Insomnia: Special Considerations for Specific

Populations of Women

Kin M. Yuen, MD, MS

FAASM, D, ABSM

Medical Director

Bay Sleep Clinic, CA

Sleep Needs Vary by Age

• Infants:– 16-18 hours of total sleep time (TST) daily– Begin nocturnal sleep with rapid eye movement

(REM) cycle

• Age 1: – ↓ to 14 hours of total daily sleep– Begins “adult pattern” of alternating nonREM to REM

cycles

Average Hours of Sleep Vary by Age

Iglowstein I, Jenni OG, Molinari L, Largo RH. Pediatrics. 2003;111:302-307.

Adolescence

• Slow-wave sleep (SWS) begins to decline• Tendency toward later time to bed and time

to rise: – Delayed sleep phase syndrome

Normal Sleep for Healthy Adults

• Average total nocturnal sleep time is 7.5-8 hours• Sleep latency: 10-15 minutes• Sleep stages of TST

– 5% stage 1– 50% stage 2– 15%-25% stages 3 and 4 SWS– 20%-25% REM

Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Sleep. 2004;27:1255-1273.

Aging

• More lighter stages of sleep (stage 1)• Less SWS

– Women with more preserved SWS objectively• Age 60->70 years

– Men 6-7% TST

– Women 17% TST

– Women with more subjective complaints

Redline S, Kirchner HL, Quan SF, Gottlieb DJ, Kapur V, Newman A. Arch Intern Med. 2004;164:406-418.

Insomnia is Highly Prevalent

• Chronic insomnia is estimated to affect 10% (range 9%-24%) of the population1

• 30% to 50% of the general population are estimated to have insomnia of any duration or severity

• “The prevalence of insomnia symptoms generally increases with age, while the rates of sleep dissatisfaction and diagnoses have little variation with age”2

1. Agency for Healthcare Research and Quality. Manifestations and Management of Chronic Insomnia in Adults.http://www.ahrq.gov/downloads/pub/evidence/pdf/insomnia/insomnia.pdf. Accessed February 11, 2008.2. Ohayon MM. Sleep Med Rev. 2002;6:97-111.

National Sleep Foundation 2003 Poll

• One or more symptoms of a sleep problem– Age 55-64: 71%– Age 65-74: 65%– Age 75-84: 64%

• Insomnia with more than 1 symptom– Women: 50%– Men: 45%

• 22% age 55-64 and 46% age 75-84 nap 1-3 times/week

National Sleep Foundation. 2003 Sleep in America Poll. http://www.kintera.org/atf/cf/{F6BF2668-A1B4-4FE8-8D1A-A5D39340D9CB}/2003SleepPollExecSumm.pdf. Accessed February 11, 2008/

Menstrual Cycle

• Early in the cycle: more airway resistance– Pain/discomfort disturbed sleep

• Later cycle– Excessive daytime sleepiness– Insomnia: trouble falling asleep, staying asleep,

nonrefreshing sleep

Hormonal Effects on Sleep

• Inconsistent reported effects on SWS• Estrogen

Turnover of norepinephrine in brain

Variable effects on REM sleep

Hormonal Effects

• Estrogen– Variable effect on REM1

• Progesterone– Sedating2

– Increases NREM2

– Lack/withdrawal: difficulty falling asleep2

1. Manber R, Kuo TF, Cataldo N, Colrain IM. Sleep. 2003;26:163-168.2. Eichling PS, Sahni J. J Clin Sleep Med. 2005;1:291-300.

Estrogen and Sleep

• Humans: REM sleep cycles1

– REM sleep latency?1

– Number of spontaneous arousals1

• Postestrogen replacement– Sleep onset latency (SOL)2

– Wake after sleep onset (WASO)– TST– REM2 and SWS3

1. Eichling PS, Sahni J. J Clin Sleep Med. 2005;1:291-300. 2. Schiff I, Regestein Q, Tulchinsky D, Ryan KJ. JAMA. 1979;242:2405-2404. 3. Manber R, Kuo TF, Cataldo N, Colrain IM. Sleep. 2003;26:163-168.

