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Obesity: Original Article |
Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Women’s Health (N.S.), Albert Einstein College of Medicine, New York, New York 10461; University of Medicine and Dentistry of New Jersey-New Jersey Medical School (N.S., G.W.), Newark, New Jersey 07103; Department of Population Health and Reproductive Medical Sciences (B.L.) and Epidemiology and Preventive Medicine (E.B.G.), University of California at Davis, and Kaiser Permanente, Davis, California 95616; Central Ligand Assay Satellite Services (D.M., R.M.) and Department of Epidemiology (M.F.S.), University of Michigan, Ann Arbor, Michigan 48109; Department of Community Health (J.A., S.C.), Brown University, Providence, Rhode Island 02912; New England Research Institutes (J.A., S.C.), Watertown, Massachusetts 02472; Division of Preventive and Behavioral Medicine, Department of Medicine (S.C., J.K.), University of Massachusetts Medical Center, Worcester, Massachusetts 02155; Endocrine Unit, Department of Medicine (J.S.F.), Massachusetts General Hospital, Boston, Massachusetts 02114; Departments of Epidemiology (G.A.G., M.S.) and Medicine (S.K.), Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095; Division of Epidemiology, Department of Health Research and Policy (J.K.), Stanford University School of Medicine, Stanford, California 94305-5405; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility (J.L.L.) and Epidemiology (L.P.), Rush Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612; and Department of Psychiatry (K.M.) and Epidemiology and Data Coordinating Center (J.S.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213
Address all correspondence and requests for reprints to: Nanette Santoro, M.D., Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Mazer 316, Bronx, New York 10461. E-mail: glicktoro{at}aol.com.
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Abstract |
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The Study of Women’s Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42–52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d (whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [estrone conjugates (E1c)] and progesterone [pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified.
Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m2 had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition.
In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Although menstrual cycles are known to become more irregular and are more likely to be anovulatory with reproductive aging, relatively little else is known about the day-to-day characteristics of reproductive hormones as women traverse the menopausal transition. Follicular phase estradiol (12) and total-cycle estrone (10) have been shown to be elevated in ovulatory cycles during the menopausal transition. A metaanalysis of early follicular phase and premenstrual serum estradiol found evidence for increased estradiol in the cycles of perimenopausal women (16). The women in these studies were largely Caucasian, and it is not known whether this observation is also true in a multiethnic cohort.
The Study of Women’s Health across the Nation (SWAN) is a multiethnic, community-based, longitudinal study of women as they traverse the menopausal transition. As a part of this study, we are examining in great detail the longitudinal characteristics of the menstrual cycles of perimenopausal women from five ethnic groups in the United States. We report herein the baseline biological and demographic characteristics and daily hormone patterns of the menstrual cycles of 833 women from SWAN who are participating in the Daily Hormone Study (DHS).
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Subjects and Methods |
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SWAN is a multiethnic cohort study of 3302 middle-aged women enrolled at seven sites throughout the United States. The design of the main cohort study has been reported previously (17). The DHS is a substudy of SWAN in which a subset of women (n = 848) collect first morning voided urine samples daily for one complete menstrual cycle or 50 d (whichever comes first) once a year. Details on specimen collection have been published previously (18). In the present communication, we report findings from the urine samples collected at the baseline examination. We measured the excreted levels of FSH, LH, estrone conjugate (E1c), and pregnanediol glucuronide (Pdg). We then used these measurements in validated algorithms (16) to evaluate the menstrual cycles for features consistent with folliculogenesis, ovulation, and corpus luteum function (see Evaluation of cycles).
Participant population
A subset of women from all SWAN clinical sites were enrolled in the DHS. This study was approved by all of the sites’ Institutional Review Boards, and written informed consent was obtained from each participant. The baseline cohort included women of Caucasian (n = 1550), African (n = 935), Chinese (n = 250), Japanese (n = 281), and Hispanic (n = 286) ethnic origins who were aged 42–52 yr. Inclusion criteria for recruitment into the DHS were: 1) an intact uterus and at least one ovary, 2) at least one menstrual period in the previous 3 months, 3) no use of sex steroid hormones in the previous 3 months, and 4) not pregnant. The reproductive status of all women in SWAN is expressed categorically as menopausal status. This definition is based on current, accepted nomenclature (19, 20, 21). Women eligible for the DHS were categorized in terms of menopausal status. Premenopausal status was defined as menses in the past 3 months, with no change over the past year in predictability of menstrual periods. Early perimenopausal status was defined as menses in the past 3 months, with less predictable periods (19, 20). Assessments of status were made at the annual visit preceding entry into the DHS.
