Symptom Interference with Work and Relationships during the Menopausal Transition and Early Postmenopause: Observations from the Seattle Midlife Women’s Health Study

Abstract

Objective:

Describe changes in symptom interference during the menopausal transition (MT) stages and early postmenopause (PM), including effects of age, MT-related factors (estrone, FSH, testosterone, MT stages), symptoms (hot flashes, depressed mood, awakening during the night, anxiety, backache, joint pain, forgetfulness, and difficulty concentrating), health-related factors (perceived health), and stress-related factors (perceived stress, cortisol).

Methods:

A subset of Seattle Midlife Women’s Health Study participants provided data during the late reproductive, early and late MT stages or early postmenopause (N=184) including menstrual calendars for staging the MT, annual health reports completed between 1990 and 2008, morning urine samples assayed for estrone glucuronide (E1G), follicle stimulating hormone (FSH) and cortisol and symptom diary ratings several times each year. Interference was rated in the diary along with symptoms, perceived health, stress, and symptoms. Multilevel modeling with an R program was used to test patterns of symptom interference related to age, MT-related factors, symptoms, health-related and stress-related factors with as many as 5656 observations. Age was centered at 47.4 years

Results:

Interference with work was significantly associated with individual covariates perceived health, stress, hot flashes, depressed mood, anxiety, difficulty getting to sleep, awakening during the night, early morning awakening, backache, joint pain, forgetfulness and difficulty concentrating (p=.01 for hot flashes, all others p<.001). A final multivariate model included perceived health, stress, depressed mood and difficulty concentrating. Interference with relationships was significantly associated with age and individual covariates perceived health, estrone, perceived stress, depressed mood, anxiety, the sleep symptoms, backache, joint pain, forgetfulness and difficulty concentrating (p=.03 for estrone, all others p<.001). A final multivariate model included perceived health, stress, depressed mood, anxiety, difficulty concentrating, and awakening during the night.

Conclusions:

Women’s reports of how much the way they felt interfered with work and relationships were influenced by both their perceived health and stress levels. Interference was also influenced by depressed mood and difficulty concentrating, suggesting that these two symptoms may be most important to address to enhance functioning during the menopausal transition and early postmenopause.

Tables of Contents Summary

Women’s experience of specific symptoms, especially difficulty concentrating and depressed mood, are associated with interference with work and relationships during the menopausal transition and early postmenopause, along with perceived health and stress. The menopause transition, itself, seems to have little direct relationship to perceived interference with daily living.

Over the past two decades scientific interest in quality of life during the menopausal transition and postmenopause has increased with the escalating proportion of women experiencing the menopausal transition. ^1–3 Estimates are that over half of the 40 million U.S. women experiencing the menopausal transition (MT) and early postmenopause (PM) report being bothered by symptoms such as hot flashes, sleep disruption, and cognitive or mood changes. ⁴ Moreover, a large proportion of women troubled by these symptoms is prompted to seek health care to alleviate them.^5,6 The challenge of helping women manage their symptoms has motivated study of the relationship of the menopausal transition, itself, and factors associated with MT to quality of life.

Exogenous ovarian steroids, principally estrogen, have been studied extensively in relation to quality of life.⁷ Results of the Women’s Health Initiative Study clinical trial (WHI-CT) indicated that preventive use of hormone therapy did not have a direct effect on indicators of quality of life and this was true of estrogen alone and estrogen plus progestin.^8,9 Results from the WHI trials suggest that effects of exogenous hormones on symptoms such as hot flashes, disrupted sleep, and mood, may mediate effects on quality of life.

In earlier work illuminating the relationship of symptoms to quality of life, Wilson and Cleary proposed that symptoms were related to overall quality of life through their impact on functional status and general health perceptions.¹⁰ Moreover, this set of relationships was modified by both individual characteristics, e.g. personality, and environmental characteristics, e.g. social and economic support.

