Prevalence of cannabis use among individuals with a history of cancer in the United States.

BACKGROUND: Patients with cancer have played a key role in advocating for legal access to cannabis, but little is known about links between cancer and cannabis use or cannabis-related beliefs. The authors used data from a national survey to study these relationships. METHODS: Nationally representative data collected by the National Survey on Drug Use and Health from 2015 to 2019 were acquired. Patterns of cannabis use and cancer history were examined and tested within age group subpopulations via domain analysis using survey weights. RESULTS: Data for 214,505 adults, including 4741 individuals (3.8%) with past (>1 year ago) cancer diagnosis and 1518 individuals (1.2%) with recent (≤1 year ago) cancer diagnosis, were examined. Cannabis use was less common in those with past (8.9%; 95% CI, 8.0%-9.8%) or recent (9.9%; 95% CI, 6.9%-11.1%) cancer diagnosis than in those without a history of cancer (15.9%; 95% CI, 15.7%-16.1%). However, when analyses were stratified by age group, those 18 to 34 years of age were more likely to report past cannabis use, and those 35 to 49 years of age were more likely to report past or recent cannabis use if they had a history of cancer. Younger patients felt that cannabis was more accessible and less risky if they had a history of cancer. CONCLUSIONS: Patients with cancer were less likely to report cannabis use, but there were different cannabis perceptions and use patterns by age. Age should be considered in studies of cannabis and cancer, and policy initiatives may be needed to aid provision of quality information on cannabis risk to those with cancer. LAY SUMMARY: Cannabis (marijuana) use is increasing in the United States, but we do not have much information on the relationship between cannabis use and cancer. We studied information from a representative group of people and found that younger patients generally reported more past and/or recent cannabis use if they had been diagnosed with cancer whereas older individuals did not. Beliefs about cannabis risk and accessibility differed by age. Clinical trials to study cannabis should account for patient age, and accurate information about cannabis should be provided to help patients with cancer make decisions about cannabis use.

The Relationship Between Hearing Loss and Substance Use Disorders Among Adults in the U.S.

INTRODUCTION: Hearing loss is common and associated with poorer health and impeded communication. Little is known about the association between hearing loss and substance use disorders in the general population. The objective of this study was to assess substance use disorder prevalence among individuals with hearing loss, versus those without hearing loss, in a nationally representative sample of adults. METHODS: Two years (2015 and 2016) of National Survey on Drug Use and Health (unweighted N=86,186) were combined to compare substance use disorders among adults with and without self-reported hearing loss. Statistical analysis included descriptive frequencies, chi-square tests, and multiple logistic regressions. Analyses were performed in 2018. RESULTS: Hearing loss prevalence across all age groups was 5.2%. Among younger age groups, after adjusting for sociodemographics, hearing loss was independently associated with an increased likelihood of experiencing a substance use disorder (ages 18-34 years, AOR=1.34, 95% CI=1.10, 1.64 vs 35-49 years, AOR=1.87, 95% CI=1.39, 2.53). Hearing loss was also associated with a greater likelihood of a prescription opioid use disorder (AOR=2.85, 95% CI=1.86, 4.39) in the group aged 18-34 years and, for the group aged 35-49 years, hearing loss increased the likelihood of both an alcohol use disorder (AOR=1.87, 95% CI=1.39, 2.53) and a prescription opioid use disorder (AOR=1.99, 95% CI=1.01, 3.91). CONCLUSIONS: Hearing loss is independently associated with substance use disorders among those aged 49 years and younger; these associations are particularly pronounced for prescription opioid use disorders in the group aged 18-34 years. Given the concern of inappropriate use of prescription opioids, this information may have implications for healthcare providers' pain management for patients with hearing loss.

Comparison of four different nerve conduction techniques of the superficial fibular sensory nerve.

