Women experience a variety of symptoms during the menopausal transition, including hot flashes and night sweats, often referred to as vasomotor symptoms. A hot flash is a sensation of intense heat, often accompanied by sweating and flushing. Hot flashes occur in an effort to dissipate heat characterized by vascular dilation. Voda [19] characterized the menopausal hot flash from women’s own experiences, exploring the question “who is the woman who has hot flashes and what are the characteristics of the hot flashes?” Using data from daily self-reports, she sought to describe the frequency, duration, trigger, origin, spread, intensity, and method of coping with hot flashes. She found that no single pattern characterized women’s experiences. Although the majority of hot flashes began on the upper body, for example, the chest or face, some women noted their hot flashes started in other parts of their body. Hot flashes tended to spread to other areas on the upper body but for some women spread to the legs and arms or back. On average, a hot flash lasted about 3 min. Women distinguished between mild, moderate, and severe hot flashes. Their coping strategies related to the duration and severity of their hot flashes. Internal strategies included ingesting a cold beverage. External strategies involved fanning oneself, showering, or opening a window. Some hot flash triggers included sleeping, work activities, recreation and relaxation, and housework. Voda’s study emphasized the variability in women’s hot flash experiences and how they managed them. In collaboration with Kay and others, Voda extended this work to characterize the experiences of both Mexican American and Anglo women [43]. They found that although Anglo women experienced hot flashes negatively, Mexican American women found positive components of meaning, for example, they viewed menopause as a natural part of life, indicating they could no longer have children, and meaning they could be confident they would not become pregnant again [43].

Hot flashes that women reported in laboratory studies were associated with a rise in skin temperature and skin conductance levels, elevated heart rate and respiratory rate, and reduced blood pH. Laboratory studies also revealed autonomic nervous system activation, such as occurs with a stress response, in mediating vasodilation and elaboration of norepinephrine following the hot flash [44–46]. Potent vasodilators such as calcitonin gene-related peptide are released during hot flashes, but not during exercise or sweating [47]. Although the etiology of hot flashes and the mechanisms stimulating vasodilation remain unclear, most investigators suggest that estrogen withdrawal or changing estrogen levels is involved.

The effects of changing estrogen levels on blood vessel structure and function are beginning to be characterized by SWAN investigators focusing on the relationship of the menopausal transition and associated physiological changes to heart disease risk. Thurston et al. [48] found that women who had hot flashes experience lower heart rate variability during the flash, indicating that the parasympathetic nervous system, which helps influence return to normal heart rate after a stressful experience, may function differently in women with hot flashes than in women who do not have hot flashes. Woods and colleagues found that women experiencing a cluster of symptoms with severe hot flashes had higher norepinephrine levels than those experiencing low severity symptoms [49]. Thurston also found that women who have hot flashes have less expansion of their arteries when blood flow is increased than do women without hot flashes [47]. Hot flashes also have been linked to calcification of the aorta seen in heart disease [48, 50] and increased carotid intima-medial thickness among midlife women [51]. There is also an association with adiposity and hot flashes that suggests that women with greater adiposity experience more severe hot flashes [52–55]. In contrast, when hot flash monitors are used to measure sternal skin conductance, higher BMI and waist circumference were associated with fewer hot flashes, but only among older women in the study [52]. In addition, there is evidence that women who experienced hot flashes have higher levels of tPA and factor VII than those without hot flashes [56]. Taken together, this work is beginning to suggest the role of hot flashes as a marker for subclinical heart disease.

Hot flashes are associated with both increased FSH and lower estrogen levels and also are associated with increased bone turnover during the menopausal transition. During the early and late stages of the menopausal transition, women with the most frequent hot flashes tended to have higher N-telopeptide levels, a marker of bone loss [57]. Moreover, low estrogen levels as well as higher FSH levels have been associated with higher levels of interleukins, for example, IL1B, linking both gonadotropins and estrogen to immune response [58] as well as to hot flashes.

