Sleep difficulties: due to menopause status, age, other factors, or all of the above?
Gerald Hurowitz, M.D.·Published 11 January 2011·12 min read
Key points
In biomedical science, it is generally surmised that symptoms associated with the transition to menopause are engendered by extant reproductive hormone fluctuations.
A goal to disentangle what is caused by menopause status from what is caused by normative aging with regard to symptoms, and especially perceived sleep, is questionable.
A prevailing perspective, in part, is that these changes include progressive ovarian follicle depletion, early cycle inhibin B reductions, and increases in follicle-stimulating hormone levels that, for a period, sustain estrogen levels, perhaps rather erratically in some women.
More pertinent might be indications that HPO hormone changes are a dominant factor in some but not in all women.
In biomedical science, it is generally surmised that symptoms associated with the transition to menopause are engendered by extant reproductive hormone fluctuations. Whether measuring hormones directly or using menopause status as a proxy, clear evidence for their sole effects is elusive, including for sleep difficulties. Using longitudinal survey data from a nationally representative Great Britain cohort study, the article by Tom et al1 in this issue of Menopause is addressed to clarifying the relationship between menopause status and sleep difficulty while accounting for age and a variety of other factors, that is, current somatic, vasomotor, and psychological symptoms; nighttime bathroom visits; and earlier measured socioeconomic status, physical and mental health, health behaviors, and the propensity to have poor sleep. The data set involved multiple repeated measures (most done annually) as reported by a large, random, social class-stratified sample of singleton birth women, born during 1 week in March 1946 and followed annually between ages 47 and 54 years. As with surveys, all data were derived from survey self-report, including sleep quality and menopause status (reported bleeding patterns). Women were classed a priori as having severe (bothered a lot by) or moderate (bothered a little by) sleep difficulties and compared with women reporting none. At each yearly assessment, women also were classed as remaining in premenopause, perimenopause, or postmenopause or transitioning from one to another stage.
Claiming importance to clinical management in the "Introduction," the authors explicated wanting to distinguish whether "sleep difficulties in midlife women are related to the menopausal transition, other risk factors (stress of psychological distress), or other age-related changes" and whether sleep issues are newly experienced or exacerbated in menopause. Given the state of current knowledge about sleep and menopause, the fact that sleep quality will vary across a large sample chosen randomly and the results in this article, these are not "either/or" issues, and the answer is "all of the above" in some women. I comment on these issues with an emphasis on framing approaches for investigating sleep during the menopausal transition.
Age
A goal to disentangle what is caused by menopause status from what is caused by normative aging with regard to symptoms, and especially perceived sleep, is questionable. Of note in relation to sleep and normative aging in both men and women, mainly from studies not accounting for menopause status in women, the amount of physically recorded (polysomnograph) deep sleep wanes with age, or at least the electroencephalographic wave amplitudes believed to represent deep sleep do. Behaviorally, sleep is said to become lighter and less stable, so typically, older adults report waking up more often during the night. Therefore, it is not surprising nor revealing that Tom and her team found that chronological "age was a risk factor" for both the moderate and severe sleep difficulty groups of women.
Written and revised by
Gerald Hurowitz, M.D.
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Most biomedical studies of outcomes associated with the menopausal transition, for example, vasomotor symptoms (VMS), sleep disruptions, sexual function, metabolic and disease risk factors, and cognitive or emotional function, are framed to show how they are attributable to ovarian hormone fluctuations or more precisely hypothalamic-ovarian (HPO) axis hormonal changes. A prevailing perspective, in part, is that these changes include progressive ovarian follicle depletion, early cycle inhibin B reductions, and increases in follicle-stimulating hormone levels that, for a period, sustain estrogen levels, perhaps rather erratically in some women. It is these among other changes that are most often seen to drive symptom and behavioral outcomes, whether any hormonal patterns are measured or not. However, supportive direct evidence is obscure, relegating hormone fluctuations to one of a number of considerations.
The HPO axis functional changes underlie the altered menstrual bleeding patterns that have been used to define the menopause stages emanating from the Stages of Reproductive Aging Workshop (STRAW, 2001). Specified was that hormonal changes (increasing follicle-stimulating hormone levels) begin in the late reproductive stage. The menopausal transition is recognized in the early phase when menstrual bleeding patterns become irregular (>7 d different from normal), progressing in the late phase to skipped menstrual cycles (two or more skipped cycles, amenorrhea for ≥60 d). Postmenopause is recognized 12 months past the final menstrual period, which, with the next 4 years, is considered early postmenopause stage and past this is considered late postmenopause stage. In this schema, high vulnerability to VMS (evidence to date shows that this is context for sleep disturbance) is said to occur in the late menopausal transition and early postmenopause stages. Because Tom and her team judged perimenopause by self-reported bleeding in the past 12 months but not in the past 3 months or decreased regularity compared with the previous year, their groups included women in the early and late menopausal transition. Similarly, the postmenopause group presumably included members in the early and late menopause. Thus, analyses according to the STRAW classifications are precluded, but of interest would be a longitudinal study that allowed classification of women according to the STRAW stages in concert with self-report measures of sleep and VMS or, better yet, subjective and objective measures of each.
