Grace W. Pien

Symptoms associated with menopausal transition and reproductive hormones in midlife women.

OBJECTIVE: To test the hypothesis that prevalence of women with menopausal symptoms of hot flushes; aches, joint pain, and stiffness; depressed mood; poor sleep; decreased libido; or vaginal dryness increases with progression through the menopausal transition. METHODS: Women in the Penn Ovarian Aging Study were assessed longitudinally for 9 years. Data were obtained from structured interviews, a validated symptom questionnaire, menstrual bleeding dates and early follicular hormone measures (estradiol [E2], follicle-stimulating hormone [FSH], and inhibin b). Menopausal stages were based on menstrual bleeding patterns. Other risk factors included age, race, history of depression, current smoking, body mass index, and perceived stress. Generalized linear regression models for repeated measures were used to estimate associations among the variables with each symptom. RESULTS: The prevalence of hot flushes; aches, joint pain, and stiffness; and depressed mood increased in the menopausal transition. Menopausal stage was associated with hot flushes (P<.001); aches joint pain, and stiffness (P<.001); and depressed mood (P=.002). Within-woman fluctuations of E2 were associated with hot flushes and aches. Poor sleep, decreased libido, and vaginal dryness were not associated with menopausal stages. There was 80% power to detect an absolute difference of 11% for libido and vaginal dryness and 17% for poor sleep in the prevalence of these symptoms in the late menopausal transition compared with premenopausal status. CONCLUSION: The study highlights the role of menopausal stages for some symptoms of midlife women and indicates that stages in the transition to menopause are associated with hot flushes; aches, joint pain, and stiffness; and depressed mood. Fluctuations of E2, decreased levels of inhibin b, and increased FSH levels were associated with these symptoms. LEVEL OF EVIDENCE: II

Sleep deprivation during pregnancy and maternal and fetal outcomes: Is there a relationship?

Sleep duration in the population has been declining. Women occupy an increasingly prominent place in the work force without reducing most of their responsibilities at home. Consequently, sleep needs are often pushed to the bottom of womens daily priority list. Prior research has indicated that sleep deprivation is associated with higher levels of pro-inflammatory serum cytokines. This is important because higher plasma concentrations of pro-inflammatory serum cytokine levels are associated with postpartum depression and adverse birth outcomes such as preterm delivery. However, little research has directly examined how sleep deprivation may affect maternal and fetal outcomes. This review summarizes the existing data on the effect of sleep deprivation during pregnancy on maternal and fetal outcomes. We review supporting evidence for the hypotheses that sleep deprivation during pregnancy increases the risk of preterm delivery and postpartum depression, and that systemic inflammation is the causal mechanism in the association. Prior research on sleep in pregnancy has been limited by varying data collection methods, subjective self-reported sleep measures, small and non-representative samples, cross-sectional designs; descriptive or non-hypothesis driven studies. Future research with longitudinal study designs is needed to allow examination of the effect of sleep deprivation on adverse maternal and fetal outcomes.

Age and Sleep Disturbances Among American Men And Women: Data From the U.S. Behavioral Risk Factor Surveillance System

STUDY OBJECTIVE Explore the prevalence of sleep-related complaints across age groups, examining effects of sex, general health, and depressed mood. DESIGN Cross-sectional analysis of data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS). SETTING Epidemiologic. PARTICIPANTS Complete-case analysis included 155,877 participants who responded to questions related to Self-Reported Sleep Disturbance (SLEEPDIST) and Self-Reported Tiredness/Lack of Energy (TIREDNESS). INTERVENTIONS None. MEASUREMENTS AND RESULTS Outcomes were self-reported complaints in response to survey questions assessing SLEEPDIST and TIREDNESS, dichotomized as reporting a complaint < 6 versus ≥ 6 nights or days, respectively, in a 2-wk period. Predictors were age, general health, and depressed mood. All analyses were adjusted for race/ethnicity, income, education, and time since last medical checkup. Across all age groups, women reported more SLEEPDIST and TIREDNESS. Poor general health, mild depressed mood, and moderate/severe depressed mood were associated with SLEEPDIST and TIREDNESS. Both SLEEPDIST and TIREDNESS generally declined across the life span, with fewest endorsements in respondents older than 80 yr. For SLEEPDIST, odds ratios (ORs, reference = 80+) declined from age 18-54 yr, rose slightly, and then declined again after age 59 yr in men. The pattern was similar for women, except a more marked rise was noted from age 40-59 yr. The pattern was similar for TIREDNESS. CONCLUSIONS Advancing age was not associated with increased Self-Reported Sleep Disturbance or Self-Reported Tiredness/Lack of Energy. These results suggest that the often-reported increase in sleep problems with age is a nonlinear phenomenon, mediated by factors other than physiologic aging.

