Sleep in Women. Sleep in Women APSS Kryger 10/3/17 3:59 PM. A Common Presentation. Topics

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1 Sleep in Women Meir H. Kryger, MD, FRCPC Sleep in Women Kryger 27 1 Meir H. Kryger, MD, FRCPC Kryger 27 2 A Common Presentation Topics At 5 years of age, the patient began having hot flashes and night sweats She complains of severely disrupted sleep She is very irritable and experiences frequent mood swings She has never been a good sleeper Her husband notes that she is a loud snorer and she moves a lot when she sleeps Women have many more sleep problems than men The problems are related to: Lifestyle Changes related to hormones Diseases that are more common in women Kryger 27 3 Kryger

2 Women Report Poor Sleep You Don t Have to Be a Male and Middle Aged to Have Sleep Apnea Women report higher rates of: Insomnia symptoms Daytime consequences Dissatisfaction with sleep Insomnia diagnoses Female/male ratio for insomnia symptoms is 1.4 After age 45 years, this ratio is 1.7 But aren t sleep problems more common in middleaged obese men? Ohayan MM. Sleep Med Rev. 22;6: Kryger 27 5 Kryger 27 6 Enlarged Tonsils Can Cause Apnea in Teenagers You Don t Have to Be a Male and Obese to Have Sleep Apnea Kryger 27 7 Kryger

3 Life-threatening Sleep Apnea Because of a Hormonal Disorder Stages of Normal Reproductive Aging in Women Stages: Final Menstrual Period (FMP) Terminology: Reproductive Menopausal transition Postmenopause Early Peak Late Early Late* Early* Late Perimenopause Duration of stage: variable variable a 1 y b 4 y until demise Menstrual cycles: variable to regular regular variable cycle length (>7 days different from normal) ³2 skipped cycles and an interval of amenorrhea (³6 days) Amen x 12 mos none Endocrine: normal FSH FSH FSH FSH Kryger 27 9 *Stages most likely to be characterized by vasomotor symptoms. FSH=elevated follicle-stimulating hormone. Soules MR, et al. Fertil Steril. 21;76: Kryger 27 1 Changes Over the Normal Menstrual Cycle Pituitary Hormones (miu/ml 1 ) Ovarian Hormones (pg/ml 1 ) Body Temperature ( C) FSH LH Estrogen Progesterone Menses Ovulation Follicular Phase Luteal Phase Days of menstrual cycle Armitage R, et al. In: Principles and Practice of Sleep Medicine. 25: Progesterone (ng/ml 1 ) Kryger Sleep Complaints During the Normal Menstrual Cycle Self-reported sleep in young healthy women 1 Sleep quality was lower during the premenstrual week and first few days of their period Total sleep time, sleep onset latency, number and duration of awakenings, and morning vigilance were not affected by the menstrual cycle Review of studies confirm few major menstrual cycle effects on sleep 2 1. Baker FC, Driver HS. J Psychom Res. 24;56: ; 2. Moline ML, et al. Sleep Med Rev. 23;7: Kryger

4 Menstrual Cycle Disorders and Sleep Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) PMS: characterized by mood and/or physical symptoms that appear in the luteal phase and remit with menses PMDD: severe, predominantly affective PMS symptoms that cause a marked negative impact on functioning at home, in the workplace, or on relationships No major reproducible differences in sleep architecture in women with PMS or PMDD Kryger Moline ML, et al. Sleep Med Rev. 23;7: Kryger What Is the Diagnosis? Polycystic Ovarian Syndrome (PCOS) Chronic anovulation and androgen excess Occurs in ~4% of women Characteristics: insulin resistance, hyperandrogenism, altered gonadotropin dynamics Frequently complicated by obesity; associated with diabetes, cardiovascular disease Kryger Guzick DS. Obstet Gynecol. 24;13: Kryger

5 Obstructive Sleep Apnea Syndrome (OSAS) Is 3 Times More Prevalent in Women With PCOS Percentage of Women Sleep Apnea PCOS (n=53) SDB Controls (n=452) 19.5* 8.3 *P=.3; P<.1. SDB=sleep-disordered breathing. Vgontzas A, et al. J Clin Endocrinol Metab. 21;86: SDB BMI < SDB BMI 32.3 Kryger Shift Work, Sleep, and Menstrual Function 36 (53%) of 68 nurses <4 years of age had menstrual changes during shift work 31 of them (86%) reported sleep disturbance vs 16 (5%) without menstrual changes (P<.1) Percentage Change in Menstrual Cycle Length Types of menstrual cycle changes (n=36) Labyak S, et al. Health Care Women Int. 22;23: Change in Menstrual Flow 18 Increased Menstrual Pain 2 Change in Bleeding Duration Kryger Effects of Oral Contraceptives (OCs) on Sleep Sleep and temperature differences were investigated in 8 women with normal menstrual cycles and 8 taking OCs Menstrual cycle phase and OC use significantly affected body temperature Sleep architecture was unaffected by menstrual cycle phase OCs had only minor consequences for sleep composition Women taking OCs had less slow-wave sleep Sleep in Pregnancy and the Postpartum Period Baker FC, et al. J Physiol. 21;53: Kryger Kryger

