Sleep in Women Across the Lifespan April 2015 Sleep Symposium Sally Ibrahim, MD, FAAP Staff, Sleep Disorders Center Assistant Professor Lerner College of Medicine of CWRU

Objectives • Discuss influences unique to women that effect sleep through the lifespan • Demonstrate sleep epidemiology according to female reproductive state • Illustrate key hormonal and physiological conditions that effect sleep disorders in women

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Gender related Sex differences Infancy

Boys: less sleep, more awakenings (observational)

Childhood

Girls: longer sleep duration (some studies) Earlier Bed time in girls (questionnaire) Boys with sleep disturbance, have more severe manifestations (behavioral)

Adolescence

Girls: longer sleep duration, more sleepiness Earlier wake time in girls Controlling for puberty, few differences (CarskadonTanner staging) More dramatic age related changes in boys (PSG)

Adulthood

Greater maturational changes in males (consistent) - Decline in delta sleep

Source: Adapted from Table 108.2 from the Principles and Practice of Sleep Medicine, 4th edition.

Sex differences in Challenging conditions Sleep deprivation • Great delta response in healthy young women

Depression • More sleep architectural differences in women than men

Theory: Greater biological flexibility and adaptation in women under challenging conditions. Principles and Practice of Sleep Medicine, 4th edition

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Biological and reproductive factors POSTMENOPAUSE MENOPAUSE POSTPARTUM PREGNANCY Pre-menopausal (Menstrual cycles)

Pregnancy

PUBERTY Postpartum PREPUBERTY

When research involves women, these factors need consideration

National Sleep Foundation (NSF) polls of Women: 1998, 2003, 2007 • Women sleep about 6.5 hours • Report sleep more than men (3-8 minutes) • More complaints about insomnia (63% vs 54%) - Transition to mid life 40-60 years

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Sleep Disorders and Gender 1-2 WOMEN

MEN

• Insomnia (1.4:1) • Restless Legs Syndrome (RLS) 2:1 • Nocturnal Related Eating (65%) • Nightmares • Sleep related headaches 4:1 • Fibromyalgia (80%) • Menstrual related hypersomnia (100%)

• Obstructive Sleep Apnea (OSA) 3:1 • REM-Sleep behavior disorder (88%) - (women have more secondary RBD, younger, less violent)3 • Parasomnias, when violent • Sleep Enuresis 3:2 (boys) • Klein-Levin Syndrome

1 Walsleben JA. Handbook of Clinical Neurology. Ch 40; 2011. 2 Krishnan V and Collop NA. Curr Opin Pulm Med 2006 3 Gender differences in RBD. Sleep Med 2015.

Sleep Disorders and Gender 1-2 WOMEN • Insomnia (1.4:1) • Restless Legs Syndrome (RLS) 2:1 • Nocturnal Related Eating (65%) • Nightmares • Sleep related headaches 4:1 • Fibromyalgia (80%) • Menstrual related hypersomnia (100%)

MEN • Obstructive Sleep Apnea (OSA) 3:1 • REM-Sleep behavior disorder (88%) • women have more secondary RBD, younger, less violent3 • Parasomnias, when violent • Sleep Enuresis 3:2 (boys) • Klein-Levin Syndrome

1 Walsleben JA. Handbook of Clinical Neurology. Ch 40; 2011. 2 Krishnan V and Collop NA. Curr Opin Pulm Med 2006 3 Gender differences in RBD. Sleep Med 2015.

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Restless Legs Syndrome • 10% general population • Female predominance: ~ 1.5 to 2 >men 1 • Gender difference explained by parity: - Nulliparous female RLS rates closer to men2 - More severe in those with a child3

• RLS effected by reproductive states -

Pregnancy: starts/increases; Delivery: declines Menses 1/3 report worsening symptoms3 Menopause- worsening RLS3 Oral contraceptives: no effect on RLS4

1Allen

RP, et al. Arch Intern Med 2005; 2 Manconi M, et al. Sleep Med Rev 2012 3Ghorayeb I, et al Sleep Med 2008; 4 Kamsheh L et al. Acta Obstet Gynecol Scand 2013.

