Which sleep disorder would the nurse monitor for in a woman who experiences menopausal symptoms

Purposes/Objectives: To compare sleep quality and disturbance, fatigue, and depressive symptoms between breast cancer survivors and healthy women experiencing hot flashes and to examine relationships among sleep and remaining variables (fatigue, depressive symptoms, and frequency of hot flashes).

Design: Cross-sectional, descriptive, comparative pilot study.

Setting: University-based outpatient setting.

Sample: 15 breast cancer survivors and 15 healthy women matched on age, race, and menopausal status. All women had untreated hot flashes (no hormone replacement therapy or other hot flash treatments).

Methods: Questionnaires (sleep quality and disturbance, fatigue, and depression); two ambulatory, 24-hour sternal skin conductance monitoring sessions (hot flash frequency); and medical records review.

Main Research Variables: Sleep quality and disturbance, fatigue, depressive symptoms, and objective hot flash frequency.

Findings: The majority of participants evidenced poor sleep quality and high sleep disturbance (73% of breast cancer survivors and 67% of healthy women above a cutoff score of 5). Sleep duration was significantly shorter for breast cancer survivors in contrast to healthy women. Nighttime flashes were experienced by 67% of breast cancer survivors and 37% of healthy women. No group differences were found in fatigue, depressive symptoms, or objective hot flash frequency. Global sleep scores were significantly positively correlated with fatigue and depression but not with hot flash frequency.

Conclusions: Findings suggest that sleep disturbance is common in menopausal breast cancer survivors and healthy women, is not necessarily related to hot flashes, and may stem from a multifactorial etiology.

Implications for Nursing: Menopausal breast cancer survivors who present with any one of these symptoms should be screened for all symptoms both during and after treatment.

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Page 2

Summary of methodology and findings of polysomnographic studies in chronological order, investigating sleep architecture measures in midlife women in relation to menopausal stages and/or hot flashes