Controls
SWAN does not include a population of younger women (i.e. aged less than 38 yr) with regular menstrual cycles. Therefore, we used historical control data from 80 women, aged 18–32 yr, who were recruited from four sites for a previous intervention study (22). They were cycling regularly, were nonsmokers, had normal screening TSH and prolactin levels, were of normal weight (between 90 and 130% normal weight for height), and did not have a history of aggressive dieting or excessive exercise. Using the same assays and laboratory as used for the DHS urine samples, LH, FSH, E1c, and Pdg were measured in daily urine samples from untreated (run-in) cycles of 29 of the women, selected randomly. Seventy-three percent of the overall sample was Caucasian, and 27% was of other, unspecified ancestry (22). No other demographic data were available on these volunteers.
To provide comparative data from younger women who constituted a more defined population, daily urine samples corresponding to one menstrual cycle from 263 women (age, 21–38 yr) with no menstrual irregularity were analyzed for estradiol and progesterone metabolites as part of a previously published study conducted by two SWAN investigators (B.L., E.B.G.) (23). The women were residents of northern California and were primarily Caucasian and Asian. Because the methods to measure hormone levels in that investigation, although similar, were not identical with those used in the current study, direct comparisons between hormone concentrations could not be made. However, cycle characteristics such as follicular and luteal phase duration could be compared.
Hormone assays
LH, FSH, E1c, and Pdg were measured using newly adapted chemiluminescent assays, previously described (18). Data were normalized for creatinine (Cr) concentration (24). Total-cycle integrated hormone concentrations were also analyzed.
Evaluation of cycles
A significant increase in Pdg concentrations was accepted as evidence of luteal activity (ELA), which is consistent with presumed ovulation. We employed a validated algorithm developed by Kassam et al. (25). The algorithm locates the 5 nadir days of Pdg in the follicular phase using moving averages throughout the cycle. A 3-fold increase in Pdg concentrations above this nadir for at least 3 consecutive days was considered ELA. Cycles with ELA were assessed to determine the probable day of luteal transition (DLT), using a modification of the previously published method of Waller et al. (26). The method of Waller et al. (26) examines the ratio of E1c to Pdg and indicates a luteal shift, or DLT, when the E1c to Pdg ratio decreases by 60%. We examined the ability of this criterion to detect the DLT in 396 of the SWAN DHS baseline cycles as a validation measure. We examined cutoffs between 25 and 75% and found an 85–92% ability to detect the DLT as measured by trained observers when a cutoff of 75% was used as the descent criterion (18). Phase-specific lengths for cycles with ELA were calculated using the DLT as d 0, excluding d 0 from both follicular and luteal phase lengths. Hormone concentrations were integrated (i.e. summed) over the total cycle and over follicular and luteal phases for cycles with ELA, using the trapezoidal rule. For isolated missing days, hormone concentrations were interpolated (26). Cycles missing hormones for more than 2 consecutive days were omitted from analyses of integrated hormones. Integrated hormones were calculable for 93.0% of ELA cycles.
Cycles with no ELA were further subdivided into those in which the collection ended due to the onset of a bleeding episode (no ELA, bleeding; n = 87) or those in which the collection was automatically terminated at 50 d without bleeding (no ELA, no bleed; n = 72). These latter cycles without ELA are the topic of a separate report.
