Sex steroid hormone profiles are related to sleep measures from polysomnography and the Pittsburgh Sleep Quality Index.

STUDY OBJECTIVES: To relate reproductive hormones (and the preceding 7-year rates of their change) to objectively and subjectively assessed sleep measures, independent of age, vasomotor symptom frequency, depressive symptoms, and body size. DESIGN: A cross-sectional sleep substudy nested in the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the menopausal transition. SETTING: Community-based. PARTICIPANTS: 365 Caucasian, African American, and Chinese women. MEASUREMENTS AND RESULTS: Sleep duration, continuity, and architecture were measured during two nights of in-home polysomnography (PSG) studies. Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, sleep diaries for medication, vasomotor symptoms, lifestyle information and questionnaires for depressive symptoms. Blood collected annually in the years prior to sleep study was assayed for follicle stimulating hormone (FSH), estradiol (E2), and total testosterone (T). More rapid rate of FSH change was significantly associated with higher delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2 was modestly and negatively associated with sleep quality. Women in the lowest total testosterone quartile at baseline had more wake time after sleep onset (WASO) than women in the highest quartile. Lower E2/T ratio, an index reflecting the increasing androgenic environment with the menopause transition, was associated with less WASO. CONCLUSIONS: More rapid rate of FSH change was associated with longer sleep duration but poor sleep quality. Women with higher T or who were closer to the completion of the transition process (as indexed by a lower E2/T) had less sleep discontinuity (less WASO).

Associations between depressive symptoms and inflammatory/hemostatic markers in women during the menopausal transition.

OBJECTIVE: To test whether depressive symptoms are related to inflammatory and hemostatic markers in women approaching menopause. METHODS: A total of 3292 women enrolled in the Study of Women's Health Across the Nation (SWAN) were followed for five years and had measures of Center for Epidemiologic Studies-Depression and high sensitivity C-reactive protein, Factor VIIc, fibrinogen, plasminogen activator inhibitor Type 1(PAI-1), and tissue-type plasminogen activator antigen (tPA-ag) up to four times during the follow-up period. Women were pre- or early perimenopausal status at study entry and were of Caucasian, African American, Hispanic, Japanese, or Chinese race/ethnicity. RESULTS: Unadjusted longitudinal mixed regression models showed that over a 5-year period, higher depressive symptoms were related to higher fibrinogen, PAI-1, and tPA-ag levels, all p < .0001. Taking into account health history, medication use, ethnicity, aging, and menopausal status, the depressive symptoms were related to fibrinogen, p < .01, and PAI-1, p < .05. Depressive symptoms were related only to fibrinogen in models that also included body mass index, p < .05. CONCLUSIONS: Depressive symptoms may be associated with cardiovascular risk in perimenopausal women in part through hypercoagulability. This is the first study to test the association of depressive symptoms and hemostatic and inflammatory markers across time.

Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN).

BACKGROUND: Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. METHODS AND RESULTS: The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. CONCLUSIONS: Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

Correlates of circulating androgens in mid-life women: the study of women's health across the nation.

CONTEXT: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. OBJECTIVE: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. DESIGN: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. MAIN OUTCOME MEASURES: Correlations of androgen measures with each other and with body mass index, waist circumference, and waist-hip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, self-reported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. RESULTS: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR = 0.32; 95% confidence interval = 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR = 1.09; 95% confidence interval = 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. CONCLUSIONS: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.

Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: We evaluated ethnic differences in the 10-year risk of myocardial infarction or coronary death derived from Framingham risk equation and in a composite measure of emerging cardiovascular disease risk factors in women and whether statistical adjustments for educational attainment, geographic location, and lifestyle attenuated the magnitude of the ethnic differences in risk. METHODS: Two thousand eight hundred thirty-four premenopausal women free of stroke, heart disease, or diabetes and aged of 42 to 52 years (1400 whites, 729 African American, 226 Hispanic, 231 Chinese, and 248 Japanese) had measurements of blood pressure, lipids and lipoproteins, waist circumference, glucose, insulin, lipoprotein(a), fibrinogen, factor VII, plasminogen activator inhibitor, tissue-type plasminogen activator antigen, and high-sensitivity C-reactive protein. Framingham risk score and number of risk factors in the top quartile of the distribution of risk factors not included in the Framingham score (called composite burden) were calculated. RESULTS: The unadjusted mean values for the two summary scores were higher among African Americans and Hispanics than other groups. Statistical adjustments for education and geographical site accounted for a majority of the ethnic differences, with an additional small effect of lifestyle for the composite burden score. Largest ethnic differences were apparent for waist circumference, lipoprotein(a), high-sensitivity C-reactive protein, and untreated blood pressure. CONCLUSIONS: A substantial part of the risk associated with ethnicity can be attributed to socioeconomic status and geographical location. As the ethnic composition of the United States population becomes more diverse, it is important to appreciate the cardiovascular disease risk factor burden present in some minority groups.

The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity.

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.

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study.

The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. 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.

Staging reproductive aging: a comparison of proposed bleeding criteria for the menopausal transition.

OBJECTIVE: A staging system for female reproductive aging has recently been proposed. Bleeding criteria are an important component of a staging system, as bleeding patterns are readily observable. Several different bleeding criteria have been proposed, but their concordance and validity have not been evaluated. Five proposed bleeding criteria or markers for the onset of early menopausal transition and four criteria for the onset of the late transition were evaluated using data from the Menstruation and Reproductive History Study, or Tremin Trust. DESIGN: Correlations between time from age 35 to each marker event were assessed using Kendall's tau correlation coefficients. Kaplan-Meier survival analysis was used to examine associations between the marker events and age at final menstrual period (FMP). RESULTS: The first occurrence of marker events for the late menopausal transition demonstrated low to high correlation (r = 0.23 to 0.77), whereas the first occurrence of marker events for the early transition stage demonstrated no correlation to moderate correlation (r = 0.0 to 0.65). After age 40, the occurrence of the marker events distinguished a subgroup of women who were more proximate to their FMP. Differences in years to FMP between women with and without the marker events were greatest in the early to mid-40s and declined with age. CONCLUSIONS: A 60-day cycle may be a desirable marker for entry into the late transition stage because of its reliability, proximity to the FMP, and ease of calculation. More work is needed to conceptually define the onset of the early menopausal transition before appropriate bleeding criteria can be established.

Disordered eating, menstrual irregularity, and bone mineral density in female runners.

PURPOSE: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS: Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS: An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION: In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

OBJECTIVE: Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. METHODS: In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes). RESULTS: Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). CONCLUSIONS: Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Isometric quadriceps strength in women with mild, moderate, and severe knee osteoarthritis.

OBJECTIVE: Quadriceps weakness is a common clinical sign in persons with moderate-to-severe osteoarthritis and results in physical disability; however, minimal data exist to establish whether quadriceps weakness is present in early stages of the disease. Therefore, our purpose was to determine whether quadriceps weakness was present in persons with early radiographic and cartilaginous evidence of osteoarthritis. Further, we sought to determine whether quadriceps strength decreases as osteoarthritis severity increases. DESIGN: Three hundred forty-eight women completed radiologic and magnetic resonance imaging evaluation, in addition to strength testing. Anterior-posterior radiographs were graded for tibiofemoral osteoarthritis severity using the Kellgren-Lawrence scale. Scans from magnetic resonance imaging were used to assess medial tibiofemoral and patellar cartilage based on a modification of the Noyes scale. The peak knee extension torque recorded was used to represent strength. RESULTS: Quadriceps strength (Nm/kg) was 22% greater in women without radiographic osteoarthritis than in women with osteoarthritis (P < 0.05). Quadriceps strength was also greater in women with Noyes' medial tibial and femoral cartilage scores of 0 when compared in women with Noyes' grades 2 and 3-5 (P < or = 0.05). CONCLUSIONS: Women with early evidence of osteoarthritis had less quadriceps strength than women without osteoarthritis as defined by imaging.

Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners.

