21 September, 2015: 

Sleep disturbances increase with advancing age in both women and men although inherent gender differences are apparent. Older women take longer to fall asleep, have greater difficulty in staying asleep, have more daytime sleepiness, less stage 1 and stage 2 NREM sleep. Older women are also more likely to develop insomnia, the restless sleep syndrome and its accompanying sleep disturbances and have more obstructive sleep apneic symptoms compared to older men [1].

Comment

Human and animal studies have shown that gender and gonadal hormones do influence the circadian and homeostatic processes, although it remains unknown whether the gender-associated differences in the sleep/wake cycle are mediated by either, or both, of these processes. The studies addressing the subject are still speculative, but there is evidence that both the sex chromosomes and gonadal hormones are very likely to contribute to these differences at cellular, organic and systemic levels, whilst environmental, social and cultural influences are also likely to further impact on these differences in sleep [2].

Sleep is divided into two states, non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM), each with independent functions and controls. These are measured by recording the electrical field activity of large groups of cortical neurons and muscle cells via polysomnography. EEG tracings will depict the differences between the vigilance states, namely wakefulness, NREM sleep and REM sleep. Wakefulness is characterized by low-amplitude/high frequency activity. High frequency beta and gamma activity are not easily seen during this slow timescale.

In the human, NREM sleep begins in stage 1, characterized by a drowsy state and the prevalent EEG frequency beginning to slow, with strong alpha activity at posterior sites and theta activity at anterior sites, namely a pattern of low-voltage, mixed frequency waveforms with vertex sharp waves. This is the lightest state of sleep and the patient can be aroused by light touch or softly calling her name. Stage 1 comprises about 2–5% of a night’s sleep. Once entering stage 1, the fast conjugate eye movements of wakefulness are replaced by slow rolling/side-to-side eye movements.

Stage 2 has a similar basic pattern but it is characterized by the presence of K complexes and sleep spindles. K complexes are isolated, large-amplitude, slow EEG waves and sleep spindles are episodic bursts of fast EEG activity lasting approximately 0.5 s of 7–14 Hz. Stage 2 NREM sleep occupies about 45–55% of the night, with sleep deepening and a higher arousal threshold being required to awaken the patient.

Stage 3 is the beginning of high-voltage, slow-wave activity sleep and, when the latter constitutes at least of 20% of the EEG activity per page, it meets the criteria for stage 3 sleep, which constitutes about 3–8% of the cycle.

Stage 4, also known as slow-wave sleep, is characterized by strong delta-wave activity of very slow frequency 0.5–4 Hz, and constitutes 10–15% of the cycle; it has the highest arousal threshold. During REM sleep, the EEG returns to a profile similar to wakefulness, with low-amplitude and high-frequency activity.

Gonadal hormones play their major role from birth organizing the neural circuitry responsible for gender differences in behavior later in life contributing to sex-specific mating behavior, aggression, arousal and stress responses. Gender will influence brain anatomy, chemistry and function. The impact of the gonadal hormones is not only confined up to birth, but the functional differences will continue to develop and become more apparent as they continue to act on the differentiated circuitry across puberty and adulthood [3].

Women spend more time in bed and sleep longer, but report a poorer sleep quality than men. Women are significantly more likely to report sleep disturbances, including difficulty in falling asleep, staying asleep, early morning wakening or insufficient sleep compared to men. Women have less wakefulness after sleep onset, less stage 1 sleep, more slow-wave sleep and more slow-wave activity during their sleep compared to men. Women go to bed earlier than men from childhood to menopause when the sex differences are no longer seen.

Data in humans come from placebo-controlled trials where estrogen therapy was administered to peri- and postmenopausal women and the findings seem to suggest that estrogen decreases latency to sleep onset, decreases wakefulness after sleep onset, increases total sleep time and decreases rate of cyclic alternating patterns. Estrogens appear to affect REM sleep but not NREM sleep, enhancing REM sleep with increased time spent in REM sleep and decreased latency to REM sleep. Progesterone exhibits sleep-promoting effects that are generated by progesterone’s actions as a GABAa receptor agonist. Progesterone increases NREM sleep, and has actions that are very similar to those of benzodiazepines. Androgens appear to have a mild positive influence on REM sleep and seem to induce sleep apnea onset in men and women [4,5].

Increased daytime sleepiness amongst women probably arises from the fact that sleep in older women is characterized by frequent awakenings, arousals and less slow-wave sleep and which results in lighter and non-restorative sleep. The amount of use of hypnotics to overcome sleep disorders among women is greater than that amongst men. The possible reasons for the changes in sleep architecture that occur in men with aging, with specific reference to the significant decrease in stages 3 and 4 sleep, may be due to age-related reductions in cortical mass, cortical metabolism or neurotransmitter levels, changes in circadian rhythms or other neuro-endocrinological activity. Men will snore more than women, although older women will have more difficulty in falling and maintaining sleep, have more sleep arousals and sleep less over weekends [6]. Research in the world of sleep is still in its infancy, but accumulating evidence supports that inherent gender differences between older women and men are apparent. This will obviously require more research to define these differences [7].

Franco Guidozzi
Chief Specialist Obstetrician and Gynaecologist
Academic Head of Department
University of the Witwatersrand, Faculty of Health Sciences
South Africa

References

1. Guidozzi F. Sleep and sleep disorders in menopausal women. Climacteric 2013;16:214-19 http://www.ncbi.nlm.nih.gov/pubmed/23205646 

2. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr Opin Pulm Med 2006;12:383-9 http://www.ncbi.nlm.nih.gov/pubmed/17053485

3. Paul KN, Turek FW, Kryger MH. Influence of sex on sleep regulatory mechanisms. J Women’s Health 2008;17:1201-8 http://www.ncbi.nlm.nih.gov/pubmed/18710368 

4. Mallampali MP, Carter CL. Exploring sex and gender differences in sleep health: a Society for Women’s Health research report. J Women’s Health 2014;23:553-62 http://www.ncbi.nlm.nih.gov/pubmed/24956068 

5. Arber S, Bote M, Meadows R. Gender and socio-economic patterning of self-reported sleep problems in Britain. Soc Sci Med 2009;68:281-9 http://www.ncbi.nlm.nih.gov/pubmed/19026480 

6. Manber R, Baker FC, Gress JL. Sex differences in sleep and sleep disorders: a focus on women’s sleep. Int J Sleep Disorders 2006;1:7-15 

7. Guidozzi F. Gender differences in sleep in older men and women. Climacteric 2015;18:715-21 http://www.ncbi.nlm.nih.gov/pubmed/26249643