Statistical analyses
Unadjusted associations of participant characteristics with ELA and with cycle and phase-specific lengths in ELA cycles were tested using 
2 tests. Multivariate logistic regression (27, 28) was used to determine corresponding adjusted associations, including age, ethnicity, body mass index (BMI), and smoking status; adjustment for site (eastern United States, midwestern United States, and West Coast) to account for study design was also included. Follicular and luteal phase lengths were considered to be short if they were less than 12 d and long if they were longer than 16 d. These divisions are based on the idealized 28-d menstrual cycle, with a follicular phase of 14 d and a luteal phase of 14 d (29). Although such data are derived from basal body temperature recordings and are thought to provide a delayed estimate of the onset of the luteal phase, subsequent detailed, daily hormonal assessments of menstrual cycles have largely confirmed an approximately 14-d length for each cycle phase (30), but it is recognized that variation between cycle segment length estimates based on different criteria might differ. All analyses of total-cycle integrated hormones were adjusted for cycle length, to account for the obvious dependence of total hormones on number of collection days.
Patterns of daily hormone excretion in cycles with ELA were examined by plotting the mean (±SE) of daily concentrations, standardized to the DLT. Subgroup differences in total-cycle integrated hormones for ELA cycles were examined using analysis of covariance (31) to adjust for total cycle length, as well as age, ethnicity, BMI, smoking status, menopausal status, and region. Similar analyses compared DHS cycles with ELA and midreproductive control cycles, adjusting for total cycle length.
Model fit was assessed using 2 goodness of fit statistics for categorical outcomes (26, 27) and residual analyses for integrated hormones (31). Integrated hormones were log-transformed for analyses, and geometric means were calculated using the antilog of the adjusted means on the log scale. The figures report mean data for all cycles indicated, with the SEM as the measurement of variance throughout.
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Results |
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Of the 3302 women in the SWAN cohort, 1443 were screened for DHS eligibility. Of the 1219 eligible women invited to complete the baseline urine collection, 848 (69.6%) women agreed to participate and provided a sufficiently complete cycle for analysis. Participants were more likely than eligible nonparticipants to be Chinese or Japanese (38.3% of DHS participants, whereas 27.8% of nonparticipants were Chinese or Japanese) and less likely to be Caucasian (30.6% vs. 35.6%) (P = 0.0078). Participants also were slightly younger than eligible nonparticipants (mean age, 47.2 vs. 47.9 yr; P < 0.0001). Participation was not associated with smoking or BMI. Seven cycles (0.8%) were omitted from analyses due to missing BMI, menopausal status, or smoking status. Eight cycles started with a surge of LH and an increase in Pdg, suggesting that periovulatory bleeding occurred and cued women to begin their urine collection at the wrong time, and were not included in subsequent analyses, yielding an analytic sample size of 833 cycles.
Compared with the rest of the SWAN cohort at the first follow-up core visit, corresponding to the beginning of the DHS, the DHS sample had a higher proportion of non-Caucasians and a lower proportion of Caucasians, reflecting the study design, which oversampled non-Caucasians (Table 1
). All DHS participants were premenopausal or early perimenopausal, according to eligibility criteria. Differences between DHS participants and other SWAN participants in age, BMI, smoking status, oral contraceptive use, and educational level reflected these ethnic- and menopausal status-related differences.
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30 kg/m2) by World Health Organization criteria (32) (mean BMI, 27.3 kg/m2). Only 3% of Chinese women had ever smoked, vs. 35% for other ethnicities (P < 0.0001). BMI also varied by ethnicity, with obesity ranging from 4–6% in Chinese and Japanese women to 58% in African-Americans (P < 0.0001). Age did not differ by ethnicity. The proportion of women who were premenopausal was 27.1%, and the remaining 72.9% were early perimenopausal.
Cycles with ELA
Associations with ELA. Overall, 674 (80.9%) cycles had ELA, and 159 (19.1%) did not. Only ELA cycles are presented for the remainder of the data; cycles without luteal activity are the topic of a separate report. The proportion of cycles with luteal activity decreased with increasing age and with menopausal status. ELA cycles were observed more often in premenopausal than in early perimenopausal women. Overweight and obese participants did not differ significantly regarding ELA status (P = 0.79); however, normal-weight women had a higher proportion of ELA cycles than either of these two groups (P = 0.05 for overweight vs. normal weight; P = 0.02 for obese vs. normal weight). The probability of having a cycle with ELA was unrelated to ethnicity or smoking status. Age and menopausal status remained significantly related to ELA status in multivariate analyses (P < 0.0001).