Hormonal Effects on Sleep

• Progesterone• NREM sleep1

– Exogenous:• Benzodiazepine-like sedation in men and women1

• Active metabolites: Pregnanolone1

• α-aminobutyric acid (GABA) receptor1 • Dose-dependent sleep onset (SO), WASO

– May sleep spindle frequency

Manber R, Armitage R. Sleep. 1999;22:540-555.

Sleep and the Menstrual Cycle

• SO and maintenance insomnia• Overall: subjective sleep complaints late

luteal phase SOL Wake after SO ↓ Sleep efficiency

Menstrual-related Sleep Disorder

• Changes in sleep architecture: – SWS– REM– SO latency – Wakefulness after SO– Sleep efficiency

Sleep and Pregnancy

• Subjective complaints– Excessive daytime sleepiness1

– Many hormones responsible Progesterone, β-human chorionic gonadotropin,

prolactin, luteinizing hormone– Fatigue, body temperature– Shortness of breath

Franklin KA, Holmgren PA, Jönsson F, Poromaa N, Stenlund H, Svanborg E. Chest. 2000;117:137-141.

Sleep and Pregnancy (cont’d)

• Severe insomnia Abdominal mass, fetal movements, bladder distention

• Others: leg cramps, acid reflux, backache• Primiparous >multiparous in sleep disturbances

Sleep in Pregnancy

• First trimester: – TST, SWS

• Second trimester: – TST nla

– SWS/REM

• Third trimester: – TST, SO

• WASO

• Arousals/awakenings(3-5x)

• REM

• SWS

• Sleep efficiency

a19% persistent problemLee KA, Zaffke ME, Baratte-Beebe K. J Womens Health Gend Based Med. 2001;10:335-341.

Pregnancy and Snoring

• 23% women report onset of snoring in pregnancy(third trimester)1

• 14% reported snoring often or always (4% of nonpregnant)1

• Snoring during pregnancy is associated with hypertension and preeclampsia2

• Obstructive sleep apnea syndrome: case reports, intrauterine growth retardation (IUGR)1

• Especially obese women3, polycystic ovary syndrome

1. Loube DI, Poceta JS, Morales MC, Peacock, MD, Mitler MM. Chest. 1996;109:885-889.2. Edwards N, Middleton PG, Blyton DM, Sullivan CE. Thorax. 2002;57:555-558.3. Franklin KA, Holmgren PA, Jönsson F, Poromaa N, Stenlund H, Svanborg E. Chest. 2000;117:137-141

Pregnancy: Periodic Limb Movement, Restless Leg Syndrome • May be associated with:

– Fe deficiency anemia – Type-2 diabetes – Uremia– Symptoms usually subside postpartum

• 15%-25%1,2 women develop restless leg syndrome in third trimester– Conservative treatment before third trimester–

avoid caffeine

1. Lee KA, Zaffke ME, Baratte-Beebe K. J Womens Health Gend Based Med. 2001;10:335-341. 2. Goodman JDS, Brodie C, Ayida GA: Restless legs syndrome in pregnancy. BMJ 1998;297:1101-1102.

Postpartum Sleep

• 30% new mothers report disturbed sleep• Sleep efficiency in first 2-4 weeks <third

trimester • Average 2 hours time of wakefulness (WASO)• First-time mothers’ sleep most disturbed• Some rebound of stage 4, but REM• Women with premature infants have TST,

WASO• Alterations in melatonin, cortisol

Wolfson AR, Lee KA. Pregnancy And The postpartum period: sleep during postpartum recovery. In: Kryger MH, Roth T, Dement W. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Saunders; 2005:1280-1281.

