Sleep disturbances result in neurological, cardiovascular and psychiatric sequelae, and as such there are significant gender differences among these disorders. ^1–3 Owing to the role of reproductive hormones, this may have a significant impact on sleep pathophysiology. Menarche, pregnancy and menopause contribute to varied manifestations of the most common sleep disorders, namely, insomnia, obstructive sleep apnea (OSA) and restless leg syndrome (RLS).^2,4 Physiological changes that occur during a woman’s life, spanning puberty, pregnancy and menopause, have significant effects on sleep, daytime functioning and quality of life. In this article, we describe some of the common sleep disorders in women, particularly insomnia, OSA and RLS.

Pubmed was searched using the terms ―women AND common sleep disorders‖ using the limits 1 January 2008 to 1 Nov 2018 & peer reviewed publications. Articles on sleep apnea, restless leg syndrome and insomnia were included, and the others excluded as indicated in the flowchart.

According to the American Academy of Sleep Medicine (AASM), the diagnostic criteria for insomnia include difficulty initiating and/or maintaining sleep, with significant daytime function impairment and mental health disturbances.¹³ In one large scale study examining the economic impact of insomnia, the prevalence of insomnia was significantly higher in women than in men, at 27% and 19% respectively.³ Among the general population, 10-15% complain of insomnia.¹⁴ At different reproductive stages women report a high frequency of insomnia with a prevalence as high as 50% reported during the perimenopausal period.^15,16 The gender differences are also apparent among different racial groups and socioeconomic status.¹⁷

Also noteworthy is the high prevalence of insomnia in women with breast cancer.^18,19 Psychiatric disorders such as depression and anxiety contribute to a higher rate of insomnia in women and insomnia in itself can exacerbate major depression.¹⁹

Psychological and behavioral interventions are effective in treating insomnia and recommended too. AASM has developed a practice parameter for these treatments.²⁰ Thirty percent of patients with insomnia have contributory poor sleep hygiene. Good sleep hygiene practices should be prescribed for all patients, in addition to other treatments, since sleep hygiene education alone is ineffective.²¹ In a study of insomnia in women with breast cancer, cognitive behavioral therapy demonstrated improvement.²²

The current Food and Drug Administration approved pharmacological treatments for insomnia include benzodiazepine receptor agonists and melatonin receptor agonists. Potential adverse effects of the former include residual sedation, memory and performance impairment, falls, undesired behaviors during sleep, somatic symptoms and drug interactions. Several other prescription medications (e.g., sedating antidepressants, antiepileptics) as off-label treatment, nonprescription drugs (e.g., sedating antihistamines) and naturopathic agents (e.g., melatonin, valerian) also are used to treat insomnia, although safety and efficacy data are limited.²¹ Postmenopausal women had longer sleep latency, less slow-wave sleep, and less deep sleep compared to premenopausal subjects. Postmenopausal women not receiving HRT had longer sleep latency than did those on treatment, suggesting that estrogens may exert a protective effect on sleep integrity.^23,24

There is no consensus on sex-specific insomnia treatment strategies for women.²⁵ In general, symptom pattern, previous treatment failure, comorbid conditions, adverse effects and medication costs should be considered before starting a hypnotic regimen. Short to intermediate-acting benzodiazepine receptor agonists or melatonin receptor agonists can be started initially. Medications can be changed or dosages increased based upon the degree of symptom improvement and adverse effects experienced.²¹ Since depression and insomnia are present more frequently in women than in men, selective serotonin reuptake inhibitors appear to be uniquely effective in their treatment.²⁵

Based on the third edition of International Classification of Sleep Disorders (ICSD-3), the diagnostic criteria for obstructive sleep apnea (OSA) includes clinical complaints of snoring, gasping, witnessed apneas, along with evidence of five or more obstructive respiratory events per hour on sleep testing. Associated manifestations commonly include daytime sleepiness and cardiovascular and cerebrovascular diseases.¹³ General population studies have revealed that the prevalence of OSA with daytime sleepiness is 2-5% in adult women and 3-7% in adult men. In the absence of hypersomnia, the disease prevalence is likely greater (24% in men and 9% in women).²⁶

The estimated prevalence of OSA is 9% in women and 24% in men.²⁷ The Wisconsin Sleep Cohort Study estimated that sleep apnea was undiagnosed in 90% of women with moderate to severe sleep apnea and suggested that under-diagnosis related to atypical symptomatology may explain much of the perceived disparity.²⁸ Several investigators have suggested that OSA may be common in pregnant women. However, the exact incidence and prevalence of sleep apnea in pregnant women is uncertain.^8,9 Loud snoring, breathing pauses during sleep and excessive daytime sleepiness are classic symptoms seen in most men with OSA, whereas atypical symptoms such as insomnia, morning headache, fatigue, tiredness, depression, and anxiety are more common presentations in women. Other less typical symptoms in women include memory loss, poor concentration, decreased libido, irritability, worsening unexplained fatigue, and tiredness which are often misdiagnosed and treated inappropriately as depression.²⁹ Obesity may be the most important risk factor for OSA. Women with OSA are more likely to be obese than are men with OSA of similar severity.³⁰ In a study of women with body mass index (BMI) >30 kg/m2, one-third of asymptomatic women were found to have OSA by polysomnographic criteria, and a significant correlation was identified between ApneaHypopnea Index (AHI) and BMI in this cohort.³¹