As Voda found, hot flashes may be barely noticeable or severe, resulting in a high degree of variability of the experience among women [19, 59]. For some, hot flashes are associated with impaired quality of life, disturbed sleep, irritability, and depressed mood, among other symptoms [60]. Thurston found that women who were most bothered by hot flashes were those with more negative affect, greater symptom sensitivity, sleep problems, poorer health, duration of hot flashes, younger age, and African American race. Bother associated with night sweats was associated with sleep problems and night sweats duration [60]. For many women, hot flashes are sufficiently bothersome to lead them to seek health care during the menopausal transition [61, 62]. Although the majority of women in most population-based studies experience hot flashes [63], it is unclear how long they persist. Barnabei and colleagues [64] found that between 23 and 37 % of participants in the Women’s Health Initiative Study who were in their 60s and 11–20 % of women in their 70s reported hot flashes. Some participants in the Melbourne study reported hot flashes for as long as 10 years after the FMP, although the average duration was 5 years [65].

In the Seattle Midlife Women’s Health Study, hot flash severity increased as women entered the late menopausal transition stage or early postmenopause. Those who used hormone therapy, had a longer duration of the early menopausal transition stage, were older at the time of their final menstrual period, and had higher levels of FSH had more severe hot flashes. Anxiety was also associated with hot flash severity. Older age at entry into the early menopausal transition stage and higher urinary estrogen (estrone) levels were associated with decreased hot flash severity.

Psychosocial/mood (stress, depressed mood) and lifestyle variables (BMI, activity level, sleep, alcohol use) were not associated with hot flash severity in this study [59]. In contrast, in daily diary studies, women reported negative affect on the same day and the day after they reported hot flashes, suggesting that negative cognitive appraisal of hot flashes and perhaps other associated symptoms are linked to subsequent experiences of negative affect [66]. Other investigations have revealed that body mass index (BMI) [67], anxiety [68, 69], and other lifestyle behaviors have been associated with hot flash severity. As one example, women who smoked reported more severe hot flashes [67].

In addition to hot flashes, women commonly experience sleep symptoms during the menopausal transition and early postmenopause. Shaver was the first to study sleep during the perimenopause using polysomnographic methods in a sleep laboratory, discovering the relationship between sleep problems and ongoing stressful life events and anxiety [70–73]. In the Seattle Midlife Women’s Health Study, women who experienced more severe difficulty going to sleep had several other symptoms such as anxiety, reported more stress, had a history of sexual abuse, rated their own health more poorly, and had greater caffeine intake and less alcohol use than women who did not have this problem. Neither estrogen nor FSH was related to difficulty getting to sleep. On the other hand, women who had more severe awakening during the night were older, were more likely to be in the late MT stage and early postmenopause, had higher FSH and lower estrogen (estrone) levels, and reported more severe hot flashes, depressed mood, anxiety, joint pain, backache, perceived stress, poorer overall health, less alcohol use, and a history of sexual abuse. Women who had more severe problems with awakening early (and not getting back to sleep) were older, reported more severe hot flashes, depressed mood, anxiety, joint pain, backache, and perceived stress, rated their health more poorly, and had higher epinephrine and lower urinary estrogen levels [74]. These findings are consistent with those of other contemporary studies [75–77]. Moreover, in the Seattle Midlife Women’s Health Study, sleep symptoms were related to other symptoms, including hot flashes, depressed mood, anxiety, and pain [74, 78]. Recent findings from a study of relationships between menopausal transition-related symptoms and EEG sleep measures indicate that hot flashes were associated with longer sleep time. Women with higher anxiety symptoms had longer sleep latency and lower sleep efficiency only if they also had hot flashes. Hot flashes and mood symptoms were unrelated to either delta sleep ratio or REM latency [79]. In this same study, elevated beta EEG power in the NREM and REM sleep in women during late perimenopause (late MT) and early postmenopause exceeded levels in pre (late reproductive stage) and early perimenopause (early MT). Elevated beta EEG power indicates increased arousal and disturbed sleep quality during the late perimenopause (late MT) and early postmenopause [80]. Sleep symptoms during the MT may be amenable to symptom management strategies that take into account women’s experiences of arousal and their ability to regulate it as well as efforts to promote women’s general health rather than focusing only on the MT.