INTRODUCTION: There are many different nerve conduction study (NCS) techniques to study the superficial fibular sensory nerve (SFSN). We present reference distal latency values and comparative data regarding 4 different NCS for the SFSN. METHODS: Four different NCS techniques, Spartan technique, Izzo techniques (medial and intermediate dorsal cutaneous branches), and Daube technique, were performed on (114) healthy volunteers. A total of 108 subjects with 164 legs were included. RESULTS: The mean latency of the Spartan technique was longest (3.9 ± 0.3 ms) while the Daube technique was the shortest (3.6 ± 0.7 ms). The mean amplitude of the Daube technique displayed the highest (15.2 ± 8.2 µV) with the Spartan technique having the lowest (8.7 ± 4.2 µV). Among the absent sensory nerve action potentials (SNAPs), the Spartan technique was absent only twice (1.2%) and the Izzo Medial technique was absent more than the other techniques (2.9%). CONCLUSIONS: All 4 techniques were reliable methods for obtaining the superficial fibular nerve SNAP, present in 95% of individuals. Muscle Nerve 56: 458-462, 2017.

Athletic activity and hormone concentrations in high school female athletes.

CONTEXT: Physical activity may affect the concentrations of circulating endogenous hormones in female athletes. Understanding the relationship between athletic and physical activity and circulating female hormone concentrations is critical. OBJECTIVE: To test the hypotheses that (1) the estradiol-progesterone profile of high school adolescent girls participating in training, conditioning, and competition would differ from that of physically inactive, age-matched adolescent girls throughout a 3-month period; and (2) athletic training and conditioning would alter body composition (muscle, bone), leading to an increasingly greater lean-body-mass to fat-body-mass ratio with accompanying hormonal changes. DESIGN: Cohort study. SETTINGS: Laboratory and participants' homes. PATIENTS OR OTHER PARTICIPANTS: A total of 106 adolescent girls, ages 14-18 years, who had experienced at least 3 menstrual cycles in their lifetime. MAIN OUTCOME MEASURE(S): Participants were prospectively monitored throughout a 13-week period, with weekly physical activity assessments and 15 urine samples for estrogen, luteinizing hormone, creatinine, and progesterone concentrations. Each girl underwent body-composition measurements before and after the study period. RESULTS: Seventy-four of the 98 girls (76%) who completed the study classified themselves as athletes. Body mass index, body mass, and fat measures remained stable, and 17 teenagers had no complete menstrual cycle during the observation period. Mean concentrations of log(estrogen/creatinine) were slightly greater in nonathletes who had cycles of <24 or >35 days. Mean log(progesterone/creatinine) concentrations in nonathletes were less in the first half and greater in the second half of the cycle, but the differences were not statistically significant. CONCLUSIONS: A moderate level of athletic or physical activity did not influence urine concentrations of estrogen, progesterone, or luteinizing hormones. However, none of the participants achieved high levels of physical activity. A significant number (17%) of girls in both activity groups were amenorrheic during the 3-month study period.

Relating smoking, obesity, insulin resistance, and ovarian biomarker changes to the final menstrual period.

To determine if smoking, obesity, and insulin resistance mediated age at final menstrual period (FMP), we examined anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH) as biomarkers of changing follicle status and ovarian aging. We performed a longitudinal data analysis from a cohort of premenopausal women followed to their FMP. Our results found that smokers had an earlier age at FMP (P < 0.003) and a more rapid decline in their AMH slope relative to age at FMP (P < 0.002). Smokers had a lower baseline inhibin B level relative to age at the FMP than nonsmokers (P = 0.002). Increasing insulin resistance was associated with a shorter time to FMP (P < 0.003) and associations of obesity and time to FMP were observed (P = 0.004, in model with FSH). Change in ovarian biomarkers did not mediate the time to FMP. We found that smoking was associated with age at FMP and modified associations of AMH and inhibin B with age at FMP. Insulin resistance was associated with shorter time to FMP independent of the biomarkers. Interventions targeting smoking and insulin resistance could curtail the undue advancement of reproductive aging.

Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause.

