Päivi Polo-Kantola

When does estrogen replacement therapy improve sleep quality

OBJECTIVE Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved. STUDY DESIGN Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures. RESULTS Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). The subjects were less tired in the mornings and in the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75). CONCLUSIONS Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them.

The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women.

Objective To evaluate the effect of estrogen replacement therapy on cognitive functioning. Methods The study consisted of two 3-month treatment periods, one with estrogen and one with the placebo, in random order, separated by a 1-month wash-out period. The study group comprised 70 healthy postmenopausal women, aged 47–65 years, with previous hysterectomy. Sixty-two women completed the study. Cognitive speed and accuracy, attention, and memory were evaluated. Serum estradiol (E2) and FSH levels were controlled at the end of the estrogen, placebo, and wash-out periods. Results Most of the cognitive tests correlated with age: older women were slower and made errors than younger women. Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance. In two out of ten visual detection tasks, recognition thresholds were longer with estrogen than with the placebo (P < .001 and P = .004). On the most demanding test of working memory, the reaction times (P = .045) and error rates (P = .043) differed between treatments, yet this finding proved to be an effect of learning rather than treatment. There was no correlation between cognitive performance and serum E2 levels. Conclusion Cognitive performance decreased with age. Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance.

Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women☆

Abstract Objective: To evaluate the effect of estrogen replacement therapy on sleep architecture, arousals, and body movements. Design: A 7-month, prospective, randomized, double-blind, placebo-controlled crossover trial. Setting: Departments of obstetrics and gynecology and a university sleep center in Turku, Finland. Patient(s): Seventy-one postmenopausal women, 4 of whom were excluded and 5 of whom withdrew from the study; the final study group consisted of 62 women. Intervention(s): Two periods of treatment with either estrogen or placebo. Main Outcome Measure(s): Polysomnography for measurement of sleep and arousals and a static charge–sensitive bed for monitoring of movements and breathing. Self-reports of climacteric symptoms for 14 days. Result(s): Estrogen effectively alleviated hot flashes, sweating, sleep complaints, and headaches. Estrogen decreased the total frequency of movement arousals but increased alpha-arousals, especially during light non–rapid eye movement sleep (stage 1). Sleep latency, distribution of sleep stages, sleep efficiency, and total sleep time were similar during treatment with estrogen and placebo. Changes in serum E 2 concentrations correlated with neither subjective nor objective sleep quality. Conclusion(s): Estrogen replacement therapy improves objective sleep quality by alleviating the frequency of nocturnal movement arousals. It also reduces climacteric symptoms, especially vasomotor symptoms. Estrogen replacement therapy does not seem to have any effect on sleep architecture.

Sleep problems in midlife and beyond.

Good sleep quality is important for good health, both physical and mental, and indeed for quality of life, performance and productivity. Sleep problems increase with age in both sexes, but women are more susceptible to them at all ages. Although menopause is considered an important milestone (the decrease in both oestrogen and progesterone has been shown to reduce sleep quality), an increase in sleep problems is already evident in midlife, as there is an increased incidence of other diseases as well as mood symptoms, which may exert an effect on sleep quality either directly or via the side-effects of the associated medications. Weight changes at midlife and the menopause may also affect sleep quality. In addition to reductions in sleep quality, specific sleep disorders, like sleep-disordered breathing and restless legs syndrome, become more prevalent in midlife and especially after menopause. Because sleep problems are commonly present in association with other conditions, rather than as isolated, independent disorders, treatment is often complex and patients generally need multiprofessional appraisal.

Breathing during sleep in menopause: A randomized, controlled, crossover trial with estrogen therapy

OBJECTIVE To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. METHODS A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P < .05. RESULTS The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P = .047) and frequency (P = .049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. CONCLUSION Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.

Climacteric symptoms and sleep quality.

OBJECTIVE To evaluate the effect of climacteric vasomotor symptoms on sleep quality measured by self-report and polysomnography in postmenopausal women. METHODS Seventy-one healthy postmenopausal women were recruited, of whom 63 completed the study. Each subject recorded climacteric symptoms and subjective sleep quality for 14 days. Sleep quality was evaluated objectively by all-night polysomnography using the static charge-sensitive bed. RESULTS During polysomnography, a high frequency of climacteric vasomotor symptoms was not associated with changes in sleep latency, percentage of sleep stages, number of arousals, sleep efficiency, or total sleep time. However, a high frequency of climacteric vasomotor symptoms (range 0-8.9, r = .60, P < .001), somatic symptoms (range 0-5.0, r = .25-.44, P < .05), and mental symptoms (range 0-5.0, r = .41-.51, P < .001) was related to impaired subjective sleep quality. In stepwise regression analysis, 32% of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). High body mass index predicted impaired objective sleep quality, such as prolonged latencies to stage-2 sleep (r = .27, P = .031) and slow-wave sleep (r = .51, P = .003) and decreased oxygen saturations (r = -.54, P < .001). Older women had decreased sleep efficiency (r = -.27, P = .030) and lower oxygen saturations (r = -.36, P = .004). Serum estradiol level had only a minor effect on objective sleep quality. CONCLUSION Impaired subjective sleep quality associated with climacteric vasomotor symptoms did not manifest as abnormalities in polysomnographic sleep recordings. Body mass index and age appeared to have the strongest effect on objective sleep quality.