Sleep-disordered breathing and pregnancy: potential mechanisms and evidence for maternal and fetal morbidity

Purpose of review This article reviews current data on pathophysiologic mechanisms by which sleep-disordered breathing during pregnancy may cause harm, and explores biological pathways for associated adverse maternal and fetal outcomes, especially pregnancy-induced hypertension and gestational diabetes. Recent findings Accumulating data indicate that snoring and sleep apnea during pregnancy are likely to increase the risk for gestational hypertension and preeclampsia. Several new studies have observed that sleep-disordered breathing and short sleep duration also increase the risk of gestational diabetes, similar to observations in the general population. There are varying levels of emerging evidence for potential mechanisms, including oxidative stress, increased sympathetic activity and inflammation, adipokine levels and insulin resistance, linking sleep-disordered breathing events during pregnancy to adverse outcomes. Summary Sleep-disordered breathing and adverse maternal–fetal outcomes such as preeclampsia and gestational diabetes share a number of mechanistic pathways, and growing data in pregnant women indicate that snoring and sleep apnea increase the risk of these and other complications for both the mother and the fetus. Nevertheless, direct evidence of the pathophysiologic mechanisms by which sleep-disordered breathing during pregnancy exerts negative effects remains sparse.

Risk factors for sleep-disordered breathing in pregnancy

Rationale Symptoms of sleep-disordered breathing (SDB) are common among pregnant women, and several studies link SDB symptoms with gestational hypertension and preeclampsia. However, few prospective studies objectively measuring SDB during pregnancy have been performed. Objectives We performed a prospective cohort study examining risk factors for third trimester SDB in pregnant women. Measurements and methods 105 pregnant women from the Hospital of the University of Pennsylvania obstetrics practices completed first and third trimester overnight polysomnography studies. We examined whether the number of SDB events per hour of sleep increased during pregnancy. We performed unadjusted and multivariable logistic regression analyses to estimate the effects of usual and pregnancy-specific characteristics on development of third trimester obstructive sleep apnoea (OSA). In secondary analyses, we examined the relationship between objectively measured SDB, hypertensive disorders of pregnancy, and other adverse maternal-fetal outcomes. Main results Mean Apnoea-Hypopnoea Index increased from 2.07 (SD 3.01) events/h at baseline (first trimester) to 3.74 (SD 5.97) in the third trimester (p=0.009). 10.5% of women had OSA in the first trimester. By the third trimester, 26.7% of women had OSA. In multivariable analyses, first trimester body mass index (BMI) and maternal age were significantly associated with third trimester OSA. Conclusions Third trimester OSA is common. Risk factors for third trimester OSA among women without baseline SDB include higher baseline BMI and maternal age.

Obstructive sleep apnea in patients undergoing bariatric surgery--a tertiary center experience.