BACKGROUND AND OBJECTIVE: The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP). DESIGN AND SETTING: This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr. MEASUREMENTS: Measures were bone mineral density (BMD), FSH to define four FSH stages, and menstrual bleeding cessation to define the FMP. Bone loss rates were reported by obesity status. RESULTS: Annualized rates of lumbar spine bone loss began in FSH stage 3, which occurs approximately 2 yr prior to the FMP (1.67%/yr); bone loss continued into FSH stage 4 (1.21%/yr). Mean spine BMD in FSH stage 4 was 6.4% less than spine BMD value in FSH stage 1. Annualized rates of femoral neck (FN) bone loss began in FSH stage 3 (0.55%/yr) and continued into FSH stage 4 (0.72%/yr). The FN difference between mean values in FSH stage 1 and FSH stage 4 was 5%. Annualized rates of spine bone loss in the 2 yr prior to the FMP were 1.7%/yr, 3.3%/yr in the 2 yr after the FMP, and 1.1%/yr in the 2- to 7-yr period after the FMP. Nonobese women had lower BMD levels and greater bone loss rates. CONCLUSIONS: Spine and FN bone loss accelerates in FSH stage 3. Bone loss also began to accelerate 2 yr before the FMP with the greatest loss occurring in the 2 yr after the FMP. Bone loss rates in both spine and FN BMD were greater in nonobese women than obese women.

Respiratory measurement utilizing a novel laser displacement technique: normal tidal breathing.

UNLABELLED: A novel technique for achieving plethysmography measurements utilizing noncontact laser displacement sensors is described. This method may have utility in measuring respiratory and pulmonary function similar to that of respiratory inductive plethysmography. The authors describe the apparatus and method and provide results of a validation study comparing respiratory excursion data obtained by (1) the laser sensor technique, (2) standard respiratory inductive plethysmography (RIP), and (3) lung volume measurements determined by pressure variations in a control volume. Six healthy volunteers (five female, one male, ages ranging from 19 to 23 years) were measured for tidal breathing excursions simultaneously via all three measurement techniques. RESULTS: Excellent correlation between the techniques was shown. Pairwise comparisons among all three measurement techniques across all subjects showed intraclass correlation coefficients of 0.995 in each case. These results indicate the laser plethysmograph (LP) system provides results that are, at a minimum, equivalent to those of the RIP at the two sites commonly measured by RIP. Use of the LP system has the potential to provide much more extensive and precise measurements of chest wall function and the respiratory musculature.

Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition.

CONTEXT/OBJECTIVE: The objective of the study was to determine whether anti-Mullerian hormone (AMH) and inhibin B are viable endocrine biomarkers for framing the menopause transition from initiation to the final menstrual period (FMP). DESIGN: We assayed AMH, inhibin B, and FSH in 300 archival follicular phase specimens from 50 women with six consecutive annual visits commencing in 1993 when all women were in the pre- and perimenopausal menopause stages. Subsequently each woman had a documented FMP. The assay results were fitted as individual-woman profiles and then related to time to FMP and age at FMP as outcomes. RESULTS: Based on annual values from six time points prior to the FMP, (log)AMH longitudinal profiles declined and were highly associated with a time point 5 yr prior to FMP [including both observed and values below detection (P < 0.0001 and P = 0.0001, respectively)]. Baseline AMH profiles were also associated with age at FMP (P = 0.035). Models of declining (log)inhibin B profiles (including both observed and values below detection) were associated with time to FMP (P < 0.0001 and P = 0.0003, respectively). There was no significant association of (log)inhibin B profiles with age at FMP. CONCLUSIONS: AMH, an endocrine marker that reflects the transition of resting primordial follicles to growing follicles, declined to a time point 5 yr prior to the FMP; this may represent a critical biological juncture in the menopause transition. Low and nondetectable levels inhibin B levels also were observed 4-5 yr prior to the FMP but were less predictive of time to FMP or age at FMP.

Change in adipocytokines and ghrelin with menopause.

