Hot Flushes and Night Sweats in Midlife : Why do Some Women Have Them and Others do Not ?

This study investigated what predicts the occurrence of hot fl ushes (HF) and night sweats (NS). A community sample of 992 women (42-60 years) answered a questionnaire to collect socio-demographic, health and menopause-related, as well as lifestyle information. Depressive mood and stress, as well as HF and NS (in terms of presence, frequency and intensity), were also assessed. Structural equation modelling was used to build a structural model to predict the occurrence of both vasomotor symptoms. Results: Stress predicted NS (β =.154; p =.006), whereas depressive mood was linked to the occurrence of HF’s (β =.149; p =.006). Being peri-menopausal and post-menopausal, among several other characteristics, were also signifi cant predictors of the occurrence of both HF and NS. This study supports a distinguished infl uence of stress and depressive mood in NS and HF respectively, probably due to the nature of psychological symptoms. Moreover, signifi cant associations between vasomotor symptoms and socio-demographic, health and menopause-related characteristics, and alcohol were confi rmed.

Many women, especially in western countries, experience hot fl ushes during midlife (Stearns et al., 2002) and these tend to increase as women pass from one menopausal status to the following one (Hardy & Kuh, 2002).However, the prevalence of vasomotor symptoms does not have a similar distribution between menopausal stages and even in a given stage, in the population of menopausal women (Melby, Lock, & Kaufert, 2005).In a longitudinal study (n = 2.229), the number of women who experience hot fl ushes (36%) is close to the number of women who do not experience hot fl ushes (29%), as a result of menopause experience (Gjelsvik, Rosvold, Straand, Dalen, & Hunskaar, 2011).
The vasomotor symptoms' prevalence varies from 14% to 51% in pre-menopause period, from 35% to 50% in peri-menopause and from 30% to 80% in post-menopause (National Institutes of Health, 2005).These symptoms are frequently identifi ed as the ones that lead to the search for medical advice during the menopausal transition (vaginal dryness, decreased libido, joints pain, among others, can also precipitate the search for medical and pharmacological help; Albertazzi, 2007).Also, hot fl ushes are the most frequent symptoms that are associated with menopause, followed by mood swing, vaginal dryness, sleep problems, night sweats, and memory loss (Asadi, Jouyandeh, & Nayebzadeh, 2012).
It has been suggested that the origin of vasomotor symptoms is related with higher follicle stimulating hormone (Randolph et al., 2005) and lower estradiol (Blümel et al., 2004).And although these symptoms are likely to occur due to the decline in the estradiol levels, there is still some debate around their mechanisms (Archer et al., 2011;Dennerstein, Dudley, Hopper, Guthrie, & Burger, 2000;Stearns et al., 2002).While around 70% of women experience them, only 15-20% perceive them as problematic due to their particular consequences (such as social embarrassment, distress and physical discomfort; Hunter & Mann, 2010).
Psychological factors have also been studied in this fi eld.It has been observed a positive relationship between stress and hot fl ushes (Gannon, Hansel, & Goodwin, 1987;Shaw, 1997).Also, a stress reduction intervention can decrease these symptoms' severity (Carmody, Crawford, & Churchill, 2006).
Depressed mood has also been associated with the presence of vasomotor symptoms (Bromberger et al., 2007;Freeman, Sammel, Lin, & Nelson, 2006;Hunter & Liao, 1995;Woods, Mariella, & Mitchell, 2002), and depression is signifi cantly higher in peri-and post-menopausal women with hot fl ushes than in their counterparts without this vasomotor symptom (Thurston & Joffe, 2012).The relation between depression and vasomotor symptoms is bidirectional, according to some studies, that have also found that previous vasomotor symptoms in perimenopausal women were associated with an increased likelihood of depression (Joffe et al., 2002).
Similarly, anxiety is strongly linked to hot fl ushes, independently of the menopausal status, estradiol levels and smoking (Freeman et al., 2005).However, it is suggested that this association is due to the overlapping of anxiety's somatic symptoms and the hot fl ushes' physical manifestations, given that these vasomotor symptoms are connected with the somatic dimension of anxiety, but not with the affective one (Lermer et al., 2011).
Because hot fl ushes may persist in some women, even concomitantly with hormone therapy (Albertazzi, 2007), and because in a minority of women these may persist until the late post-menopause (Huang et al., 2008), it is important to explore which factors are signifi cant predictors of the incidence of vasomotor symptoms.Therefore, the aim of this study is to build a structural model for hot fl ushes and night sweats' occurrence, using a sample of pre-, peri-and post-menopausal women with and without vasomotor symptoms.Specifi cally, we will explore if psychological variables (namely, depressive mood, anxiety and stress), health and menopause-related factors, lifestyle and socio-demographic characteristics, can predict the presence of these two vasomotor symptoms.Moreover, it is also our objective to demonstrate if there are signifi cant differences between participants in different menopausal statuses, regarding hot fl ushes and night sweats' severity, and frequency of anxiety, depressive mood and stress symptoms.Finally, we will analyze if women with vasomotor symptoms differ signifi cantly from women without them in terms of psychological symptoms (anxiety, stress and depressive mood).