BackgroundThe patient population that is evaluated for bariatric surgery is characterized by a very high body mass index (BMI). Since obesity is the most important risk factor for obstructive sleep apnea (OSA), sleep disordered breathing is highly prevalent in this population. If undiagnosed before bariatric surgery, untreated OSA can lead to perioperative and postoperative complications. Debate exists whether all patients that are considered for bariatric surgery should undergo polysomnography (PSG) evaluation and screening for OSA as opposed to only those patients with clinical history or examination concerning sleep disordered breathing. We examined the prevalence and severity of OSA in all patients that were considered for bariatric surgery. We hypothesized that, by utilizing preoperative questionnaires (regarding sleepiness and OSA respiratory symptoms) in combination with menopausal status and BMI data, we would be able to predict which subjects did not have sleep apnea without the use of polysomnography. In addition, we hypothesized that we would be able to predict which subjects had severe OSA (apnea–hypopnea index (AHI) > 30).MethodsThree hundred forty-two consecutive subjects, evaluated for bariatric surgery from November 1, 2005 to January 31, 2007 underwent overnight polysomnography and completed questionnaires regarding sleepiness, menopausal status, and respiratory symptoms related to OSA. Apneas and hypopneas were classified as follows: mild apnea 5 ≤ AHI ≤ 15, moderate apnea 15 < AHI ≤ 30, and severe apnea AHI > 30.ResultsThe overall sample prevalence of OSA was 77.2%. Of these, 30.7% had mild OSA; 19.3% had moderate OSA, and 27.2% had severe OSA. Among men, the prevalence of OSA was 93.6% and 73.5% among women. The mean AHI (events per hour) for men with OSA was 49.2 ± 35.5 and 26.3 ± 28.3 for women with OSA. Separate logistic regression models were developed for the following three outcomes: AHI ≥ 5 events per hour, AHI > 15 events per hour, and AHI > 30 events per hour. When predicting these three levels of OSA severity, the area under the curve (AUC) values were: 0.8, 0.72, and 0.8, respectively. The negative predictive value for the presence of sleep apnea (AHI ≥ 5) was 75% when using the most stringent possible cutoff for the prediction model.ConclusionsThe prevalence of OSA in all patients considered for bariatric surgery was greater than 77%, irrespective of OSA symptoms, gender, menopausal status, age, or BMI. The prediction model that we developed for the presence of OSA (AHI ≥ 5 events per hour) has excellent discriminative ability (evidenced by an AUC value of 0.8). However, the negative prediction values for the presence of OSA were too low to be clinically useful due to the high prevalence of OSA in this high-risk group. We demonstrated that, by utilizing even the most stringent possible cutoff values for the prediction model, OSA cannot be predicted with enough certainty. Therefore, we advocate routine PSG testing for all patients that are considered for bariatric surgery.

Gender differences in the clinical manifestation of obstructive sleep apnea

Obstructive sleep apnea (OSA) has been historically described as a disease primarily of men. However, it is now widely recognized that OSA in women is not as rare as was originally believed. The alarming degree to which OSA is clinically underdiagnosed in women raises the critical concern that women manifest OSA differently. The purpose of this review is to examine the issue of clinically significant gender differences in OSA disease manifestation, which pose unique challenges to diagnosis and management. Within this review, current findings regarding gender differences in OSA polysomnographic features and demographic factors, symptom presentation, functional status, comorbidities, health care utilization, and therapeutic management have been reviewed. Further research in this field is proposed to examine the impact of gender on functional status in individuals with OSA, and the potential gender differences in therapeutic management, particularly the response to continuous positive airway pressure (CPAP) treatment. Additional studies describing the clinical manifestations in men and women at different levels of OSA severity may substantially contribute to the ability to identify and treat OSA in women across a wide spectrum of disease severity.

Update on Sleep and Its Disorders

Inadequate sleep and sleep disorders have important adverse consequences on multiple systems. This review covers three areas: (a) Genetic determinants of sleep disorders. Common gene variants with small effects have been identified for both restless legs syndrome and narcolepsy with cataplexy. Rare variants with large effects have been found in familial phase advance syndrome and in subjects with short sleep durations. (b) Obstructive sleep apnea (OSA). OSA is an oxidative stress disorder. Prospective cohort studies show an increased risk of cardiovascular events in patients with untreated severe OSA. (c) The impact of sleep disorders on obesity and diabetes. Inadequate sleep results in changes in insulin resistance and in hormone levels leading to increases in appetite. Hence, inadequate sleep is associated with development of obesity. OSA is also an independent risk factor for insulin resistance; treatment of OSA can improve insulin sensitivity.

