Massachusetts Women's Health Study Research Articles

Depression in midlife women: what have we learned from longitudinal studies?

As the world's population of midlife women grows, researchers and clinicians have increasingly focused their attention on women's health. The purpose of this paper is to review published longitudinal studies of depression in midlife women. Several longitudinal studies of midlife women have included measures of depression on more than one occasion. Three revealed an association between perimenopause and depression: the Massachusetts Women's Health study, the Melbourne Women's Health study, and the South-East England study. Results in two of these three suggested that vasomotor symptoms (hot flashes) were associated with higher depression scores. None of the other studies found a significant association between menopause transition and depression scores. Data from the Seattle Midlife Women's Health Study were used in a cluster analysis. The most prevalent patterns were low CES-D scores in a non-depressed range over all measurement points, with no particular pattern of change across the menopause transition. Menopause transition does not appear to be associated with depression in most longitudinal studies. The lack of association of depression with menopause suggests that the social environment in which women experience menopause might be more significant than the biological changes associated with cessation of menses.

Digit preference in year at menopause: Data from the study of women's health across the nation

PURPOSE: To assess possible digit preference in self-reported year at natural menopause, and to determine whether equal proportions is an appropriate reference distribution.METHODS: Data are from the cross-sectional telephone interview from the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-ethnic study of women aged 40–55. Analyses included 2151 naturally menopausal respondents, who were asked the year their periods stopped. Using a chi-square test, we compared the distribution of the terminal digit for year of final menstrual period (FMP) to an equal proportions (EP) distribution assigning 10% probability of each of the 10 digits. Departures from EP, however, may be accurate and may reflect the observed age distribution of subjects rather than digit preference. Thus, we stratified by year of interview to determine if the distribution was the same across years—suggesting digit preference—or if it varied systematically. We then estimated an expected distribution of terminal digit for year of FMP, using prospectively collected data (not subject to digit preference or recall bias) from the Massachusetts Women's Health Study, applied to the SWAN age distribution. The SWAN terminal digit distribution was compared with this expected distribution.RESULTS: Terminal digit for year at FMP exhibited a strong departure from EP (χ2 = 841.60, p < 0.001), with highest frequencies for digits 4 and 5. Stratifying by year of interview, the distribution was shifted one digit in 1997 compared with 1996, consistent with unbiased reporting. Using the expected distribution as the reference reduced the chi-square statistic by a factor of 7 (χ2 = 119.51, p < 0.001).CONCLUSIONS: The distribution of terminal digits for reported year at FMP was far from uniform, but departures from EP were consistent with results expected from an independent prospective study. These results suggest that EP may not be an appropriate reference for studies of digit preference, particularly those with a restricted age range.

Is there an association between menopause status and sexual functioning?

The purpose of this study was to address whether: (1) there is an association between menopause status and various aspects of sexual functioning, and (2) the relative contributions of menopause status and other variables to various aspects of sexual functioning. Analyses are based on 200 women from the Massachusetts Women's Health Study II, a population-based sample of women transitioning through the menopause who were not HRT users, who had not had a surgical menopause, and who had partners. The women were classified as pre-, peri-, or postmenopausal according to menstrual cycle characteristics. Estradiol, estrone, and follicle-stimulating hormone were also measured. Sexual functioning was measured in terms of satisfaction, desire, frequency of sexual intercourse, belief that interest declines with age, arousal compared with a younger age, difficulty reaching orgasm, and pain. Predictor variables included sociodemographics, health, vasomotor symptoms, psychological variables, partner variables, and lifestyle behaviors. Menopause status was significantly related to lower sexual desire, a belief that interest in sexual activity declines with age, and women's reports of decreased arousal compared with when in their 40s. Menopause status was unrelated to other aspects of sexual functioning in either unadjusted or multiple regression analyses. In analyses in which log estradiol (E2) was included in addition to menopause status, log E2 was only related to pain. In multiple regression analyses, other factors such as health, marital status (or new partner), mental health, and smoking had a greater impact on women's sexual functioning than menopause status. Menopause status, but not E2, is related to some, but not all, aspects of sexual functioning. This may be due to menopause per se or other factors associated with menopause and aging (e.g., increased sexual dysfunction among aging men). Menopause status has a smaller impact on sexual functioning than health or other factors.

A longitudinal study of weight and the menopause transition: results from the Massachusetts Women's Health Study.

Results of past studies of menopause and weight are inconsistent, in part because of problems in study design and analyses, such as retrospective assessment of age at menopause and failure to control for confounding factors. To address such shortcomings, we conducted multivariate analyses on longitudinal data from a large, community-based sample of initially pre- and perimenopausal women who were making the transition through menopause. Data were from the second phase of the Massachusetts Women's Health Study, a cohort of 418 women aged 50-60 years in 1986. We assessed the relationship between menopause transition and weight, after accounting for previous weight; age; and the behavioral factors of smoking, exercise, and annual ethanol consumption. Menopause status was defined in terms of months of amenorrhea. The association of hormone replacement therapy and weight also was examined. Menopause transition was not consistently associated with increased weight, and use of hormone replacement therapy was not significantly related to weight. Behavioral factors--particularly exercise and ethanol consumption--were more strongly related to weight than was menopause transition. These results are consistent with findings from other studies that suggest that the weight increases experienced by middle-aged women in the United States are not a result of the menopause transition.