Participants
A mainly community sample of 992 women in pre-, peri-and post-menopause, recruited in the city of Lisbon, was included in the present study.Ages ranged from 42 to 60 years old.

Procedure
This cross-sectional study encompasses a community sample, which was mainly recruited through schools and universities in the city of Lisbon.The inclusion criteria in this research were gender (female), literacy and age (between 42 and 60 years old).The American Psychological Association's standards on the ethical treatment of participants were followed.A written informed consent form was delivered to all participants, explaining the aims of the study, emphasizing that the participation in this research was voluntary and that participants could interrupt their collaboration at any time, without any consequences.

Measures
Vasomotor Symptoms.The instruments included the hot fl ushes and night sweats' items from the Menopause Symptoms' Severity Inventory, MSSI-38 (Pimenta, Leal, Maroco, & Ramos, 2012), which evaluates the two symptoms, both in terms of frequency and intensity, in a fi ve-point Likert-type scale (from 0 to 4) that ranges from "never" to "daily or almost every day", and from "not intense" to "extreme intensity", respectively.Hot fl ushes and night sweats' absence was defi ned as a "never" (0) and a "not intense" (0) answer, regarding the assessment of both frequency and intensity of the symptoms.Women who reported, in the frequency scale, an answer above 0 (that is, 1, 2, 3 or 4), independent of the intensity level, were classifi ed as having hot fl ushes, or night sweats.Hence, regarding vasomotor symptoms, participants were divided in two different groups: the ones who had vasomotor symptoms and the ones who did not have these symptoms.
Depression, Anxiety and Stress.To evaluate stress, anxiety and depressive mood, a Portuguese adaptation of the Depression, Anxiety and Stress Scales (Lovibond & Lovibond, 1995;Pais-Ribeiro, Honrado, & Leal, 2004) was applied.Each subscale encompasses seven items which are evaluated in a 4-point Lykert-type scale, ranging from 1 ("did not apply to me") to 4 ("it applied to me most of the time").The instrument presented good psychometric properties.
Menopausal and Health-Related Variables.The menopausal status was defi ned according to the Stages of Reproductive Aging Workshop's +10 criteria (Harlow et al., 2012).Women in pre-menopause presented an absence of changes in their menstrual cycle.Peri-menopausal participants would report variable cycle length (a difference of more than seven days, than usual) or had skipped two or more cycles, having an amenorrhea interval superior to sixty days.Post-menopausal women had at least a twelvemonth period of amenorrhea.
Besides menopausal status, the use of hormone therapy, herbal/soy products or nothing to manage menopausal symptoms was also asserted.In addition, the search for medical help to manage these symptoms was also controlled.
Health status (both physical and psychological), as well as menopausal status, were self-reported.The participants were inquired about presence of a recent disease and of a psychological problem.
Lifestyle.Alcohol, hot beverages and coffee intake, smoking, physical exercise and body mass index (BMI) were assessed.
Lifestyle habits were explored in terms of presence/absence, amount and/or frequency.Hence, physical exercise was measured in terms of times per week, and during how many minutes the participant exercised; a mean value of weekly frequency and duration was used in the multivariate model.Coffee intake, when present, was assessed in a four-option scale, ranging from "occasionally" to "more than fi ve per day".Alcohol intake, when observed, was measured both in terms of frequency ("daily", "every weekend" or "rarely") and quantity ("until I feel drunk", "moderately" or "less than a glass per occasion"); a mean value of both translates the alcohol consumption variable in the structural model.Finally, for current smokers, smoking was quantifi ed in a 6-point Likert-type scale that ranged from "less than 10 cigarettes per month", until "more than 40 cigarettes per day"; this quantifi cation integrated the structural equation model to assert the infl uence of smoking on the occurrence of hot fl ushes and night sweats.
Socio-Demographic Characteristics.Socio-demographic factors such as age, marital status, parity, professional status, educational level and family annual income were explored.