6 Pregnancy and Postpartum Sleep Changes Hormone levels Sleep disruption Sleep disruption Accompanying symptoms Accompanying symptoms 13 Postpartum rd Trimester 2 nd Trimester High Progesterone No progesterone peaks levels (3-4 Progesterone ng/ml) rises, but from No estrogen placenta (2-3 more slowly (5-1 ng/ml) Fluctuating prolactin levels with ng/ml) breastfeeding Leg cramps, heartburn, nasal congestion, increased Sleep urinary Infant difficulties care, frequency feeding related to Urinary frequency increased First-time mothers urinary have greatest diminishes; sleep disruption more daytime frequency Increased Breast-feeding daytime mothers sleepiness, awake energy fatigue longer at night Difficulty with sleeping positions Daytime Discomforts: Increased sleepiness daytime irregular sleepiness and uterine Snoring contractions, may begin shortness fatigue of Napping breath, may breast occur tendernessrisk of sleep apnea, Morning/evening Risk of postpartum nausea depression hypertension Sleep characteristics More Tendency sleeping wake to time sleep than at later night prior into the More morning wake time during to Possible Issues pregnancy of RLS co-sleeping and PLMand bed the sharing night Sleep architecture Less Increased SWS SWS Less SWS SWS=slow-wave sleep; RLS=restless legs syndrome; PLM=periodic leg movements. Kryger Kryger Wolfson AR, Lee KA In: Principles and Practices of Sleep Medicine. 25: Sleep Problems During Pregnancy Pregnancy-induced Hypertension (PIH) PIH, or preeclampsia, occurs in 5%-1% of pregnancies Risk factors First pregnancy, >1-year interval between pregnancies, multiple pregnancy, age <2 or >35 years, overweight, history of hypertension, kidney disease, diabetes Symptoms Excessive edema, severe headache, dizziness/ nausea, blurred or double vision, sleepiness Kryger Wolfson AR, Lee KA. In: Principles and Practice of Sleep Medicine. 25: Kryger

7 PIH and Sleep PIH associated with: Periodic limb movements Frequent arousals from sleep Snoring Implications of Snoring During Pregnancy Pregnancy is associated with altered breathing The rate of snoring increases from 4% in nonpregnant women to 14%-23% in pregnant women Snoring is associated with a greater risk of: Hypertension Preeclampsia Babies with lower Apgar scores and fetal growth retardation Izci B, et al. Am J Respir Crit Care Med. 23;167:137-14; Wolfson AR, Lee KA. In: Principles and Practice of Sleep Medicine. 25: Kryger Izci B, et al. Am J Respir Crit Care Med. 23;167: Kryger Implications of Snoring in Pregnancy Implications of Snoring in Pregnancy: Risk Factors for PIH Habitual Snorers (n=113) Infrequent Snorers (n=289) Characteristic OR 95% CI P Habitual snoring <.5 Percentage * Smoking NS Weight before delivery, kg Age at delivery, years Hypertension Preeclampsia Any Edema Edema of the Face EDS *P<.1; P<.5; P<.1. Any edema indicates edema of the face, hands, legs, or feet; EDS=excessive daytime sleepiness. Franklin KA, et al. Chest. 2;117: Kryger OR=odds ratio; CI=confidence interval; NS=not significant. Franklin KA, et al. Chest. 2;117: Kryger

8 Snoring During Pregnancy: Infant Outcomes Sleep Apnea Percentage Habitual Snorers (n=113) 7.1* 2.6 Small for Gestational Age Apgar Score 7 After 1 min Infrequent Snorers (n=289) Apgar Score 7 After 5 min Case-control study comparing sleep-related breathing in obese pregnant women (n=11) and normal-weight pregnant women (n=11) Significantly more sleep-related disordered breathing in obese than normal-weight women Apnea-hypopnea indexes (1.7 events/h vs.2 events/h, P<.5) 4% oxygen desaturations (5.3 events/h vs.3 events/h, P<.5) Snoring times (32% vs 1%, P<.1) Of the obese women: 1 had preeclampsia and sleep apnea, and 1 delivered a baby with growth retardation *P<.5; p=.1; P=.1 Franklin KA, et al. Chest. 2;117: Kryger Maasilta P, et al. Chest. 21;12: Kryger 27 3 OSA Improves After Delivery of Baby Before Frequency of Awakenings Due to Leg Cramps Increases During Pregnancy 8 75 After SaO 2 Percentage of Awakening Due to Leg Cramps Nonpregnant 1st Trimester 2nd Trimester 3rd Trimester Edwards et al. Sleep. 25. Kryger Wolfson AR, Lee KA. In: Principles and Practice of Sleep Medicine. 25: Kryger