Authors, Year	Participants	Methodology	Findings	Comment
Erlik et al., 198175	9 postmenopausal women (30–55 y, within 1–5 y of surgical or natural menopause; all with complaints of frequent and severe HFs) and 5 premenopausal women	• 3 consecutive lab PSG studies (first two nights were not recorded).• Objective hot flash monitoring (finger temperature + sternal skin conductance).• Premenopausal women studied in the follicular phase.• Focused on waking episodes. • Also investigated effects of E2 in 4 women (not discussed here).	• Post- vs. pre-menopausal women had more waking episodes.• 45 of 47 HFs recorded were associated with a waking episode within 5 min before or after HF onset.• Not all awakenings (40.3%) coincided with a HF. • For 25 of the HFs, onset of waking generally preceded maximal change in skin conductance.	• Shows association between HFs and waking. However, not all details of methods and results are provided, and HF methodology precedes standardization.67
Shaver et al., 198872	Women aged 40–59 y; 20 premenopausal, 32 perimenopausal; 24 postmenopausal	• Two consecutive lab PSG studies (first was adaptation night).• FSH measures used to confirm menopausal staging. • Participants recorded HFs in daily diaries and signaled perceived HFs during the night with an event marker.	• Similar PSG measures in all groups apart from progressive lengthening of REM latency across pre-, to peri- to post-menopausal groups. • Secondary analysis showed that peri- and post- menopausal women who reported HFs on daily diaries (39 symptomatic: 20 Peri, 19 Post) had longer TIB, longer ROL, and a trend for poorer SE than others. Controlling for age and depression, the group difference in SE became significant.	• Suggests that menopausal status has little impact on PSG measures in generally-healthy women. • PSG may differ in women symptomatic for HFs, although HFs were subjectively evaluated and not all women reported HFs on lab nights.
Woodward and Freedman, 199474	Postmenopausal women with (n=12) and without (n=7) hot flashes	• One home PSG study. • Objective hot flash monitoring (sternal skin conductance).	• Women with vs. without HF had more awakenings, stage changes, intermittent wake, and Stage 4 sleep, with less Stage 3 sleep and a shorter first REM period. • HF number in the 2h-period before sleep correlated with SWS in second period, however, number of HF during sleep did not correlate with total amount of SWS.	• HFs, as measured objectively, are associated with more sleep disturbance.• Stage 4 was higher in women with HF, but SWS overall did not differ between groups. • Limited by small sample and one PSG.
Polo- Kantola et al., 199970	63 healthy postmenopausal women aged 47–65 y; 75% had had a hysterectomy and/or oophorectomy and taken HT in the past.	• One night of PSG (placebo night).• Body movements, breathing patterns, and heart rate recorded with a static charge-sensitive bed.• Daily HF intensity (scale of 1–10) assessed with a diary for 14 days before PSG study. • Serum samples confirmed high FSH and low estradiol levels in all women.	• HFs did not correlate with any PSG or body movement measure. • Estradiol correlated negatively with movement arousals in SWS. FSH did not correlate with any measure.	• Findings suggest that perceived HF severity is unrelated to sleep architecture. • Limited by single night PSG and use of self- report HFs over past 14 days, with average HF severity scores being quite low.
Sharkey et al., 200371	Women aged 45–56 y; 13 premenopausal, 12 postmenopausal	• Two consecutive lab PSG studies.• FSH levels confirmed menopausal staging.• Premenopausal women studied in follicular phase. • None of the women had sleep complaints.	• PSG measures were similar apart from more Stage 1 and longer latency to SWS in premenopausal vs. postmenopausal. • Exploratory comparison of 5 women who reported HFs during recordings vs. others revealed no difference.	• Menopausal status has little impact on PSG measures in good sleepers. • Limited by small sample, although well- characterized and includes 2 PSGs.