OSA: Epidemiology and Gender • Male predominance not as strong ─ - 2-3:1 Male: Female (vs. 8-10:1)1 • Prevalence (AHI ≥ 5; Wisconsin Cohort) 2  OSA: 26% males vs. 13% females  OSAS: 11% vs. 4% females  Higher prevalence in older women:  Prevalence: (AHI ≥15):  3% young females  9% older females  Risks: age, obesity, menopause3 1 3

Young T et al. NEJM 1993; 2 Peppard PE et al Am J Epidemiol 2013; Bixler Am J Respir Crit Care Med 2001;

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Data Adapted from Peppard PE et al Am J Epidemiol 2013

• Increase in women (and men): by 14-55%3

Fat distribution Greater visceral fat distribution in men 6 Leptin (respiratory stimulant) higher females 2

Neurochemic al control mechanisms

Arousal response

Upper airway size/length Sex hormones

Total soft issue, tongue palate mass predicts AHI1

Upper airway collapsibility

Gender difference in OSA

Less airway collapsibility with external load 1 •

Airway Instability •

Lower hypocapnic Apnea Threshold (AT) 3 - controlling for progesterone/menstruation - Testosterone increases AT  instability in men 4 Pcrit- no difference5

1Kapsimalis

et al Part 1, Sleep 2002 2Kapsimalis F, et al Part 2 Sleep 2002; XS. J. Appl Physiol. 2000; 4 Zhou XS. J Appl. Physiol 2008; 5 Rowley et al, J Appl Physiol 2001; 6 Harada Y et al Ann Am Thorac Soc 2014

3 Zhou

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OSA in Women • Presentation of insomnia/ mood disorder; 23x less likely to report typical symptoms1; snoring strongest predictor2 • Milder; Greater REM-related OSA3 :obesity • Higher diabetes incidence(16 y f/u; adjusted) 4 • Treatment - Positive Airway Pressure (PAP) therapy: CPAP / AutoPAP - PAP: improvement in function (mood, sleepiness/fatigue, outcomes)5 1 Redline

S, et al. Am J Resp Crit Care Med 1994; 2Young T. Arch Intern Med 1996; 3Koo,BB et al. Sleep Breath 2008; 4 Celen YT et al JCSM 2010 5ChenSan S et al, JCSM 2012

Insomnia is more common in women • Epidemiology - Women 41% higher risk than men - Older women 73% higher risk than men • Co-morbid insomnia higher prevalence in women (anxiety, depression, PTSD, chronic pain) • Effected by reproductive status Phillips. J Women’s Health. 2008

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Reproductive Status and Sleep Reproductive Status

Insomnia sxs

Sleep disorder

Childbearing Age

67%

34% (15% w/o kids)

Pregnancy

84%

40%

Post Partum *

84%

---

Perimenopausal

59%

43%

Postmenopausal

---

42%

National Sleep Foundation (NSF). Summary findings of the 2007 Sleep in America Poll, 2007. PDF Available at www.sleepfoundation.org * first time this group polled

Childbearing Women POSTMENOPAUSE MENOPAUSE Pre-menopausal (Menstrual cycles)

PREGNANCY

PUBERTY PREPUBERTY

POSTPARTUM

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Menstrual cycle

Source: Wikipedia

Sleep Effects of Menstrual Cycle Subjective • NSF Poll 2007: 33% disturbed sleep during menstruation • Questionnaire studies1 • Late Luteal Phase (LP)/ pre-menstrual: Hypersomnia, insomnia symptoms, and poor sleep quality

Objective • EEG changes (increased REM in LP)1 • Circadian temperature decline blunted in LP2 • Effects on Breathing3 • Pulmonary function test in asthmatics controls: Worse in follicular phase • Luteal phase improves 1Driver

and Baker. Sleep Med Rev 1998. 2Cagnacci et al, Chrono Int. 2002; 3 Farha et al. Am J Respir Crit Care Med 2009

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Menstrual cycle effects on AHI • AHI is greater in follicular phase than Luteal • Greatest effect on AHI is seen in REM sleep (Edwards, J of HTN 1999 n=13; mean age 37)

Protective role of Progesterone   



Increases ventilatory chemo-responsiveness Increase resting ventilation Pharyngeal dilator muscle activity  greater in Luteal Phase (LP)  less in postmenopausal women  increased with hormonal replacement Higher activity genioglossus muscle in LP

E Follicular

P Luteal Phase

Kapsimalis Sleep 2005

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Reproduction and Sleep • Polycystic Ovarian Syndromeirregular menstruation/reproduction • Higher prevalence of OSA1

• Circadian effects on reproduction2 - Irregular shifts  irregular menstruation - Shift workers report abortions, worse pregnancy outcomes: prematurity - SCN- Estrogen and progesterone rec.

