Properly identifying and managing sleep disturbances during menopause can improve women’s overall quality of life.

Mrs XYZ is a 47-year-old female schoolteacher with three children. She used to be a good sleeper all her life; however, over the past 2 years, she has been complaining of unrefreshed sleep, daytime sleepiness, and fatigue. She wakes up several times at night, feeling very hot all over her body, and wakes up to use the bathroom two to three times a night. She has difficulty concentrating at work, and is seeking help for her problems.

This story is probably told by 5,000 women who enter menopause every day in the United States. This case highlights a common complaint encountered during menopause and its transition. It is no surprise considering that the prevalence of sleep disturbances increases by 50% to 100% for perimenopausal and postmenopausal women compared with premenopausal women.¹

Menopause is a natural part of the aging process. According to the World Health Organization, menopause is defined as the permanent cessation of menstrual periods that occurs naturally. Natural menopause is recognized after 12 consecutive months without menstrual periods that are not associated with a physiologic (lactation) or pathologic cause. In the United States, most women experience menopause between 40 and 58 years of age, with a median age of 52.²

Menopause heralds a constellation of distressing symptoms, which play havoc with the body. The symptoms linked to menopause are: sleep disturbances, hot flashes, night sweats, and vaginal dryness. In addition, a woman may have painful intercourse, mood and cognitive problems, somatic symptoms, urinary incontinence, and bleeding problems.²

In this article, we have briefly outlined common causes of sleep disturbance and its management in perimenopausal women.

Sleep and Menopause
Women report the most sleeping problems from perimenopause to postmenopause. Factors associated with difficulty sleeping in middle-aged women are: menopausal status (late perimenopause), oophorectomy (removal of the ovary) without hormone replacement, Caucasian ethnicity, higher education, vasomotor symptoms, psychosocial symptoms, increase in perceived stress, lower quality of life, less physical activity, smoking, and arthritis.³

Generally, postmenopausal women are less satisfied with their sleep and as many as 61% report insomnia symptoms.⁴ The National Sleep Foundation has reported that 20% of menopausal and postmenopausal women sleep less than 6 hours per night during the workweek, while only 12% of premenopausal women (with the exception of pregnant women) sleep less than 6 hours.⁵ Snoring has also been found to be more common and severe in postmenopausal women. The prevalence of clinically defined sleep apnea—apnea/hypopnea index >10 plus the presence of daytime symptoms including daytime sleepiness, hypertension, or some other cardiovascular symptom—for premenopausal women was 0.6% compared to 1.9% for postmenopausal women.⁶

Data on self-reported symptoms in older women reveal the following problems:

• increased latency to sleep onset
• increased nighttime awakenings
• nighttime waking episodes are longer
• increased fragmentation of sleep
• increased daytime sleepiness and fatigue.¹

Impaired sleep can lead to difficulty concentrating at work, memory problems, anxiety, and overall poor quality of life. There are important implications for mood, behavior, and cognitive performance.

Possible Etiologies Of Sleep Disturbance
• Vasomotor Symptoms: Poor sleep has been attributed to endocrine changes and only secondarily to psychological factors.⁷ One particularly disturbing symptom arising due to low estrogen levels is hot flashes, which affects 75% to 85% of women around menopause.⁴ Prior to hot flashes, the body temperature rises and is accompanied by an awakening. Hot flashes last an average of 3 minutes leading to less sleep efficiency. While total sleep time may not suffer, sleep quality does. Hot flashes may lead to frequent awakenings and sleep fragmentation resulting in daytime fatigue.

• SDB and Snoring: These may be at least partially due to metabolic/hormonal factors. Studies⁷ have examined the role of progestational hormones in sleep apnea. The level of awake genioglossus EMG is higher in the luteal phase, followed by the follicular phase, and is lowest in postmenopausal women. Progesterone levels fall after menopause, and progestogens have been shown to stimulate ventilation during the luteal phase. Thus, these patients may have decreased ventilatory drive and hypotonia in pharyngeal muscles due to low levels of progesterone. This can further deteriorate during deep stages of sleep resulting in apneic symptoms.

• Increased Obesity: Whether this is a specific menopausal effect or simply reflects aging is unclear⁷; however, this increasing central obesity may explain the association between menopause and the prevalence of sleep apnea.

• Nocturia: This is another problem that can cause multiple nighttime awakenings as well as cause the quality of sleep to suffer. This could be an age-related problem vs menopause. Lin et al⁸ have demonstrated that occurrence of nocturia was significantly higher in the elderly age group.

• Depression: Insomnia seen in menopausal women may well be due to concurrent psychopathology, with the most common being depression. The single strongest risk factor of chronic insomnia is depression followed by female gender. Kloss et al9 have shown that self-report ratings of depressive symptoms, trait anxiety, hot flashes, and dysfunctional beliefs and attitudes about sleep significantly correlated with poor sleep quality. It may also be possible that the primary sleep disturbance gives rise to depression. This highlights the interplay between physiological and psychological mechanisms among perimenopausal women.

• RLS and PLMD: The prevalence of these disorders increases with age and can be contributory to the sleep problems in middle-aged women.

Thus, the sleep disturbances experienced by women around menopause are multifactorial in origin and are best managed using a multidisciplinary approach.