Avis and colleagues found evidence from the Study of Women and Health Across the Nation (SWAN) cohort of midlife women indicating that global quality of life was influenced more by marital status and perceived stress than by MT stages. In addition, they found that effects of menopausal transition stages on health-related quality of life were a function of symptoms. Health status, lifestyle characteristics, and social circumstances also influenced health-related quality of life.^1,2 Most recently Avis and colleagues reported longitudinal findings that hot flashes, night sweats, urine leakage, poor sleep, depressed mood, perceived stress and stressful life events influenced health-related quality of life as measured by the SF-36.³

Understanding how symptoms women experience during the MT and early PM influences quality of life is an important challenge for investigators and requires consideration of the effects of symptoms on everyday life, such as the burden they create and the degree to which they interfere with typical activities. Burden has been estimated as a sum of the number of symptoms or the product of the occurrence and severity of symptoms. ^11,12 Symptom interference has been defined as the degree to which a symptom such as hot flashes interferes with daily activities, including work, social, leisure, sleep, mood, concentration, relationships, sexuality, and enjoyment.¹³ The impact of symptoms women experience during the menopausal transition is likely to be related to the primary and salient roles performed by midlife women, including their employment roles and their capacity to engage in relationships with their families and others.¹⁴ Moreover, perceived interference may be differentially related to the type of symptoms women experience. For example, interference with work may be influenced by difficulty concentrating and interference with relationships by mood symptoms.

In addition, interference with work and relationships may reflect women’s sensitivity to their symptoms as a function of stressful environments, as well as physiologic arousal, as indicated by perceived stress and cortisol levels, respectively.¹⁴ Arousal refers to a state of physiologic responsiveness to sensory stimuli, associated with emotional and motor reactivity.¹⁵ Generalized central nervous system arousal is indicated by electro cortical activity associated with behavioral change, alertness, and vigilance, leading to motivated responses that involve involving somatic and autonomic outflow. Arousal may also be associated with enhanced interoception or awareness of symptoms, as is seen with symptom amplification.^16,17 Women who perceive their symptoms as severe may experience heightened arousal or symptom amplification that may, in turn, be perceived as interfering with their role performance at work or in relationships.

To date there has been little research attention to the relationship between symptoms and interference with everyday life, with the exception of Carpenter’s studies of breast cancer survivors experiencing hot flashes.¹⁸ The purposes of the analyses reported in this paper are to describe changes in levels of symptom interference during the MT and early PM, including effects of age, and assess the relationships between interference with work and relationships and MT-related factors (estrone, FSH, MT stages), symptoms (hot flashes, depressed mood, difficulty getting to sleep, awakening during the night, early morning awakening, anxiety, backache, joint pain, forgetfulness, and difficulty concentrating), health-related factors (perceived health), and stress-related factors (perceived stress, cortisol). (See Preliminary Model, Figure 1)

Figure 1.

Factors Influencing Interference During the Menopausal Transition and Early Postmenopause

Methods

Sample

The data for these analyses are part of a larger longitudinal study of the MT, the Seattle Midlife Women’s Health Study (SMWHS). In the parent study, women entered the cohort between 1990 and early 1992 when most were not yet in the MT or were in the early stages of the transition to menopause. To be eligible for the parent study the participants were 35 to 55 years of age, had a period within the previous 12 months, still had at least one ovary and a uterus, were not pregnant or lactating, and could read and speak English.¹⁹ Screening all households within selected multi-ethnic neighborhoods in Seattle (11,222 households) yielded 820 women eligible for the study and 508 were able to participate in an interview during the recruitment window. After completing an initial in-person interview (n=508) administered by a trained registered nurse interviewer, participants (n=367) began providing data annually by questionnaire, menstrual calendar, and health diary.

The sample for this study (N=184) is a subset of the parent study sample (N=508). Eligible participants were those who, in addition to meeting the original eligibility entrance criteria, contributed ratings from the health diary for at least one occasion about interference with work and relationships and were in either the late reproductive, early or late MT stages, or early PM during the course of the study. Also excluded from the data analyses were any occasions with estrogen, progestin, androgen or SERM use, pregnancy and up to 3 months postpartum, lactation, hysterectomy, bilateral oophorectomy, chemotherapy, radiation or endometrial ablation.