Young et al., 200343	Probability sample of 589 pre-, peri-, and post-menopausal [with/without HT] women aged 31–68 y (98% Caucasian); analysis performed on 1024 observations from the group.	• One lab PSG study on between 1 and 3 visits, 4 y apart (~65% of the sample had at least one follow-up study). Data from all available nights were used in combined cross-sectional/ longitudinal models.• Occurrence of HFs assessed by interview/ questionnaire before bed in 412 women.• Menopausal stages determined from self-reported menstrual history. 15% used HT and 19% had hysterectomy/oophorectomy. • Considered potential confounding factors including age, BMI, caffeine and alcohol use, exercise, and AHI.	• Post- vs. pre-menopausal had more SWS (16.4% vs. 12.9%) and better SE (86.3% vs. 84.0%).• Peri- vs. pre-menopausal had more SWS (16.0 % vs. 12.9%) and less Stage 1 (7.6% vs. 8.9%).• Post-menopausal women with vs. without HT had more Stage 1 (9.2% vs. 8.1%) and less SWS (15.4% vs. 17.4%). • In sub-group analysis, PSG measures did not differ between women with or without self-reported HFs; this group’s characteristics are not specified so severity of HFs is unclear.	• Large, population-based study, controlling for age and other confounders, shows better sleep in peri- and post-menopausal than pre- menopausal women.• Unclear how many women changed menopausal stage across follow-ups; 35% of peri/ postmenopausal group were >10y postmenopausal at baseline. • Effect of surgical menopause is not explored.
Lukacs et al., 2004159	14 young/cycling (20–30 y), 37 older (40–50 y): 15 cycling, 12 ovariectomized + E2, 10 postmenopausal	• One lab PSG study with frequent blood sampling (stressor).• Reproductive hormone sampling. • Excluded women reporting HFs.	• All three older age groups had longer wake time and poorer SE than young group. • Age, but not E2, was associated with more wake and poorer SE.	• Suggests age-related and not menopausal stage-related sleep deficit in response to a stressor. • Limited by lack of baseline PSG.
Freedman and Roehrs, 200476	Women aged 46–51 y; 11 premenopausal, 12 postmenopausal with HF, 8 postmenopausal without HF	• Three consecutive lab PSG studies (first was adaptation/screening for sleep disorders).• Objective hot flash monitoring (sternal skin conductance).• Premenopausal women studied in follicular phase (confirmed with E2 levels). • Examined HF-wake events.	• No group differences in any PSG variables (averaged for both nights).• Women in HF group had 1–18 (median 5) HF per night, with most in Stage 2 (40%) and wake (34.2%). • Of awakenings occurring within 2 min of a HF, 55.2% occurred before and 40% after a HF; 5% occurred simultaneously.	• Presence of objective HF’s was not associated with disturbed sleep. • Well controlled study with two PSGs, objective HF measures, and micro-analysis of HF-wake events, although sample is small.
Freedman and Roehrs, 200677	Women aged 46–53 y; 12 premenopausal, 6 postmenopausal without HF, 18 postmenopausal with HF	• Four lab PSG studies (first was adaptation/ screening night).• One night warm (30 C), one night neutral (23 C), one night cold (18 C).• Objective hot flash monitoring (sternal skin conductance).• Premenopausal women studied in follicular phase (confirmed with E2 levels). • Examined HF-wake events.	• PSG measures (3 nights averaged) were similar in all groups apart from more awakenings in postmenopausal with HF vs. premenopausal group.• HF group had more arousals in the first half of the night than other two groups.• Of awakenings within 5 min of a HF, 59% occurred after and 26% before a HF in the first half of the night; 21% of awakenings occurred after and 64% before a HF in the second half.• Few HFs occurred in REM sleep. • Fewer awakenings on the cold night and fewer HFs in the first half of the cold night than other nights.	• Findings suggest that HF-wake associations differ according to halves of the night, with more HF-induced awakenings in the first half. Authors hypothesize fewer HF-induced awakenings in the second half may relate to more REM sleep since HFs are suppressed in REM sleep.• Cold suppressed HFs. • Limited by small sample and multiple levels of analysis of ambient temperature and halves of night.
Freedman and Roehrs, 2007128	102 women, aged 44–56 y (64% postmenopausal), with difficulty sleeping	• One lab PSG study. • Objective hot flash monitoring (sternal skin conductance).	• Major predictors of sleep efficiency were periodic limb movement index; apnea-hypopnea index; arousals related to sleep disorders; total number of arousals)	• Shows importance of considering sleep disorders in midlife women with sleep complaints: 53% of the group met criteria for a sleep disorder.
Kalleinen et al., 2008160	21 premenopausal (45–51 y), 29 postmenopausal (59–71 y), 11 young (20–26 y)	• Two lab PSG studies (first was adaptation).• Young women taking oral contraceptives.• Premenopausal and young women studied in early follicular phase.• Serum FSH and E2 used to confirm staging. • HF frequency in past 6 months determined from questionnaire.	• No differences in PSG measures between pre- and post-menopausal groups.• Pre- and post-menopausal groups vs. young: less TST, lower SE, less SWS, more wake time, lower delta power (slow wave activity). • No group differences in HF reports.	• Effect of age on sleep architecture is strong, with differences between young and older groups but not between midlife pre- and post- menopausal groups. • Limited by small sample; does not evaluate effects of HFs on sleep.
