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Nighttime hot flashes, sleep disruption linked to mild depression in estrogen-deprived women
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Healthy, premenopausal women exposed to a temporary decline in estradiol were more likely to experience mild depressive symptoms if they perceived nighttime hot flashes along with sleep disruption, according to study results.
“We had hypothesized that sleep disruption alone would explain the widely observed association between [hot flashes] and mild mood disturbance in surgical and natural menopause,” Hadine Joffe, MD, MSc, associate professor of psychiatry at Harvard Medical School, and colleagues wrote. “However, we observed a strong, independent effect of subjectively reported nighttime [hot flashes] on the development of depressive symptoms. Because objectively measured nighttime [hot flashes] were not linked with mood changes, our data suggest that the extent of alertness and/or awakening for long enough to consciously experience and recall these nocturnal symptoms may be integral to this observation.”
Joffe and colleagues analyzed data from 29 premenopausal women with regular menses, but without sleep disorders or hot flashes (mean age, 27 years; 65.5% white; 65.5% never married; 70% college graduates; 65.5% full- or part-time employed). After completing baseline mood and sleep questionnaires, all women received 3.75 mg per day of the gonadotropin-releasing hormone agonist leuprolide in the midluteal phase. Researchers measured serum estradiol, luteinizing hormone and follicle-stimulating hormone levels to confirm ovarian suppression. Women used diaries to self-report hot flashes twice daily (morning and nighttime) and sleep diaries to measure bedtime, final wake-up time, time to fall asleep, number of awakenings and wake time after sleep onset. Researchers reassessed depressive symptoms and sleep parameters at 4 weeks; physiological hot flashes were recorded objectively using a skin-conductance monitor. Primary outcome was change in depressive symptoms from baseline to 4 weeks using the Montgomery-Asberg Depression Rating Scale (MADRS; range, 0 to 60; higher score signaling greater depressive symptoms). Researchers used linear regression models to assess the association between the frequency of hot flashes and sleep parameters on changes in depressive symptoms.
Within the cohort, 20 women (69%) reported developing hot flashes beginning on average 11.1 days after receiving leuprolide; median number of reported hot flashes was 3.8 each night and 3.6 each day.
In univariate analysis, researchers found the sleep parameters, including increases in light sleep, number of transitions to wake, non-REM arousals, subjective sleep quality and reductions in perceived sleep efficiency, all predicted worsening depressive symptoms (P < .045). The number of self-reported nighttime hot flashes was also associated with worsening depressive symptoms (P = .006); there was an observed mean increase of 3.2 points on MADRS from baseline to 4 weeks for every additional nighttime hot flash reported (95% CI, 1-5.4). However, there was no association observed between objectively measured nighttime hot flashes (P = .11) or self-reported daytime hot flashes and change in mood (P = .28).
In bivariate models, results for self-reported nighttime hot flashes persisted after adjustment for changes in objectively measured sleep efficiency, time spent in stage N1 sleep, increases in non-REM arousals and transitions to wake (P .05). Nighttime hot flash frequency remained a predictor of worsening depressive symptoms after further adjustment for changes in self-reported sleep efficiency, wake time after sleep onset, sleep-onset latency and sleep questionnaire scores.
“Both sleep disruption and nighttime hot flashes, but not daytime hot flashes, independently contribute to mood disturbance in women whose estrogen levels have fallen during menopause,” Joffe told Endocrine Today. “These results suggest that women reporting nighttime hot flashes and sleep disruption should be screened for mood disturbance, and that treatment of mood disturbance in this population should include therapies that improve sleep interruption as well as nighttime hot flashes.” – by Regina Schaffer
For more information:
Hadine Joffe, MD, MSc, can be reached at Brigham and Women’s Hospital, 75 Francis St., Thorn 1111, Boston, MA 02115; email: hjoffe@partners.org.
Disclosure: Joffe reports receiving grant support from Merck and serving as a consultant or adviser for Merck, Mitsubishi Tanabe, NeRRe Therapeutics and Noven.
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