OBJECTIVE: To identify nutrients, foods, and dietary patterns associated with stress fracture risk and changes in bone density among young female distance runners. DESIGN AND SETTING: Two-year, prospective cohort study. Observational data were collected in the course of a multicenter randomized trial of the effect of oral contraceptives on bone health. PARTICIPANTS: One hundred and twenty-five female competitive distance runners ages 18-26 years. ASSESSMENT OF RISK FACTORS: Dietary variables were assessed with a food frequency questionnaire. MAIN OUTCOME MEASUREMENTS: Bone mineral density and content (BMD/BMC) of the spine, hip, and total body were measured annually by dual x-ray absorptiometry (DEXA). Stress fractures were recorded on monthly calendars, and had to be confirmed by radiograph, bone scan, or magnetic resonance imaging. RESULTS: Seventeen participants had at least one stress fracture during follow-up. Higher intakes of calcium, skim milk, and dairy products were associated with lower rates of stress fracture. Each additional cup of skim milk consumed per day was associated with a 62% reduction in stress fracture incidence (P < .05); and a dietary pattern of high dairy and low fat intake was associated with a 68% reduction (P < .05). Higher intakes of skim milk, dairy foods, calcium, animal protein, and potassium were associated with significant (P < .05) gains in whole-body BMD and BMC. Higher intakes of calcium, vitamin D, skim milk, dairy foods, potassium, and a dietary pattern of high dairy and low fat were associated with significant gains in hip BMD. CONCLUSIONS: In young female runners, low-fat dairy products and the major nutrients in milk (calcium, vitamin D, and protein) were associated with greater bone gains and a lower stress fracture rate. Potassium intake was also associated with greater gains in hip and whole-body BMD.

Psychometric evaluation of the Insomnia Symptom Questionnaire: a self-report measure to identify chronic insomnia.

STUDY OBJECTIVES: The objective was to psychometrically evaluate the Insomnia Symptom Questionnaire (ISQ), a self-report instrument designed to establish a clinically relevant case definition of insomnia consistent with widely used insomnia classification criteria, using methods from classical test theory and item response theory (IRT). METHODS: The ISQ was evaluated using IRT algorithms in a cohort of 362 pre-, peri- and post-menopausal women recruited for the SWAN (Study of Women's Health Across the Nation) Sleep Study. This yielded a dichotomous outcome consistent with the presence/absence of insomnia. The internal consistency and criterion validity of the dichotomized ISQ were compared to traditional measures of sleep from sleep diaries, polysomnography, and the Pittsburgh Sleep Quality Index using kappa statistics, and indices of sensitivity, specificity, positive and negative predictive value (PPV), and likelihood ratio tests (LRs). RESULTS: The ISQ identified 9.8% of the sample as meeting insomnia, consistent with established diagnostic criteria. Reliability was established with Cronbach alpha (alpha = 0.89). The ISQ had high specificity (> 90%), but sensitivity, PPV, NPV, and LRs varied according to which sleep measure was used. Concurrent validity was not confirmed with any of the traditional sleep summary measures (kappas < 0.30). CONCLUSIONS: The ISQ captures the multidimensionality of insomnia better than traditional sleep measures as it ascertains symptoms of insomnia that are based on DSM-IV and RDC criteria. The high specificities suggest that the ISQ has a high probability of correctly identifying those without insomnia and would be a cost-effective tool in large observational studies in which the prevalence of insomnia is likely to be about 10%. Further evaluation of the ISQ, including validation against clinical interviews, is warranted.

Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?

OBJECTIVES: This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort. BACKGROUND: Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples. METHODS: SWAN (Study of Women's Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging. RESULTS: Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging. CONCLUSIONS: Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.

Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition.

