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Original Article |
Departments of Population Health and Reproduction (B.L.L.) and Epidemiology and Preventive Medicine (E.B.G.), University of California, Davis, California 95616; Department of Obstetrics and Gynecology (N.S.), Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461; Departments of Epidemiology (M.F.S., D.S.M.) and Obstetrics and Gynecology (J.F.R.), University of Michigan, Ann Arbor, Michigan 48109; Department of Preventive and Behavioral Medicine (S.C.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; and Department of Obstetrics and Gynecology and Women’s Health (G.W.), University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark New Jersey 07103
Address all correspondence and requests for reprints to: Bill L. Lasley, Ph.D., Center for Health and the Environment, University of California, Davis, One Shields Avenue, Davis, California 95616. E-mail: . bllasley{at}ucdavis.edu
Abstract
In this report, 3029 women between the ages of 42 and 54 yr from five ethnic groups were studied for 2 yr. Log circulating dehydroepiandrosterone sulfate (DHEAS) concentrations were highest among Chinese and Japanese and lowest among African Americans and Hispanics, and this pattern persisted after adjustment for age, smoking, and log body mass index (BMI). With the exception of Japanese women, log BMI was negatively related to log circulating DHEAS. The magnitude of this association varied by ethnic group, and the decline in log circulating DHEAS levels with higher log BMI was steepest for Chinese and least steep for Hispanics. The relationship between log DHEAS and log BMI was positive for Japanese. DHEAS levels did not decline at a steady rate during the menopausal transition and transiently increased in some women and increased, on average, during the transition to late perimenopause. These increases tended to be larger for Chinese, Hispanic, and Japanese than for African Americans and Caucasians, although the interactions were not statistically significant. Changes in circulating testosterone and, to a lesser extent, estradiol were correlated to changes in DHEAS. These data have importance in understanding the endocrinology of the menopausal transition, defining the relationship of adrenal steroid production during declining ovarian function and determining a rationale regarding DHEAS supplementation for older women.
THERE IS RELATIVELY constant decline in circulating dehydroepiandrosterone and its sulfate (DHEAS) in adults of approximately 2% per year (1, 2, 3, 4). While this decline is well documented in both men and women (5, 6), it is more consistent in older men than in older women (7). This gradual decline in DHEAS is thought to be the result of attenuated adrenal 17–20, desmolase activity in later life (8) and not related to gonadal function in the adult (9).
There is a long-standing tenet that DHEAS plays a major role in preventing diseases of aging because more than 80% of its secretion is lost between the ages of 20 and 70 yr (2) and because it is an abundant circulating steroid and potentially an important androgen and estrogen precursor. DHEAS replacement has been reported to improve natural killer cell function (10) and T lymphocyte binding (11) and to function as an adjuvant to influenza vaccine in the elderly (12). Lower DHEAS has been associated with the development of atherosclerosis (13) and insulin resistance (14, 15). Exogenous DHEAS enhanced insulin postreceptor action in vitro (16). In studies of low DHEAS doses in postmenopausal women, there was increased IGF-I and improved mood (17, 18), but some evidence of reductions in high-density lipoprotein cholesterol (17). Other studies have not demonstrated the effectiveness of DHEAS supplementation on improvements in mood (19). The role of DHEAS in the aging process, thus, remains an intriguing biological question.
The association of low circulating DHEAS with cardiovascular mortality has not been consistent in two population studies of women (13). Furthermore, in a 10-yr longitudinal study, decreased circulating DHEAS levels were associated with increased mortality in older men whereas the opposite was true for women of the same age group (20). Other studies of DHEAS replacement in the elderly found little or no positive effect of DHEAS replacement on different measures of health status (21, 22, 23, 24, 25). Moreover, animal studies involving chronic DHEAS supplementation have not demonstrated an increase in survival (26). One explanation for these conflicting findings is the potential for a gender- specific role of DHEAS in aging and disease processes. Certainly, the wisdom of promoting DHEAS supplementation to ameliorate the development of disease in older women may be predicated on having additional information about ovarian and adrenal androgen production during and following the menopause to understand its impact on health.