OBJECTIVES: To determine if ghrelin and adipocytokine (leptin, adiponectin, resistin) levels vary with menopause stage or with estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) concentrations measured in three stages of the menopause transition. METHODS: A study of adipocytokines and menopause was nested in a population-based, longitudinal study of Caucasian women [Michigan Bone Health and Metabolism Study (MBHMS)]. Annual serum and urine samples, available from the MBHMS repository, were selected to correspond to the pre-, peri-, and postmenopause stages of the menopause transition. Participants included forty women, stratified into obese versus non-obese groups based upon their baseline body mass index, who had specimens corresponding to the three menopause stages. RESULTS: Mean resistin levels were approximately two times higher during premenopause compared to peri- or postmenopause. There were significantly lower adiponectin and higher ghrelin levels in the perimenopause stage, compared to either the pre- or postmenopause stage. Increases in FSH concentrations were significantly and positively associated with higher leptin in non-obese women (P<0.01) but not in obese women (P<0.23). Increases in FSH concentrations were also significantly (P<0.005) and positively associated with higher adiponectin concentrations but were negatively associated with ghrelin concentrations (P<0.005). Associations remained following adjustment for waist circumference, waist circumference change, chronological age, and time between measures. CONCLUSIONS: Menopause stages and underlying FSH changes are associated with notable changes in levels of the metabolically active adipocytokines and ghrelin and these changes may be related to selected health outcomes observed in women at mid-life.

Oestrogen metabolites in relation to isoprostanes as a measure of oxidative stress.

OBJECTIVE: Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16alpha-hydroxyoestrone (16alpha-OHE1) are thought to curtail the greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related oestrogen levels to F(2a)-isoprostane levels, a biomarker of oxidative stress. DESIGN AND PARTICIPANTS: Data were obtained from 1647 women, aged 47-57 years, participating in the fifth annual follow-up of the Study of Women's Health Across the Nation (SWAN), a study of the menopausal transition. MEASUREMENTS: Serum E2 and urinary 2-OHE1 and 16alpha-OHE1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and urinary F(2a)-isoprostanes were measured by enzyme immunoassay (EIA). RESULTS: F(2a)-isoprostane concentrations were elevated in women who smoked, a behaviour associated with increased oxidative stress, but not in stages of the natural menopause. Mean F(2a)-isoprostane concentrations among pre- and postmenopausal women who smoked were 1082 and 1064 pg/ml, respectively, values double those in pre- (343 pg/ml) and postmenopausal (379 pg/ml) nonsmoking women. 2-OHE1 and F(2a)-isoprostane concentrations were positively and highly correlated (partial correlations rho(Y|X) = 0.44 and rho(Y|X) = 0.43 in pre- and postmenopausal women, respectively). Similarly, 16alpha-OHE1 concentrations were positively and highly correlated with F(2a)-isoprostane concentrations (rho(Y|X) = 0.52 and rho(Y|X) = 0.59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F(2a)-isoprostanes only in postmenopausal women (rho(Y|X) = 0.20). Associations were adjusted for age, body mass index (BMI), race/ethnicity, lipids, physical activity level and alcohol consumption. CONCLUSIONS: This study does not support the commonly held hypothesis that levels of endogenous E2 or its oestrone metabolites favourably modify oxidative stress by decreasing F2(a)-isoprostane levels.

Endogenous estradiol and its association with estrogen receptor gene polymorphisms.

We evaluated potential associations between single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol (E2) concentrations in women of 4 races/ethnicities. The study population was drawn from participants in the Study of Women's Health Across the Nation (SWAN). A total of 1,538 African American, Caucasian, Chinese, and Japanese women from SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood for sex steroid hormone analyses and consenting to lymphocyte transformation from which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 ESR2 SNPs (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Mean E2 level was 196.0 +/- 4.0 pmol/L in women who were premenopausal and perimenopausal (with blood drawn on days 2 through 5 of the menstrual cycle follicular phase); however, mean E2 levels in Chinese and Japanese women were lower (155.7 +/- 10.6 pmol/L and 170.0 +/- 10.3 pmol/L, respectively) than in African American (196.4 +/- 8.1 pmol/L, P <0.05) or Caucasian women (210.7 +/- 5.9 pmol/L, P <0.002). The ESR1 rs3798577 CC genotype was associated with lower circulating E2 concentrations in African American women (P <0.07) and explained about 1% of the variation in circulating E2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was associated with significantly lower circulating E2 concentrations that explained about 4% of the variation. Circulating E2 concentrations were not strongly or consistently associated with selected polymorphisms for the estrogen receptor genes. The 2 strongest associations explained <4% of the total variation in the circulating E2 concentrations.

