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Neighborhood walkability and sex steroid hormone levels in women

India-Aldana, Sandra; Rundle, Andrew G; Clendenen, Tess V; Quinn, James W; Arslan, Alan A; Afanasyeva, Yelena; Koenig, Karen L; Liu, Mengling; Neckerman, Kathryn M; Thorpe, Lorna E; Zeleniuch-Jacquotte, Anne; Chen, Yu
BACKGROUND:Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels. OBJECTIVE:We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women. METHODS:We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors. RESULTS:In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results. CONCLUSION/CONCLUSIONS:Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
PMID: 36088991
ISSN: 1096-0953
CID: 5332702

Temporal reproducibility of IgG and IgM autoantibodies in serum from healthy women

Clendenen, T V; Hu, S; Afanasyeva, Y; Askenazi, M; Koenig, K L; Hulett, T; Liu, M; Liu, S; Wu, F; Zeleniuch-Jacquotte, A; Chen, Y
Autoantibodies are present in healthy individuals and altered in chronic diseases. We used repeated samples collected from participants in the NYU Women's Health Study to assess autoantibody reproducibility and repertoire stability over a one-year period using the HuProt array. We included two samples collected one year apart from each of 46 healthy women (92 samples). We also included eight blinded replicate samples to assess laboratory reproducibility. A total of 21,211 IgG and IgM autoantibodies were interrogated. Of those, 86% of IgG (n = 18,303) and 34% of IgM (n = 7,242) autoantibodies showed adequate lab reproducibility (coefficient of variation [CV] < 20%). Intraclass correlation coefficients (ICCs) were estimated to assess temporal reproducibility. A high proportion of both IgG and IgM autoantibodies with CV < 20% (76% and 98%, respectively) showed excellent temporal reproducibility (ICC > 0.8). Temporal reproducibility was lower after using quantile normalization suggesting that batch variability was not an important source of error, and that normalization removed some informative biological information. To our knowledge this study is the largest in terms of sample size and autoantibody numbers to assess autoantibody reproducibility in healthy women. The results suggest that for many autoantibodies a single measurement may be used to rank individuals in studies of autoantibodies as etiologic markers of disease.
PMID: 35418192
ISSN: 2045-2322
CID: 5201972

Gut Microbiota and Subjective Memory Complaints in Older Women

Wu, Fen; Davey, Samuel; Clendenen, Tess V; Koenig, Karen L; Afanasyeva, Yelena; Zhou, Boyan; Bedi, Sukhleen; Li, Huilin; Zeleniuch-Jacquotte, Anne; Chen, Yu
BACKGROUND:Epidemiological studies that investigate alterations in gut microbial composition associated with cognitive dysfunction are limited. OBJECTIVE:To examine the association between the gut microbiota and subjective memory complaints (SMCs), a self-reported, validated indicator of cognitive dysfunction. METHODS:In this cross-sectional study of 95 older women selected from the New York University Women's Health Study (NYUWHS), we characterized the gut microbial composition using 16S rRNA gene sequencing. We estimated odds ratio (OR) from beta regression which approximates the ratio of mean relative abundances of individual bacterial taxon from phylum to genus levels by binary (2+ versus < 2) and continuous SMCs. RESULTS:Women reporting 2 or more SMCs had higher relative abundances of genus Holdemania and family Desulfovibrionaceae compared with those reporting one or no complaint. Compared with women with < 2 SMCs, the relative abundances of Holdemania and family Desulfovibrionaceae were 2.09 times (OR: 2.09, 95% confidence interval [CI]: 1.38-3.17) and 2.10 times (OR: 2.10, 95% CI: 1.43-3.09) higher in women with 2+ SMCs, respectively (false discovery rate (FDR)-adjusted p = 0.038 and 0.010, respectively). A dose-response association was observed for genus Sutterella and family Desulfovibrionaceae. Every one-unit increase in SMCs was associated with 25% and 27% higher relative abundances of Sutterella (OR: 1.25; 95% CI: 1.11-1.40) and Desulfovibrionaceae (OR: 1.27; 95% CI: 1.13-1.42), respectively (FDR-adjusted p = 0.018 and 0.006, respectively). CONCLUSION/CONCLUSIONS:Our findings support an association between alterations in the gut bacterial composition and cognitive dysfunction.
PMID: 35570486
ISSN: 1875-8908
CID: 5249152