Aligned with HPO axis hormonal fluctuations is the consideration of "windows of vulnerability" for experiencing symptoms like hot flashes, insomnia, or depressed mood as a function of ovarian hormonal fluctuations across reproductive stages. Although evidence is not extensive, Soares and Zitek comment on symptom vulnerability that crosses reproductive stages characterized by HPO hormone fluctuations, that is, during the menstrual cycle, pregnancy, and menopause. For example, they cite the observation that depression at menopause has been correlated with depression at premenstruum and postpartum. To reiterate, most attempts to link actual hormonal concentrations to symptom or behavioral health outcomes have failed to produce convincing evidence, implying that rapid or erratic hormone fluctuations might be more important than absolute hormone levels. Therefore, revealing dynamic temporal patterns of HPO axis hormonal changes as context for physical and cognitive/emotional changes deserves more attention.
Often, symptoms are assessed for an association with menopause status or stage as a proxy indicator for exposure to HPO axis hormone fluctuations. Indeed, sleep problems are reported by more women in the perimenopause or postmenopause stages than in the premenopause stage, and the prevalence escalates over the course of transition, suggestive of a contributing role. This was corroborated in the Tom et al study. After adjusting for age, most (moderate sleep difficulties) or all (severe sleep difficulties) of the women who were transitioning through natural menopause (as compared with premenopause) or had a hysterectomy had increased odds of self-reported sleep difficulty. Other large sample studies have revealed that rather than related to menopause status directly, perceived poor sleep quality was positively related to self-reported hot flashes, an indicator of menopause, but not to menopause status directly. Even objective sleep has not been related to menopause status, except perhaps in the context of hot flash activity. Thus, it remains equivocal as to whether sleep is disturbed by menopausal HPO hormone changes directly, indirectly, or both.
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Other factors
More pertinent might be indications that HPO hormone changes are a dominant factor in some but not in all women. When women in the Tom et al study were divided by their subjective evaluation of how bothersome their sleep disturbances were evident was the differential impact of menopause status versus other factors, that is, the vasomotor, somatic, and psychological symptoms and waking at night to use the toilet. For the group of women who reported being a little bothered by their sleep (moderate), increased odds of sleep difficulties seen by menopause status disappeared when other concurrently measured factors were taken into account, except in women who had undergone hysterectomies. These results support prior observations that sleep difficulties during the menopausal transition in some women are more related to other changes or sensations. However, after the same adjustments were done for the menopause status groups who reported being a lot bothered by their sleep difficulties (severe), the odds of reporting sleep difficulties were not reduced, suggesting that menopause status was dominantly influential. Women reporting more severe sleep bother might be construed as vulnerable to menopausal ovarian hormone shifts impacting sleep, regardless of other contextual factors. Thus, menopause status (hormone fluctuations) may be the unparalleled contributor to perceived sleep quality in some but not all women during the menopausal transition, and maybe not the majority. According to Tom et al, most women (72%) who reported sleep difficulty fell into the moderate category.
The observations by Tom and her team regarding sleep quality subgroups are different from but parallel to observations we have made of two sleep subgroups of midlife women. We found no influence of menopause status on reported or recorded sleep quality. However, using both modalities and comparing women reporting poor sleep (insomnia) with midlife women reporting good sleep, one group had insomnia that was not corroborated on sleep recordings. They had high psychological distress and general somatic symptom scores, although VMS scores were not comparatively augmented. Another group reporting insomnia that was corroborated with recordings had high self-reported VMS scores but not comparatively high psychological distress or somatic symptom scores. From these data, perceived poor sleep in some women seemed to be more a function of high life strain and psychological distress than ovarian hormone fluctuations, and in others, sleep interference seemed much more probably influenced by menopause status, presumably the hormone shifts in menopause.
