Menopause-related sleep disturbances affect temper, metabolism

Menopause-related sleep fragmentation has downstream effects on mood, daytime wellbeing and metabolism, even when women meet recommended guidelines for normal sleep duration, according to a speaker.

Sleep interruption among midlife women is highly prevalent during the menopause transition and after, Hadine Joffe, MD, MSc, executive director of the Connors Center for Women’s Health and Gender Biology, director of the Women’s Hormone and Aging Research Program and the Paula A. Johnson Professor of Psychiatry in the Field of Women’s Health at Brigham and Women’s Hospital and Harvard Medical School, said during a plenary symposium at the North American Menopause Society Annual Meeting. Menopause-related sleep disturbances, primarily caused by vasomotor symptoms, are characterized by repeated middle-of-the-night awakenings. This wake time after sleep onset, or WASO, is associated with multiple sleep stage transitions and cortical arousal, even in the setting of normal total sleep time.

Joffe is executive director of the Connors Center for Women’s Health and Gender Biology, director of the Women’s Hormone and Aging Research Program and the Paula A. Johnson Professor of Psychiatry in the Field of Women’s Health at Brigham and Women’s Hospital and Harvard Medical School.

“When we see these women with a reasonable amount of sleep, but their sleep is disrupted and the [sleep] quality is poor, their daytime mood, wellbeing and metabolism may be affected,” Joffe said. “The public health message to get enough sleep is out there, and it is hugely important, but we have not yet attended to the priority for women across menopause: Fix your WASO. This is the most important problem for the midlife women we take care of.”

Role of hot flashes

Menopausal hot flashes tend to occur during wakeful periods at night or during periods of light sleep, Jaffe said; however, data show nighttime awakenings after sleep onset occur even in the absence of hot flash events.

“If [a woman] is having two or three hot flashes, she is likely having terrible sleep the rest of the night,” Joffe said.

Despite repeated awakenings, total sleep time is not necessarily shortened across the menopause transition or due to vasomotor symptoms, Joffe said. It is unclear if documented increases in total sleep time observed after menopause mark an improvement in sleep or a compensatory strategy due to poor quality sleep, she said.

“This is important, because insomnia is often associated with a shortening of total sleep time, but for midlife women, it is not about short sleep,” Joffe said. “They are getting about 6 and a half to 7 hours of sleep, and in fact, there may be more total sleep time after menopause. They get more total sleep time, but for those with hot flashes, the quality of the sleep is bad.”

Along with an increase in fragmented sleep, the rate of obesity also increases markedly among women aged 40 years and older, and body fat increases among approximately half of women during and after menopause, Joffe said. Estradiol withdrawal is hypothesized to be the primary driving factor for body fat gain, but visceral adipose tissue accrues in perimenopause even before the onset of hypoestrogenism, she said.

“Notably, the visceral adiposity accumulates before the final menstrual period, even when estradiol is still intermittently produced,” Joffe said. “Given how common sleep disturbances are and that short sleep time is known to induce metabolic changes, we are investigating whether the menopause-pattern sleep fragmentation is contributing to this propensity toward weight gain.”

Cross-sectional data from the SWAN study show worse sleep, assessed via electroencephalogram (EEG), is associated with metabolic syndrome, and worse multi-dimensional sleep is associated with higher adiposity among menopausal women. Sleep fragmentation perturbs the hypothalamic-pituitary-adrenal axis, possibly underlying adverse health outcomes in women during and after the menopause transition.

Additionally, nutrient utilization data, assessed via indirect calorimetry, show even if a woman maintains a normal diet, sleep fragmentation and estradiol withdrawal shift metabolism from fat to carbohydrate oxidation, contributing to a propensity to gain weight even in the context of normal total sleep time.

“When we are trying to understand the central role of menopause-related sleep disruption in midlife, it is all about interruption and fragmentation,” Joffe said.

Strategies for improving sleep

Experimental approaches suggest psycho-physiological relaxation and stress reduction techniques can improve sleep among midlife women, Fiona C. Baker, PhD, director of the Human Sleep Research Program of SRI International, said during the symposium. Women with insomnia have increased EEG-measured arousal and lack recovery in vagal activity in anticipation of stress, whereas cardiac stress reactivity is blunted in women with insomnia, Baker said. SWAN data also show chronic stress predicts poor sleep.

In a pilot study published in the Journal of Behavioral Medicine in October 2019, researchers evaluated the effect of a novel, acute behavioral experimental manipulation —combined immersive audio-visual relaxation and biofeedback — for 16 women with menopausal insomnia. Women underwent the biofeedback intervention across the falling asleep period and a night with no pre-sleep arousal manipulation on two random nights. Researchers found that while using immersive audio-visual respiratory biofeedback, overall heart rate variability increased and heart rate was reduced by a mean 5 bpm (P < .01), reflecting downregulation of autonomic pre-sleep arousal, compared with no manipulation. Heart rate continued to be lower during sleep, and participants had fewer awakenings and sleep stage transitions on the manipulation night compared with the control night (P < .05).

Fiona C. Baker

“This novel pre-sleep relaxation/biofeedback technique not only improved sleep, but also led to the women feeling less stressed and more alert the following morning,” Baker said.

Clinical trial data also suggest cognitive behavioral therapy for insomnia, which incorporates relaxation techniques, improves sleep quality and reduces sleep-related interference from hot flashes in peri- and postmenopausal women with insomnia, Baker said.

“There is a lot we are learning about understanding insomnia that develops during the menopause transition, the potential role of stress and hyperarousal,” Baker said. “We are beginning to see there might be ways to use behavioral techniques targeting hyperarousal, but clearly more work is needed to see if we can effectively use these techniques to reduce stress, lower autonomic arousal and improve sleep.”

References:

De Zambotti M, et al. J Behav Med. 2019; doi:10.1007/s10865-019-00020-9.

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North American Menopause Society