Total cycle length.
Among cycles with ELA, total cycle length was significantly associated with ethnicity, age, BMI, and menopausal status (Table 2). Hispanic women had more long cycles (33 d) and fewer short cycles (
22 d). Women age 49 yr and older had the largest proportion of both longer and shorter cycles. Women with BMIs greater than 25 kg/m2 had longer cycles on average than did women with lower BMIs. Early perimenopausal women were more likely than premenopausal women to have a long cycle. Smoking was not related to total cycle length. In multivariate analyses, only age remained significantly associated with total cycle length (P < 0.0054), although differences between women with a BMI of 25 kg/m2 or less and those with a BMI greater than 25 kg/m2 were marginally statistically significant (P < 0.10). BMI accounted for ethnic differences in total cycle length (P value for adjusted ethnic differences = 0.50).
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Daily hormone dynamics of ELA cycles.
On average, daily hormone concentrations were highest in women with BMIs of 25 kg/m2 or less (Fig. 1), except for E1c, which did not vary by BMI before adjustment for other participant characteristics. Length-adjusted BMI differences in mean total-cycle FSH, LH, and Pdg were statistically significant (P < 0.01). On adjustment for other factors, particularly ethnicity, the adjusted mean total-cycle E1c was 1369.4 ng/mg Cr for women with a BMI of 25 kg/m2 or less vs. 1174.1 ng/mg Cr for women with a BMI greater than 28 kg/m2; these adjusted BMI-related differences were statistically significant (P = 0.0007). Length-adjusted total-cycle integrated Pdg and E1c varied significantly by ethnicity, with higher Pdg and lower E1c in Chinese and Japanese women (Fig. 2 and Table 3). BMI largely accounted for the apparent ethnic difference in Pdg (P value after adjusting for BMI = 0.996).
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49 yr) had higher total-cycle integrated FSH, but lower total-cycle integrated Pdg compared with younger women. Additional adjustment for ethnicity, BMI, smoking status, and menopausal status had little impact on age-related differences. Women who had never smoked had significantly higher length-adjusted total-cycle integrated Pdg, but smoking status was not statistically significantly related to integrated Pdg in multivariate analyses (P = 0.23).
Total-cycle FSH was higher in early perimenopausal compared with premenopausal women, and this difference was accounted for in part by age (adjusted P = 0.12).
Comparisons with historical, midreproductive-aged controls.
Figure 3 depicts daily urinary hormone patterns of SWAN DHS ELA cycles with the profiles from 29 midreproductive-aged control cycles. The SWAN ELA DHS cycles had consistently higher daily FSH and LH. Peak Pdg was higher in the midreproductive-aged cycles than in SWAN cycles. Daily E1c was very similar for the two groups of cycles. Between-group length-adjusted differences in total-cycle integrated hormones were consistent with daily patterns, with significantly higher integrated FSH (430.8 vs. 171.0 mIU/mg Cr; P < 0.0001) and LH (66.2 vs. 30.9 mIU/mg Cr; P < 0.0001) in the SWAN cycles, lower integrated Pdg in the SWAN cycles (53.8 vs. 70.4 µg/mg Cr; P = 0.009), and no difference in E1c (1285.7 vs. 1272.3 ng/mg Cr; P = 0.88).
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presents differences between the two groups of ELA cycles regarding total cycle length and phase-specific length. Short follicular phases were more than twice as common in the DHS cycles as in cycles from midreproductive-age women, and conversely, long follicular phases were half as likely in the DHS cycles. Differences in total cycle length were similar to those seen for follicular phase length. Midreproductive-age women were somewhat more likely to have a short luteal phase and a long luteal phase than DHS women.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Sherman and Korenman (33) reported long follicular phases, low gonadotropins, and low serum progesterone production throughout the luteal phase in six obese women of midreproductive age believed to be at risk for infertility and irregular menses. The similarities of the patterns of the cycles we observed in SWAN women with BMIs greater than 25 kg/m2 and those observed by Sherman and Korenman (33) are striking. Others have reported similar hormonal alterations in women with very high BMI, i.e. greater than 30 kg/m2, who are cycling regularly (34). Taken together, these data imply that women with higher BMIs may have an increased likelihood of chronic cycle dysfunction, even with apparently ovulatory cycles. Longitudinal data from SWAN may help to identify the characteristics associated with both obesity and menstrual cycle dysfunction.
