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Estrogen-induced sleep improvement in postmenopausal women was related to reduction in climacteric symptoms, such as hot flushes
MEN OPA U S E
Estrogen-induced sleep improvement in postmenopausal women was related to reduction in climacteric symptoms, such as hot flushes PolodKantola P, Erkkola R, Helenius H, Irjala K, Polo O. When does estrogen replacement therapy improve sleep quality? Am J Obstet Gynecol 1998; 178: 1002d1009
OBJECTIVE To determine the effectiveness of estrogen replacement therapy in improving the quality of sleep in postmenopausal women and to identify factors predictive of estrogen-induced sleep improvement. DESIGN Randomized, double-blind, crossover, placebocontrolled trial. Allocation was in blocks, from a central source. Duration of the study consisted of 3 months each of estrogen and placebo, with a month of washout in between. SETTING University hospital in Finland. PATIENTS 71 healthy postmenopausal women, with FSH '30 U/L and estradiol (140 pmol/L, and previous hysterectomy for benign indication, were recruited through a newspaper notice. Substance abusers were excluded. Mean age was 56 (range 47–65) years and 76% had previously used estrogen for a mean 41 months (range 1 month – 21 years). Five women withdrew from the study and three women were excluded, leaving 63 women in the analysis. INTERVENTION Two types of transdermal estrogen therapy were used: women 455 years received estrogen gel 2.5 g/day and women '55 years received an estrogen patch 50 lg/24 hours. The women were randomized to receive either estrogen for 3 months, then placebo for 3 months or placebo first, then estrogen. MAIN OUTCOME MEASURES Baseline insomnia and sleepiness assessed by the Basic Nordic Sleep Questionnaire, comparison of subjective sleep improvement on the two treatments
Commentary In spite of the importance of sleep disturbance to menopausal women, there is surprisingly little research into the problem. This paper, therefore, is a welcome addition. Menopausal women suffer a number of sleep disturbances, including insomnia, frequent awakenings, reduced sleep efficiency and alterations in sleep stages. Women with sleep disturbances suffer a number of measurable impairments in daytime function, including memory and reaction time. Sleep disturbance has been proposed to lead to some of the mood and irritability complaints in menopause. Sleep disturbance is common in women with hot flushes, and sleep fragmentation has been found more frequently in women with hot flushes than without. Although estrogens are prescribed to alleviate sleep disturbance, there are no data to demonstrate whether the benefit is solely related to controlling flushes, or whether estrogens have an independent action on sleep quality. This study used a standard double-blind crossover design with washout, and demonstrated an improvement in sleep quality in women regardless of whether they were experiencing menopausal symptoms. The decision to use two different preparations of estrogen was not well
^ 1999 Harcourt Brace & Co. Ltd
assessed with a visual analogue scale (0–10) at the end of the second treatment period, subjective climacteric symptoms assessed on a 0–5 scale, serum estradiol. MAIN RESULTS When on estrogen therapy compared to placebo, on average, the women felt their sleep was improved, they were less tired, were less restless during the night and awakened less frequently, and they fell asleep more quickly ( p(0.001). Estrogen did not improve snoring ( p"0.10). In a sub-group of 15 women without vasomotor symptoms, sleep was similarly improved with estrogen. The mean serum estradiol level while on estrogen therapy was 307$328 (range 44–1938) pmol/L. Nine women with estradiol (90 pmol/L did not experience sleep improvement while on estrogen; however, estradiol levels were not otherwise predictive of sleep improvement. For the whole group, the severity of insomnia at baseline was not related to sleep improvement on estrogen, except for the effect of falling asleep more easily (r"0.26, p"0.04). However, in the patients without hot flushes, the severity of insomnia did predict sleep improvement on estrogen (r"0.62–0.76, p40.01). The alleviation of other climacteric symptoms (such as hot flushes, anxiety, sweating, muscular pain, palpitations and memory problems) while on estrogen was significantly correlated with sleep improvement. CONCLUSION In postmenopausal women, estrogen replacement therapy resulted in sleep improvement, compared with placebo. Estrogen-induced sleep improvement was related to improvement in other climacteric symptoms, such as hot flushes. Women without hot flushes also had improved sleep with estrogen.
