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Rochelle Goldberg, MD, FCCP, FAASM, DABSM Associate Professor, Internal Medicine Sidney Kimmel Medical College Thomas Jefferson University, Philadelphia PA Sleep Medicine Director, Main Line Health System
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List common sleep disorders and relevance for women at specific life stages
Identify risks of sleep disorders during pregnancy and post-partum
Describe the sleep changes and disorders during menopause
Review different treatment options and special considerations during life stages
DISORDERS
Insomnia
Restless legs syndrome (RLS) ◦ Periodic Limb Movements
in Sleep (PLMs)
Obstructive sleep apnea (OSA)
Narcolepsy/ Hypersomnia
LIFE STAGES
Child bearing years ◦ Pregnancy
◦ Post-partum
Menopause
Insomnia more common in women at all ages ◦ Girls 3.6 fold increase (3.4 to 12.2%) around menarche ◦ Boys 2.1 fold (4.3-9.1%) ◦ Female predominance continues into older age
Zhang J et al. Sleep 2016. 39(8):1563-1570
Restless legs syndrome ◦ Gender preference beginning with menarche ◦ Women:men almost 2:1 ratio
High prevalence during pregnancy Zhang J et al. JPsychosoRes 2014. 76(2):158-164
OSA ◦ Less “typical” symptoms in women
Pregnancy ◦ Two patients of concern for all sleep disorders’ treatment
Sleep symptoms Problems maintaining sleep
Early morning waking
Extended sleep onset
Associated symptoms 1st (69.9%): nausea, nocturia, back pain
3rd (23.7%): fetal activity, heartburn, leg cramps, dyspnea Flacco FL et al. ObstetGynecol 2010. 155(1):77-83
Mindell J et al. SleepMed 2015. 16(4):483-488
Reichner CA. ObstetMed 2015. 8(4):168-171
0.00%20.00%40.00%60.00%
Severity
0
20
40
60
80
1st 2nd 3rd
% by trimester
Hormonal changes ◦ Lower arousal threshold, increase fragmentation
Insomnia/ sleep deprivation ◦ Increased inflammatory state
Increased risks for mother and fetus
Other risks ◦ Gestational diabetes, elevated BP, depression
Labor and delivery ◦ Increased pain perception, longer duration of labor
◦ Increased C-sections, preterm labor and delivery LeeKA etal. AmJObstetGyn 2004.19(6):241-246
The dreaded “category C” Address nocturia and pain complaints • Behavioral measures=first line
Good sleep habits, adequate TST, Cautious napping Relaxation techniques, exercise,
prenatal yoga, massage Formal CBT-I
Benzodiazepines, selective benzodiazepine agonists, diphenhydramine
Medications cross placenta=potential fetal risk
Congenital malformations, preterm or low birth weight
3rd trimester: floppy baby or withdrawal
Conclusions? Unclear as study results vary and many do not address confounding factors (smoking, alcohol and maternal medical history) ◦ LiQ etal.JAllergyClinImmunolPrac2013.1(6):66-74
◦ GilboaSM et al. BirthDefectsRes2009. 85(2):137-50.
Maternal issues ◦ Postpartum depression, increased stress
• Infant issues: Lactation Many medications found in breast milk
Sedating effects on infant
Parting Question ◦ What is the potential risk to mother and child if insomnia is
NOT treated?
MarquesM etal. PsychRes 2011.186(2-3):272-280.
Reid KJ et al.Sleep2017.40(5)
Menopausal transition
Sleep fragmentation, nocturnal awakenings, poor sleep quality
Nocturia, Vasomotor symptoms
Ciano C et al. JObstetGynecolNeonatalNurs2017. 46(6):804-813
Gursoy AY etal. Climacteric2015.18(6):790-796
0
10
20
30
40
50
60
70
Associations ◦ Increased age, medical conditions, weight gain
◦ Lower melatonin levels circadian and sleep stability
Insomnia Risk ◦ Baseline depression, daytime sleepiness
◦ CNS active medication use
Health Risks ◦ Cardiovascular disease, metabolic syndrome
DanbyFW. AnnIntMed2005. 143(11):845-846.