Increased body weight may alter hormone metabolism and clearance in several complex ways. Obese women have lower SHBG levels, and therefore, may have a greater proportion of their circulating estradiol in the free fraction (35, 36). Free estradiol is more biologically active, and may exert more negative feedback, resulting in lower circulating gonadotropins. Our findings are consistent with this hypothesis. Greater BMIs might also influence urinary hormone measures without affecting circulating hormones through its influence on Cr excretion. Women with greater BMIs have more lean body mass and muscle as well as more fat mass. Urinary Cr increases directly with BMI (37) but inversely with age (38). These relationships were observed in our participants. One would therefore predict that normalizing urinary hormonal data to Cr would result in lower hormone values for larger women and higher hormone values for older women. To determine whether age- and BMI-related differences in Cr accounted for between-group differences in integrated Cr-normalized hormones, we conducted supplemental analyses, using linear regression to model total-cycle integrated raw (not Cr-normalized) hormones as a function of participant characteristics, adjusting for total-cycle integrated Cr. The resulting estimated associations between integrated hormones and participant characteristics did not differ substantially from those presented herein, and statistical findings were not altered.
There were some differences in cycle and hormone patterns among ethnic groups. Much of this variation was explained by other factors, particularly BMI. Only E1c remained associated with ethnicity after adjusting for BMI. Japanese and Chinese women had the lowest whole cycle E1c excretion among all the ethnic groups. This difference persisted even after adjusting for concurrent menopausal status. This finding may imply intrinsic differences in hormone production and/or metabolism in these women, or may reflect a different rate of transit toward the final menstrual period not accounted for by adjusting for this definition of menopausal status. The lower E1c we observed in the cycles of the Chinese- and Japanese-American women is consistent with the baseline early follicular phase serum data from the overall SWAN cohort (36). Lower urinary estrogen in Asian women compared with Caucasian and African-American women has been reported previously (39), as have lower plasma estrogen levels (40). These findings have been conjectured to be related to increased dietary intake of substances, such as isoflavones, that might alter enteric estrogen metabolism (40). Isoflavone interventions have not documented alterations in hypothalamic-pituitary feedback (41), but premenopausal Asian women given isoflavones were noted to have a resultant decrease in luteal phase serum estradiol (42). On the other hand, the possibility that these cross-sectional data indicate that the Chinese and Japanese women within our cohort are approaching menopause more slowly than the other ethnic groups is possible, because these women reported later final menstrual periods in the SWAN cross-sectional survey (43) and had fewer women with premature menopause, i.e. final menses before age 40 (44).
Not surprisingly, older age was associated with greater cycle variability such as longer and more irregular cycles. Smoking was associated with reduced luteal progesterone metabolite excretion. These findings confirm and extend those previously reported by others (45, 46) concerning the deleterious effects of aging and smoking on menstrual cycles and may provide mechanistic support for the observation that smokers have decreased ovarian reserve and an earlier age at menopause (46). Follicular phase progesterone has been noted to be higher in smokers compared with nonsmokers in some studies (45). This has been attributed to greater adrenal gland production of progesterone and progesterone metabolites. Our results indicate that both age and smoking are associated with higher overall gonadotropin output and a lesser capacity for normal corpus luteum function.
In comparison to midreproductive-aged women, SWAN women have higher levels of FSH and LH excretion. However, we see no failure of ovarian responsiveness to gonadotropin production, because E1c was similar in both populations. Because estrogen was not low in the SWAN women relative to younger women, the marked elevation of FSH throughout the cycle must be due to other factors. Our data are consistent with the hypothesis that another regulator of FSH, such as inhibin, is deficient in older reproductive-aged women, because differences in steroidal feedback throughout the cycle cannot explain the elevated FSH and LH that we and others have observed.