Menstrual cycle markers of ovarian aging and sex steroid hormone genotypes.

We related variation in 4 sex steroid genes to 3 phenotypic indicators of ovarian aging, including no evidence of luteal activity as a marker of anovulatory cycles, shorter or longer menstrual cycle lengths, and the profiles of metabolites of estrogens, progesterone, follicle-stimulating hormone, and luteinizing hormone measured in urine samples collected daily across a menstrual cycle in women aged 43 to 53 years. The study sample included 485 menstruating women without hormone therapy who had collected daily urine hormone samples across 1 menstrual cycle or 50 days, whichever occurred first. There were 14 single nucleotide polymorphisms from 4 genes, including estrogen receptor-alpha (ESR1), estrogen receptor-beta, aromatase, and 17beta hydroxysteroid dehydrogenase type 1, related to ovarian aging phenotypes that include the presence or absence of luteal activity, menstrual cycle lengths < or > 24 to 31 days, and profiles of urinary hormone metabolites. Women with the TT genotype of ESR1 rs3798577 have evidence of advanced ovarian aging compared with women with the CT or CC genotypes, after adjustment for race/ethnicity, chronologic age, and race/ethnicity-specific body mass index. Further, women with the TC and CC genotypes of ESR1 rs2234693 may have a greater likelihood of more advanced ovarian aging than do women with the TT genotype, adjusting for covariates. Using a candidate gene approach, 2 ESR1 polymorphisms are related to 3 phenotypic markers of ovarian aging, suggesting a possible role for the ESR1 gene in the timing of the menopausal transition.

Sex steroid hormone polymorphisms, high-density lipoprotein cholesterol, and apolipoprotein A-1 from the Study of Women's Health Across the Nation (SWAN).

We evaluated potential associations between single nucleotide polymorphism (SNP) variants in estrogen receptor (ERalpha and ERbeta) genes, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A-1 (apoA-1) concentrations in women of 4 races/ethnicities. Participants included 1,520 African American, Caucasian, Chinese, and Japanese women from the Study of Women's Health Across the Nation (SWAN) who were premenopausal or perimenopausal and who were also enrolled in the SWAN Genetics Study, which collected blood for lipid analyses and carried out lymphocyte transformation from which DNA was extracted and genotyped. We evaluated SNPs from ERalpha and ERbeta genes (ESR1 and ESR2, respectively), including ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, ESR1 rs3798577, ESR2 rs1255998, ESR2 rs1256065, and ESR2 rs1256030. The mean HDL cholesterol and apoA-1 values for these women were 1.47 mmol/L and 1.51 g/L, respectively. Japanese women with the ESR1 rs3798577 TC genotype had significantly lower apoA-1 (P=0.02) and HDL cholesterol levels (P=0.03) than did those with the TT genotype. African American women with the ESR1 rs728524 GG genotype had higher HDL cholesterol levels than did women with the AA or AG genotypes (P=0.05). ESR2 rs1256030 and ESR2 rs1256065 genotypes were associated with HDL cholesterol concentrations in Chinese women (P=0.05). Although associations were identified between the ESR1 and ESR2 SNP variants and lipids in these women, these associations were not consistently observed across the 4 racial/ethnic groups, nor were the associations consistently inclusive of both HDL cholesterol and apoA-1. These genetic variants provide limited evidence of associations with lipids that may help explain the cardioprotective effect of premenopausal status in women.