Statistical Analysis
Missing values were imputated for variables, where its frequency was lower than 10% of the sample.This was done using the mean interpolation method.
The distribution of the studied variables was explored with SPSS Statistics (v. 19, IBM SPSS Inc, Chicago, IL).
To explore if there were differences between the three menopausal statuses, regarding stress, anxiety and depressive symptoms' frequency, as well as hot fl ushes and night sweats' severity, a one-way ANOVA followed by post-hoc Tukey's test was performed in order to identify the groups were means were statistically significant different from each other.Variances' homogeneity was confi rmed and a Student t-test was implemented to evaluate the differences regarding stress, anxiety and depressive mood levels between participants with and without vasomotor symptoms (hot fl ushes and night sweats) using SPSS Statistics (v. 19,IBM SPSS Inc,Chicago,IL).
Multicollinearity between the independent variables was explored with the variance infl ation factor (VIF) given by SPSS Statistics (v. 19, IBM SPSS Inc, Chicago, IL).All variables should present a value below 5, indicating the absence of collinearity (Maroco, 2010;Weisberg, 1985).Because in the structural model anxiety evidenced a VIF above this value (that is, equal to 66), this variable was excluded from the structural model, since it showed multicollinearity with other independent variables.
To test the structural model for the occurrence of hot fl ushes and night sweats, a structural equation model was built relating the dependent variable (the two vasomotor symptoms in terms of presence/absence) with the twenty independent variables (namely, age, parity, marital and professional status, income, education, presence of a recent psychological problem or a disease, transition from pre-to peri-menopause and from peri-to post-menopause, use of hormone therapy or herbal/soy products to manage menopause symptomatology, search for medical help to deal with menopause, alcohol and coffee intake, smoking, physical exercise, body mass index, stress and depressive mood).The model was evaluated with SPSS AMOS software (v. 18, IBM SPSS Inc, Chicago, IL).The quality of fi t of the structural model was given by chi-square statistics (X 2 /df), comparative fi t index (CFI), goodness of fi t index (GFI) and root mean square error of approximation (RMSEA), using the reference values indicative of good fi t currently practiced in structural equation modelling (Byrne, 2001;Maroco, 2010).A two-step approach was employed to evaluate the structural model.First, the factor's measurement model was evaluated to demonstrate an acceptable fi t.Thereafter, the structural model, encompassing the two dependent and the twenty independent variables, was adjusted and the signifi cance of the structural trajectories was evaluated.

Results
After receiving the informed consent form and agreeing to participate in the research, a sample of 1,003 Portuguese women completed all instruments adequately (45 were excluded due to insuffi cient information).Of these, 992 gave suffi cient information to be classifi ed in one of the three menopausal statuses and were included in the present study.As shown, the assessed variables account for 20% and 25% of the occurrence of the night sweats and of the hot fl ushes' variability, respectively.
The signifi cant structural weights of each variable as a predictor of hot fl ushes and night sweats presence are shown in Table 2.  Table 3 evidences the mean levels of vasomotor symptoms' severity, and of stress, anxiety and depressive mood symptoms' frequency, as well as, the differences between the three menopausal statuses.
To explore if there are signifi cant differences between women who have, and those who do not have, vasomotor symptoms in relation to depressive mood, anxiety and stress, the two groups were compared.The results are presented in the Table 4.