Postpartum Depression and Sleep

• Nighttime labor (↑oxytocin) and sleep disruptions (third trimester) associated with depressed mood after childbirth

• REM latencies associated with depressed mood• Likely multifactorial; heightened reaction to stress

Postpartum Depression

• Baby blues– Very common: 50%-80% of all new mothers– 2 weeks after delivery: about Day 3 to Day 5

• Postpartum depression– 10%-20% of new mothers– May last up to 1 year– Major depression symptoms– 50% with past history of depression– Insomnia to overwhelming fatigue– Negative feelings toward baby, resentment

• Postpartum psychosis– Rare: 0.1% of new mothers– 3 weeks after delivery– Past history of bipolar disorder

Cohen LS, Altshuler LL, Harlow BL, et al. JAMA. 2006;295:499-507.

Persistent Major Depression

• Of 201 women who discontinued antidepressants, 86 (43%) relapsed throughout pregnancy

• 82 controls maintained medication, 21 (26%) relapsed – Hazard ratio 5.0, 2.8-9.1; P<0.001

Cohen LS, Altshuler LL, Harlow BL, et al. JAMA. 2006;295:499-507.

Pregnancy Summary 1

• First trimester– ↑ TST

• Second trimester– ↓ SWS and REM sleep

• Third trimester– Fragmented sleep

Pregnancy Summary 2

• General decrease in parasomnia• Beware of new onset snoring before

second trimester; correlation with preeclampsia• Restless legs movement more common in

third trimester• Postpartum depression in 10%-20% of

new mothers– Antidepressants (eg, selective serotonin reuptake

inhibitors [SSRIs] may be justified)

Cohen LS, Altshuler LL, Harlow BL, et al. JAMA. 2006;295:499-507.

Narcolepsy1,2

• Disability/early maternity leave• Letter to employer to allow naps• Avoid medications during first trimester and

when nursing• If benefit outweighs risks:

– Cataplexy: GHB/SSRIs – Insomnia: GHB or zolpidem – Excessive daytimes sleepiness: weaker

stimulants/modafinil – Pregnancy test before initiating medications?

1. Morgenthaler TI, Kapur VK, Brown T, et al. Sleep. 2007;30:1705-1711. 2. Wise MS, Arand DL, Auger RR, Brooks SN, Watson NF; American Academy of Sleep Medicine. Sleep. 2007;30:17121727.

Stimulants

Drug Indication/Warning

Modafinil For ages 16 to 65; nursing caution

α-hydroxybutyrate (GHB) (Xyrem) >16; not for use while nursing

Pemoline >16; not for use while nursing

Atomoxetine >Age 6

Dexedrine >Age 3

Ritalin >Age 6 (not for use during pregnancy?)

1. The Physician’s Desk reference Web site. http: www.pdr.net. Accessed March 10, 2008.2. Wake-Promoting Medications: Efficacy and Adverse Effects. In: Kryger MH, Roth T, Dement W. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Saunders; 2005:1280-1281.

Insomnia and Menopause

Cláudio N. Soares, MD, PhD, FRCPCAssociate Professor of Psychiatry and

Behavioral Neurosciences Director, Women’s Health Concerns Clinic

McMaster University, Ontario, CanadaLecturer in Psychiatry

Harvard Medical School

Boston, Massachusetts

Disclosures

• Grants/research support: National Alliance for Research on Schizophrenia and Depression (NARSAD); Eli Lilly and Company; AstraZeneca Pharmaceuticals LP (Canada); Physicians Service Incorporated (PSI) (Canada); Allergen, Inc. (Canada)

• Consultant: Forest Laboratories, Inc.; GlaxoSmithKline (Canada); Neurocrine Biosciences, Inc.; Sepracor Inc.; Concert Pharmaceuticals; Wyeth Pharmaceuticals Inc.

