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Adverse effects of induced hot flashes on objectively recorded and subjectively reported sleep: results of a gonadotropin-releasing hormone agonist experimental protocol

Joffe, Hadine MD, MSc1; White, David P. MD2; Crawford, Sybil L. PhD3; McCurnin, Kristin E. BS4; Economou, Nicole BA1; Connors, Stephanie BS1; Hall, Janet E. MD4

doi: 10.1097/GME.0b013e31828292d1
Original Articles

Objective The impact of hot flashes on sleep is of great clinical interest, but results are inconsistent, especially when both hot flashes and sleep are measured objectively. Using objective and subjective measurements, we examined the impact of hot flashes on sleep by inducing hot flashes with a gonadotropin-releasing hormone agonist.

Methods The gonadotropin-releasing hormone agonist leuprolide was administered to 20 healthy premenopausal volunteers without hot flashes or sleep disturbances. Induced hot flashes were assessed objectively (skin conductance monitor) and subjectively (daily diary) during 1-month follow-up. Changes from baseline in objective sleep quality (actigraphy) and subjective sleep quality (Pittsburgh Sleep Quality Index) were compared between women who developed and women who did not develop objective hot flashes and, in parallel analyses, subjective hot flashes.

Results New-onset hot flashes were recorded in 14 (70%) women and reported by 14 (70%) women (80% concordance). Estradiol was universally suppressed. Objective sleep efficiency worsened in women with objective hot flashes and improved in women without objective hot flashes (median decrease, 2.6%; median increase, 4.2%; P = 0.005). Subjective sleep quality worsened more in those with subjective hot flashes than in those without subjective hot flashes (median increase in Pittsburgh Sleep Quality Index, 2.5 vs 1.0; P = 0.03). Objective hot flashes were not associated with subjective sleep quality, nor were subjective symptoms linked to objective sleep measures.

Conclusions This experimental model of induced hot flashes demonstrates a causal relationship between hot flashes and poor sleep quality. Objective hot flashes result in worse objective sleep efficiency, whereas subjective hot flashes worsen perceived sleep quality.

From the 1Center for Women’s Mental Health, Department of Psychiatry, Massachusetts General Hospital, and 2Division of Sleep Medicine, Department of Internal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; 3Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; and 4Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Received August 24, 2012; revised and accepted December 11, 2012.

Funding/support: This work was supported by grant 5R01MH082922 (H.J.) and by the Massachusetts General Hospital Claflin Distinguished Scholar Award (H.J.).

Financial disclosure/conflicts of interest: H.J. has received grant support from Cephalon/Teva, serves on the advisory board of Noven, and is an unpaid consultant to Sunovion. D.P.W. has served as Chief Medical Officer for Philips Respironics, and currently serves as Chief Scientific Officer for Apnicure, Inc. All other authors have nothing to disclose.

Address correspondence to: Hadine Joffe, MD, MSc, Center for Women’s Mental Health, Massachusetts General Hospital, Suite 2000, Simches Research Building, 185 Cambridge Street, Boston, MA 02114. E-mail:

© 2013 by The North American Menopause Society.