Performance-based physical functioning in African-American and Caucasian women at midlife: considering body composition, quadriceps strength, and knee osteoarthritis.

In 2000, body composition, x-ray-defined knee osteoarthritis, and self-reported knee pain information from a cross-sectional, community-based study of 211 African-American and 669 Caucasian women in southeast Michigan (mean age, 47 years) was related to performance-based physical functioning measures to characterize development of functional limitations. Body composition was assessed with bioelectrical impedance. Functioning measures were gait assessment, timed walk, timed stair climb with and without videography, and isometric quadriceps strength. Knee osteoarthritis was determined by Kellgren-Lawrence score from radiography, whereas knee pain was self-reported. Almost 31% of mid-aged women walked at functionally inadequate speeds, and over 12% walked at speeds considered typical of frailty in older women. Ten percent of women had skeletal muscle mass levels less than a proposed cutpoint for increased physical disability risk in older adults. Gait measures correlates included increasing age, increasing fat mass (in kilograms), knee joint pain, and reduced quadriceps strength. Stair climbing correlates included skeletal muscle mass (in kilograms) and its change, painful knee osteoarthritis, and reduced quadriceps strength. Race differences in walking measures and stair climbing time diminished when the authors accounted for other factors. Compromised physical functioning began earlier than expected, with indications that approximately 12-31% of women might benefit from interventions to forestall future decline.

Osteoarthritis of the knee: comparison of MR imaging findings with radiographic severity measurements and pain in middle-aged women.

PURPOSE: To prospectively compare magnetic resonance (MR) imaging-defined abnormalities of osteoarthritis (OA) of the knee with radiographic severity measurements of OA of the knee and self-reported pain. MATERIALS AND METHODS: This study was approved by the institutional review board of University of Michigan. Informed consent was obtained for this HIPAA-compliant study. Knee MR imaging was performed in 117 women (mean age, 46 years; range, 32-56 years) from a community-based arthritis study (n = 1053) with 30 women in each of four categories: (a) no pain and no OA of the knee, (b) no pain and OA of the knee, (c) pain and no OA of the knee, and (d) pain and OA of the knee. OA of the knee was defined from radiographs. Two hundred thirty-two eligible knees had Kellgren-Lawrence scores for OA of the knee as follows: grade 0, 115 (49.6%); grade 1, 33 (14.2%); grade 2, 66 (28.4%); grade 3, 17 (7.3%); and grade 4, one (0.4%). MR images were assessed for location and severity of defects of cartilage, bone marrow edema (BME), osteophytes, subchondral cysts, sclerosis, meniscal and/or ligamentous tears, joint effusion, synovial cysts, and synovitis. MR imaging findings were compared with radiographic severity of OA of the knee (Kellgren-Lawrence scale) and self-reported pain with analysis of variance, t tests, and contingency table analyses. RESULTS: Defects of cartilage (higher than grade IIA) were found in 75% of knees; BME was found in 57% of knees (<1 cm, 41%; >1 cm, 16%). Large BME lesions were common in the pain and OA of the knee group (P = .001); this group was significantly more likely to have defects of cartilage (P = .001); meniscal tears (P = .001); and osteophytes, subchondral cysts, sclerosis, joint effusion, and synovitis (P < .001). Defects of cartilage, osteophytes, sclerosis, meniscal or ligamentous tears, joint effusion, and synovitis were strongly related to increasing Kellgren-Lawrence grade (P < .001). CONCLUSION: In middle-aged women, there were significant associations between pain, radiographic severity of OA of the knee, and seven MR imaging-identified parameters.

Elevated serum fluoride concentrations in women are not related to fractures and bone mineral density.