Sowers et al., 200834	365 women (ethnically diverse) in the SWAN sleep study: pre- or early peri-menopausal (n=246), late perimenopausal (n=78), and post-menopausal (n=41). All women were pre- or early-perimenopausal (menses in previous 3 months, but increased irregularity) at baseline (5–7 y before sleep study).	• 3 consecutive home PSG studies (first was adaptation/screening night). SWAN sleep study overlapped 5th, 6th, and 7th annual Core SWAN visits.• Premenopausal women studied in follicular phase.• Excluded women with surgical menopause or those using HT.• HFs assessed with a morning diary. • Serum samples from Core SWAN baseline visit and then annually for the next five-seven years were analyzed for Estradiol, FSH, Testosterone. Hormone measures at Core SWAN baseline visit and at the Core visit temporally preceding the sleep study (by 3–6 months) were examined in relation to PSG measures. Slopes of rates of change over time (5 to 7 y) were also related to PSG.	• Higher FSH at the core visit preceding PSG was associated with more WASO and higher AHI; these associations were no longer significant after adjustment for covariates (age, body size, ethnicity).• A greater rate of change in FSH from baseline to PSG was associated with more SWS and longer TST.• A FSH cutoff of 40 mIU/ml was not associated with PSG.• E2 was unrelated to PSG but a lower E2/ Testosterone ratio preceding the sleep study was associated with less WASO.• Lower testosterone at the baseline visit was associated with more WASO at PSG. • As a covariate in the analysis, no consistent effects were found for HFs.	• Longitudinal study that shows associations between hormone changes in midlife women approaching and transitioning menopause with PSG sleep.• A faster rate of change in FSH, possibly reflecting a faster hormone re-equilibration over time, was associated with longer sleep and more SWS (but poorer reported sleep quality). Further work is needed to understand these complex hormone-sleep interactions. • Many study strengths, such as longitudinal hormone analyses; however, PSG was sampled once, and blood samples were not proximal to PSG study and may have missed capturing some of the fluctuations.
Hachul et al., 2010161	524 premenopausal (38.8 ± 10.4 y) and 407 postmenopausal (55.9 ± 7.9 y) women, all with sleep complaints.	• One lab PSG study, including clinical sleep measures.• Premenopausal women classified according to menstrual cycle (regular or irregular), use of hormonal contraceptives, whether they were premenstrual, and if they had dysmenorrhea. • Postmenopausal women were divided into early and late, according to STRAW criteria.9 They were also classified based on HT and presence of HFs (questionnaire).	• Postmenopausal vs. premenopausal women had lower SE and %REM, and more %SWS (unadjusted for age).• Postmenopausal women 1.5 times more likely to have AHI>5, in analysis adjusted for age and BMI.• Premenopausal women with irregular vs. regular menstrual cycles had less Stage 2 sleep (unadjusted for age).• Late vs. early postmenopausal women had lower SE and higher AHI. • HFs and HT were not associated with SE<85% or AHI≥5 (adjusted analysis).	• Findings show modest effect of menopausal stage on PSG measures. Also, postmenopausal women are more likely to have clinically significant AHI (>5) vs. premenopausal women. • Some analyses are limited due to lack of adjustment for age. Also, while irregular menstrual cycles were evaluated, it is unclear if some of these women were perimenopausal.
Kravitz et al., 201173	343 women aged 48–58y (ethnically diverse) in the SWAN sleep study: pre- or early peri-menopausal (n=222), late perimenopausal (n=73), and post-menopausal (n=48).	• 3 home PSG studies (first was adaptation/ screening night).• Premenopausal women studied in follicular phase.• Excluded women with surgical menopause or those using HT.• HFs assessed with a morning diary.• Data was averaged for both nights where available.• Covariates included HFs, AHI, menopausal stage, sociodemographics, mood, health. • Focused analysis on HF-mood associations.	• Post-menopausal group had shorter sleep onset latency than pre/early perimenopausal group.• Women reporting HFs on either night (n=91) vs. those not reporting HFs had longer sleep duration but less %SWS.• Significant HF-state anxiety interaction for SE and sleep onset latency (increase in sleep onset latency and decrease in SE for each unit increase in anxiety in women with vs. without HFs). • Ethnicity influenced sleep measures.	• In this large, ethnically-diverse group, perceived HFs were not associated with poorer SE or more PSG-wake. Rather, they moderated the association between anxiety and poorer sleep, and were associated with longer sleep duration. • Limited by use of self-report HFs, and 65% of sample were pre-/early-perimenopausal, with majority not reporting HFs.