• Speaker’s bureau: AstraZeneca Pharmaceuticals LP (Canada); Forest Laboratories, Inc.; GlaxoSmithKline (Canada); H. Lundbeck A/S (Canada); Pfizer Inc.; Wyeth Pharmaceuticals Inc. (Canada)

Insomnia Is More Prevalent In Women1,2

• Various studies have identified female gender as a strong risk factor for insomnia

• Overall, women are about 1.4 times more likely to report insomnia than men

• Heightened psychiatric morbidity and different impact of sex steroids may play an important role

1. Ohayon MM. Sleep Med Rev. 2002;6:97-111.2. Soares CN, Murray BJ. Psychiatr Clin North Am. 2006;29:1095-1113.

Risk Factors for Insomnia1-3

Age/ Gender

Medical Psychiatric Social LifestyleSleep

Environment• Female• Elderly

• Primary sleep disorder• Obesity• Pain • Arthritis• Alzheimer’s disease• Parkinson’s disease• Heart disease• Respiratory disease• Gastrointestinal disease• Sleep apnea, restless

leg syndrome• Thyroid disorder• Menopause

• Depression• Anxiety• Tension• Substance or

alcohol abuse• Mania or

hypomania• Stress• Worry• Conditioning

• Marital separation

• Divorce• Death of spouse• Unemployment• Poor working

conditions• Lower social

status

• Smoking• Drinking alcohol or

drinks containing caffeine in the afternoon or evening

• Exercising close to bedtime

• Irregular schedule• Night-shift work

• Temperature • Lighting• Noise• Interruptions• Partner’s sleep

habits

1. Buscemi N, Vandermeer B, Friesen C, et al. (Prepared by the University of Alberta Evidence-based Practice Center, under Contract No. C400000021.) AHRQ Publication No. 05-E021-2. Rockville, Md: Agency for Healthcare Research and Quality. June 2005. Available at: http://www.ahrq.gov/downloads/pub/evidence/pdf/insomnia/insomnia.pdf. Accessed January 29, 2008.

2. Doghramji PP. J Clin Psychiatry. 2004;65(suppl 16):23-26.3. Doghramji PP. J Clin Psychiatry. 2001;62(suppl 10):18-26.

Insomnia and Comorbid Conditions:An Important Factor During Menopause?

• Insomnia is highly prevalent among patients with other medical and psychiatric illnesses and may:– Worsen clinical outcomes and impact

quality-of-life (QoL)1

– Predispose patients to recurrence2

– Persist despite treatment of the primary condition3

– What happens during the menopausal transition?

1. Katz DA, McHorney CA. J Fam Pract. 2002;51:229-235.2. Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Am J Epidemiol. 1997;146:105-114.3. Ohayon MM, Roth T. Psychiatr Res. 2003;37:9-15.

What about women during the menopausal transition

and postmenopausal years?

1. Kronenberg F. Ann N Y Acad Sci. 1990:592:52-68.2. Bachmann GA. J Reprod Med. 2005;50:155-165. 3. Cedars MI, Evans M. Menopause. In: Scott JR, Gibbs RS, Karlan BY, Haney AF, eds. Danforth‘s Obstetrics and Gynecology.

Philadelphia, PA: Lippincott Williams & Wilkins; 2003:721-737.4. Bromberger JT, Meyer PM, Kravitz HM, et al. Am J Public Health. 2001;91:1435-1442. 5. Schmidt PJ, Haq N, Rubinow DR. Am J Psychiatr. 2004;161:2238-2244. 6. Dennerstein L, Dudley E, Burger H. Fertil Steril. 2001;76:456-460. 7. Dugan SA, Powell LH, Kravitz HM, et al. Clin J Pain. 2006;22:325-331.