CONTEXT: A previous report from the Study of Women Across the Nation indicated a rise in dehydroepiandrosterone sulfate (DHEAS) during the menopausal transition using data from three annual visits. OBJECTIVE: Our objective was to examine changes in DHEAS with chronological and ovarian aging, expanding the original analyses to include 10 yr of annual data. DESIGN: A longitudinal observational study and cross-sectional analyses of baseline data were conducted. OUTCOME MEASURES AND SUBJECTS: DHEAS, age, menopause status, ethnicity, smoking, weight, and height were assessed in 2886 women from five ethnic groups aged 42-52 yr at entry. Hysterectomy, bilateral oophorectomy, and hormone use were excluded. RESULTS: Cross-sectional analysis at baseline showed a linear decline in circulating log-transformed DHEAS with increasing age for either the entire cohort (2.81% per year) or for individual ethnicities. A similar negative association with baseline age (2.44% decline per year) was seen in longitudinal linear mixed modeling including observations from premenopause through late postmenopause, an additional 0.33% decline/year. In contradistinction, a late-transition rise in DHEAS was detected when the same women were analyzed by ovarian status. The average increase in mean circulating DHEAS level between early and late menopause transition, beyond changes predicted by aging, was 3.95%, followed by an average decline of 3.96% during the late postmenopause. Approximately 84.5% of the women had an estimated within-woman increase in DHEAS from premenopause/early perimenopause to late perimenopause/early postmenopause. CONCLUSION: These observations underscore differences between cross-sectional and longitudinal studies and the importance of considering ovarian status. Additional investigations regarding adrenal contribution to sex steroids in mid-aged women are warranted.

Bone mineral density and fractures among alcohol-dependent women in treatment and in recovery.

Women are at higher risk for osteoporosis, but most of the literature examining the effect of alcohol abuse on bone mineral density (BMD) has been in men. The aim of this study was to determine differences in BMD and fracture prevalence among women in treatment for alcohol abuse, in recovery and non-alcohol-dependent women. This cross-sectional study was completed at two residential substance abuse centers in Iowa (USA). The patients were Caucasian women, aged 18-70 years, in treatment for alcohol abuse and dependence ( n=228); in recovery and abstaining from alcohol ( n=156); and women with no history of alcohol abuse ( n=447). The main outcome measures were femoral neck and lumbar spine BMD measured by dual-energy X-ray absorptiometry (DXA); self-reported lifetime fracture prevalence. After adjusting for age and menopausal status, women in treatment had BMDs that were 7.7% ( p<0.01) and 6.3% ( p<0.01) lower at the femoral neck and lumbar spine, respectively, than non-alcohol-abusing women, and 4.8% lower at both bone sites ( p<0.01) than women in recovery. Femoral neck BMD of women in recovery was 3.1% lower ( p<0.01) than in non-alcohol-dependent women; however, the difference was not significant following multivariate analysis. Women in treatment and recovery reported more fractures during childhood and early adolescence than non-alcohol-dependent women ( p<0.01). Women in recovery also reported significantly greater numbers of fractures following sobriety than their paired non-alcohol-dependent counterparts. Alcohol abuse and dependence was associated with lower femoral neck and lumbar spine BMD. Women with histories of alcohol dependence had a higher lifetime prevalence of fractures, including time periods before the onset of problem drinking and following abstinence, suggesting that factors other than acute intoxication contributed to the greater fracture prevalence.

DDT metabolite and androgens in African-American farmers.

BACKGROUND: The ubiquitous dichlorodiphenyltrichloroethane (DDT) metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is an androgen receptor antagonist. Data on potential antiandrogenic activity of DDE in humans are limited. METHODS: The relations between concentrations of plasma DDE and several serum androgens (total testosterone, bioavailable testosterone, 5alpha-dihydrotestosterone, and free androgen index) were examined in 137 North Carolina black male farmers, using multiple linear regression. RESULTS: Participants ranged in age from 30 to 88 years (mean = 62 years). Most had farmed for about 30 years and 27% reported having used DDT. The median DDE level was 7.7 microg per liter (1213 microg per kg lipid), slightly higher than in other recent studies. Overall, concentrations of DDE and androgens were unrelated. Total testosterone decreased 2% (95% confidence limits [CL] = -9%, 5%) per increase in interquartile distance of lipid-adjusted DDE. The percentage change in other hormones was similarly negligible. However, among those whose DDE level was in the top tenth percentile, compared with all others, total testosterone and free androgen index were lower by 23% (CL= -40%, 1%) and 22% (CL =-41%, 4%) respectively. Plasma androgen levels decreased with age, a relation that has previously been studied only in whites. CONCLUSIONS: Studies of more highly exposed populations may be needed to evaluate effects, if any, of DDE.