Evolution of sleep-disordered breathing and blood pressure during menopausal transition.

The purpose of this study was to investigate how the blood pressure increase observed during menopausal transition is affected by sleep-disordered breathing and the menopause itself. Further, we aimed to find new sleep-disordered breathing related markers that would predict the development of hypertension. Sixty-four community-dwelling premenopausal women aged 45-47 years were studied. Polysomnography, serum follicle stimulating hormone, forced expiratory volume in 1 s, and a physical examination were performed at baseline and again after 10 years of follow-up. Indices for sleep apnea/hypopnea and inspiratory flow-limitation were determined. Regression models were used to study the relationships between variables. Changes in the apnea-hypopnea index or serum follicle stimulating hormone were not significant for blood pressure change. An increase in morning blood pressure during the follow-up period was associated with a body mass-index increase. An increase in evening blood pressure was associated with an increase in inspiratory flow-limitation during non-rapid eye movement sleep. Incident hypertension during the follow-up was associated with hypopnea (median hypopnea index 7.6/h, p = 0.048) during rapid eye movement sleep at baseline. Users of menopausal hormone therapy had a lower rapid eye movement sleep apnea-hypopnea index (1.6/h vs. 6.9/h, p = 0.026) at baseline whereas at follow-up users and non-users did not differ in any way. The progression of menopause or the use of menopausal hormone therapy had a minimal effect on blood pressure in our population. The effects of inspiratory flow-limitation on blood pressure profile should be studied further.

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Sleep during menopausal transition: a 10-year follow-up.

STUDY OBJECTIVES: A 10-year observational follow-up study to evaluate the changes in sleep architecture during the menopausal transition. METHODS: Fifty-seven premenopausal women (mean age 46 years, SD 0.9) were studied at baseline and after a 10-year follow-up. At both time points, polysomnography (PSG) was performed, and the serum follicle-stimulating hormone (S-FSH) concentration was measured. Linear regression models were used to study the effects of aging and menopause (assessed as change in S-FSH) on sleep. RESULTS: After controlling for body mass index, vasomotor, and depressive symptoms, higher S-FSH level was associated with longer sleep latency (B 0.45, 95% confidence interval [CI]: 0.07 to 0.83). Aging of 10 years was associated with shorter sleep latency (B -46.8, 95% CI: -77.2 to -16.4), shorter latency to stage 2 sleep (B -50.6, 95% CI: -85.3 to -15.9), decreased stage 2 sleep (B -12.4, 95% CI: -21.4 to -3.4), and increased slow-wave sleep (B 12.8, 95% CI: 2.32 to 23.3) after controlling for confounding factors. CONCLUSIONS: This study suggests that PSG measured sleep of middle-aged women does not worsen over a 10-year time span due to the menopausal transition. The observed changes seem to be rather age- than menopause-dependent.

Sleep and Sleep Disorders in the Menopausal Transition.

The menopausal transition is associated with an increase in insomnia symptoms, especially difficulty staying asleep, which negatively impacts quality of life. Vasomotor symptoms are a key component of sleep disruption. Findings from polysomnographic studies are less consistent in showing disrupted sleep in menopausal transition independent of aging; further prospective studies are needed. Hormone therapy alleviates subjective sleep disturbances, particularly if vasomotor symptoms are present. However, because of contraindications, other options should be considered. Further work is needed to develop preventive and treatment strategies for alleviating sleep disturbances to ensure better health, quality of life, and productivity in midlife women.

Sleep During Menopausal Transition: A 6-Year Follow-Up.

Study Objectives: Menopausal transition is associated with increased dissatisfaction with sleep, but the effects on sleep architecture are conflicting. This prospective 6-year follow-up study was designed to evaluate the changes in sleep stages and sleep continuity that occur in women during menopausal transition. Methods: Sixty women (mean age 46.0 years, SD 0.9) participated. All women were premenopausal at baseline, and at the 6-year follow-up, women were in different stages of menopausal transition. Polysomnography was used to study sleep architecture at baseline and follow-up. The effects of aging and menopause (assessed as change in serum follicle-stimulating hormone [S-FSH]) on sleep architecture were evaluated using linear regression models. Results: After controlling for body mass index, vasomotor, and depressive symptoms, aging of 6 years resulted in shorter total sleep time (B -37.4, 95% confidence interval [CI] -71.5 to (-3.3)), lower sleep efficiency (B -6.5, 95%CI -12.7 to (-0.2)), as well as in increased transitions from slow-wave sleep (SWS) to wakefulness (B 1.0, 95%CI 0.1 to 1.9), wake after sleep onset (B 37.7, 95%CI 12.5 to 63.0), awakenings per hour (B 1.8, 95%CI 0.8 to 2.8), and arousal index (B 2.3, 95%CI 0.1 to 4.4). Higher S-FSH concentration in menopausal transition was associated with increased SWS (B 0.09, 95%CI 0.01 to 0.16) after controlling for confounding factors. Conclusions: A significant deterioration in sleep continuity occurs when women age from 46 to 52 years, but change from premenopausal to menopausal state restores some SWS.