A recent report, based on an animal model of the menopause transition, reported that circulating DHEAS concentrations do not exhibit a continuous fall in all older female laboratory macaques. Indeed, there was an indication of an upward inflection of the DHEAS concentration profile in the interval immediately preceding menopause (27). This finding in the nonhuman primate, coupled with the finding that older women are less likely to exhibit a continuous fall in circulating DHEAS levels compared with men, suggest that an interaction does exist between ovarian status and adrenal androgen production. Because most of the existing data relating to DHEAS production profiles in women have been obtained from cross-sectional studies involving relatively small numbers of relatively homogenous subjects with unknown menopausal status, the possibility that circulating DHEAS levels are related to ovarian status in some women has not been well examined.
To elucidate the role of ovarian status and DHEAS production, the pattern of circulating DHEAS was characterized in 3250 women of five ethnic groups followed over a two-yr time period through the stages of the menopausal transition. The objectives of the broader study that generates this report—the Study of Women’s Health Across the Nation (SWAN)—was to identify endocrine changes associated with the progressive stages of the menopausal transition in middle-aged women and relate these changes to ethnicity and medical, reproductive, and lifestyle variables. The data presented demonstrate that circulating DHEAS levels do not decline at a steady rate during the menopausal transition and, in fact, DHEAS may increase transiently during this time in some women. These data have importance in understanding the endocrinology of the menopausal transition, including the relationship of adrenal steroid production during declining ovarian function, and ultimately may determine a rationale for a DHEAS supplementation regimen in older women.
Subjects and Methods
Sample selection
This report is based on data collected at the baseline and two annual follow-up evaluations of SWAN participants, who comprise a longitudinal, prospective, multiethnic, multidisciplinary, population-based study of the natural history of the menopausal transition. The SWAN sampling and recruiting procedures were implemented in seven United States locations: Boston, Massachusetts; Chicago, Illinois; metropolitan Detroit, Michigan; Los Angeles, California; Newark, New Jersey; Pittsburgh, Pennsylvania; and Oakland, California. A two-stage recruitment process was used. First, during 1995–1997, a cross-sectional survey was conducted, by phone at most sites and in-person for about half of the women in two sites with African Americans as their minority sample, to assess eligibility for enrollment into a cohort study and to collect health, reproductive, demographic, and lifestyle data. Eligibility criteria for the cross-sectional survey were: age 40–55 yr, self-designated as in the targeted racial/ethnic group for the site, residence near one of the seven clinic sites, use of English or one of the other selected languages (Spanish, Japanese, Cantonese), and ability to give verbal consent to participation.
In the second stage of recruitment, members of the longitudinal cohort were identified and recruited. A total of 16,065 women participated in the cross-sectional survey, and 3,302 of these were enrolled in the longitudinal cohort (28). The recruitment goal for the longitudinal study was for each of the seven clinical centers to obtain community-based samples of approximately 450 women [non-Hispanic Caucasian women and one designated minority group (African American, Chinese, Hispanic, and Japanese)] in a proportion specific for each site.
The eligibility criteria for SWAN enrollees at baseline included: age 42–52 yr, intact uterus and at least one ovary, not currently using exogenous hormone preparations affecting ovarian function, at least one menstrual period in the three previous months, and self-identification with one of each site’s designated race/ethnic group.
Measures
Identical protocols, data collection instruments, and specimen collection were implemented across the seven clinical sites, supported by a written manual of operations, common training, and standardization of research staff. Menopausal status was based on self-report using two questions from the cross-sectional survey: 1) Compared with a year ago, has the number of days between the start of one menstrual period and the start of your next menstrual period become less predictable? and 2) Have you had a period in the last 3 months? Participants were classified as premenopausal if they reported no decreased menstrual predictability and menses in the prior 3 months, and early perimenopausal if they reported menses in the prior 3 months with decreased predictability. Late perimenopause was defined as 3–11 months of amenorrhea.
Primary race/ethnicity was self-defined as black or African American, non-Hispanic Caucasian, Chinese or Chinese American, Japanese or Japanese American, or Hispanic (Central American, Cuban or Cuban American, Dominican, Mexican or Mexican American, Puerto Rican, South American, Spanish or other Hispanic). Non-Hispanic Caucasians were used as the reference group. Height (centimeters) and weight (kilograms) were measured using a stadiometer and calibrated scales, respectively. Body mass index (BMI) was calculated as weight (kilograms)/height (meters2). Age and current smoking behavior were also self-reported. Seven smoking questions were adapted from the American Thoracic Society standard questions (29). Cigarette smoking was categorized as never, former, or current smoker and number of cigarettes currently smoked per day.