Physiological Symptoms Hot flashes (day and night)1

Sleep disturbances1,2

Urogenital complaints3

Somatic Symptoms Aches and pain7

Fatigue1

Psychological Symptoms Irritability1,2

Depressive symptoms4,5

Mood disturbances1

Low libido6

Menopausal Women Report a Variety of Symptoms: Physiological, Psychological, and Somatic

Menopausal Transition(lasts average of 5

years)

Postmenopause(recognized

12 months post-final menstrual period (FMP))

Early Late Early Late

Perimenopause

Variable cycle length

≥2 skipped cycles and interval of

amenorrhea

Am

en

orrh

ea

x 12

mo

nth

sNone

FMP

Premenopausal years

Hormonal fluctuations

Adapted from: Cedars MI, Evans M. Menopause. In: Scott JR, Gibbs RS, Karlan BY, Haney AF, eds. Danforth‘s Obstetrics and Gynecology. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:721-737.

Menopause

Postmenopausal years

1. Soares CN. Expert Rev Neurother. 2007;7:1285-1293. 2. Rocca W, Bower JH, Maraganore DM, et al. Neurology. 2007;69:1074-1083.3. Almeida OP, et al. Arch Gen Psychiatry. 2007; In press.

Window of Vulnerability1-3

• Heightened prevalence of mood and sleep disturbances during periods of intense hormone variability/fluctuation

• Adverse outcomes resulting from the disruption of hormone milieu

1. Soares CN, Almeida OP, Joffe H, Cohen LS. Arch Gen Psychiatry. 2001;58:529-534. 2. Rocca WA, Bower JH, Maraganore DM, et al. Neurology. 2007;69:1074-1083.

Window of Opportunity1,2

• A stable hormone milieu or hormone interventions may exert a prophylactic (eg, neuroprotective) effect

• Hormone intervention/modulation may exert a therapeutic effect

Sleep and Menopause

• Peri- and postmenopausal women have more sleep complaints than younger women1

• 41% of early perimenopausal women report sleep difficulties2; many are at higher risk for developing depressive symptoms

• Frequent awakenings• Difficulty falling back to sleep• Difficulty falling asleep

1. Young T, Rabago D, Zgierska A, Austin D, Laurel F. Sleep. 2003;26:667-672.2. Gold EB, Sternfeld B, Kelsey JL, et al. Am J Epidemiol. 2000;152:463-473.

Sleep and Menopause (cont’d)

• Frequent awakenings suggest insomnia is secondary to vasomotor symptoms1

• More common in women with surgical menopause

• However, waking episodes may occur in absence of hot flashes2,3

1. Woodward S, Freedman RR. Sleep. 1994;17:497-501.2. Polo-Kantola P, Erkkola R, Irjala K, et al. Obst Gynecol. 1999;94:219-224.3. Harlow B, et al. Arch Gen Psychiatry. In press.

Sleep-disordered Breathing in Menopause

• The prevalence of obstructive sleep apnea syndrome (OSAS) in women appears to increase with age. Diminishing progesterone levels during menopause may be a cause of OSAS, as progesterone is a known respiratory stimulant and upper airway dilator1

• Increased body weight associated with menopause may also be a cause. However, menopause is associated significantly with increased risk of OSAS, independently of body weight2

• Some of this effect may be mediated by testosterone, which may decrease the threshold for the occurrence of apnea3

1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. N Engl J Med. 1993;328;1230-1235.2. Young T, Rabago D, Zgierska A, Austin D, Laurel F. Sleep. 2003;26:667-672.3. Zhou XS, Rowley JA, Demirovic F, Diamond MP, Badr MS. J Appl Physiol. 2003;94:101-107.

Treatment of Insomnia in Symptomatic Women During Menopausal Transition or Postmenopause1-5

• Overall, sleep hygiene measures, sleep agents, and behavioral approaches might be helpful

• Few studies have focused on these specific subpopulations. Among these, positive results have been described with use of:

- Hormonal therapy

- Antidepressants (with comorbid conditions)

- Hypnotic agents1. Dorsey CM, Lee KA, Scharf MB. Clin Ther. 2004;26:1578-1586.2. Polo-Kantola P, Erkkola R, Irjala K, Pullinen S, Virtanen I, Polo O. Fertil Steril. 1999;71:873-880.3. Gambacciani M, Ciaponi M, Cappagli B, et al. Maturitas. 2005;50:91-97.4. Joffe H, Soares CN, Petrillo LF, et al. J Clin Psychiatry. 2007;68:943-950. 5. Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L. Obstet Gynecol. 2006;108:1402-1410.

