Nighttime Hot Flashes Associated With Mild Depression

During menopause, women who experience more hot flashes at night are more likely to experience worsening mood.

A woman’s perceived, though not objective, number of nighttime hot flashes may be associated with mild depressive symptoms during menopause, as suggested by new data published in the Journal of Clinical Endocrinology & Metabolism.

Hadine Joffe, MD, MSc, of Brigham and Women’s Hospital and Dana Farber Cancer Institute at Harvard Medical School in Boston , and colleagues administered the gonadotropin-releasing hormone agonist leuprolide to healthy, premenopausal women to mimic the drop in estrogen levels experienced during menopause. To assess changes in mood, the researchers measured depressive symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) at baseline and after receiving 3.75 mg leuprolide daily for 4 weeks. Hot flashes were both self-reported and measured physiologically (ie, objectively).

A total of 29 healthy premenopausal women aged 18 to 45 years (mean age: 27.3 years) participated in the study. Estradiol levels decreased to 20 pg/mL after 2 weeks of treatment with leuprolide and remained suppressed at postmenopausal levels throughout the study, according to the researchers.

Study results showed that 20 participants (69%) developed hot flashes about 11 days after initiating leuprolide, with women reporting a median of 3.8 hot flashes per night and 3.6 per day. The proportion of hot flashes occurring during nighttime compared with daytime varied, however, with some participants experiencing most hot flashes during the day and others experiencing the majority at night. A median of 3 objectively measured hot flashes occurred per night.

In terms of mood, at baseline, mean MADRS score was 1.0 and mean BDI score was 0.9. Overall, mean MADRS score increased by 3.1 points after treatment (P =.005), although the researchers found considerable between-subject variability. For example, 24% of participants experienced a ≥5-point increase in MADRS score from baseline, whereas 38% experienced no change. One participant demonstrated clinically significant depression, with a score greater than 15 points. The researchers also noted that the sleep item on the MADRS accounted for 27% of each person’s total score.

Depressive symptoms appeared to increase in proportion with the number of perceived nighttime hot flashes (P =.006), according to univariate analyses. Each additional nighttime hot flash correlated with a 3.2-point (95% confidence interval, 1-5.4) increase in MADRS score from baseline. However, neither the number of objectively measured hot flashes (P =.11) nor the number of daytime hot flashes (P =.28) were associated with mood.

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Parallel analyses run using the MADRS subscore without the sleep item or the total BDI score as the dependent measures yielded similar results.

“When women were awake long enough to later recall nighttime hot flashes, that perception contributed to mood disturbance in women whose estrogen levels had fallen,” Dr Joffe said in a press release. “The association was independent of sleep disruption that the women experienced.”

The researchers also found that mood deterioration was associated with decreased sleep efficiency, an increase in time spent in light sleep (stage N1), the number of arousals during non-REM sleep, and the rate of transitions to wake and to stage N1 sleep (P <.045).

In adjusted models, the association remained for the perceived number of nighttime hot flashes, increases in arousals during non-REM sleep, time in light sleep, transitions to wake, and reduced sleep quality (P ≤.05).

Additionally, the researchers noted that ovarian suppression with leuprolide was likely linked to an adverse effect on sleep in some but not all participants, with wake time after sleep onset ranging from an additional 140.3 minutes to 22.8 fewer minutes spent awake.

“The results of our research suggest menopausal women who report experiencing nighttime hot flashes and sleep disruption should be screened for mood disturbances,” Dr Joffe said. “Any treatment of mood symptoms in this population also should incorporate efforts to address sleep and nighttime hot flashes.”

The researchers highlighted several limitations, including the small sample size due to the study’s experimental design, evaluation of short-term effects of ovarian suppression, and the fact that while the researchers were able to offer a model for surgical menopause that may be applicable to natural menopause, the results may not be generalizable to women who experience a more gradual decrease in estradiol during the transition.

Disclosures: Several researchers report relationships with one or more of the following: Merck, Noven, Mitsubishi Tanabe, NeRRe Therapeutics, Takeda, Jaymac Pharmaceuticals, DSM Nutritionals, GOED, Otsuka, Lundbeck, Genentech, JDS Therapeutics, Sage, Sunovion, Janssen/Johnson & Johnson, Apnicure Inc, Philips Respironics, NightBalance, Center for Integration of Medicine and Innovative Technology, Department of Defense, Milton Family Foundation, American Sleep Medicine Foundation, Servier, Foramis, GrandRounds, American Board of Internal Medicine, Marathon Pharmaceuticals, Alkermes Inc, AstraZeneca, Bristol-Myers Squibb/Otsuka, Ortho-McNeil, Foramis, Cephalon Inc, Lundbeck, Noven, and JDS Therapeutics. One researcher also has a patent pending for a home sleep monitoring device.


  1. Joffe H, Crawford SL, Freeman MP, et al. Independent contributions of nocturnal hot flashes and sleep disturbance to depression in estrogen-deprived women. J Clin Endocrinol Metab. 2016;101:3847-3855. doi: 10.1210/jc.2016-2348.
  2. Nighttime Hot Flashes May Spark Mild Depression [press release]. Washington, DC: Endocrine Society News Room; September 28, 2016. Accessed October 3, 2016.