UMass Chan Medical School Faculty Publications


Independent Contributions of Nocturnal Hot Flashes and Sleep Disturbance to Depression in Estrogen-Deprived Women

UMMS Affiliation

Division of Preventive and Behavioral Medicine, Department of Medicine

Publication Date


Document Type



Endocrinology, Diabetes, and Metabolism | Psychiatry and Psychology | Women's Health


CONTEXT: Women are at increased risk for mood disturbance during the menopause transition. Hot flashes (HFs), sleep disruption, and fluctuating estradiol levels correlate with menopause-associated depression but co-occur, making cause and effect relationships difficult to disentangle.

OBJECTIVE: Using a GnRH agonist (GnRHa) experimental model, we investigated whether depressive symptoms are associated with HFs and/or are explained by concomitant sleep fragmentation in the absence of estradiol fluctuation.

DESIGN AND INTERVENTION: Depressive symptoms, objective polysomnographic sleep parameters, subjective sleep quality, serum estradiol, and HFs were assessed before and 4 weeks after open-label depot GnRHa (leuprolide 3.75-mg) administration.

SETTING: Academic medical center.

PARTICIPANTS: Twenty-nine healthy nondepressed premenopausal volunteers (mean age, 27.3 years).

RESULTS: Serum estradiol was rapidly and uniformly suppressed. HFs developed in 69% of the subjects. On univariate analysis, worsening of mood was predicted by increases in time in light sleep (stage N1), number of transitions to wake, non-REM arousals, subjective sleep quality, and reductions in perceived sleep efficiency (all P < .045), as well as the number of nighttime (P = .006), but not daytime (P = .28), HFs reported. In adjusted models, the number of nighttime HFs reported, increases in non-REM arousals, time in stage N1, transitions to wake, and reduced sleep quality remained significant predictors of mood deterioration (P

CONCLUSIONS: Depressive symptoms emerged after estradiol withdrawal in association with objectively and subjectively measured sleep disturbance and the number of nighttime, but not daytime, HFs reported. Results suggest that sleep disruption and perceived nighttime HFs both contribute to vulnerability to menopause-associated depressive symptoms in hypoestrogenic women.

DOI of Published Version



J Clin Endocrinol Metab. 2016 Oct;101(10):3847-3855. Epub 2016 Sep 28. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of clinical endocrinology and metabolism

PubMed ID