The 184 eligible participants at the beginning of the longitudinal study were midlife women with a mean age of 40.8 years, 16 years of education, and a median family income of approximately $39,000. Most (86%) of the eligible participants at the start were employed, and 73% were married or partnered. The women described themselves as follows: 5% African American, 9% Asian American, 86% White. As seen in Table 1, women included in these analyses compared to those who were ineligible were slightly younger at the beginning of the study, had slightly higher incomes and years of education, and were more likely to be white. They were similar with respect to employment status and marital status.

Table 1.

Sample Characteristics at Start of Study (1990–1991) of the Eligible and Ineligible Women in the Mixed Effects Modeling Analyses of Interference with Work or Relationships.

Characteristic	Eligible Women (n=184) Mean (SD)	Ineligible Women (n=324) Mean (SD)	p value*
Age (years)	40.8 (4.0)	42.2 (4.9)	<.001
Years of education	16.0 (2.7)	15.4 (3.0)	0.03
Family income ($)	39,200 (14,600)	37,600 (16,900)	0.01
Characteristic	N (Percent)	N (Percent)	p value**
Currently employed
Yes	159 (86.4)	279 (86.1)	0.92
No	325 (13.6)	45 (13.9)
Race/ethnicity			<.001
African American	9 (4.9)	49 (15.1)
Asian /Pacific Islander	16 (8.7)	27 (8.3)
White	158 (85.9)	233 (72.0)
Other (Hispanic, Mixed)	1 (0.5)	15 (4.6)
Marital Status			0.36
Married/partnered	134 (72.8)	214 (66.0)
Divorced/widowed/not partnered	37 (20.1)	88 (27.2)
Never married/partnered	13 (7.1)	22 (6.8)

^*Independent t-test

^**Chi-square test

Procedure

Data for this study were obtained from 3-day health diaries, health questionnaires, first morning voided urine specimens and menstrual calendars. Diary data were obtained on days 5, 6 and 7 of the menstrual cycle monthly from 1990 through 2000 and then quarterly from 2001 through 2008. Urine assays were from first morning voided urine specimens collected on day 6 of the menstrual cycle from late 1996 through 2000 and then quarterly from 2001 through 2005. The health questionnaires were mailed annually to all active participants. Each occasion of urine and diary data was matched to within 6 or fewer days of each other. Each occasion of health questionnaire and diary data was matched to within 6 months of each other.

Measures

The concepts and measures used in these analyses form a preliminary model as shown in Figure 1 for interference with work and relationships: age; MT-related factors (MT stage, urinary estrone glucuronide, FSH); health-related factors (perceived health); stress-related factors (perceived stress, cortisol); symptoms (hot flashes, depressed mood, anxiety, difficulty getting to sleep, awakening during the night, early morning awakening, backache, joint pain, difficulty concentrating and forgetfulness). Figure 1 guided the multivariate model testing.

Interference with work and relationships

Interference with work and relationships was assessed in the diaries by asking the following questions: How much did the way you felt today interfere with your work or school? With your relationships? Women responded by rating interference on a scale where 0 indicated not at all and 6 indicated a lot or extremely.

Menopausal transition-related factors.

Menopausal transition-related factors included MT stage, urinary estrone glucuronide, testosterone and FSH. Using menstrual calendar data, women not taking any type of estrogen or progestin were classified according to stages of reproductive aging: late reproductive, early MT, late MT, or early PM, based on staging criteria developed by Mitchell, Woods and Mariella¹⁹ and validated by the ReSTAGE collaboration.^20–22 The names of stages match those recommended at the Stages of Reproductive Aging Workshop (STRAW).²³ The time before the onset of persistent menstrual irregularity during midlife was labeled the late reproductive stage when cycles were regular. Early stage was defined as persistent irregularity of more than 6 days absolute difference between any two consecutive menstrual cycles during the calendar year, with no skipped periods. Late transition stage was defined as persistent skipping of one or more menstrual periods. A skipped period was defined as double the modal cycle length or more for the calendar year. In the absence of a modal cycle length, a population-based cycle length of 29 days was used.²⁴ Persistence meant the event, irregular cycle or skipped period, occurred one or more times in the subsequent 12 months. Final menstrual period (FMP) was identified retrospectively after one year of amenorrhea without any known explanation. The date of the FMP is synonymous with the term menopause. Early PM was within five years after the FMP.

Urinary assays.