Aetiology and treatment of sleep disturbances during perimenopause and postmenopause

The sudden and predictable cessation of ovarian endocrinological function at menopause results in a marked decrease of endogenous estrogen and progestogen secretion. In addition to cessation of menstruation, a wide range of biological functions, including sleep, are affected. Sleep disturbances are more common in women than in men and their incidence increases with age. There are 2 distinct mechanisms by which menopause is known to affect sleep quality. One is menopausal insomnia, which can be considered as part of the symptomatology of the climacterium. Another is sleep-disordered breathing, where impairment of sleep quality is secondary to sleep apnoea or partial upper airway obstruction during sleep. The former is effectively controlled with conventional estrogen replacement therapy, whereas the latter could potentially be improved with progestogens. Many age-related conditions without a direct link with the menopause should also be considered when treating postmenopausal sleep disorders.

Sleep and the menopause - do postmenopausal women experience worse sleep than premenopausal women?

Objective To examine the sleep characteristics in three cross-sectional populations: young, premenopausal and postmenopausal women, and the associations between sleep, menopause, mood and cognitive performance. Study design Twenty-one premenopausal (45–51 years), 29 postmenopausal (59–71 years) and 11 young (20–26 years, using oral contraceptives) women were recruited. Polysomnography was used to measure objective sleep quality. Subjective sleep quality, sleepiness and mood were assessed using questionnaires. Cognitive performance was investigated by means of three attentional tests. Results Total sleep time in pre- and postmenopausal women was similar (404.9 and 384.7 minutes), but shorter than in young women (448.2 minutes, P = 0.030 and <0.003, respectively). Sleep efficiency followed the same pattern, being 84.3% in premenopausal (P = 0.027), 80.2% in postmenopausal (P < 0.003) and 93.4% in young women. Pre- and postmenopausal women had less slow wave sleep (duration or activity) and more wake time after sleep onset (duration or frequency). Insomnia complaints were more frequent after the menopause (P = 0.023). Sleepiness and mood scores were similar in all groups. Reaction speeds slowed with increasing age. After the menopause, better cognitive performance was associated with more rapid eye movement sleep. Conclusion Objective sleep measures differed significantly between the young and postmenopausal groups. These differences may be more because of the physiology of ageing than the rapid changes across the menopause, since similar sleep characteristics were already present in the premenopausal women. The increase in sleep complaints after menopause was not associated with sleepiness or disturbances in objective sleep quality, mood or cognitive performance.

Serum estrogen level, attention, memory and other cognitive functions in middle-aged women.

OBJECTIVE To evaluate the relationship between serum estradiol level and cognitive processing efficiency and memory. METHODS Sixty-three healthy women aged 45-65 years were recruited through a newspaper announcement. The subjects were divided into two subgroups (low-estrogen group, n = 37 and high-estrogen group, n = 26) according to their serum follicle stimulating hormone (FSH) and estradiol levels. In the high-estrogen group, estrogen was either endogenous or supplied by estrogen replacement therapy. Automatic and controlled cognitive processing and attentional resources were measured using CogniSpeed software, together with conventional tests of cognitive performance: similarities, digit span, digit symbol, block design, object naming and recall, paired word associates (PWA) recall, Benton visual retention and paced auditory serial addition test (PASAT). The Beck depression inventory was also assessed. RESULTS Cognitive reaction speeds were similar in both groups. Women with low estrogen levels made more errors in the vigilance test (sustained attention, p = 0.040). There were no differences in short-term or long-term memory, or verbal, visual or working memory between the study groups. Older women were slower in the ten-choice reaction time (10-CRT) test (r = 0.25, p = 0.047) and made more errors in the test of suppressing attention (Stroop incongruence test; r = 0.34, p = 0.007) and in the sustaining attention test (vigilance test; r = 0.47, p < 0.001). Depression scores did not correlate with cognitive variables. CONCLUSIONS Cognitive performance was well preserved in healthy middle-aged women. Cognitive speed, accuracy, attentional resources and memory did not show impairment with decline of serum estrogen level in this age group.

Obstetric Risk Factors and Autism Spectrum Disorders in Finland

OBJECTIVE To examine the relationship between obstetric risk factors and childhood autism, Asperger syndrome, and other pervasive developmental disorders (PDDs). STUDY DESIGN Registry-based case-control study from all singleton births in Finland from 1990-2005. Cases with childhood autism, Asperger syndrome, or PDD (n = 4713) were identified from the Finnish Hospital Discharge Register. Each case was matched to 4 controls on sex, date of birth, and place of birth. Information on obstetric risk factors was from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. RESULTS When adjusted with confounders, childhood autism was associated with maternal high blood pressure (OR 1.49, 95% CI 1.1-2.1, P = .018), Apgar scores less than 7 (1 minute, OR 1.46, 95% CI 1.1-2.0, P = .021), and neonatal treatment with monitoring (OR 1.40, 95% CI 1.02-1.9, P = .038). PDD was associated with induced labor (OR 1.25 95% CI 1.1-1.5, P = .007), planned cesarean delivery (OR 1.34, 95% CI 1.1-1.7, P = .009), 1-minute Apgar scores 7-8 ( OR 1.22, 95% CI 1.1-1.4, P = .008) and less than 7 (OR 1.34, 95% CI 1.03-1.8, P = .032), and neonatal intensive care unit treatment (OR 1.52, 95% CI 1.2-2.0, P = .003). Asperger syndrome was associated only with 1-minute Apgar scores 7-8 (OR 1.19, 95% CI 1.03-1.4, P = .018). CONCLUSIONS Low Apgar scores as well as conditions requiring neonatal special follow-up are important risk factors for childhood autism and PDD. These findings suggest that fetal distress is a potential risk factor for these disorders, but not for Asperger syndrome.