Depressed mood is also a commonly experienced symptom during the menopausal transition and early postmenopause. In the Seattle Midlife Women’s Health Study, age was associated with slightly lower depressed mood (CES-D) scores. Being in the late MT stage was significantly related to experiencing depressed mood, although there was no effect of being in the early MT stage or the early postmenopause. Hot flash severity, life stress, family history of depression, history of postpartum blues, sexual abuse history, BMI, and use of antidepressants were also individually related to depressed mood. Neither FSH nor estrogen was related to depressed mood [81–83]. Several investigator groups have now identified the menopausal transition as a period of vulnerability to depressed mood [84–87]. There is a suggestion that variability of hormonal levels (estrogen, FSH) is related to depressed mood, although there is no evidence that estrogen levels themselves are related [87–89]. Of interest is that testosterone rise has been associated with depressed mood in a subset of the SWAN study participants [85] and DHEAS associated with depressed mood symptoms but not major depression in the Penn Ovarian Aging Study participants [90]. A recent assessment of SWAN participants who responded to a Structured Clinical Interview for DSM-IV Axis Disorders (SCID) revealed that compared to women who were premenopausal, those who were in the perimenopause or early postmenopause were 2–4 times more likely to experience a major depressive episode, even when prior depression history, upsetting life events, psychotropic medication use, hot flashes, and serum levels or changes in reproductive hormone levels were taken into account. Although women in the late menopausal transition stage are vulnerable to depressed mood, factors that account for depressed mood earlier in the lifespan continue to have an important influence and should be considered in studies of etiology and therapeutics. Of interest is that depressive symptoms during midlife are related to progression of coronary artery calcification, a risk factor for cardiovascular disease [91].

Women complain of forgetfulness and difficulty concentrating commonly during this period of life. Seattle Midlife Women’s Health Study participants who experienced more severe difficulty concentrating were slightly older, reported more anxiety, depressed mood, nighttime awakening, perceived stress, poorer perceived health, and were employed. The best predictors of forgetfulness included slightly older age, hot flashes, anxiety, depressed mood, awakening during the night, perceived stress, poorer perceived health, and history of sexual abuse.

Menopausal transition-related factors were not significantly associated with difficulty concentrating or forgetfulness. Considering women’s ages and the context in which they experience the menopausal transition may be helpful in understanding women’s experiences of cognitive symptoms [92]. Studies of functional changes in memory during the menopausal transition indicate that aside from a period of slightly reduced learning, there are no significant changes in memory function during this period of the lifespan. The minor slowing of learning during the late menopausal transition stage disappears during the early postmenopause [93–95].

Although women experience pain symptoms throughout the lifespan, there is some evidence that pain symptoms are influenced by estrogen [96]. In the Seattle Midlife Women’s Health Study, women experienced a slight increase in back pain with age and a significant increase in back pain during the early and late MT stages and early postmenopause, but estrogen, FSH, and testosterone levels were unrelated to back pain [78]. Perceived stress and lower overnight urinary cortisol levels were associated with more severe back pain; history of sexual abuse and catecholamines did not have a significant effect. Those most troubled by symptoms of hot flashes, depressed mood, anxiety, nighttime awakening, and difficulty concentrating reported significantly greater back pain. Of the health-related factors, having worse perceived health, exercising more, using analgesics, and having a higher BMI were associated with more back pain, but alcohol use and smoking did not have significant effects. Having more formal education was associated with less back pain, but parenting, having a partner, and employment were unrelated. Age was associated with increased severity of joint pain, but menopausal transition-related factors, such as stage or hormone levels, were unrelated. Symptoms of hot flashes, nighttime awakening, depressed mood, and difficulty concentrating were each significantly associated with joint pain, as was poorer perceived health, more exercise, higher BMI, and greater analgesic use. History of sexual abuse was the only stress-related factor significantly related to joint pain severity. Based on these findings which are consistent with those of others [97–100], clinicians working with women traversing the menopausal transition should be aware that managing back and joint pain symptoms among midlife women requires consideration of their changing biology as well as their ongoing life challenges and health-related behaviors. Moreover, the relationship between pain and sleep symptoms should be considered, including sleep hygiene interventions [78].