Investigative frames
Although much evidence is pursued to declare HPO axis hormone fluctuations as the preeminent culprits in creating menopause-related symptom or behavioral manifestations, the Tom et al study exemplifies the value in broadening the frame for identifying factors that would more accurately predict or explain them across individuals. The emphasis on HPO axis function in explaining menopause manifestations perhaps stems from a common frame for biomedical science, held over from the germ theory idea used early in the origins of understanding infectious disease, that a specific type of microorganism causes a specific disease. Using a biomedical frame, it has been typical to design studies of health-related phenomena as if looking for the "cause" (ie, generalizable single or dominant instigator) of the phenomenon. Implicit in this approach is that if we know the cause, the "cure" will become evident. Even in the realm of common infectious diseases, obviating the completeness of the germ theory were observations that some healthy people carry germs (pathogens) but have no symptoms of disease and that some early conditions, for example, scurvy, were not attributable to germs. Similarly, in this day and age, within industrialized societies, microorganisms are rarely detectable in evolving chronic diseases, that is, not in those with detectable pathologly prevalent nor those that fall in the ever-increasing functional disorder category. These comments are made in no way to denigrate the importance or necessity of what is now the classic biomedical frame but to argue that framing of health science beyond this disease science approach is needed.
Increasingly clear in our society is that most diseases/illnesses are chronic and attributable to no one dominant factor but rather a variety of personal style (eg, temperament) and lifestyle behaviors. People at risk for disease/illness often include those prone to be stress hyperaroused or display aggression or depression or those who smoke, abuse alcohol, overeat, underexercise, lack sleep, or engage in risky sexual behaviors. When explaining phenomena such as sleep, which is a function of people in interface with their environments, salient factors to explaining disturbances are likely to include combinations of "person" vulnerability (both body and mind) factors and "environmental" risk (both physical and social) factors. Thus, more attention in human health science might be paid using a human health ecology frame and going beyond a "one size fits all" approach. The search is for sets of contributing factors rather than any dominant instigator. Indeed, as seen in the Tom et al article, after adjusting for age, a set of ecological factors, including somatic vasomotor and psychological symptoms and waking to use the toilet at night, among others, impacted perceived sleep quality. Moreover, multiple factors in person and environmental realms are likely to be differentially influential in inducing or worsening symptoms or behaviors in people, thereby defining subsets of people by factor configurations, also revealed in the Tom et al study according to the two sleep groups. One can see the challenges and complexities inherent in this approach as it necessitates multivariate data collection and analyses that will reveal multiple clusters of predictive or explanatory factors, thus defining subgroups of people requiring multimodal treatments/interventions tailored to particular configurations of contributing factors.
Sleep problems as newly experienced or exacerbated
With regard to the initial question of whether sleep issues are newly experienced or exacerbated in menopause, Tom et al neglected to comment further in the "Results" or "Discussion" sections, and from the explicated data, few insights emerged. Indicating that many women did not declare preexisting sleep problems, Tom et al showed in their Table 1 that about 17% of the women at age 43 years reported trouble with sleep once or twice a week or 3 to 10 times per month for a minimum of 4 months duration. By age 48 years, nearly 38% of the women were reported to be a little (moderate) or a lot (severe) bothered by trouble sleeping, and this increased by 10% more to 48% by age 54 years. Unclear is whether the 38% at age 48 years includes the 17% of women with longstanding sleep problems and what proportion of them were pre or already in transition to menopause (thought for most to begin by the mid-40s), and chances are good that for many, life factors were impacting their perceptions. A difficulty in interpreting or assessing these data is that the sleep history and the repeated, current sleep quality items are not comparable. The former requires a response according to frequency and the latter requires a subjective evaluative/interpretive response, if poor sleep is perceived. In US samples, insomnia prevalence is estimated to be about 30% at any one time, and about 10% are classed as having enduring insomnia. Thus, the propensity to chronic insomnia is likely to be a factor contributing to menopause sleep manifestations in only a minority of women.
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Summary
The Tom et al study reveals that menopause status is imperfectly related to perceived sleep quality in women transitioning through to menopause. In the women classed by how bothersome they reported their sleep to be, menopause status (assumed HPO axis hormone changes) seemed to highly affect the odds of reporting sleep distress in a portion (one group and the smallest group). Perhaps, equivocal findings from other studies regarding menopausal transition status and perceived sleep quality stem from inadequate characterization of contributing factors and identification of clusters of factors as defining of subgroups. As I have editorially commented before, in the context of transition to menopause, multiple factors in varying configurations in different women are likely to be explanatory for what contributes to perceived sleep quality. Such factors will include a variety of psychosocial ones (eg, life strain, affectivity, social milieu, and family history) along with biological factors (eg, genetic propensity, anthropometrics, and hormonal fluctuations).
### Shaver, Joan L.F. PhD, RN, FAAN University of Arizona, Tucson, Arizona Financial disclosure/conflicts of interest: None reported.
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