Lampio L etal.Maturitas2016.94:137-142
Non-pharmacolgic: ◦ CBT-I, sleep restriction (SRT), (sleep hygiene in combo)
◦ YOGA
Medications: ◦ Goals for short term
◦ Combination with behavioral measures?
◦ Consider melatonin?
◦ Reassess treatment response regularly
Drake CL et al. Sleep 2019. 42(2)
Afonso RF etal. Menopause 2012. 19(2):183-193
Less fatigue, sleepiness
More energy, better productivity
Only CBT-I improved emotional well-being
Insomnia remission resulted in better reported overall health, social interactions; less pain, fewer hot flashes
Kalmbach DA. JCSM 2019 15(7)
More common in pregnant women than general population
Preexisting RLS may worsen with pregnancy and parity
Pregnancy related RLS carries 4 fold risk for chronic RLS later in life
Prevalence overall 21%, increasing from 1st to 3rd trimester; back to 4% after delivery ◦ Chen S etal. SleepMedRev 2018.40:43-54
◦ Dunietz GL etal. JClinSleepMed 2017.13(7):863-870
◦ Cesnik E etal. Neurology 2010.75(23):2117-2020.
Symptoms ◦ poor sleep quality, poor daytime function and sleepiness
Severity ◦ Moderate (2-3/week)to severe (4 +/ week)
Mechanism ◦ Iron deficiency, increased prolactin, estrogen and
progesterone; unclear
Health risks ◦ Gestational hypertension and diabetes, preeclampsia, preterm
birth, low birth weight (? Data) Oyieng’o DO etal. ClinicalTher2016. 38(2):256-274
Screening is important
Non-pharmacologic ◦ Low impact exercise
◦ Avoid exacerbating factors (coffee, alcohol and nicotine)
◦ Massaging/ vibrating pads
• Medication
◦ Assess iron stores
◦ Additional iron supplement (note prenatal vits standard)
◦ Prescription meds: lowest dose, shortest time
◦ Consider other medications that exacerbate RLS, ?wean Picchietti DL etal. SleepMedRev 2015. 22:64-77
Mechanisms ◦ Hormonal, aging and medical co-morbidities, and
medications(antidepressants, antipsychotics)
Treatment ◦ Existing medication review, weaning options ◦ Avoid alcohol, caffeine, nicotine ◦ Exercise ◦ Massage pads and similar ◦ Dopamine agonists, alpha-1-ligands
Allen RP etal. ArchInternMed 2004.164(2):196-202
Phillips B etal. ArchInternMed 2000.160(14):2137-2141
Women Men
Insomnia, restless legs, depression, nightmares, palpitations, hallucinations
BMI and aging
CVD, atrial fibrillation, hypertension ◦ Higher risk for heart failure
The usual snoring, apnea, nocturnal awakenings, sleepiness
BMI and aging CVD, atrial fibrillation,
hypertension
Prevalence 6-15%
Most common endocrine disorder in women of reproductive age
Associated with obesity, reduced fertility, insulin resistance, type 2 diabetes mellitus, depression, impaired quality of life
Overlapping comorbities with OSA
Limited studies on prevalence of OSA in PCOS pts
Endocrine society guidelines 2013, 2014 ◦ Screening overweight PCOS pts for OSA
Kahal H et al. ClinicalEndocrinology 2017. 87:313-319
Snoring is common
Risk higher with preexisting HTN and DM
Screening for preexisting sleep apnea and development during pregnancy; postpartum reassessment for OSA change
Heaths risks for untreated apnea ◦ Maternal
◦ Fetal
Izci B et al.EurRespirJ 2006.27(2):321-327
Ayyar L et al.SleepMedClin 2018.13:349-357.