Urinary assays were performed in our laboratories using a first-voided morning urine specimen provided on day 6 of the menstrual cycle, if menstrual periods were identifiable. For women with no bleeding or spotting or extremely erratic flow, a consistent date each month was used. Women abstained from smoking, caffeine use, and exercise before the urine collection. Urine samples were preserved with sodium ethylenediaminetetraacectic acid and sodium metabisulfite and frozen at –70°C. All specimens, standards and controls were tested in duplicate and those with a coefficient of variance above 15% were repeated. A BioRad Quantitative Urine control and a pooled in-house urine control were included in all assays, and a member of the standard curve was repeated after every ten unknowns to monitor assay performance. In general, all samples from a calendar year were assayed during the next calendar year and multiple samples from each participant were assayed in the same batch during each year. All endocrine concentrations were corrected for variations in urine concentration by expressing the hormone level as a ratio to the concentration in the same urine specimen.

Urinary estrone glucuronide (E₁G)

Urinary estrone glucuronide (E₁G) was selected to assess estrogens because it is stable, can be reliably measured without special preparation, and is highly correlated with serum estradiol levels.^25–30 Urinary E₁G was measured by a competitive enzyme immunoassay (EIA) that cross-reacts 83% with estradiol glucuronide and less than 10% with free estrone, estrone sulfate, estriol glucuronide, estradiol and estriol ²⁷. The assay is described in detail elsewhere ²⁷. The lower limit of detection for the assay was 3.1nmol/L. Average recovery from a urine matrix of low, medium and high E₁G standard doses was 101% .²⁷ Intra- and inter-assay coefficients of variation (CV) were 2.1% and 9.6%, respectively, for an external (BioRad) urine control (mean concentration 2.1ng/mL); and 2.8% and 14.5%, respectively, for an internal urine control (mean concentration 1.59 ng/mL) (determined using the method of Robard from 20 randomly selected plates).

Urinary FSH

Urinary FSH was assayed using Diagnostic Products Corporation (DPC) Double Antibody FSH Kit, using a radioimmunoassay (RIA) was designed for the quantitative measurement of FSH in serum and urine. The procedure is described in detail elsewhere³¹. The reporting range for urine FSH was 2.0 to 100mIU/mL; the minimum detectable concentration was 1.6 mIU. The inter-assay variation was 7.1% and the intra-assay variation was 3.7% (N=205). FSH, as well as other assays was adjusted for urinary creatinine which was assayed in urine specimens using the method of Jaffe³². The inter-assay variation (run to run) was 6.7% and the intra-assay variation was 3.1% (N = 405).

Stress-related factors.

Stress-related factors included perceived stress and urinary cortisol. Perceived stress was assessed in the diary with a question “how stressful was your day?” that women rated from 1 (not at all) to 6 (extremely, a lot). Brantley, Waggoner, Jones, & Rappaport³³ found that a global stress rating and the sum of stress ratings across multiple dimensions correlated significantly (r=.35, p<.01).

Urinary cortisol

Urinary cortisol levels were determined by radioimmunoassay using Coat-A-Count Cortisol Kit (Siemens Medical Solutions, Los Angeles, CA) and is described in detail elsewhere.³⁴ Coat-A-Count Cortisol is designed for the quantitative measurement of unbound cortisol (hydrocortisone, Compound F) in serum, urine, and heparinized plasma. The assay is highly specific for cortisol and has extremely low cross-reactivity with other steroids, except for prednisolone. In our laboratory the reporting range for this urinary cortisol assay is 1 to 50 ug/dl, the minimum detectable concentration is 0.2 ug/dL. Inter-assay precision was calculated for each of three samples from the results of 20 extractions each. The coefficients of variation (inter-assay) ranged from 8.2% to 12.5% for samples ranging from 0.9 to 8.3 ug/dL. The intra-assay coefficient of variation was 4.6% (N=376) using a pooled in-house control (3.6ug/dl). There were no significant differences in cortisol values when we compared the DCM extraction to values obtained with an additional chromatographic purification step using a disposable SepPak C-18 cartridge, after initial DCM extraction. Recovery rates ranged from 88.4 to 96.5% when samples were spiked with three cortisol solutions of 5, 10, and 20 ug/dL.