Phlebotomy was performed in the morning after an overnight fast. Participants were scheduled for venipuncture on d 2–5 (and d 2–7 from January 1996 through June 1996) of a spontaneous menstrual cycle occurring within 60 d of recruitment. Two attempts were made to obtain a day 2–5 sample. If a timed sample could not be obtained, a random fasting sample was taken within 90 d of recruitment. Blood was refrigerated before centrifugation 1–2 h after phlebotomy, and the serum was aliquotted, frozen, and batched for shipment to the central laboratory. Samples were catalogued and assayed continuously on arrival.
Hormone assays
The DHEAS assay used in this study was a competitive immunoassay using the ACS-180 automated analyzer (Bayer Corp., Tarrytown, NY) using chemiluminescent technology. The assay uses a rabbit polyclonal anti-DHEAS antibody, goat antirabbit IgG labeled with superparamagnetic particles (PMP), and DHEAS labeled with dimethylacridunium (DMAE). Ten microliters of serum are required for this assay. Samples were batched in groups of one assay per day, which included 152 samples in each batch. The SWAN reporting range for DHEAS is 1.52–450 µg/dl (actual assay range, 1.52–1020 µg/dl). The assay is standardized against DHEAS obtained from Steraloids, Inc. (Newport, RI). The estradiol assay was a competitive immunoassay run on ACS-180 (Bayer Corp.) with an off-line incubation. Standards, quality control preparations, and serum samples were manually pipetted into 12 x 75 polypropylene tubes with a dilution of antibody reagent and incubated. All tubes were then placed on an automated analyzer with the appropriate reagents. Estradiol in the sample competes with DMAE-labeled estradiol for binding to rabbit anti-estradiol antibody (antibody reagent) monoclonal mouse antirabbit IgG, which is coupled to PMP, 1.0 ml serum allowing for repeats, and sufficient dead volume. The SWAN reporting range for the estradiol assay is 1–200 pg/ml. The ACS Estradiol-6 Master Curve standards are manufactured and evaluated by gas chromatography-mass spectrometry. The testosterone assay was a competitive chemiluminescent immunoassay that uses testosterone labeled with DMAE, a polyclonal rabbit anti-testosterone antibody and a monoclonal mouse antirabbit antibody, which is coupled to PMP. Forty-five microliters of serum are required for the assay, in addition to sufficient dead volume for aspiration and repeat. The SWAN reporting range for the testosterone assay is 10–100 ng/dl (actual assay range, 2–478 ng/dl). The ACS testosterone assay is standardized analytically and confirmed by gas chromatography-mass spectrometry. The inter- and intra-assay coefficients of variation for DHEAS, estradiol, and testosterone assays in this study were 11.34% and 9.74%, 9.4% and 8.51%, and 8.78% and 6.59%, respectively.
Statistical analyses
Although data were from the first three visits of the SWAN cohort, women with an observed transition to postmenopause within the 2 yr were excluded because of their short time to transition (n = 186). Women with a surgical menopause (hysterectomy and/or bilateral oophorectomy) by the third visit were excluded (n = 65), as were 22 women with missing data. Excluded women were more likely to be older (mean age, 48.1 vs. 46.2 yr; P < 0.0001) and heavier (mean BMI, 28.2 vs. 27.1 kg/m2; P = 0.02) than the 3029 women in the analytic sample. Excluded women were also more likely to be African American and Hispanic and less likely to be Caucasian and Japanese (P = 0.0006). For women initiating exogenous hormone use after the baseline visit, data were truncated before initiation of use.