Overall low ◦ Modified STOP-Bang study
15.4% intermediate risk, 3% high risk
62.5% sensitivity, 82.1% specificity for preeclampsia
◦ Prospective study nulliparous women
Low prevalence
If untreated OSA increased gestational HTN and DM
Older mothers with increased BMI
Assisted vaginal delivery and C-section
Lincott DG et al. SoAfricanJAnaesthAnalgesia 2017. 23(1):6-10
Varied results ◦ confounders re maternal health, other risk factors
IUGR, low birth weight, preterm delivery Placenta impact from OSA ◦ Increased placenta weight assoc with OSA severity and fetal
adiposity; independent of maternal BMI; leptin mechanism? Kidron D et al; Sleep 2019. 42(6)
Older mothers with higher BMI ◦ Preterm birth, low birth weight ◦ low Apgar scores, still birth ◦ increased NICU admissions
Troung KK, Guilleminault C.ExpertRevRespMed 2018. 12(3): 177-189
Small studies
Probable favorable impact on other reported risks (maternal and fetal)
Reduce or treat preeclampsia and eclampsia
No data for other treatments, such as OAT, on maternal fetal risks and outcomes at this time
◦ Lincott NC et al. SoAfrJAnaesthAnalgesia 2017. 23(1):6-10
Sex hormone changes ◦ Decreased estrogen and progesterone
Progesterone increases ventilatory drive, hypercapnic response and increases upper airway dilatory muscle tone; effects mediated by estrogen receptors
Leptin ◦ Hunger suppressing adipokine ◦ Stimulates breathing ◦ Pre-menopausal women leptin > men
More resistance to airway collapse
◦ Menopause, increased abdominal obesityleptin resistance JClinSleepMed 2005. 1(3)
AHI by BMI quartiles AHI by Neck Circumference
Quartiles
0
5
10
15
20
25
30
1 2 3 4
postmenopausal premenopausal
0
5
10
15
20
25
30
35
40
1 2 3 4
postmenopausal premenopausal
Cognition ◦ Both OSA and menopause are associated with cognitive
decline
◦ Early menopausal population with OSA showed greater cognitive issues than those without OSA
◦ Suggests another area for treatment recognition and intervention. Chitra L et al. Chest2014. 146(4) meeting abstract
Cardiovascular disease
Depression
Weight loss
Positive airway pressure
Oral appliances
Positional modification
Nasal airway splints
Upper airway nerve
stimulation
NOT hormonal therapy
Narcolepsy Type 1 (25), controls (75) ◦ Similar pregnancy outcomes ◦ Higher prevalence gestational DM, heavier birth weight, longer duration of breast feeding Calvo-Ferrandiz E, Peraita-Adrados R. JSleepRes 2018. 27(2): 268-272.
Narcolepsy Type 1 and Type 2 (249 subjects) ◦ Type 1 higher weight gain, impaired glucose metabolism, anemia, C-
section rate, neonatal adverse events (not severe) ◦ Maurovich-Horvat E et al. JSleepRes 2013. 22(5):496-512.
Treatment considerations ◦ No practice parameters for care of this patient population ◦ Most medications cross placenta and into breast milk
Low risk for teratogenicity, limited data ◦ Treatment survey (sleep experts)-varied responses
Most discontinued meds at conception Reduced or unchanged dosing during lactation
Thorpy M. SleepMed2013.14(4):367-376.
There are still unknowns:
Limited studies, small population sizes
However, we know that sleep disorders in general contribute to quality of life impairment and other health risks
And, it is now recognized that women and men are “entitled” to these disorders, though presentations may vary; and sometimes include 2 patients at once.
Thus, we should continue to:
Target patient and provider education on sleep disorders
Focus materials for subspecialists, particularly obstetrics
Encourage screening tool development, validation and use
Support more large population and prospective studies