Campbell et al., 201144	321 pre- or early peri- menopausal (189), late perimenopausal (73), and postmenopausal (59) women, aged 48–58y (ethnically diverse) in the SWAN sleep study.	• Methods described above for Kravitz et al., 2011. • Analysis focused on PSG and EEG frequency analysis (central electrode).	• None of the PSG measures differed by menopausal stage.• Neither total delta (slow wave) power nor across-the-night decline in delta power differed by menopausal stage.• Beta and sigma EEG power in NREM were higher in late peri- and post-menopausal groups than the pre/ early-perimenopausal group. • Beta EEG power was higher in women reporting HFs vs. not.	• While PSG measures and delta power do not differ by menopausal stage, high beta EEG power in sleep suggests higher arousal level in late peri- and post-menopausal women, after controlling for age and other covariates. Increased arousal is partly explained by HF frequency. • Provides comprehensive EEG analysis in addition to PSG.
Joffe et al., 201379	29 healthy premenopausal women (18–45 y), treated with a gonadotropin-releasing hormone agonist to mimic menopause. Participants divided into 3 groups: persistent / frequent HF (n=10); persistent/ infrequent HF (n = 10); no HFs (n=9).	• Premenopausal volunteers received a single injection of GnRHa leuprolide.• One lab screening PSG + 4 at-home PSGs, two before and two after GnRHa (4 weeks later) treatment.• HFs assessed with diaries over 4-week period + objective HF monitoring on PSG nights (sternal skin conductance). • Serum reproductive hormone levels measured.	• Women who developed HFs reported a median of 1.6 HFs per night and 1.9 HFs per day in the week before PSG studies. A median of 3 HFs were recorded on post-treatment PSGs.• There was, on average, a 62% increase from baseline in PSG-WASO, 35% increase in number of awakenings, and 6% increase in Stage N1 sleep, for each HF reported. • Nocturnal HFs recorded correlated with PSG- WASO (wake increased by, on average, 6.3 min per HF). 66% of recorded HFs were associated with an awakening (within 5 min of HF).	• Results from this experimental model show that PSG measures of wake increase in relation to the number of HFs (reported and measured).• Majority (66%), but not all, of HFs were associated with an awakening. Also, additional awakenings occurred independent of HFs. • Strengths are the experimental design, use of objective and subjective measures of HFs and isolation of HF effects from age-related sleep changes.
de Zambotti et al., 201469	34 women (50.4±2.7 y) in menopausal transition or early postmenopausal, who had ≥ 1 recorded HF on ≥ 1 PSG recording.	• Between 1–5 lab PSG studies per subject, with a total of 222 HFs recorded. • Menopausal staging according to STRAW criteria.9 • Objective HF monitoring on PSG nights (sternal skin conductance). • Quantified HF-wake relationship and calculated a new index: HF-associated wake time.	• HF-associated wake contributed, on average, 27.2% of total WASO on a given night, with a large inter- subject range (0–89%).• 69.4% of HFs coincided with an awakening; 19.8% did not disturb sleep and 10.8% occurred after waking.• Few (3.6%) HFs occurred in REM. • Perceived WASO correlated with HF-associated wake time.	• Provides objective evidence that HFs are closely linked with awakenings. Also, HF- associated wake contributes a significant proportion of WASO in women with HFs. • Given the close association of wake and HFs, they may be driven by a common central process; however, results are correlational.
de Zambotti et al., 201546	33 women (43–52 y) in menopausal transition (16 with insomnia disorder, 17 without sleep complaints) and 11 premenopausal women (18–27 y) without sleep complaints.	• One lab PSG study (after adaptation/ screening night).• All studies in the follicular phase.• Blood sample collected at same time as sleep study for hormone analysis. • Menopausal staging according to STRAW criteria.9 • Objective HF monitoring on PSG nights (sternal skin conductance). • Investigated relationships between FSH and Estradiol with PSG measures, with age and BMI as covariates.	• Higher FSH was associated with lower SE, longer sleep onset latency, more WASO, more Stage N1 sleep, less REM, and a greater arousal index.• Higher estradiol was associated with a better SE, less WASO, more N2, and a lower arousal index.• In separate analysis by group, there were no significant hormone-sleep relationships in the group with insomnia. • Only 4 women had recorded HFs.	• Shows an association between FSH and PSG-measures of wakefulness in pre- and peri- menopausal women without sleep complaints. However, this relationship is not evident in the presence of insomnia, possibly due to other dominate factors that influence sleep in this group. • Results of this cross-sectional study are correlational and therefore do not imply causation.