Baseline characteristics of women in the analytic sample were summarized, and ethnic groups were compared using contingency tables and ANOVA. The associations of DHEAS with concurrent chronological age, smoking, menopause status, ethnicity, BMI, estradiol, and testosterone were estimated by repeated measures linear regression (30), accounting for within-woman correlation. All analyses including ethnicity also were adjusted for site, to account for the study design (28). A log transformation was applied to all hormone variables and to BMI to handle right-skewness. Within-woman changes in log DHEAS corresponding to menopause transitions, pre- to early perimenopause, pre- to late perimenopause, and early peri- to late perimenopause, were computed from the estimated linear regression models.
Results
Participants
The 3029 subjects in the analytic sample were mainly Caucasian (47.7%) but were approximately evenly distributed in terms of pre- vs. early perimenopausal status (Table 1
). By design, no participants were late perimenopausal at baseline. Age did not differ significantly by ethnicity. The two Asian groups tended to have fewer smokers, lower BMI, and slightly lower circulating estradiol levels. Mean circulating DHEAS levels were highest in Chinese and lowest in African Americans and Hispanics. Mean circulating testosterone was lowest among Hispanics.
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Combining data across ethnic groups, longitudinal analyses of log DHEAS generally showed an expected age- dependent decrease in log DHEAS, particularly between 45–50 yr, after which mean levels rose. This rise occurred concurrently with an increase in the percentage of subjects who were late perimenopausal but was only slightly dampened when adjusted for ovarian status and other subject characteristics (Fig. 1). Stratification by ethnicity indicated a somewhat stronger age-related decline among Caucasians than among other ethnic groups, but the interaction between ethnicity and categorized age was not statistically significant.
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DHEAS concentrations were highest, on average, among Chinese and Japanese and lowest among African Americans and Hispanics (Fig. 2), a pattern that persisted after adjustment for age, smoking, and log BMI. Combining all ethnic groups, log DHEAS declined with increasing log BMI (P = 0.0022). With the exception of Japanese women, log BMI was significantly and negatively related to log DHEAS. The magnitude of this association varied significantly by ethnic group (P = 0.0092). The decline in log DHEAS with higher log BMI was steepest for Chinese and least steep for Hispanics, and the relation between log DHEAS and log BMI was positive for Japanese. A comparison of the last two sets of bars in Fig. 3, corresponding to adjusted means computed at log BMI = 3.13 (25th sample percentile) and log BMI = 3.46 (75th sample percentile), respectively, reflects these ethnic differences.
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In general, adjustment for age, smoking, and log BMI increased the estimated transition-related changes in log DHEAS relative to unadjusted mean changes (Table 2). Combining all ethnic groups, the mean change in log DHEAS among women transitioning from pre- to early perimenopause was not significantly different from 0. In contrast, after adjustment for other factors, the mean change in log DHEAS associated with transition to late perimenopause, either from pre- or early perimenopause, was positive and statistically significant. Comparing ethnic groups, transition-related changes tended to be larger, on average, for Chinese, Hispanic, and Japanese women than for African American and Caucasian women. Interactions between ethnicity and status were not statistically significant, however, due to smaller sample sizes. Thus, the observed ethnic differences should only be interpreted as suggestive.
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Current smoking was positively associated with log DHEAS (P = 0.0045). Log DHEAS did not differ significantly for past and never-smokers, nor was average number of cigarettes per day significantly associated with log DHEAS among current smokers.
Estradiol, testosterone, and DHEAS
Longitudinal analyses of log estradiol showed an age-related decline, accelerating around age 49 (Fig. 3
). Adjustment for ethnicity, smoking, menopause status, and log BMI had little impact on the relation with age. The magnitude of the positive correlation of log DHEAS with log estradiol, although statistically significant, was small (<0.10) before and after adjustment for other subject characteristics, and did not vary significantly by ethnicity (Table 3).