Can Follicle-Stimulating Hormone be used to Define Menopausal Status?

To assess the ability of the level of follicle-stimulating hormone (FSH) to distinguish among premenopausal, perimenopausal, and postmenopausal women. We examined cross-sectional and longitudinal data from the second phase of the Massachusetts Women's Health Study (1986 to 1995), a population-based cohort of 427 premenopausal and perimenopausal women identified from the first phase of the Massachusetts Women's Health Study (1981 to 1986). Boxplots of FSH levels throughout the menopausal transition displayed considerable overlap. Logistic regressions and their resulting receiver operating characteristic curves further demonstrated that, although FSH is a statistically significant predictor of menopausal status, no single value of FSH is expedient for distinguishing premenopausal from perimenopausal or perimenopausal from postmenopausal women. FSH alone is not an effective predictor of transition into the perimenopausal or postmenopausal period. Specifically, the frequently recommended FSH cutoff of 40 IU/L is inappropriate by itself for clinical determination of postmenopausal status.

Interviewer effects in a cohort study. Results from the Massachusetts Women's Health Study.

Although interviewer error is widely recognized as an important source of variation in epidemiologic investigations, scant published information exists documenting the impact of interviewer variation on study findings. Using data from the Massachusetts Women's Health Study, a population-based cohort study of 2,569 middle-aged women (1982-1987), the authors evaluated interviewer variation in responses to different types of questions, and assessed the impact of interviewer variation on inferences derived from study data. Respondent sociodemographic and lifestyle characteristics were similar for the four study interviewers at the first follow-up. No interviewer variation was detected for questions concerning recall of specific events, but responses to questions regarding recall of subjective or personal information or those which required further probing did differ significantly by interviewer. Adjustment for interviewer effects had no impact on the conclusions obtained from one analysis of predictors of depression, despite significant interviewer variation in the outcome and predictor variables, but it did change conclusions from an analysis of the impact of support networks on psychological symptoms, wherein the interviewer variable was strongly related to the outcome after data were controlled for predictor variables. Given these findings, examination of data for interviewer effects is advisable despite incorporation of quality control measures in a study's design.

Regression calibration method for correcting measurement-error bias in nutritional epidemiology

Regression calibration is a statistical method for adjusting point and interval estimates of effect obtained from regression models commonly used in epidemiology for bias due to measurement error in assessing nutrients or other variables. Previous work developed regression calibration for use in estimating odds ratios from logistic regression. We extend this here to estimating incidence rate ratios from Cox proportional hazards models and regression slopes from linear-regression models. Regression calibration is appropriate when a gold standard is available in a validation study and a linear measurement error with constant variance applies or when replicate measurements are available in a reliability study and linear random within-person error can be assumed. In this paper, the method is illustrated by correction of rate ratios describing the relations between the incidence of breast cancer and dietary intakes of vitamin A, alcohol, and total energy in the Nurses' Health Study. An example using linear regression is based on estimation of the relation between ultradistal radius bone density and dietary intakes of caffeine, calcium, and total energy in the Massachusetts Women's Health Study. Software implementing these methods uses SAS macros.

Endogenous Estrogens: Relationships Between Estrone, Estradiol, Non-Protein Bound Estradiol, and Hot Flashes and Lipids

To test the hypothesis that the concentrations of estrone, estradiol, and free estradiol give separate information on the presence of hot flashes, lipid levels, and changes in lipid levels over a 3-year time span, we used longitudinal data from the Massachusetts Women's Health Study. We also examined whether sex hormone-binding globulin (SHBG) is associated with these end points. Two hundred and forty-one women who were initially pre- or peri-menopausal were followed for a 3-year period (1986-1990). Over this time estrogen levels declined by 32-45% and SHBG concentrations increased 81%. The three estrogen measures were highly correlated, and all three were negatively associated with the presence of hot flashes, but free estradiol did not add to the information provided by estrone and estradiol. None of the three estrogens was associated concurrently with any lipid levels. The SHBG concentration was not associated with hot flashes but was related to the concentrations of triglycerides and apoprotein-B (negatively) and to the log high-density li-poprotein-cholesterol (HDL-C) and log apoprotein A-I (Apo-A-I) concentrations (positively). Changes in estrogen levels were unrelated to changes in triglycerides and HDL-C. Change in estrone levels was positively associated with change in Apo-A-I but estradiol and free estradiol were negatively associated with change in Apo-A-I. In conclusion, our data indicate that, although highly intercorrelated, the three estrogen measures cannot be used interchangeably in predicting the selected end points, hot flashes, and lipids.