Health-related factors.

Health-related factors included perceived health which was measured in the diary from the beginning of the study using the question “how healthy did you feel today?” Women rated their perceived health from 1 (not at all) to 6 (extremely, a lot).

Symptoms.

Hot flash severity was assessed several times each year in the symptom diary in which women rated their symptoms from 0 (not present) to 4 (extreme). Depressed mood (feeling sad or blue), anxiety, difficulty getting to sleep, awakening during the night, early morning awakening, backache, joint pain, difficulty concentrating, and forgetfulness were assessed in a similar fashion.

Analyses

Mixed effects modeling using the R library^35–39 was used to test a preliminary model (Figure 1) to determine whether age, MT stage, factors related to the MT, stress-related factors, symptoms, and health-related factors were significant predictors of each of the interference ratings over time. Age was centered at the group mean to enable the interpretation of the effect of age on interference with work and relationships.

The initial series of models tested age alone as a predictor of each of the interference ratings. Using interference with work as an example, we first postulated a model that overall levels of interference with work could differ from woman to woman (random intercept), but the scores would change with age in a common manner (fixed slope). The second model extended the first to postulate that each woman had a different mean level of interference with work and rate of change (random intercept, random slope). The best fitting model (fixed or random slope) was assessed by using maximum likelihood estimation with Akaike Information Criterion (AIC).³⁹ When the best fitting model was found, that model was extended by adding covariates iteratively to test the effect on interference with work over time. Next, all covariates that significantly improved the model fit to the data when entered individually were added simultaneously into a final multivariate model for each of the interference ratings. Finally, a reduced final model was considered using only the significant variables from the final model. Because we were using these analyses as a basis for explanation and to stimulate further mechanistic studies, a p value of .05 was used as the criterion for significance. Different numbers of women and observations occurred with each variable tested because the analysis required pairing of observations of the outcome and predictor variables at each time point (See Tables 2 and 4). A description of the mathematical model which provides the foundation for the analytic approach is provided in detail elsewhere. ⁴⁰

Table 2.

Random Effects Models for Interference with Work with Age as Predictor (β₂) and with Individual Covariates (β₃)

	Mean Values (p values)			Standard Deviations			Number
Predictor	β1*	β2*	β3*	σ1**	σ2**	σε**	Women	Observations
Age (47.4)	0.96	−0.02 (.06)	-	0.63	0.07	0.88	184	5652
Health-related factors
Perceived health	2.28 (<.001)	−0.006 (.55)	−0.34 (<.001)	0.63	0.08	0.84	184	5652
Menopausal Transition Factors
MT-stage	0.99 (<.001)	−0.02 (.09)		0.63	0.08	0.88	184	5652
Early			−0.06 (0.26)
Late			−0.02 (0.82)
Early PM			0.02 (0.82)
Estrone glucuronide (log10) (1.2)	0.99 (<.001)	−0.01 (0.22)	−0.04 (0.46)	0.65	0.08	0.87	130	4797
FSH (log10) (1.1)	0.98 (<.001)	−0.01 (0.17)	0.05 (0.12)	0.65	0.08	0.87	130	4796
Stress-related factors
Perceived Stress	−0.02 (.77)	−0.01 (.44)	0.42 (<.001)	0.50	0.06	0.81	184	5652
Cortisol log10 (1.5)***	0.98 (<.001)	−0.01 (0.23)	−0.04 (0.31)	0.64	0.08	0.87	130	4650
Symptoms
Hot flashes	0.94 (<.001)	-0.02 (.02)	0.05 (0.01)	0.63	0.08	0.88	184	5652
Depressed mood	0.76 (<.001)	−0.01 (.11)	0.36 (<.001)	0.60	0.08	0.85	184	5652
Anxiety	0.68 (<.001)	−0.01 (.26)	0.36 (<.001)	0.55	0.07	0.86	184	5652
Difficulty Getting to Sleep	0.91 (<.001)	−0.02 (.07)	0.14 (<.001)	0.63	0.08	0.88	184	5652
Awakening during the night	0.89 (<.001)	−0.02 (.03)	0.11 (<.001)	0.63	0.07	0.88	184	5652
Early Awakening	0.89 (<.001)	−0.02 (.04)	0.11 (<.001)	0.63	0.07	0.88	184	5652
Backache	0.90 (<.001)	−0.02 (.08)	0.09 (<.001)	0.63	0.08	0.88	184	5652
Joint Pain	0.90 (<.001)	−0.02 (.04)	0.08 (<.001)	0.62	0.08	0.88	184	5652
Forgetfulness	0.87 (<.001)	−0.02 (.02)	0.24 (<.001)	0.61	0.08	0.87	184	5652
Difficulty Concentrating	0.76 (<.001)	−0.02 (.06)	0.44 (<.001)	0.59	0.08	0.85	184	5652