Sleep Hygiene Rules1,2

Rule Rationale

1. Curtail time in bed Excessive time in bed can lead to fragmentation of sleep

2. Keep a regular sleep schedule (especially morning rise time)

Stabilization of circadian rhythms; limits time in bed (rule 1)

3. Eliminate the bedroom clock Watching the clock can lead to rumination and worry during nighttime wakefulness

4. Exercise in the afternoon/early evening

May deepen sleep and if timed correctly, may shorten sleep onset

5. Avoid caffeine, nicotine, and alcohol

All can negatively impact sleep. Caffeine and nicotine are stimulants. Metabolism of alcohol disrupts sleep

1. Stepanski EJ, Wyatt JK. Sleep Medicine Reviews. 2003;7:215-225.2. Hauri P. The sleep disorders. 2nd ed. Kalamazoo, Michigan: Upjohn Pharmaceuticals, 1977.

Sleep Hygiene Rules1,2 (cont’d)

Rule Rationale

6. Eat a light bedtime snack Avoids awakenings from drop in blood sugar at night

7. Sleep in a quiet, dark bedroom Noise and light cause awakenings from sleep. Light also impacts circadian rhythms

8. Enhance sleep environment Comfortable temperature, good mattress

9. Avoid “trying” to sleep Reduces development of anxiety/worry about sleeplessness

10. Limit or avoid daytime napping

Daytime napping reduces the amount of sleep needed at night

1. Stepanski EJ, Wyatt JK. Sleep Medicine Reviews. 2003;7:215-225.2. Hauri P. The sleep disorders. 2nd ed. Kalamazoo, Michigan: Upjohn Pharmaceuticals, 1977.

Estrogen in the Management of Sleep Disturbance

• Estrogen improves sleep quality in menopause• Improvement in sleep only partially associated

with reduction in hot flashes• Estrogen is likely impacting sleep independent of

vasomotor symptoms

Sleep Improvements With Hormone Therapy

• Sleep disturbance improved in symptomatic and asymptomatic women

Polo-Kantola P, Erkkola R, Helenius H, Irjala K, Polo O. Am J Obstet Gynecol. 1998;178:1002-1009.

Sleep Improved

More Tired

More Restless

Less Awakenings

Harder Falling Asleep

More Morning Tiredness

Sleep Generally ImprovedFully

DisagreeNo

DifferenceFully Agree

Low-dose Hormone Therapy With Micronized Progesterone or Medroxyprogesterone Acetateand Sleep• Low-dose Estrogen

(Premarin 0.3 mg) improved sleep scores over placebo

• Micronized progesterone (MP) had a greater benefit than medroxyprogesterone acetate (MPA) 2.5 mg

aP<0.05 vs corresponding baseline and control group levelsbP<0.05 corresponding control and CE + MPA group valuesGambacciani M, Ciaponi M, Cappagli B, et al. Maturitas. 2005;50:91-97.

Vasomotor Score

Sleep Score

Control Group CE 0.3+MPA CE 0.3+P

10

8

6

4

2

0

Weeks

0 4 8 12

0 4 8 12

10

8

6

4

2

0

aa a

a a a

b b b

Weeks

Effects of Hormone Therapy on Sleep Polysomnography in Postmenopausal Women

Treatment n Main Findings

Oral CEE 0.625 mg/day1 + MPA 20 mg/day (7 days)

9 NEGATIVE: No improvement in PSG parameters

Oral CEE 0.625 mg/day2

+ norgestrel 0.15 mg/day(10 days, 12 weeks)