The normal menopause transition

This paper presents analyses from perhaps the largest and most comprehensive prospective cohort study of mid-aged women — the Massachusetts Women's Health Study (MWHS) — with numbers sufficient to provide, for the first time, stable estimates of parameters in the normal menopause transition. The three questions addressed in this analysis are (i) what are the natural menopause transitions and when do they occur, (ii) what factors affect these transitions and (iii) what signs and/of symptoms accompany these transitions? The data were obtained primarily from 5 years of follow-up of 2570 women in Massachusetts who were aged 45–55 years as of January 1, 1982. An initial baseline cross-sectional survey (T o) yielded a total of 8050 completed responses with an overall response rate of 77%. From this cross-sectional sample a cohort of approximately 2570 women was identified, consisting of women who had menstruated in the preceding 3 months and who had not undergone removal of the uterus and/of ovaries. Prospective study of the cohort consisted of six telephone contacts (T 1-T 6) at 9-month intervals with excellent retention of the respondents. A subset of the full cohort was defined that consisted of women who were premenopausal (rather than perimenopausal) at baseline (T O) ( n = 1178). Confirming prior reports, the age at natural menopause occurred at 51.3 years with a highly significant median difference (1.8 years) between current smokers and non-smokers. The new analyses reported here on median age at inception of perimenopause (47.5 years) and factors affecting it are consistent with findings for age at last menstrual period, particularly the overwhelming effect of smoking. Smokers tend to have not only an earlier but also a shorter perimenopause. The length of the perimenopausal transition (estimated at nearly 4 years) has not been previously reported. Moreover, the highest rate of physician consultations is observed among those with longer perimenopause transitions. The relationship between menopause transitions and symptom reporting appears to be transitory, with reported rates showing an increase in the perimenopause and a compensatory decrease in the postmenopause. The implications of combined hormone replacement therapy for future research on menopause in industrial societies is discussed in relation to these findings.

The normal menopause transition.

This paper presents analyses from a comprehensive prospective cohort study of mid-aged women [the Massachusetts Women's Health Study (MWHS)], with numbers sufficient to provide stable estimates of parameters in the normal menopause transition. Three questions are addressed: what are the natural menopause transitions and when do they occur; what factors affect the transitions; and what signs and/or symptoms accompany the transitions? The data were obtained primarily from 5 years of follow-up of 2,570 women in Massachusetts who were aged 44-55 years as of January 1, 1982. Prospective study of the cohort consisted of six telephone contacts (T1 -T6 ) at 9 month intervals with excellent retention. A subset of the full cohort was defined that consisted of women who were premenopausal (rather than perimenopausal) at baseline (To ) (n = 1,178). Confirming prior reports, the age at natural menopause occurred at 51.3 years with a highly significant median difference (1.8 years) between current smokers and non-smokers. The new analyses reported here on median age at inception of perimenopause (47.5 years) and factors affecting it are consistent with findings for age at last menstrual period. Smokers tend to have not only an earlier but also shorter perimenopause. The length of the perimenopausal transition, estimated at about 3.5 years, has not been previously reported. The relationship between menopause transitions and symptom reporting appears to be transitory, with reporting rates showing an increase in the perimenopause and a compensatory decrease in postmenopause. The implications of combined hormone replacement therapy for future research on menopause in industrial societies is discussed in relation to these findings.

A longitudinal analysis of women's attitudes toward the menopause: results from the Massachusetts Women's Health Study

This paper examines women's attitudes towards menopause in a large representative sample of middle-aged women. Data were derived from the Massachusetts Women's Health Study (MWHS) which is a prospective study of 2565 women aged 45–55, randomly sampled throughout Massachusetts. The paper addressed the following questions: (1) What are women's attitudes towards the menopause and how do attitudes change as a function of menopause? (2) What variables are related to attitudes towards menopause? and (3) Do attitudes towards menopause predict subsequent symptom reporting during menopause? Results showed that the majority of women reported relief or neutral feelings about the cessation of menses and that feelings became more positive as women experienced menopause. Negative attitudes towards menopause were related to general symptom reporting and depression. Additionally, negative attitudes prior to menopause were related to subsequent symptom reporting during menopause. These results suggest that the so-called menopause syndrome may be more related to personal characteristics than to menopause per se.

The effect of widowhood on health: A prospective analysis from the Massachusetts women's health study

Previous research has consistently demonstrated adverse physical and psychological effects following the death of a spouse. Conclusions regarding the effects of widowhood have been hampered, however, by such methodological limitations as lack of adequate comparison groups, non-random samples of the widowed, and lack of data on pre-widowhood status. This paper examined the physical and psychological effects of widowhood in a randomly sampled cohort of women, aged 45–55 years at baseline, who were followed prospectively for five years. Analyses employed a design in which women whose spouses died during the course of the study ( N = 76) were compared to age-matched married controls ( N = 1625). The following two questions were addressed: (1) What are the physical and psychological effects of widowhood? and (2) What is the effect of widowhood on socioeconomic factors, social support and health behavior? Following the death of a spouse, the percentage of widows reporting psychological symptoms increased. The widows did not report higher rates of physical symptoms or a decrease in health. Widows had higher rates of health care utilization, in particular, taking prescribed medication, which were in part for mental health reasons. There was no evidence of changes in health behaviors among the widows, but social support increased following widowhood and more widows reported a decrease in income. The results highlight the importance of controlling for pre-widowhood status when studying the consequences of widowhood and provide additional evidence that widowhood may not adversely affect physical health for women.