^*β_1, β_2, β₃ are the fixed effects (group averages) for the intercept, slope and covariate.

^**σ_1, σ_2, σ_ε are the random effects (variability) for the intercept, slope and residual error.

^***Oral and inhaled corticosteroid use removed from analyses.

Table 4.

Random Effects Models for Interference with Relationships with Age as Predictor (β₂) and with Individual Covariates (β₃)

	Mean Values (p values)			Standard Deviations			Number
Predictor	β1*	β2*	β3*	σ1**	σ2**	σε**	Women	Observations
Age (47.4)	1.21	−0.03 (.001)	-	0.81	0.08	0.80	184	5656
Health-related factors
Perceived health	2.48 (<.001)	−0.02 (.05)	−0.33 (<.001)	0.77	0.08	0.76	184	5656
Menopausal Transition Factors
MT-stage	1.24 (<.001)	−0.03 (.02)		0.81	0.08	0.80	184	5656
Early			−0.04 (0.47)
Late			−0.07 (0.27)
Early PM			−0.05 (0.55)
Estrone glucuronide (log10) (1.2)	1.25 (<.001)	−0.03 (0.01)	−0.10 (0.03)	0.82	0.09	0.79	130	4782
FSH (log10) (1.1)	1.24 (<.001)	−0.03 (0.01)	−0.002 (0.93)	0.82	0.08	0.79	130	4864
Stress-related factors
Perceived Stress	0.28 (<.001)	−0.02 (.01)	0.39 (<.001)	0.70	0.06	0.74	184	5656
Cortisol log10 (1.5)***	1.24 (<.001)	−0.03 (0.004)	0.05 (0.12)	0.81	0.08	0.80	130	4628
Symptoms
Hot flashes	1.21 (<.001)	−0.03 (.001)	−0.01 (0.52)	0.81	0.08	0.80	184	5656
Depressed mood	0.89 (<.001)	−0.03 (.001)	0.54 (<.001)	0.75	0.06	0.74	184	5656
Anxiety	0.83 (<.001)	−0.02 (.01)	0.46 (<.001)	0.70	0.06	0.76	184	5656
Difficulty Getting to Sleep	1.13 (<.001)	−0.03 (.001)	0.22 (<.001)	0.79	0.08	0.80	184	5656
Awakening during the night	1.11 (<.001)	−0.03 (<.001)	0.14 (<.001)	0.80	0.07	0.80	184	5656
Early Awakening	1.11 (<.001)	−0.03 (<.001)	0.15 (<.001)	0.79	0.07	0.80	184	5656
Backache	1.13 (<.001)	−0.03 (.002)	0.11 (<.001)	0.80	0.08	0.80	184	5656
Joint Pain	1.15 (<.001)	−0.03 (<.001)	0.08 (<.001)	0.79	0.08	0.80	184	5656
Forgetfulness	1.12 (<.001)	−0.03 (<.001)	0.23 (<.001)	0.79	0.07	0.80	184	5656
Difficulty Concentrating	0.99 (<.001)	−0.03 (<.001)	0.48 (<.001)	0.76	0.07	0.77	184	5656

^*β_1, β_2, β₃ are the fixed effects (group averages) for the intercept, slope and covariate.

^**σ_1, σ_2, σ_ε are the random effects (variability) for the intercept, slope and residual error.

^***Oral and inhaled corticosteroid use removed from analyses.