Discussion
In this community sample, women with hot fl ushes and night sweats presented signifi cantly higher levels of stress, anxiety and depressive mood.Regarding the menopausal status, post-menopausal women always presented more severe hot fl ushes and night sweats compared with their peri-menopausal counterparts.However, these two menopausal statuses did not differ signifi cantly in terms of depressive mood, stress and anxiety.Therefore, given the results of the univariate analysis, the frequency of anxiety, depressive mood and stress symptoms is only statistically different when considering the presence of vasomotor symptoms (instead of taking into account the menopausal status) in peri-and post-menopausal women (although in the fi rst analysis -regarding the presence/ absence of vasomotor symptoms -pre-menopausal women are included, they are a small part of this sample; that is, 31 participants and 57 women in pre-menopause reported hot fl ushes and night sweats, respectively).
Although there is strong evidence that vasomotor symptoms are one of the few clinical manifestations strongly associated with the hormonal fl uctuation observed in the peri-menopause (Deecher & Dorries, 2007), these symptoms have been reported in some studies by premenopausal women (Freeman et al., 2005).In the present study this was observed: as mentioned before, 12% and 21% of women in pre-menopause reported hot fl ushes and night sweats, respectively.
It could be hypothesized that this translates a limitation on the assessment of the menopausal status -in this study a  self-report method based on STRAW+10 criteria (Harlow et al., 2012) was used -which could evidence that, although the menstrual period of these participants did not evidence alterations, minimal hormonal changes (not translated in manifest menstrual alterations) might promote these vasomotor symptoms.Also, it can be thought that socio-cultural factors (such as the identifi cation with menopausal-peers), as well as the perception of age progressing towards an age interpreted as "menopausal", might infl uence the interpretation of elevated body temperature (for reasons other than hormonal) as vasomotor symptoms.Despite these hypotheses, the assessment of the menopausal status through age and self-assessment of the menstrual history, as done in the present research, has been evidenced as a more accurate way of determining the menopausal status rather than using the presence of particular symptoms (such as vasomotor symptoms) or hormone levels given by laboratory tests (Bastian, Smith, & Nanda, 2003).
The structural model encompassing socio-demographic, health, menopause-related, lifestyle and psychological variables (stress and depressive mood), demonstrates that there are several factors that can predict the presence of vasomotor symptoms in midlife women.Age progression was a signifi cant variable in relation to the appearance of hot fl ushes.Also, being married (or in a relationship) and having less children (or no children) predicted the presence of both vasomotor symptoms.In other studies, being divorced was associated with bothersomeness of vasomotor symptoms (Avis, Crawford, & McKinlay, 1997) and parous women evidenced a higher frequency of vasomotor symptoms (Progetto Menopausa Italia Study Group, 2005).
Menopausal status (namely, being peri-and postmenopausal), as well as medical help sought to manage menopause, significantly predicted the occurrence of both hot fl ushes and night sweats.This is congruent with researches which evidence that the vasomotor symptoms result from the decrease in endogenous estrogens (Blümel et al., 2004;Randolph et al., 2005), and are the most common reason to search for medical help search to deal with menopause (Albertazzi, 2007;Avis et al., 1997;Guthrie, Dennerstein, Taffe, & Donnelly, 2003;Whitcomb, Whiteman, Langenberg, Flaws, & Romani, 2007).
The use of herbal/soy products was signifi cantly associated with both vasomotor symptoms.These results are consistent with other studies (Haimov-Kochman & Hochner-Celnikier, 2005;Thurston & Joffe, 2012).A review on herbal products' effi cacy for the treatment of menopausal symptoms has concluded that there is no convincing evidence and that the data on these products is doubtful given the poor methodology used in studies that document benefi ts of the herbal therapies and safety concerns (namely, regarding the use of kava; Huntley & Ernest, 2003).Therefore, the use of natural products for the treatment of hot fl ushes and night sweats should receive further attention and be thoroughly researched.However, it is reasonable to think that women without symptoms are less likely to use herbal/soy products.In addition, it can be hypothesized that some women with bothersome symptoms may have opted, or have been suggested to use natural products, in alternative to the hormonal therapy.
The physical health status (specifi cally, the presence of a recent disease) was also signifi cant in the prediction of night sweats.This outcome supports a previous study where a health status qualifi ed as excellent was linked to a decrease in night sweats, but not in hot fl ushes (Sievert et al., 2006).