OSA is a chronic disease requiring long-term, multidisciplinary management. Several treatment options are available and patients should be active participants in the treatment decision process. Positive Airway Pressure therapy (PAP) is the treatment of choice for all degrees of OSA and may be delivered in Continuous Positive Airway Pressure (CPAP), bilevel PAP, or auto titrating PAP modes.³² An in-laboratory polysomnography is the preferred approach to titrate to optimal PAP parameters.³³ In a prospective study of 1,116 women for 88 months, adequate CPAP therapy administered after controlling for age, BMI, previous cardiovascular history, hypertension and diabetes, reduced the relative risk from 3.50 (95% confidence interval 1.23 - 9.98) to 0.55 (95% confidence interval 0.17 - 1.74). These data strongly suggest that CPAP therapy may reduce cardiovascular death in patients with severe OSA.³⁴ Oral appliances (mandibular repositioning or tongue retaining devices) may improve upper airway patency. To date, most treatment trials have been conducted in male patients and few trials have included sufficient number of women to define differences in the efficacy of various modalities in female patients.³²

Compliance is a major challenge and there is no consensus on the findings. In contrast to prior studies indicating no significant gender differences in regards to CPAP compliance³⁵, more recent population-based prospective studies indicate that female patients used CPAP more frequently than their male counterparts.³⁶ However another recent study reported that compliance was not different between women and men.³⁷

In a prospective crossover study, postmenopausal women with OSA were treated with estrogen alone, and with an estrogen-progestin combination. Both treatment strategies reduced OSA, with a 50% reduction of AHI following estrogen-progesterone treatment and a 25% reduction following estrogenonly therapy.³⁸ Estrogen effects were further studied in two groups of postmenopausal women (one receiving HRT and the other untreated); treated women had better polysomnographic sleep parameters than untreated subjects.³⁹ Women with established cardiovascular disease experience greater mortality when prescribed HRT⁴⁰ and with the higher incidence of major cardiovascular events in OSA patients overall, the potential for harm is significant. Further long-term outcome studies are needed to evaluate the net effect of HRT on postmenopausal women with OSA. Despite its demonstrated efficacy, HRT is not a recommended treatment for perimenopausal OSA at this time.^38,39

Behavioral therapy, including sleep hygiene, weight reduction, exercise, alcohol avoidance, and bedtime sedatives are important adjuncts to PAP.

This movement disorder is characterized by an urge to move the leg, typically during rest, which is relieved by activity.¹³ The prevalence ranges from 4% to 29% in the general population and increases with age.^41,42 Prevalence is higher among women at 13.9% , compared to. 6.1% among men in another cohort analysis.⁴³ RLS often is underdiagnosed. In a large multinational primary care population of 23,052 patients, 68% of women had RLS; however, only 12.9% received the diagnosis, despite 64.8% reporting their RLS symptoms to a physician. Published data on women with RLS are few and more research focusing on the symptoms and treatment options for women is needed to tailor both diagnostic and treatment strategies.⁴² Although the mechanism of this disease is unknown, iron deficiency and dopaminergic dysfunction is thought to be an underlying component.^44–46 The current consensus theory on the pathophysiology of RLS is the “iron dopamine hypothesis”.⁴⁷ Iron is a cofactor for the enzyme tyrosine hydroxylase, which performs a rate-limiting enzymatic step in the formation of dopamine.

In a cohort study of women studied during and after pregnancy, 26% were found to have RLS during pregnancy (with symptoms being most common during the third trimester), which tended to disappear after delivery. Affected women had lower hemoglobin concentrations compared to non-affected women,⁴⁸ supporting the theory that iron status may contribute to RLS.

RLS is also associated with increased morbidity and mortality in women. In a prospective study involving greater than 70,000 women, a positive correlation between RLS and coronary artery disease was found. An elevated risk for cardiac disease was appreciated in women with RLS for more than a 3-year duration.⁴⁹ Iron-deficiency anemia, pregnancy, smoking, neuropathy, rheumatoid arthritis, multiple sclerosis, diabetes, kidney disease, caffeine and alcohol consumption, use of H2-receptor blockers and some antidepressant medications have been linked to RLS.^33,44,46

The management of RLS is multimodal and encompasses both pharmacological and non-pharmacological treatments. The non-pharmacologic management of RLS includes behavior modification and lifestyle changes as well as cognitive-behavioral treatments which are discussed in greater detail else-where.⁵⁰ Avoidance of certain foods (e.g., caffeine, alcohol) and drugs (e.g., antihistamines, neuroleptics, some dopamine antagonists) can be helpful. Selective serotonin receptor blockers, tricyclic antidepressants, and lithium may worsen RLS symptoms and should be avoided whenever possible.⁵¹ AASM has developed recommendations for pharmacotherapy which range from iron supplementation, dopamine agonists, membrane stabilizing agents, benzodiazepines to opioids.⁵² These include levodopa, ropinirole, pramipexole, rotigotine, cabergoline, pergolide, gabapentin, gabapentin enacarbil, pregabalin, clonazepam, oxycodone, tramadol, methadone. Iron supplementation is beneficial solely when ferritin levels and iron studies indicate a deficiency. Appropriate clinical evaluation is important in patients who report worsening of symptoms while on dopamine agonists as this may suggest augmentation. Moreover, drugs such as cabergoline, pergolide along with opioids require special monitoring.⁵⁴

Sleep is essential for women to live a functional, productive life. Sleep disorders are far more common in women than previously appreciated and presenting symptoms often differ from those in men. Although insomnia is more prevalent among women, it can constitute an atypical presentation of other sleep disorders such as OSA in them. Postmenopausal women carry a higher risk of OSA and should receive PAP therapy; if they fail to improve with optimal PAP therapy other treatment options should be discussed. RLS is common among women of all ages, but it is more frequent during pregnancy. Correction of iron deficiency and use of dopaminergic medications can be helpful for treatment.

This article is a brief overview of common sleep disorders in women and does not encompass many other sleep disorders seen in women. Women are often under-represented in studies and more research involving women is required to further understand the unique needs in this population.