Hot flashes and sleep disruption contribute independently to the development of depression in menopause, judging from the findings of a recent study.
In that study, 29 premenopausal women, aged 18-45 years, received a single dose of the GnRH agonist leuprolide in order to induce hypoestrogenism and ovarian suppression for the study period. The women in the study had no history of primary sleep disturbances, low estrogen levels, or depression, according to Hadine Joffe, MD, director of the Women’s Hormone and Aging Research Program at Harvard Medical School, in Boston, and her associates.
All the study participants underwent baseline mood evaluation using both the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI). Existing sleep disturbances were ruled out at baseline with sleep diaries, questionnaires, and two ambulatory screening polysomnography (PSG) studies.
After 4 weeks of administration of leuprolide, depressive symptoms had developed among most of the women in the study. The mean MADRS score was 4.1, and overall, it was 3.1 points higher than it had been at baseline. One woman had a 15-point increase in her score, suggesting significant depression. The MADRS score increased by at least 5 points in 24% of the women and remained unchanged in 38%, reflecting variability among the women on the impact of leuprolide on depressive symptoms, the investigators reported (J Clin Endocrinol Metab. 2016 Sep 20. doi: 10.1210/jc.2016-2348).
Leuprolide universally suppressed estradiol to postmenopausal levels in the women within 2 weeks. Hot flashes developed in 20 (69%) women, with a median of 3.6 hot flashes during the day and 3.8 at night. The median number of objectively measured nighttime hot flashes per night was 3.
Changes to sleep patterns varied widely for each woman; for example, wake time after sleep onset ranged from an additional 140 minutes to 23 fewer minutes for one woman. There was a correlation between the number of subjectively reported nighttime hot flashes with increased sleep fragmentation as measured by PSG. The number of reported nighttime hot flashes was associated with an increase in depressive symptoms that was disproportionate to the number of nighttime hot flashes reported, according to the findings of a univariate analysis. The number of daytime hot flashes had no such effect.
In light of these findings, Dr. Joffe and her associates urged clinicians to screen women who report nighttime hot flashes and sleep interruption for mood disturbance. “Treatment of those with menopause-related depressive symptoms should encompass therapies that improve sleep interruption as well as nocturnal [hot flashes],” they wrote.
The study was sponsored by the National Institute of Mental Health. Dr. Joffe has received grant support from Merck and has served as a consultant/adviser for Merck, Mitsubishi Tanabe, NeRRe Therapeutics, and Noven.