9 Restless Legs Syndrome (RLS) Pregnancy is a risk factor for initial or worsening RLS Frequency during pregnancy: 11%-27% Pregnancy-related RLS is typically mild, transitory, and most troublesome during the third trimester Additional Common Causes of Sleep Disruption During Pregnancy Nocturia Noted as the main reason for disturbed sleep during pregnancy Particularly troublesome during the first and third trimesters Heartburn Begins during the second trimester and often continues through pregnancy Manconi M, et al. Sleep Med. 24;5: Kryger Kryger Postpartum Depression? Postpartum Depression Most common complication of childbearing 13% of women after delivery (19% in 27 SIM Poll) Begins within 4 weeks after delivery Symptoms include depressed mood or markedly diminished interest or pleasure in activities, accompanied by 4 or more of the following: Appetite disturbance Sleep disturbance Physical agitation or psychomotor slowing Fatigue Feelings of worthlessness or excessive or inappropriate guilt Decreased concentration or ability to make decisions Recurrent thoughts of death or suicidal ideation Kryger Wisner KL, et al. N Eng J Med. 22;37: Kryger

10 Postpartum Sleep Is Terrible Drug Use in Pregnancy 42% rarely or never get a good night s sleep 47% have nobody to help them at night 48% have baby sleep in parent s room (crib) 22% have baby sleep in parent s bed 2% have driven while drowsy with children in car Drugs are not recommended during pregnancy except in exceptional circumstances Dosages should begin with half of the lowest recommended, because of increased sensitivity Lactating women should consider alternatives to breast-feeding because long-term effects on newborn growth and neurodevelopment are not known Results are from the 27 Sleep in America poll. Kryger Wolfson AR, Lee KA. In: Principles and Practice of Sleep Medicine. 25: Kryger The Menopausal Transition and Sleep Frequency of Sleep Complaints Percentage reporting trouble sleeping in a prospective birth cohort study among 1498 UK women Percentage Premenopausal Postmenopause HRT Users Perimenopause Hysterectomy Kryger HRT=hormone replacement therapy. Kuh DL, et al. Br J Obstet Gynaecol. 1997;14: Kryger

11 Factors Contributing to Sleep Difficulties Community-based health survey in 12,62 women, aged 4-55 years Significant risk factors for sleep difficulties (multivariate analysis): Menopausal status Caucasian ethnicity Higher levels of educational attainment Vasomotor symptoms Psychological symptoms Increased perceived stress Poorer self-perceived health Lower quality of life Less physical activity Current smoking Arthritis Health Problems Impacting Sleep in Midlife Women Kravitz HM, et al. Menopause. 23;1: Kryger Kryger Hot Flashes and Night Sweats Impact of Estrogen Therapy (ET) or Hormone Therapy (HT) on Sleep Hot flashes affect 75%-85% of perimenopausal and menopausal women Associated with reduced self-reported sleep quality Associated with impaired objective sleep quality in some studies but not others ET/HT is the most effective therapy for vasomotor symptoms Most data support role of ET/HT in improving selfreported and objectively measured sleep quality Moline ML, et al. Sleep Med Rev. 23;7: ; Polo-Kantola P, et al. Obstet Gynecol. 1999;94: ; Woodward S, Freedman RR. Sleep. 1994;17: Kryger Erlik Y, et al. JAMA. 1981;245: ; Moline, ML et al. Sleep Med Rev. 23;7: ; Moe KE. In: Principles and Practice of Sleep Medicine. 25: Kryger