Epidemiologic studies of the relations between drinking-water fluoride levels and bone mineral density (BMD) and fracture are characterized by disparate conclusions and an absence of information about individual circulating fluoride levels. This study relates serum fluoride concentrations, which reflect individual fluoride exposures, to BMD and bone fractures. Data are from 1300 female residents of 3 small communities in which the water fluoride concentrations were 52.6 or 210.4 micromol/L. Circulating serum fluoride concentrations were assessed by ion-specific electrode. Fluoride intake was estimated from interviews describing water and water-based beverage consumption and duration of residence in the community. BMD was measured by dual-energy X-ray densitometry and single-photon densitometry. Self-reported fractures were confirmed by medical record abstraction. The mean serum fluoride concentration in the high-fluoride community, 2.11 +/- 0.05 micromol/L, was significantly higher than serum fluoride concentrations in the control and high-calcium communities with water fluoridation to 52.6 micromol/L. The mean serum fluoride concentrations in these latter 2 communities were 1.6 +/- 0.04 and 1.22 +/- 0.05 micromol/L, respectively. Serum fluoride was not significantly related to BMD after adjusting for covariates including age and body size. The mean distal radius BMD, however, was significantly higher in the high-fluoride community. Serum fluoride concentrations were not related to incident osteoporotic fractures with 4 y of observation. Serum fluoride concentrations were not associated with BMD or osteoporotic fractures among female residents of communities with water fluoride concentrations of 52.6 or 210.4 micromol/L.

Estrogen receptor genotypes and their association with the 10-year changes in bone mineral density and osteocalcin concentrations.

We conducted a 10-yr prospective study of peak bone mass and its change in 604 women, aged 24-44 yr at study initiation, and related changes in bone mineral density (BMD) and osteocalcin (OCN) concentrations to estrogen receptor (ER) alpha gene polymorphisms in 442 of these women. We examined the association of ER alpha PvuII and XbaI polymorphisms with the 10-yr change in lumbar spine (LS) and femoral neck (FN) BMD, measured by densitometry, as well as serum OCN levels, after accounting for weight and menstrual status change. The women were members of the Michigan Bone Health Study, a population-based longitudinal study of BMD. There was a linear loss of LS BMD and curvilinear loss of FN BMD from peak bone mass over a 10-yr period. Women homozygous for the ER alpha gene variant without an XbaI restriction site (XbaI -/- genotype) had higher FN BMD and less change in LS over time. Women homozygous for the ER alpha gene variant without a PvuII restriction site (PvuII -/- genotype) had less LS BMD change over time as well as higher FN BMD. However, this higher FN BMD was dependent upon the rate of bone turnover as estimated from serum OCN change over time. The ER alpha genotype associations were statistically significant in explaining the rate of perimenopausal bone loss and its turnover; however, BMI or becoming postmenopausal contributed more to the magnitude of the difference in bone change.

Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN.

We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42-52 yr, in the Study of Women's Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance. After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance. The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women.

Lead in breast milk and maternal bone turnover.

OBJECTIVE: Our purpose was to determine whether breast milk lead (Pb) levels are correlated with maternal blood Pb levels, bone loss, or bone turnover during reproduction. STUDY DESIGN: Data were collected prospectively at 0, 1.5, 3, 6, and 12 months after delivery in 15 lactating and 30 bottle-feeding women. Variables included breast milk Pb (inductively coupled mass spectrometry), maternal blood Pb (atomic absorption spectrophotometry), osteocalcin (radioimmunoassay), and bone mineral density change (dual-energy x-ray absorptiometry). RESULTS: Mean Pb breast milk concentrations were 6.1, 5.6, 5.9, and 4.3 ng/mL at the 1.5, 3, 6, and 12 months post partum, whereas mean maternal blood Pb concentrations were 1.4, 1.6, 1.7, and 1.4 microg/dL at 0, 3, 6, and 12 months post partum. The 5.6% bone loss and significant bone turnover were related to breast milk Pb levels but not to postpartum maternal blood Pb levels. Maternal and breast milk Pb values were modestly correlated at 1 to 2 months. CONCLUSIONS: Bone loss and bone turnover were related to breast milk Pb levels. In these women, there was no evidence that either high maternal blood or breast milk Pb concentrations are a major public health concern.