Results

Results in Table 2 describe all 6 model parameters for interference with work. The intercept (β₁) 0.96, was the initial or baseline mean value for interference with work at age 47.4 for this population. Age was centered at 47.4 years, the mean age for the women whose data from the entire longitudinal study were used in the following analyses, to enhance interpretation of the effect of age on interference with work. When age effects on interference with work were analyzed using a random intercept, fixed slope model vs. a random intercept, random slope model, the latter provided a significantly better fit to the data (AIC 15228 vs. 15141, p <.0001). When age was considered alone using a random effects model, at age 47.4 the mean level of interference at baseline was .96 (β₁), with a decrease of .02 from baseline (β₂) per year (p=.06, not statistically significant).

The slope (β₂) is the mean increase or decrease from baseline for interference with work per year of age, while the covariate value (β₃) is the mean change, increase or decrease, from the intercept for interference with work with each unit of change in the covariate. For example, the hot flash response range is from 0–4. With hot flash severity as a covariate with age in the equation the mean level of interference with work at age 47.4 for this population at the start of the study (β₁) was 0.94. The level of interference with work decreased from baseline by 0.02 units (β₂) per year of age during the study (age effect) and for every 1 unit increase in hot flash severity, interference with work increased from baseline by 0.05 units (β₃), a small but statistically significant effect (p=.01) (See Table 2).

When interference with work was analyzed over time by age and with each covariate added individually, interference with work was not associated significantly with age or any of the menopausal transition factors, including menopausal transition stages, estrone or FSH (See Table 2). Perceived health was significantly related to interference with work (β₃=−.34, p<.001), such that women who perceived their health to be better reported less interference with work. In addition, perceived stress, but not cortisol, was associated with greater interference with work (β₃=.42, p<.001). All of the symptoms were each significantly associated with an increase in interference with work: hot flashes (β₃=.05), depressed mood (β₃=.36), anxiety (β₃=.36), difficulty getting to sleep (β₃=.14), awakening during the night (β₃=.11), early awakening (β₃=.11), back pain (β₃=.09), joint pain (β₃=.08), forgetfulness (β₃=.24), and difficulty concentrating (β₃=.44) (p=.01 for hot flashes and p<.001 for all other symptoms). When all significant covariates were considered in a multivariate model with age as the measure of time, perceived health (β₃=−.24), perceived stress (β₃=.35), depressed mood (β₃=.09) and difficulty concentrating (β₃=.17) were each significantly related to interference with work (all p<.001) (See Table 3). No longer significant in the final model were hot flashes, anxiety, difficulty getting to sleep, awakening during the night, early awakening, backache, joint pain, and forgetfulness.

Table 3.

Final Random Effects Model for Interference with Work with Age as Predictor and Other Significant Covariates Entered Simultaneously

(N = 184; observations = 5652)
	Beta Coefficient	Standard Error/Standard Deviation	p value
Fixed effects
β1 intercept	0.93	0.08	<.001
β2 Age (−47.4) years	0.001	0.01	.85
β3 Perceived Health	−0.24	0.01	<.001
β4 Perceived Stress	0.35	0.01	<.001
β5 Depressed mood	0.09	0.02	<.001
β6 Difficulty Concentrating	0.17	0.02	<.001
Random effects
b1 Intercept σ1		0.51
b2 Age (−47.4) years σ2		0.07
bε residual σε		0.77

When interference with relationships was analyzed over time by age and with each covariate added individually, older women perceived less interference with relationships (β₃=−.03, p=.001) (See Table 4). Of the MT-related factors, estrone levels were associated with less interference with relationships (β₃=−.10, p=.03), but neither menopausal transition stages nor FSH had a significant effect. As was true for interference with work, perceived health (β₃=−.33) was associated with less interference with relationships and perceived stress (β₃=.39), but not cortisol, was associated with increased interference with relationships, (both p=<.001). Of the symptoms, depressed mood (β₃=.54), anxiety (β₃=.46), difficulty getting to sleep (β₃=.22), awakening during the night (β₃=.14), early awakening (β₃=.15), back pain (β₃=.11), joint pain (β₃=.08), forgetfulness (β₃=.23), and difficulty concentrating (β₃=.48) were each associated with a significant increase in interference with relationships (all p values were <.001). Hot flashes did not have a significant effect on interference with relationships. When all significant covariates were considered in a multivariate model, the best predictors included perceived health (β₃=−.19), perceived stress (β₃=.27), depressed mood (β₃=.30), anxiety (β₃=.08), difficulty concentrating (β₃=.12) and awakening during the night (β₃=.03) (p=.02 for awakening during the night and p<.001 for all other covariates) (See Table 5). No longer significant in the final model were age, estrone, difficulty getting to sleep, early awakening, backache, joint pain, and forgetfulness.