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), although the rise at age 51 was less pronounced than for log DHEAS. Log testosterone was strongly positively correlated with log DHEAS for all ethnicities (Table 3). The magnitude of this correlation varied significantly across ethnic groups even after adjustment for age, menopause status, and log BMI and was strongest in Hispanics and Caucasians and weakest in Japanese. Discussion
There is evidence of a gender-specific difference in the profiles of DHEAS decline with age (7), suggesting a potential gonadal-adrenal interaction. However, most reports characterizing a pattern of DHEAS decline with increasing age have resulted from cross-sectional studies, precluding the opportunity to observe the actual profiles of individuals across time or the variation in patterns that may be experienced during the life course of these individuals (1, 2, 3, 4). With rare exception, adrenal activity or circulating adrenal steroid hormone levels have not previously been linked to specific stages of ovarian status during the menopausal transition (31, 32). The present report is the first to document the longitudinal changes in DHEAS concentrations in a large number of women within the context of their carefully defined ovarian status and to examine the consistency of those observed changes among women of different ethnic groups. Although ovarian status was self-evaluated in this study, the criteria used were conservative enough to prevent the subjects from assigning themselves to stages later than was probable. The self-evaluation of ovarian status was made as simple as possible to minimize classification errors. Subjects had to recognize only abnormal changes in their menstrual calendar to self-identify as no longer premenopausal. A complete lack of menstrual periods for 1 yr was required to self-classify as postmenopausal. Whereas some subjects may not have detected or reported the earliest indicators of the menopausal transition, this error would not have a great impact on the relationships reported here because the hormonal correlates are more strongly correlated to the later stages of the menopausal transition. Thus, the results of this study indicate that observable change in ovarian function is related to circulating adrenal steroid levels in some middle-aged women and supports the premise of a gonadal-adrenal interaction.
Shideler et al. (27) also reported a failure of DHEAS to exhibit a persistent decline during the menopausal transition using the nonhuman primate as a model of the human menopausal transition. Earlier reports from animal models, parallel to reports in human populations, were either cross-sectional or did not focus on either gender- or ovarian stage-specific differences (33). Cross-sectional data had revealed an increased variance in circulating DHEAS in older female but not male macaque monkeys. When Shideler et al. (27) analyzed longitudinal data from daily profiles of urinary hormone metabolites to explain the increased variance (33), there was a rise in DHEAS during the menopause transition. Thus, observations in both humans and macaque monkeys suggest a rise in DHEAS concentrations during the menopausal transition. The magnitude and duration of that rise with respect to the last menstrual period remain to be elucidated.
DHEAS lacks a cognate receptor but can be metabolized to either a potent androgen or a potent estrogen, capable of interacting with nuclear steroid receptors and affecting cellular function. DHEAS seems to be converted primarily to testosterone and androstenedione in both men and women (23), and, in the present study, circulating DHEAS was concordant with testosterone in terms of the age-related patterns of decline. In contrast, our estradiol age-related patterns bore little resemblance to DHEAS. This suggests DHEAS production is associated with concomitant testosterone production via peripheral conversion in older women. Future studies should examine the dynamics of estrogen metabolism excretion and the kinetics of receptor binding with respect to this DHEAS profile in the menopausal transition.
Whereas several reports indicate the postmenopausal ovary has the ability to secrete androgens (34, 35, 36), Couzinet et al. (37) recently demonstrated that, in the absence of adrenal function, postmenopausal women averaging 12 yr after menopause had no detectable circulating androgens and that their postmenopausal ovaries were devoid of gonadotropin receptors and steroidogenic enzymes. These observations suggest that the postmenopausal ovary as early as 5 yr after menopause is not a source of androgens (37). The parallel changes in DHEAS and testosterone that we report here support the concept that testosterone is derived from an adrenal, not ovarian, source and suggest that the adrenal may be a primary source of androgen production after menopause. Subsequent analysis of SWAN data, as these same women complete the menopausal transition, should provide critical information in this regard. Moreover, ethnicity, psychosocial, lifestyle, and genetic factors may influence possible adrenal weak androgen axis activation during the latter stages of the menopausal transition and into the postmenopause.
In the present study, circulating concentrations of DHEAS during midlife reveal ethnic-specific differences. After adjustment for age, BMI, and current smoking, Chinese and Japanese women had the highest mean DHEAS levels whereas the lowest mean levels were observed in the African American and Hispanic cohorts (Fig. 2). In general, higher BMI was associated with lower DHEAS levels, a relationship more apparent in Chinese and less apparent in Hispanics. This association was positive, however, in Japanese. Thus, the greatest ethnic difference observed in terms of the association of BMI and DHEAS was between the Chinese and Japanese cohorts.