Treatment Options Pharmacotherapy
• Menopause Hormonal Therapy: Treatment with estrogen or the combination of estrogen and progesterone has been found to help relieve menopausal symptoms. They are very effective in allaying hot flashes. Estrogen is helpful for sleep disturbance and improving quality of life; however, selective use is recommended, as there are some serious side effects with this therapy. The Women’s Health Initiative conducted a large clinical trial of postmenopausal women taking estrogen or a combination of estrogen and progesterone therapy. They reported increased incidence of coronary events, thromboembolic events, and stroke. With the estrogen/progesterone combination, the risk of breast cancer also increases; hence, caution is recommended when women are on hormonal therapy. If hormonal therapy fails to give relief, then causes such as depression, stress, psychosocial factors, RLS, and PLMD should be explored.

• Tibolone: This synthetic steroid compound with relatively weak hormonal activity is effective for hot flashes and sleep disturbances; however, the drug is not available in the United States. It has been used in Europe for almost 20 years.²

• Antidepressants: Examples such as paroxetine and venlafaxine may decrease hot flashes to a moderate degree in symptomatic women.²

• Gabapentin: This drug demonstrates a benefit in hot flash frequency and sleep in one study. More studies are needed to replicate the result.²

Alternative Therapy
Phytoestrogen (a plant hormone) and isoflavones may have some mitigating effects on hot flashes. Soy products are rich in phytoestrogens and may be recommended. Phytoestrogens are also available in over-the-counter nutritional supplements like ginseng, extract of red clover, and black cohosh.²

Exercise
Exercise in general improves quality of sleep. It seems to be more effective if performed early in the day. Shelley Tworoger, research fellow at the Department of Epidemiology, Harvard School of Public Health, Boston, says a possible explanation is that morning exercise could help set circadian rhythms or the body’s internal clock, which in turn regulates sleep-inducing hormones such as melatonin. Or it could be that exercising at night increases body temperature, whereas body temperature must go down to induce sleep.⁵ But neither of these hypotheses has been proven.

Treatment of OSA
The incidence of OSA doubles in postmenopausal women compared to premenopausal women. Patients can present with snoring, gasping episodes, witnessed apneas, and unrefreshed sleep. It is a treatable condition that is often overlooked and should be ruled out in these women. Treatment options include CPAP therapy, oromaxillary surgery, oral/dental appliances, and weight loss for those who are overweight.

Other Treatment Suggestions
Relaxation techniques such as meditation and yoga can help reduce stress and aid in falling asleep. Avoiding large meals before bedtime as well as nicotine, caffeine, alcohol, and other stimulants can also help menopausal women fall asleep. As mentioned before, hot flashes are prevalent so temperature can also play a role in helping these women fall asleep. It is suggested that they dress in light (or layered) clothes and maintain a comfortable room temperature.

Short-term treatment with nonbenzodiazepine agents like zolpidem or zaleplon can be sometimes considered to break the cycle of insomnia while the above therapies are initiated.

Undiagnosed sleep disturbances may contribute to fatigue and muscle aches, cognitive dysfunction, anxiety, and depression. Patients may attribute their sleep problems to normal changes in menopause and, hence, may not report them until specifically asked. National Institutes of Health-sponsored studies are under way (Study of Women’s Health Across the Nation),¹⁰ which will enhance our understanding of sleep difficulties in middle-aged women. Recognition, proper identification, and effective management of sleep disturbances during menopause can go a long way in improving overall quality of life in this population.

Neha H. Badheka, MD, is an extern; Mohamed T. Sameen, MD, DABSM, is medical director; and Russell Rozensky, RRT, CPFT, RPSGT, is supervisor at the John T. Mather Memorial Hospital Sleep Apnea Center, Port Jefferson, NY.

References
1. Moe KE. Reproductive hormones, aging, and sleep. Semin Reprod Endocrinol. 1999;17:339-348.
2. National Institutes of Health State-of-the-Science Conference Statement. Management of menopause-related symptoms. Ann Intern Med. 2005; 142:1003-1013.
3. Rosenthal MB. Epidemiology, sleep, and menopause. Menopause. 2003;10:4-5.
4. Menopause and sleep. Available at: http://health.torontotime.com/women_
sleep/menopause_and_sleep. Accessed July 13, 2005.
5. Carlin Flora. Sleep-deprived in menopause. Available at: http://cms. psychologytoday.com/articles/index.
php. Accessed July 13, 2005.
6. Bixler EO, Vgontzas A. Investigating menopause and sleep. Available at: http://sleep-medicine.advanceweb.com/
common/Editorial/Editorial.aspx. Accessed July 13, 2005.
7. Kryger MH, Roth T, Dement WC, eds. Principles and Practices of Sleep Medicine. 3rd ed. Philadelphia: WB Saunders Company; 2000:26-42, 1103-1112.
8. Lin TL, Ng SC, Chen YC, Hu SW, Chen GD. What affects the occurrence of nocturia more: menopause or age? Maturitas. 2005;50:71-77.
9. Kloss JD, Tweedy K, Gilrain K. Psychological factors associated with sleep disturbance among perimenopausal women. Behav Sleep Med. 2004; 2:177-190.
10. Kravitz HM, Ganz PA, Bromberger J, et al. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause. 2003;10:19-28.