Performance of an automated polysomnography scoring system versus computer-assisted manual scoring.

STUDY OBJECTIVES Manual scoring of polysomnograms (PSG) is labor intensive and has considerable variance between scorers. Automation of scoring could reduce cost and improve reproducibility. The purpose of this study was to compare a new automated scoring system (YST-Limited, Winnipeg, Canada) with computer-assisted manual scoring. DESIGN Technical assessment. SETTING Five academic medical centers. PARTICIPANTS N/A. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Seventy PSG files were selected at University of Pennsylvania (Penn) and distributed to five US academic sleep centers. Two blinded technologists from each center scored each file. Automatic scoring was performed at Penn by a YST Limited technician using a laptop containing the software. Variables examined were sleep stages, arousals, and apnea-hypopnea index (AHI) using three methods of identifying hypopneas. Automatic scores were not edited and were compared to the average scores of the 10 technologists. Intraclass correlation coefficient (ICC) was obtained for the 70 pairs and compared to across-sites ICCs for manually scored results. ICCs for automatic versus manual scoring were > 0.8 for total sleep time, stage N2, and nonrapid eye movement arousals and > 0.9 for AHI scored by primary and secondary American Academy of Sleep Medicine criteria. ICCs for other variables were not as high but were comparable to the across-site ICCs for manually scored results. CONCLUSION The automatic system yielded results that were similar to those obtained by experienced technologists. Very good ICCs were obtained for many primary PSG outcome measures. This automated scoring software, particularly if supplemented with manual editing, may increase laboratory efficiency and standardize PSG scoring results within and across sleep centers.

Poor sleep in relation to natural menopause: A population-based 14-year follow-up of midlife women

ObjectiveThis study aims to estimate the prevalence and predictors of moderate/severe poor sleep in relation to the final menstrual period (FMP) in midlife women. MethodsAnnual assessments were conducted in a population-based cohort of 255 women. All were premenopausal at cohort enrollment and reached natural menopause during the 16-year follow-up. The outcome measure was severity of poor sleep, as reported by participants in annual interviews for 16 years and as evaluated in relation to the FMP. ResultsThe annual prevalence of moderate/severe poor sleep largely ranged from about 28% to 35%, with no significant differences in any year relative to the FMP for the sample overall. When sleep status was stratified at premenopausal baseline, premenopausal sleep status strongly predicted poor sleep around the FMP. Women with moderate/severe poor sleep in premenopause were approximately 3.5 times more likely to have moderate/severe poor sleep around menopause than those with no poor sleep at baseline in adjusted analysis (odds ratio, 3.58; 95% CI, 2.50-5.11; P < 0.0001), whereas mild poor sleepers in premenopause were approximately 1.5 times more likely to have moderate/severe poor sleep around menopause (odds ratio, 1.57; 95% CI, 0.99-2.47; P = 0.053). There was no significant association between poor sleep and time relative to the FMP among women who had no poor sleep at premenopausal baseline. Hot flashes were significantly associated with poor sleep (odds ratio, 1.79; 95% CI, 1.44-2.21; P < 0.0001 in adjusted analysis) but had no interaction with baseline sleep severity (interaction P = 0.25), indicating that hot flashes contributed to poor sleep regardless of baseline sleep status. ConclusionsFindings show a high prevalence of moderate/severe poor sleep in midlife women, with only a small “at-risk” subgroup having a significant increase in poor sleep in relation to the FMP. Sleep status at premenopausal baseline and concurrent hot flashes strongly and consistently predict poor sleep in the menopausal transition. Overall, poor sleep does not increase around the FMP and frequently occurs in the absence of hot flashes, indicating that sleep difficulties in the menopausal transition in generally healthy women are not simply associated with ovarian decline.