Table 5.

Final Random Effects Model for Interference with Relationships with Age as Predictor and Other Significant Covariates Entered Simultaneously

(N = 184; observations = 5656)
	Beta Coefficient	Standard Error/Standard Deviation	p value
Fixed effects
β1 intercept	0.97	0.08	<.001
β2 Age (−47.4) years	−0.01	0.01	.10
β3 Perceived Health	−0.19	0.01	<.001
β4 Perceived Stress	0.27	0.01	<.001
β5 Depressed mood	0.30	0.02	<.001
β6 Anxiety	0.08	0.02	<.001
β7 Difficulty Concentrating	0.12	0.02	<.001
β8 Awakening at Night	0.03	0.01	.02
Random effects
b1 Intercept σ1		0.67
b2 Age (−47.4) years σ2		0.05
bε residual σε		0.67

Discussion

Interference with work and relationships is salient to midlife women who are juggling responsibilities in their employment roles as well as in their families and relational networks. ¹⁴ The results reported here reflect some common factors related to interference with both work and relationships: perceived health, perceived stress, depressed mood, and difficulty concentrating. Unique to interference with relationships was anxiety and night-time awakening.

Women who perceived their health as very good or excellent were less likely to experience interference with either their work or relationships. Women who perceived greater stress reported greater interference with either work or relationships. Perceived health and stress may affect the evaluation of interference with roles both directly and indirectly. In a model that included both perceived health and perceived stress, effects of some symptoms on interference with work (hot flashes, anxiety, difficulty getting to sleep, awakening during the night, early awakening, backache, joint pain, and forgetfulness) were no longer significant. The aggregate of symptoms may influence women’s evaluations of their health and perceptions of stress, and in turn, health and stress may influence directly the perception of interference. In addition, our earlier analyses indicated that severity of symptoms such as hot flashes was associated with perceived stress during the menopausal transition, thus supporting the possibility of an indirect effect of symptoms on interference with roles.¹⁴ These indirect effects should be tested in future studies.

Depressed mood and difficulty concentrating both accounted for significant variance in interference with work and relationships. Depressed mood affects work performance in studies of occupational stress.^41,42. Likewise, difficulty concentrating would interfere with performance in occupations that require vigilance. Depressed mood and difficulty concentrating also limit involvement with others such that women’s ability to parent, engage in a relationship with a partner, or care for others would be affected. Given that these relationships have high salience for midlife women, these symptoms would likely be disruptive. ⁴³.

Both anxiety and awakening during the night directly affected interference with relationships, even when perceived health and perceived stress were included in a multivariate model. Anxiety and awakening during the night may be indicators of arousal, a mechanism hypothesized to account for amplification of symptoms.¹⁷ Relationships, especially with children or a partner, may be the most vulnerable to symptoms linked to arousal. Given the high salience of family and friend relationships to midlife women, these symptoms may be more disruptive to relationships than to occupational roles.⁴³

Limitations of this study include the need for replication of the findings in a larger and more diverse population, such as the SWAN cohort. In addition, specification of a causal model that includes indirect effects as consistent with those we propose above will be important to elaborate the relationships among the menopause-transition related factors, symptoms, and interference with work and relationships.

Although the data presented here suggest important effects of symptoms on interference with role performance, future studies would benefit from the inclusion of functional assessment of the effects of symptoms on role performance. In addition, future work incorporating physiologic indicators of arousal would be helpful in understanding the mechanisms by which symptoms and perceived stress affect interference with work and relationships.

Conclusions

There is evidence that specific symptoms, especially difficulty concentrating and depressed mood, are related to interference with work and relationships during the menopausal transition and early postmenopause, even when perceived health status and stress are taken into account. The menopause transition, itself, seems to have little direct relationship to perceived interference with daily living.