justified, and it is puzzling that the authors would have then assigned women by age group to receive one treatment or the other. Women close to the age of menopause are typically more symptomatic than older women; older women may have other ageing related contributors to sleep disorders. Age is an important variable that was not independently analysed in this publication. By using different estrogen preparations in these two age groups, a potential confounder was introduced, and it will be difficult to answer questions about how sleep quality may differ in its responsiveness to treatment with age. The primary outcome in this study was estrogen-induced sleep improvement. A sleep questionnaire was administered at the baseline. On a daily basis, subjects commented on menopausal symptoms, including only a general question on sleeping problems. A detailed analysis of sleeping problems was not done until after the study, as a look-back over the two phases of treatment. From a methodological point of view, this is really a retrospective assessment of sleep, and it is hard to expect great accuracy in reporting of sleep from up to seven months earlier. More reliable information could have been obtained from a daily reporting of sleep characteristics. To address this design
Evidence-based Obstetrics and Gynecology (1999) 1, 37d38
37
weakness, the retrospective analysis of sleep could have been compared to the daily symptom reporting of sleeping problems. Nonetheless, the authors have demonstrated improvements in sleep in all women, suggesting a very marked effect. The question of whether sleep disturbance contributes to daytime menopausal symptoms has not been answered, and is of interest to women and their physicians. It is
38
Evidence-based Obstetrics and Gynecology (1999) 1, 37d38
useful and important that both symptomatic and asymptomatic women benefited from treatment. Sleep disorders can be added to the list of conditions for which benefit from estrogen has been demonstrated. Jennifer Blake, MD McMaster University, Hamilton, Canada
^ 1999 Harcourt Brace & Co. Ltd
Estrogen-induced sleep improvement in postmenopausal women was related to reduction in climacteric symptoms, such as hot flushes PolodKantola P, Erkkola R, Helenius H, Irjala K, Polo O. When does estrogen replacement therapy improve sleep quality? Am J Obstet Gynecol 1998; 178: 1002d1009
OBJECTIVE To determine the effectiveness of estrogen replacement therapy in improving the quality of sleep in postmenopausal women and to identify factors predictive of estrogen-induced sleep improvement. DESIGN Randomized, double-blind, crossover, placebocontrolled trial. Allocation was in blocks, from a central source. Duration of the study consisted of 3 months each of estrogen and placebo, with a month of washout in between. SETTING University hospital in Finland. PATIENTS 71 healthy postmenopausal women, with FSH '30 U/L and estradiol (140 pmol/L, and previous hysterectomy for benign indication, were recruited through a newspaper notice. Substance abusers were excluded. Mean age was 56 (range 47–65) years and 76% had previously used estrogen for a mean 41 months (range 1 month – 21 years). Five women withdrew from the study and three women were excluded, leaving 63 women in the analysis. INTERVENTION Two types of transdermal estrogen therapy were used: women 455 years received estrogen gel 2.5 g/day and women '55 years received an estrogen patch 50 lg/24 hours. The women were randomized to receive either estrogen for 3 months, then placebo for 3 months or placebo first, then estrogen. MAIN OUTCOME MEASURES Baseline insomnia and sleepiness assessed by the Basic Nordic Sleep Questionnaire, comparison of subjective sleep improvement on the two treatments
Commentary In spite of the importance of sleep disturbance to menopausal women, there is surprisingly little research into the problem. This paper, therefore, is a welcome addition. Menopausal women suffer a number of sleep disturbances, including insomnia, frequent awakenings, reduced sleep efficiency and alterations in sleep stages. Women with sleep disturbances suffer a number of measurable impairments in daytime function, including memory and reaction time. Sleep disturbance has been proposed to lead to some of the mood and irritability complaints in menopause. Sleep disturbance is common in women with hot flushes, and sleep fragmentation has been found more frequently in women with hot flushes than without. Although estrogens are prescribed to alleviate sleep disturbance, there are no data to demonstrate whether the benefit is solely related to controlling flushes, or whether estrogens have an independent action on sleep quality. This study used a standard double-blind crossover design with washout, and demonstrated an improvement in sleep quality in women regardless of whether they were experiencing menopausal symptoms. The decision to use two different preparations of estrogen was not well
^ 1999 Harcourt Brace & Co. Ltd
assessed with a visual analogue scale (0–10) at the end of the second treatment period, subjective climacteric symptoms assessed on a 0–5 scale, serum estradiol. MAIN RESULTS When on estrogen therapy compared to placebo, on average, the women felt their sleep was improved, they were less tired, were less restless during the night and awakened less frequently, and they fell asleep more quickly ( p(0.001). Estrogen did not improve snoring ( p"0.10). In a sub-group of 15 women without vasomotor symptoms, sleep was similarly improved with estrogen. The mean serum estradiol level while on estrogen therapy was 307$328 (range 44–1938) pmol/L. Nine women with estradiol (90 pmol/L did not experience sleep improvement while on estrogen; however, estradiol levels were not otherwise predictive of sleep improvement. For the whole group, the severity of insomnia at baseline was not related to sleep improvement on estrogen, except for the effect of falling asleep more easily (r"0.26, p"0.04). However, in the patients without hot flushes, the severity of insomnia did predict sleep improvement on estrogen (r"0.62–0.76, p40.01). The alleviation of other climacteric symptoms (such as hot flushes, anxiety, sweating, muscular pain, palpitations and memory problems) while on estrogen was significantly correlated with sleep improvement. CONCLUSION In postmenopausal women, estrogen replacement therapy resulted in sleep improvement, compared with placebo. Estrogen-induced sleep improvement was related to improvement in other climacteric symptoms, such as hot flushes. Women without hot flushes also had improved sleep with estrogen.
justified, and it is puzzling that the authors would have then assigned women by age group to receive one treatment or the other. Women close to the age of menopause are typically more symptomatic than older women; older women may have other ageing related contributors to sleep disorders. Age is an important variable that was not independently analysed in this publication. By using different estrogen preparations in these two age groups, a potential confounder was introduced, and it will be difficult to answer questions about how sleep quality may differ in its responsiveness to treatment with age. The primary outcome in this study was estrogen-induced sleep improvement. A sleep questionnaire was administered at the baseline. On a daily basis, subjects commented on menopausal symptoms, including only a general question on sleeping problems. A detailed analysis of sleeping problems was not done until after the study, as a look-back over the two phases of treatment. From a methodological point of view, this is really a retrospective assessment of sleep, and it is hard to expect great accuracy in reporting of sleep from up to seven months earlier. More reliable information could have been obtained from a daily reporting of sleep characteristics. To address this design
Evidence-based Obstetrics and Gynecology (1999) 1, 37d38
37
weakness, the retrospective analysis of sleep could have been compared to the daily symptom reporting of sleeping problems. Nonetheless, the authors have demonstrated improvements in sleep in all women, suggesting a very marked effect. The question of whether sleep disturbance contributes to daytime menopausal symptoms has not been answered, and is of interest to women and their physicians. It is
38
Evidence-based Obstetrics and Gynecology (1999) 1, 37d38
useful and important that both symptomatic and asymptomatic women benefited from treatment. Sleep disorders can be added to the list of conditions for which benefit from estrogen has been demonstrated. Jennifer Blake, MD McMaster University, Hamilton, Canada
^ 1999 Harcourt Brace & Co. Ltd