Lifestyle factors can signifi cantly infl uence the degree of vasomotor symptoms' reporting (Avis et al., 1997).In particular, daily alcohol consumption has been described as a habit that increases the probability of incidence and bothersomeness of night sweats (Sievert et al., 2006).In this study, only alcohol intake predicted one of the vasomotor symptoms.Therefore, higher alcohol intake was linked to the presence of night sweats.This emphasizes a conclusion drawn in prior researches which identify alcohol as a risk factor for vasomotor symptoms (Kandiah & Amend, 2010;Progetto Menopausa Italia Study Group, 2005;Shaw, 1997;Sievert et al., 2006).Smoking, coffee, physical exercise and BMI were not signifi cant predictors of the occurrence of night sweats or hot fl ushes, in this sample.
The different infl uences of the two psychological variables in the vasomotor symptoms, namely stress predicting night sweats (but no hot fl ushes) and depressive mood predicting hot fl ushes (and not night sweats) might be related with the nature of the psychological symptoms itself.
Individuals with higher stress levels have been identifi ed as having lower sleep effi ciency, higher latency on the fi rst stage of sleep and increased arousal (Drake, Richardson, Roehrs, Scofi eld, & Roth, 2004).Another study has reported that vasomotor symptoms are associated with sleep disturbance and poor sleep continuity and quality (Kravitz et al., 2008).Since higher levels of stress predicted the occurrence of night sweats, this relation can be mediated by the sleep disturbance that results from higher levels of stress.
Furthermore, it has been found that in a non-clinical sample of women with varying degrees of depressed mood, in women with higher scores of depressed mood, the negative affect was observed more signifi cant during the morning; additionally, an improvement in depressive mood was evidenced in the evening (Murray, 2007).It is hypothesized that this diurnal nature of the depressed mood might partially explain the connection of depressive mood with hot fl ushes' occurrence, but not with night sweats.Moreover, it had already been highlighted that menopausal women were more likely to experience hot fl ushes if they were depressed (Juang, Wang, Lu, Lee, & Fuh, 2005), stressed, anxious or with negative affect (Thurston & Joffe, 2012).Furthermore, this study has also demonstrated that women with hot fl ushes present a signifi cantly higher depressive mood than their counterparts without hot fl ushes.
The variables assessed account for 20% and 25% of the occurrence of night sweats and hot fl ushes' variability, respectively.Hence, variables, other than the included in this study, may have an impact in the emergence of vasomotor symptoms.For example, a structural model predicting the severity of both hot fl ushes and night sweats in a sample of symptomatic women (that is, who evidenced vasomotor symptoms in the previous month) showed that perceived control over vasomotor symptoms was the strongest and most signifi cant predictor of the symptoms' severity; moreover, that structural model explained 67% and 72% of the variability of hot fl ushes and night sweats' severity, respectively (Pimenta, Leal, Maroco, & Ramos, 2011).And although vasomotor symptoms are strongly associated with hormonal variations (Dennerstein et al., 2000) there might be other non-hormonal variables that account for the presence of vasomotor symptoms in midlife women.
The sample size (992 participants) was adequate for this type of statistical analysis given it was applied a rule of thumb of ten subjects per manifest variable, as is current practice in structural equation modelling (Kline, 2005;Maroco, 2010).Nevertheless, the fact that this research has a cross-sectional design, and that it uses a sample where a signifi cant part of the participants has a college degree, limits the generalization of these results.
In conclusion, this research shows that vasomotor symptoms' occurrence might be predicted by several variables, namely, socio-demographic characteristics (age, marital status and parity), menopausal status, medical help-seeking (to manage menopause), use of herbal/soy therapies, health status, alcohol intake and psychological symptoms (depression and stress).Moreover, the different infl uences of the two psychological variables in the vasomotor symptoms, namely stress predicting night sweats (but no hot fl ushes) and depression predicting hot fl ushes (and not night sweats), might be related with the nature of the psychological symptoms itself.Additionally, it was concluded that participants with hot fl ushes and night sweats presented signifi cantly higher levels of stress, anxiety and depression.

Figure 1 .
Figure 1.Causal model of hot fl ushes and night sweats' occurrence.

Table 1
Table 1 describes the participants.Characterization of the Participants in Relation to Socio-Demographic, Health and Menopause-Related and Lifestyle Variables

Table 2
Structural Weights of Independent Variables (socio-demographics, health and menopause-related, lifestyle, stress and depressive mood) in Relation to the Dependent Variables (presence of vasomotor symptoms)

Table 3
Mean Scores for Vasomotor and Psychological Variables and Differences between the Three Menopausal Statuses Note.MD=mean difference; SE=standard error.*p≤.001.

Table 4
Comparison of Women With and Without Hot Flushes (HF) and Night Sweats (NS) Regarding Levels of Stress, Anxiety and Depressive Mood *p≤.001.