Baker et al., 2015142	72 women (43–57 y) in menopausal transition (38 with insomnia disorder, 34 without sleep complaints)	• One lab PSG study (after adaptation/ screening night). • Menopausal staging according to STRAW criteria.9 • Objective HF monitoring on PSG nights (sternal skin conductance).• Blood sample to measure FSH, E2, and progesterone (to assess menstrual phase). • Models considered menopausal transition (early vs. late), insomnia diagnosis, menstrual phase, HFs, and depressive symptoms.	• Women with insomnia had shorter TST, more WASO, and more beta EEG power in REM than non-insomniacs. PSG results were concordant with self-reported sleep from daily diaries.• Women with vs. without HFs had more awakenings/h and longer time in bed.• Women with insomnia vs. without were more likely to have ≥ 1 recorded HF. • Presence of HFs was unrelated to spectral EEG measures.	• Suggests that insomnia developed in the menopausal transition is linked with a PSG- defined sleep deficit.• HFs play a role in a poorer sleep profile. • Suggests subgroups of women (with insomnia, HFs) may have disrupted PSG during the menopausal transition. However, analysis is based on a single PSG.
Hachul et al., 2015162	Women aged 20–80 y; 339 premenopausal, 53 early postmenopausal (<5 y), 118 late postmenopausal (>5 y), 25 using hormone therapy (HT) or isoflavones.	• One lab PSG study, including clinical sleep measures.• Postmenopausal status confirmed with serum FSH levels.• Premenopausal was defined as having an ongoing menstrual cycle. They were studied regardless of menstrual phase. • HFs (yes/no) determined from questionnaire.	• In analysis adjusting for age, BMI, blood pressure, and neck, waist and hip circumference, postmenopausal women had more %N3 (SWS) and higher AHI, and lower SaO2 measures than premenopausal women. There were no differences in early vs. late postmenopausal groups in adjusted analysis. • Women with vs. without HFs had a longer sleep onset latency.	• Findings show a modest effect of postmenopausal stage on sleep, independent of age and other confounders, with postmenopausal women having more SWS and higher AHI, associated with lower oxygen saturation levels, than premenopausal women. • Limited due to lack of an adaptation night or control of menstrual phase. Also, comparison does not include perimenopause.
Bianchi et al., 201680	28 healthy premenopausal women (18–45 y), treated with a gonadotropin-releasing hormone agonist to mimic menopause.	• Protocol is described above in Joffe et al. (2013). • Analysis focused on correlation between HF frequency (objective and self-report) and treatment-related change in sleep-stage transition rates to Wake or Stage N1 sleep.	• TST and TIB correlated with recorded number of HFs.• After adjusting for time in each sleep stage, most HFs occurred in wake (51%) and Stage N1 sleep (18.8%), with few in REM (5.6%).• 80% HFs occurred before or coincident with an awakening; this pattern was evident in both halves of the night. • Reported, but not recorded, HFs correlated with an increase in transition rate to Wake or Stage N1 sleep.	• Findings from this experimental model support a link between HFs and sleep interruption.
Lampio et al., 201745	60 premenopausal women (46 y old) at baseline, studied 6 y later. At follow-up: 23 postmenopausal; 12 menopausal transition (irregular cycles); 12 premenopausal (regular cycles); 6 hysterectomy; 7 hormonal intra-uterine device.	• One lab PSG study each at baseline and 6 years later (follow-up). Included clinical sleep measures and spectral EEG analysis.• Serum reproductive hormone levels measured on day of sleep study.• Premenopausal women studied in follicular phase. • Considered BMI, HFs, depression symptoms in analysis.	• In adjusted analysis, aging 6 years was associated with shorter TST, lower SE (by 6.5%), increased transitions from SWS to wake, and increased WASO, awakenings/h, and arousals/h.• In adjusted analysis, an increase in FSH of 1 unit was associated with an increase of 0.09% in SWS [e.g. increase of 37 units over 6 years is associated with an increase of 3.3% SWS]. • There was no significant association between age or FSH with AHI or SWA, in adjusted analysis.	• In this follow-up design, stronger relationships are shown between aging versus a change in FSH (continuous marker of the menopausal transition) with changes in PSG measures. Authors hypothesize that the positive relationship between FSH and SWS may reflect a coping mechanism for increased age- related sleep fragmentation.