Predictors of sleep disturbance in menopausal transition.

OBJECTIVE: This follow-up study aimed to evaluate risk factors for menopausal sleep disturbances already identifiable before menopause. METHODS: At baseline, all 81 women were premenopausal. At year-five follow-up, 27 of the women were premenopausal, 40 postmenopausal, and 14 postmenopausal and using hormone therapy. We used the Basic Nordic Sleep Questionnaire to study sleep; additional questionnaires evaluated risk factors for sleep impairment. RESULTS: Sleep quality differed only marginally between the groups. The following baseline variables were associated with impaired sleep quality at follow-up: depressive symptoms increased the risk of nocturnal awakenings (OR 1.16 (95%CI 1.02-1.32), p=0.025), morning tiredness (OR 1.22 (95%CI 1.06-1.40), p=0.007), daytime tiredness (OR 1.24 (95%CI 1.06-1.44), p=0.007) and propensity to fall asleep during work or leisure time (OR 1.18 (95%CI 1.01-1.37), p=0.036). Personal crises increased the risk of longer sleep latency (OR 5.46 (95%CI 1.13-26.32), p=0.035) and of propensity to fall asleep when not active (OR 5.41 (95%CI 1.42-20.83), p=0.014). Use of medications affecting the CNS increased the risk of worse general sleep quality (OR 11.44 (95% CI 1.07-121.79), p=0.044). Perceived impaired general health (OR 2.87 (95%CI 1.04-7.94), p=0.043) and frequent night sweats (OR 10.50 (95%CI 2.25-49.01), p=0.003) increased the risk of difficulty falling asleep. CONCLUSIONS: Various premenopausal health-related factors seem to predict poor sleep in menopausal transition. Menopause itself appears to have only minor effects. Thus, it is essential to identify high-risk women to allow timely interventions that may prevent the development of sleep disturbances at menopause.

Sleep in midlife women: effects of menopause, vasomotor symptoms, and depressive symptoms.

OBJECTIVE: This study aims to evaluate subjective sleep quality in premenopausal and postmenopausal women and to study its association with night sweats, hot flashes, and depressive symptoms. METHODS: A total of 158 healthy women were recruited; 107 were premenopausal (44-48 y) and 51 were postmenopausal (53-58 y). Sleep quality was evaluated with the Basic Nordic Sleep Questionnaire, night sweats and hot flashes were evaluated with a specific symptom questionnaire, and depressive symptoms were evaluated with the Beck Depression Inventory. RESULTS: Postmenopausal women had poorer general sleep quality (P < 0.001), slept more restlessly (P = 0.020), and had more nocturnal awakenings (P = 0.015). However, the frequency of difficulty falling asleep, snoring, witnessed apnea, or use of sleep medication was similar between the groups. Furthermore, sleep latency, morning tiredness, or daytime tiredness did not differ between the groups. Postmenopausal women did not report more unintentional falling asleep at work or during leisure time; however, when not active, they dozed off more easily than premenopausal women (P < 0.001). Postmenopausal women had more night sweats (P < 0.001), hot flashes (P < 0.001), and depressive symptoms (P < 0.001). Even a low frequency of night sweats disturbed sleep in postmenopausal women, whereas only frequent night sweats were disturbing in premenopausal women. Depressive symptoms disturbed sleep regardless of menopause status. CONCLUSIONS: Maintenance insomnia, most evidently because of night sweats and hot flashes, seems to be the major type of insomnia in postmenopausal women and has to be considered when choosing insomnia treatment for this group. Initiation of sleep and daytime vitality are not, in general, affected by menopause.

Subjective sleep in premenopausal and postmenopausal women during workdays and leisure days: a sleep diary study.

OBJECTIVE: This study aims to evaluate subjective sleep in premenopausal and postmenopausal women by assessing differences between workdays and leisure days. METHODS: Ninety-one regularly working women-of which 58 were premenopausal (aged 44-48 y) and 33 were postmenopausal (aged 53-58 y)-were recruited. A 14-day sleep diary was used to investigate total sleep time (TST), nocturnal sleep time (ST), sleep latency, and number of awakenings after workdays and leisure days. RESULTS: TST (P = 0.002 during the 14-d period, P < 0.001 during workdays) and ST (P < 0.001 and P < 0.001) were shorter, and the number of awakenings (P = 0.033 and P = 0.043) during the entire 14-day period and after workdays was higher in postmenopausal women than in premenopausal women. No differences were observed during leisure days. Falling asleep took longer in postmenopausal women during the entire 14-day period (P = 0.011), during workdays (P = 0.040), and during leisure days (P = 0.010). After adjustment for the depression score, TST and ST during the 14-day period (P = 0.006 for TST, P = 0.004 for ST) and during workdays (P < 0.001 and P < 0.001) remained shorter in postmenopausal women. CONCLUSIONS: Self-reported sleep problems are more common in postmenopausal women than in premenopausal women, and the difference is more pronounced during workdays than during leisure days. These observations suggest that postmenopausal women have the capacity for good sleep but are more vulnerable to sleep problems related to work-related stress.