SCN

Ovary

• Sleep deprivation: LH amplitude increases2,3 1Tasali

E. et al. Sleep Med Clin 2008; 2Mahoney MM, Int. Journal of Endocrinology 2010; 3Principles and Practice of Sleep Medicine, 4th edition Image: healthysleep.med.harvard.edu

Sleep in Pregnancy

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Sleep Across Pregnancy Trimester

1st

2nd

3rd

(weeks 1-12)

(weeks 13-28)

(weeks 29-40)

Sleep Duration

↑

─ Normalizes

↓

Sleep Efficiency

↓

↓

↓↓

Slow Wave Sleep

↓

↓ (↑ compared with 1st)

↓

Nocturnal awakenings

─/↑

↑

↑↑↑

↑↑

↑↑↑

Progesterone /Estrogen Symptoms

fast↑ N/V (Placental growth)

Fetal movements; restlessness

GERD, pain, Swelling, urinary frequency

Pregnancy is NOT protective against OSA 

Subjective: Snoring increases over pregnancy; Postpartum, OSA symptoms improve /resolve. 1



Objective 1st Prospective cohort [n=105] with PSG OSA (AHI ≥5)2  10% 1st Trimester  26.7% 3rd Trimester.  AHI final trimester reduced by 1/3 Postpartum 3 Risks: higher baseline BMI and maternal age Pregnancy: gravid uterus, airway edema, weight 

 

1 Ibrahim and Foldvary-Schaefer. Neur Clinic 2012; 2 Pien GW et al. Thorax 2013 3 Champagne K et al. Eur Respir J 2009

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Identifying Sleep Disorders in Pregnancy Prospective Cohort, n=189 Early Pregnancy Late Pregnancy

Sleep Disorders in Pregnancy 60

*

50

*

*

40

*

(%) 30

*

20

*

10 0 Insomnia

Excessive Sleepiness

RLS

Short Sleep Poor Sleep Duration Quality

Snoring

Adapted from: Facco FL et al. Oby Gyn 2010

Adverse Effects of Sleep Disturbance on Pregnancy • Short sleep duration1, 2 - Gestational Diabetes (GDM), preeclampsia, Pregnancy Induced Hypertension (PIH) • Snoring/OSA (even non-obese) 2,3 - GDM, Preeclampsia, PIH - Mechanism: ?inflammatory markers

1 3

• Objective ( n=30 pregnant) 4 - GDM: shorter sleep, more WASO, more Future: treatment of arousals Pregnancy related - OSA Odds: 6.6 (BMI adjusted) sleep disorders Williams et al Sleep 2010; Facco et al Am J Obstet Gynecol 2010 • ? improved Ibrahim and Foldvary-Schaefer Neurol Clin 2012

4 Reutrakul

2

S. et al J Clin Endocrinol Metab 2013.

outcomes

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Most incidence of • Limited sleep ( pre-menopausal1 • Mechanisms: - Lower lean body mass / obesity - Sex hormones: • Inverse Relationship AHI and HRT use • HRT1 (E): reduced AHI by ~ 25%; (P): further improves 4

OSA Prevalence2 (AHI ≥10 + symptoms)

Pre0.6% menopausal Post no HRT Post on HRT Men Women

2.7% 0.5% 3.9% 1.2%

1 Kapsimalis et al Sleep 2005; 2 Bixler Am J Respir Crit Care Med 2001; 3 Shahar E. et al AJRCCM 2003 4 Pickett 1989;

Conclusions: Women and sleep • Sleep in the female lifespan is dynamic, making research complex • Circadian pacemaker effected by ovarian hormones; suggests hormones may influence sleep patterns directly. • Hormonal differences ( in woman’s cycles and women vs. men) play key roles in sleep disorders • The presentation of sleep disorders in women may be different than in men. • Women are more likely to experience changes in sleep quality during biological transitions, menstruation, pregnancy.

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