We used two midreproductive-aged control groups to provide complementary information that would assist in comparison. Neither group is perfectly representative of the SWAN DHS cross-sectional baseline. The 29 control women who were assayed in an identical laboratory were selected to be between 90 and 130% of normal weight for height. They are likely to have a lower BMI than the SWAN women. Thus, they might be expected, on the basis of the known hormonal covariates of BMI (i.e. Cr and urinary hormones), to have higher FSH, LH, E1c, and Pdg. Additional supplemental analyses compared the DHS women with BMIs less than 25 kg/m2 to the midreproductive-aged women. The corresponding differences between DHS and midreproductive cycles in terms of integrated hormones were larger for FSH and LH than analyses that included all DHS cycles, regardless of participant BMI. The difference in mean integrated Pdg, however, was smaller and not statistically significant (P = 0.26), but there was no impact of this supplemental analysis on the between-group difference in integrated E1c. A second control population of 263 women from a prior study (23) was also used to derive follicular and luteal phase lengths. These women were from the West Coast, but they represented a more community-based sampling of factory workers and were demographically similar to the SWAN baseline DHS cohort. However, their hormonal data cannot be directly compared, because the assays were run in different laboratories using different reagents.
Longer total cycles and longer follicular phases, on average, were associated with early perimenopausal status. Although age and menopausal status were correlated, adjustment for menopausal status had little impact on the subgroup differences reported herein.
The menopausal transition appears to be an "irregularly irregular" process with marked cycle-to-cycle variability (10). A cross-sectional report such as this one can provide information about between-women variation and describe the panoply of cycle types and their interrelationships. Luteal cycles only were included in this report, because they can be readily standardized to the DLT, yet 19.1% of cycles were not luteal even at this relatively early stage in the menopausal transition. Planned serial study of these women with an annual menstrual cycle is underway and will help to provide more longitudinal data about individual women’s menopausal experience. It is currently not known to what extent one cycle in one woman can predict subsequent reproductive hormonal patterns.
In summary, in this study of a large cohort of U.S. women, we have shown that the predictability of luteal activity in premenopausal and early perimenopausal women is most strongly affected by body size, age, and ethnicity. Whole-cycle hormone levels were lower in women with greater BMIs. Ethnicity appears to play a role in hormone patterns apart from body size. Because this report is cross-sectional, it is not yet possible to ascertain whether the differences we observed are due to a different rate of progress through the menopausal transition based on body size or ethnicity, or whether these differences will persist throughout the study. For the time being, it appears that the early menopausal transition is characterized by a rise in FSH and LH and minimal degrees of corpus luteum failure, as indicated by decreased Pdg excretion. The lack of change in estrogen metabolite excretion in women in the early transition compared with younger, midreproductive-aged women indicates that the ovary retains responsiveness to gonadotropin input, whereas follicle reserve is greatly reduced.
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Acknowledgments |
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Footnotes |
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Project Officers: Taylor Harden, Carole Hudgings, Marcia Ory, and Sheryl Sherman. Steering Committee Chair: Jennifer L. Kelsey, Ph.D., and Susan Johnson, M.D.
Abbreviations: BMI, Body mass index; Cr, creatinine; DHS, Daily Hormone Study; DLT, day of luteal transition; E1c, estrone conjugates; ELA, evidence of luteal activity; Pdg, pregnanediol glucuronide; SWAN, Study of Women’s Health across the Nation.
Received September 10, 2003.
Accepted February 3, 2004.
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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 H. M. Kravitz, I. Janssen, N. Santoro, J. T. Bromberger, M. Schocken, S. A. Everson-Rose, K. Karavolos, and L. H. Powell Relationship of Day-to-day Reproductive Hormone Levels to Sleep in Midlife Women Arch Intern Med, November 14, 2005; 165(20): 2370 - 2376. [Abstract] [Full Text] [PDF]
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 M. K. Melby, M. Lock, and P. Kaufert Culture and symptom reporting at menopause Hum. Reprod. Update, September 1, 2005; 11(5): 495 - 512. [Abstract] [Full Text] [PDF]
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 G. Weiss, J. H. Skurnick, L. T. Goldsmith, N. F. Santoro, and S. J. Park Menopause and Hypothalamic-Pituitary Sensitivity to Estrogen JAMA, December 22, 2004; 292(24): 2991 - 2996. [Abstract] [Full Text] [PDF]
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