There is a great deal of interest in the effects of the menopausal transition on sexual desire. In the Seattle Midlife Women’s Health Study, women experienced a significant decrease in sexual desire during the late MT stage and early PM [100]. Those with higher urinary estrone (E1G) and testosterone (T) reported significantly higher levels of sexual desire, whereas those with higher FSH levels reported significantly lower sexual desire. Women using hormone therapy also reported higher sexual desire. Those reporting higher perceived stress reported lower sexual desire, but history of sexual abuse did not have a significant effect. Those most troubled by symptoms of hot flashes, fatigue, depressed mood, anxiety, difficulty getting to sleep, early morning awakening, and awakening during the night also reported significantly lower sexual desire, but there was no effect of vaginal dryness. Women with better perceived health reported higher sexual desire, and those reporting more exercise and more alcohol intake also reported greater sexual desire. Having a partner was associated with lower sexual desire. Women’s sexual desire during the menopausal transition and early postmenopause is related to both her biology as well as the social situation in which she finds herself [101–103].

As studies of the menopausal transition and symptoms have progressed, it is increasingly evident that women experience multiple symptoms with some experiencing multiple severe symptoms. Moreover, researchers studying symptom have identified the importance of studying co-occurring symptoms or symptom clusters as a basis for identifying mechanisms that may be common to several symptoms or explain relationships among symptoms. As an example, Joffe and colleagues have found that induced hot flashes objectively recorded influence sleep efficiency, creating fragmentation. Subjective hot flashes are associated with perceived poor sleep quality [106]. In addition, investigators studying symptom clusters are concerned about identifying therapeutics that will maximize effects of an intervention on all or most symptoms and minimize the likelihood that a therapy will have positive effects on one symptom but exacerbate others [107]. Cray and colleagues identified three clusters of symptoms women experienced during the menopausal transition and early postmenopause [108]. Among these were clusters of (1) low severity symptoms of all types (hot flashes, mood, sleep disruption, cognitive, pain, and tension symptoms; (2) moderately severe hot flashes along with moderate levels of other symptoms; and (3) low severity hot flashes with moderate levels of all other symptoms (Fig. 31.5). The high hot flash cluster versus the low symptom severity cluster was associated with being in the late menopausal transition stage as well as with higher levels of FSH, lower levels of estrogen, higher norepinephrine, and lower epinephrine levels. The moderate severity symptom cluster versus the low severity cluster was associated only with having lower epinephrine levels [109].

In contrast to a symptom cluster, a syndrome is a pattern of symptoms that is presumably disease-specific and results from a common underlying mechanism. Avis and colleague demonstrated a lack of evidence for a “menopausal syndrome” despite some evidence linking some of the symptoms in clusters to endocrine dynamics during the menopausal transition [110].

Given the global nature of health care, it is important to focus on women’s experiences of menopause in many parts of the world. To date much of this body of work has been conducted in economically developed countries, often incorporating measures common to Western cultures. A detailed review of the symptoms women experience around the globe is beyond the scope of this chapter. Nonetheless, Leidy Sievert [111] has led development of research culminating in identification of ways in which diverse populations of women experience menopause. Her work includes a biocultural model in which environment, culture, and biology intersect to influence the expression of hot flashes. Leidy Sievert elaborates that environment prompts consideration of the climate and altitude in which women live their lives and that culture warrants consideration of practices related to marriage, religion, attitudes, medicalization, hysterectomy practices, smoking, reproductive patterns, and diet. Finally, because different populations of the world have different genetic characteristics, they also may have differing hormone levels and sweating patterns. Thus, the variation across populations and the variation within populations of women are complex and together influence women’s individual experiences. Indeed, Leidy Sievert points out that cross-country comparative studies illustrate the differences between cultures, while cross-cultural study of menopause can facilitate understanding of women’s place in society and the influence of social context on symptom experience [112]. In a comparison of symptom experiences across countries, women from different countries report some similar symptoms but may cluster their symptoms differently. For example, expression of somatic with emotional complaints varies across populations, possibly reflecting comfort with expression of emotional symptoms [113]. Both Avis [110] and Locke [114] have provided compelling data about the diversity of the menopause experience and associated symptoms.