33 NEGATIVE: No improvement in PSG parameters

Oral CEE 0.625 mg/day3

(4 weeks)7 POSITIVE: Improvement of sleep efficiency,

decrease in awakenings, decrease in HF

Transdermal estradiol4

50 g/d (7 months)62 POSITIVE: Decrease of movement arousals

Oral CEE 0.625 mg/day5

+ MPA 5 mg/day or micronized PROG 200 mg/day (6 months)

21 POSITIVE: Improvement of sleep efficiency, reduction of WASO, improvement of QoL among women receiving micro PROG, but not MPA

CEE, conjugated equine estrogens; PROG, progesterone; HF, hot flashes; WASO, wake time after sleep onset 1. Pickett CK, Regensteiner JG, Woodard WD, et al. J Appl Physiol. 1989;66:1656-1661.2. Purdie DW, Empson JA, Crichton C, Macdonald L. Br J Obstet Gynaecol. 1995;102:735-739.3. Scharf MB, McDannold MD, Stover R, Zaretsky N, Berkowitz DV. Clin Ther. 1997;19:304-311.4. Polo-Kantola P, Erkkola R, Irjala K, et al. Fertil Steril. 1999;71:873-880.5. Montplaisir J, Lorrain J, Denesle R, Petit D. Menopause. 2001;8:10-16.

Treatment With Escitalopram vs MHT for Menopause-related Depression and Quality-of-Life

• Changes from baseline in depressive scores (MADRS), and in QoL (MENQOL) and after 8 weeks of treatment with escitalopram (n=16) or hormone therapy (n=16); LOCF analyses

Soares CN, Arsenio H, Joffe H, et al. Menopause. 2006;13:780-786.

0

5

10

15

20

25

MADRS Baseline

MADRS Week 8

MENQOL Baseline

MENQOL Week 8

Med

ian

Sco

res

Escitalopram Hormone Therapy

0

3

6

9

12

Me

dia

n S

co

res

(P

QS

I) Escitalopram

Hormone Therapy

Escitalopram vs Hormone Therapy on Sleep Among Depressed and Menopausal Women

• Hormone therapy: improvement in PSQI total scores, sleep quality, disturbance (P<0.05). Escitalopram: improvement in PSQI total scores, sleep quality, daytime dysfunction (P<0.05)

Soares CN, Arsenio H, Joffe H, et al. Menopause. 2006;13:780-786.

Treatment of Depression and Menopause-related Symptoms With the Serotonin-norepinephrine Reuptake Inhibitor Duloxetine

Joffe H, Soares CN, Petrillo LF, et al. J Clin Psychiatry. 2007;68:943-950.

Wake Time After Sleep OnsetSleep Maintenance

a aa

a

aP<0.01

Change in Nighttime Hot Flashes

0

10

20

30

40

50

60

70

Baseline Week1 Week 2 Week 3 Week 4

Min

ute

s (m

ed

ian

)

PlaceboEszopiclone

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

Total Awakenings

Awakeningsdue to HF Severity

Le

ast

Sq

ua

res

Me

an

P<0.05

P=0.03

P=0.9

PlaceboEszopiclone

Eszopiclone Treatment During Menopausal Transition: Sleep Effect and Impact on Menopausal Symptoms

Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L. Obstet Gynecol. 2006;108:1402-1410.

In Summary…

• Hormone variations may contribute to the development of some mood, sleep, and somatic complaints—windows of vulnerability

• Hormone milieu and/or hormone interventions may attenuate the risk for/severity of these complaints—windows of opportunity

In Summary…(cont’d)

• Insomnia appears to be more prevalent in aging women and may occur in the absence of HF

• Estrogen therapy may improve subjective sleep quality and well-being. Improvement may occur regardless of the presence of HF; the use of different progestins may attenuate the benefits

In Summary…(cont’d)

• Studies on hormone therapy and objective sleep quality measures, including sleep-disordered breathing, have shown mixed results

• Antidepressants may be effective, particularly with comorbid HF, depression and/or anxiety

• Hypnotics may be an effective, safe treatment for insomnia and improvement of daytime function during menopause