimated when assessed by self-report,30
however, and it is possible that more objective or precise quantification may have yielded a different pattern of associations with flushing symptoms.
Limited previous research has explored the role of calorie consumption and other dietary factors in influencing women’s experience of hot flushes.31–33
Although we did not find an association between total calorie intake and self-reported bothersome hot flushes in our study, it is possible that the effects of the PRIDE intervention on hot flushes may be mediated by changes in consumption of specific nutrient components or the timing of meals, and further research involving more detailed analysis of dietary habits may be helpful in addressing this issue.
Several other limitations of this research should be noted. First, participants in PRIDE had urinary incontinence at baseline, which may limit the generalizability of our findings to women without incontinence. Urinary incontinence is associated with decreased overall health and depression in women, which have the potential to influence the perceived bothersomeness of other health-related symptoms. To date, however, epidemiologic research has not supported an association between incontinence and menopause in women,34
and in the PRIDE population itself, we found no evidence that women with more bothersome hot flushes had more severe or frequent incontinence at baseline.
Second, hot flushes were assessed by a single self-report measure emphasizing the bothersomeness of symptoms during the past month, which may be vulnerable to memory and reporting biases and which may reflect not only the frequency of symptoms but also the effect of symptoms on women’s sense of well-being. Additional research using more detailed self-report measures of flushing frequency, such as hot-flush symptom diaries, may be helpful in confirming these findings and in assessing for possible differential effects on flushing frequency vs bothersomeness.
Finally, a greater proportion of women were lost to follow-up in the control than in the intervention group. If women who were lost to follow-up experienced greater improvement in hot flushes than those who remained in the study, this could result in overestimation of the main intervention effect on flushing in these analyses. Nevertheless, participants who drop out of weight management trials are often those who experience less improvement in weight or associated symptoms, and thus we might expect the greater loss to follow-up in the control group to bias our results toward the null.
From a clinical perspective, our findings suggest that women who are overweight or obese and have bothersome hot flushes may be counseled that behavioral weight loss efforts may decrease the burden of their symptoms. Further research is needed to assess for other biophysiologic factors associated with weight loss that may influence these symptoms in women who are overweight or obese. It should also evaluate whether women’s perceptions of self-management success while attempting to change their lifestyle or lose weight may modify their experience of these symptoms.