12 Use of ET/HT Following the Women s Health Initiative (WHI) Study Total estimated prescriptions dispensed in Ontario, Canada for hormone replacement therapy (HRT) and serotonergic antidepressants (SA) to women aged years from January 21 to June 23 No. of Prescriptions 6, 5, 4, 3, 2, 1, Period 1 Period 2 HRT Prescriptions SA Prescriptions WHI and Heart and Estrogen/progestin replacement (HERS) Studies: What Now? 22 HRT should never be used 28 HRT probably OK in many McIntyre RS, et al. CMAJ. 25;172: Kryger ET=estrogen therapy; EPT=combined estrogen/progestogen therapy. Utian WH, et al. Menopause. 24;11; Kryger Gender and Obstructive Sleep Apnea Syndrome Considered primarily a disease of men Reports from clinics suggest a male/female ratio of 6:1 or greater More recent epidemiologic studies have found that that the ratio is 2-4:1 33% of the apnea population is female More frequent in post- than premenopausal women Underrecognized in women due to underreporting and/or alternate diagnosis of depression Obesity There is a worldwide epidemic of obesity Females referred to our lab are 1% heavier now compared with 1 years ago (average increase in BMI=3.4) Kapsimalis F, Kryger MH, et al. Sleep. 22;25; Kryger Kryger

13 $7 OSAS females heavy healthcare users Sleep Apnea and HT Use Menopause is a significant risk factor for sleep apnea in women, but HT use is associated with reduced risk $6 $5 $4 $3 $2 $1 OSAS BMI Controls Normal Wt Controls With HT No HT OSAS OA/HI>15 SNORE+ SNORE 2.7( ).5 (.1-3.8) 5.5( ) 1.1 (.3-4.3) 9.7( ) 3.8 ( ) 14.8 ( ) 9.8 ( ) Prevalence (95% confidence interval) $ 9th year before year before Year of diagnosis Premenopausal women served as the reference group. OSAS, Sleep Disorders Clinic Criteria: OA/HI 1 and daytime symptoms. OA/HI=obstructive apnea/hypopnea index; SNORE+=snoring + mild SDB (<OA/HI<15); SNORE=snoring with no SDB (OA/HI=). Bixler EO, et al. Am J Crit Care Med. 21;163: Kryger 27 5 Kryger 1/3/17 3:59:5 PM 49 Depression and Menopausal Transition Other Medical Conditions Associations between depressed mood and hormonal changes are controversial Recent evidence from a longitudinal cohort study suggests: Depressive symptoms are increased during the transition to menopause but decrease after menopause Relationship remained after adjustment for history of depression, severe PMS, poor sleep, age, race, and employment status Hormonal changes appeared to contribute to dysphoric symptoms Sleep problems are associated with a range of other medical conditions Coronary heart disease Irritable bowel syndrome Fibromyalgia Gastroesophageal reflux disease Pain Freeman EW, et al. Arch Gen Psychiatry. 24;61:62-7. Kryger Schwartz S, et al. J Psychom Res. 1999;47: ; Elsenbruch S, et al. Am J Gastroenterol. 22;97: ; Jennum P, et al. J Rheumatol. 1993;2: ; Raiha I, et al. Scand J Gastroenterol. 1993;28: ; McCracken LM, Iverson GM. Pain Res Manag. 22;7: Kryger

14 What Is the Diagnosis? What Is the Diagnosis? Hair loss Eyebrow loss Puffy eyes Kryger Kryger Hypothyroidism Distinguishing Age-related vs Menopausal Impacts on Sleep Menopausal symptoms become less common with time Goiter Other problems (depression, underlying medical conditions) become predominant causes of sleep problems with time Kryger Kryger

15 Managing Perimenopausal/Menopausal Sleep Problems First, ensure that poor sleep hygiene is not a contributing factor Second, look for other possible causes (eg, depression, hypothyroidism, apnea, arthritis) Third, consider a primary sleep disorder Then, look for menopause-related symptoms Use of Alternative Medicines Use of herbal stimulants and sedatives increased 38% between 199 and 1997 among US adults Knowledge of efficacy and possible adverse effects is inadequate Alternative medicines are MEDICINES Kryger Gyllenhall C, et al. Sleep Med Rev. 2;4: Kryger Herbal Stimulants and Sedatives Take-home Messages Stimulants Caffeine Ephedrine (Ma huang) Yohimbe Ginseng Siberian ginseng Sedatives Valerian German chamomile Kava Lavender Hops Lemon balm Passion flower Complaints of poor sleep are more common in women May be associated with reproductive cycle related disorders or events Menstrual cycle disorders Pregnancy, postpartum Menopausal transition These may be acting to cause sleep problems alone or in combination with other factors such as medical conditions Gyllenhall C, et al. Sleep Med Rev. 2;4: Kryger Kryger

16 Female OSAS Cases Use Healthcare Resources years Before Diagnosis Dollars Spent on Healthcare (millions) Female OSAS cases Obese controls from National Population Health Survey (NPHS) Non-obese controls from NPHS Diagnosis Before diagnosis After diagnosis Kryger