These women from the five ethnic groups were recruited at different geographic sites using locally effective, population-based techniques for cohort recruitment (28). This resulted in a large and diverse sample with respect to educational levels, income, and lifestyles and enhances the likelihood that information about these DHEAS profiles can be considered representative of the general population.
Potentially, lifestyle differences (including smoking, which was controlled for) among the ethnic groups in the SWAN sample could account for the differences in observed patterns of circulating DHEAS. For example, differences in perceived stress or stress from menopausal symptoms has been demonstrated among the ethnic groups in SWAN (38, 39, 40), and this may influence the patterns of DHEAS expression. However, our evaluation of this hypothesis did not reveal either perceived stress or vasomotor symptom intensity as the underlying factors in the ethnic-specific patterns of DHEAS (data not shown). Nonetheless, we recognize that this report is concerned with measures from three time points covering a 2-yr period and that it will be important to re-examine this question with the context of a longer follow-up including the final menstrual period.
The findings from this study cannot be extrapolated yet to the probability of healthy aging. Because this study encompasses 2 yr, it is not possible to draw conclusions related to the presence or absence of chronic diseases. This study does, however, demonstrate that DHEAS profiles are associated with ovarian status in older women and have clear ethnic differences, suggesting the importance of continued follow-up of the population for measures of health status. This follow-up can then address individual differences in DHEAS profiles as well as the timing and potential ethnic predisposition for increased circulating DHEAS.
In summary, the absence of a uniform predictable decline in circulating DHEAS in women undergoing the menopause transition is described. Similar to the subhuman primate, circulating DHEAS concentrations transiently increase in some individuals, and this transient increase is linked to the latter stages of the menopause transition. In the present study, changes and variability of DHEAS in the latter menopause transition differed according to ethnic group. The linkage of ovarian function to adrenal function underscores the importance of characterizing ovarian status when studying women and highlights the need for further mechanistic elucidation of the pathways responsible for transient adrenal androgen activation.
Acknowledgments
This manuscript was reviewed by the Publications and Presentations Committee of SWAN and has its endorsement. We thank the study staff at each site and all of the women who participated in SWAN.
Footnotes
This work was supported in part by grants from the NIH (U01-NR04061, U01-AG12531, U01-AG12505, U01-AG12554, U01-A12539, U01-AG12535, U01-AG12546, U01-AG12553).
The SWAN was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Office of Research on Women’s Health of the NIH. Supplemental funding from the National Institute of Mental Health, the National Institute on Child Health and Human Development, the National Center on Complementary and Alternative Medicine, the Office of Minority Health, and the Office of AIDS Research is also gratefully acknowledged.
Clinical centers: University of Michigan, Ann Arbor, Michigan (U01-NR04061, Mary Fran Sowers, PI); Massachusetts General Hospital, Boston, Massachusetts (U01-AG12531, Robert Neer, PI 1994–1999; Joel Finkelstein, current PI); Rush University, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois (U01-AG12505, Lynda Powell, PI); University of California, Davis/Kaiser, California (U01-AG12554, Ellen Gold, PI); University of California, Los Angeles, California (U01-A12539, Gail Greendale, PI); University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey (U01-AG12535, Gerson Weiss, PI); and the University of Pittsburgh, Pittsburgh, Pennsylvania (U01-AG12546, Karen Matthews, PI). Central laboratory: University of Michigan, Ann Arbor, Michigan (U01-AG12495, Central Ligand Assay Satellite Services, Rees Midgley, PI). Coordinating center: New England Research Institutes, Watertown, Massachusetts (U01-AG12553, Sonja McKinlay, PI). Project officers: Taylor Harden, Carol Hudgings, Marcia Ory, Sheryl Sherman. Steering Committee chair: Jennifer L. Kelsey, current; Christopher Gallagher, 1994–1996.
Abbreviations: BMI, Body mass index; DHEAS, dehydroepiandrosterone sulfate; DMAE, dimethylacridunium; PMP, superparamagnetic particles; SWAN, Study of Women’s Health Across the Nation.
Received January 10, 2002.
Accepted May 2, 2002.
References
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|
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) adjustment for age, current smoking, menopausal status, log BMI, ethnicity, site, and the interaction between ethnicity and log BMI. Also shown is the percentage of women at each year of age who have transitioned to late perimenopausal status (
).