Neighborhood Walkability and Mortality in a Prospective Cohort of Women

India-Aldana, Sandra; Rundle, Andrew G; Zeleniuch-Jacquotte, Anne; Quinn, James W; Kim, Byoungjun; Afanasyeva, Yelena; Clendenen, Tess V; Koenig, Karen L; Liu, Mengling; Neckerman, Kathryn M; Thorpe, Lorna E; Chen, Yu
BACKGROUND:There is a paucity of prospective cohort studies evaluating neighborhood walkability in relation to the risk of death. METHODS:We geocoded baseline residential addresses of 13,832 women in the New York University Women's Health Study (NYUWHS) and estimated the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) for each participant circa 1990. The participants were recruited from 1985 to 1991 in New York City and followed for an average of 27 years. We conducted survival analyses using Cox proportional hazards models to assess the association between neighborhood walkability and risk of death from any cause, obesity-related diseases, cardiometabolic diseases, and obesity-related cancers. RESULTS:Residing in a neighborhood with a higher neighborhood walkability score was associated with a lower mortality rate. Comparing women in the top versus the lowest walkability tertile, the hazards ratios (and 95% CIs) were 0.96 (0.93, 0.99) for all-cause, 0.91 (0.86, 0.97) for obesity-related disease, and 0.72 (0.62, 0.85) for obesity-related cancer mortality, respectively, adjusting for potential confounders at both the individual and neighborhood level. We found no association between neighborhood walkability and risk of death from cardiometabolic diseases. Results were similar in analyses censoring participants who moved during follow-up, using multiple imputation for missing covariates, and using propensity scores matching women with high and low neighborhood walkability on potential confounders. Exploratory analyses indicate that outdoor walking and average BMI mediated the association between neighborhood walkability and mortality. CONCLUSION:Our findings are consistent with a protective role of neighborhood walkability in obesity-related mortality in women, particularly obesity-related cancer mortality.
PMID: 34347687
ISSN: 1531-5487
CID: 5039302

Breast cancer risk factors and circulating anti-Müllerian hormone concentration in healthy premenopausal women

Clendenen, Tess V; Ge, Wenzhen; Koenig, Karen L; Afanasyeva, Yelena; Agnoli, Claudia; Bertone-Johnson, Elizabeth; Brinton, Louise A; Darvishian, Farbod; Dorgan, Joanne F; Eliassen, A Heather; Falk, Roni T; Hallmans, Göran; Hankinson, Susan E; Hoffman-Bolton, Judith; Key, Timothy J; Krogh, Vittorio; Nichols, Hazel B; Sandler, Dale P; Schoemaker, Minouk J; Sluss, Patrick M; Sund, Malin; Swerdlow, Anthony J; Visvanathan, Kala; Liu, Mengling; Zeleniuch-Jacquotte, Anne
CONTEXT/BACKGROUND:In a previous study we reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies. OBJECTIVE:Assess whether risk factors for breast cancer are correlates of AMH concentration. DESIGN/METHODS:Cross-sectional. PARTICIPANTS/METHODS:3831 healthy premenopausal women (aged 21-57, 87% aged 35-49). SETTING/METHODS:Ten cohort studies, general population. RESULTS:Adjusting for age and cohort, we observed positive associations of AMH with age at menarche (p<0.0001) and parity (p=0.0008), and an inverse association with hysterectomy/partial oophorectomy (p=0.0008). Compared to women of normal weight (BMI 18.5-24.9 kg/m 2, AMH was lower (relative geometric mean difference 27%, p<0.0001) among women who were obese (BMI>30). Current oral contraceptive use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, p<0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, p=0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40/≥40), associations of AMH with BMI and oral contraceptives were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (p-interaction<0.05). CONCLUSION/CONCLUSIONS:This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and suggests that most of the associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
PMID: 34157104
ISSN: 1945-7197
CID: 4918342

Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study

Koenig, Karen L; Scarmo, Stephanie; Afanasyeva, Yelena; Clendenen, Tess V; Ueland, Per Magne; Zeleniuch-Jacquotte, Anne
BACKGROUND/OBJECTIVES/OBJECTIVE:Folates found in natural foods are thought to protect against cancer. However, folic acid (FA), a synthetic form of folate used in supplements and fortified foods, may increase breast cancer risk if present in unmetabolized form (UMFA) in the circulation. This study examined the associations of serum UMFA and 5-methyltetrahydrofolate (5-mTHF), the predominant form of circulating folate, with breast cancer risk. SUBJECTS/METHODS/METHODS:We conducted a nested case-control study in a prospective cohort. In total, 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1059 controls. Serum UMFA and 5-mTHF were measured using liquid chromatography-tandem mass spectrometry in stored serum samples, and 5-mTHF was corrected for storage degradation. RESULTS: = 0.08). CONCLUSIONS:Circulating UMFA was not associated with breast cancer risk. These results apply to countries without mandatory FA food fortification. Studies are needed in countries with mandatory fortification, where levels of UMFA are much higher than in our study.
PMID: 32317749
ISSN: 1476-5640
CID: 4397082

Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model

Clendenen, Tess V; Ge, Wenzhen; Koenig, Karen L; Afanasyeva, Yelena; Agnoli, Claudia; Brinton, Louise A; Darvishian, Farbod; Dorgan, Joanne F; Eliassen, A Heather; Falk, Roni T; Hallmans, Göran; Hankinson, Susan E; Hoffman-Bolton, Judith; Key, Timothy J; Krogh, Vittorio; Nichols, Hazel B; Sandler, Dale P; Schoemaker, Minouk J; Sluss, Patrick M; Sund, Malin; Swerdlow, Anthony J; Visvanathan, Kala; Zeleniuch-Jacquotte, Anne; Liu, Mengling
BACKGROUND:Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50. METHODS:In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers. RESULTS:The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer. CONCLUSIONS:AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
PMID: 30890167
ISSN: 1465-542x
CID: 3735042

Circulating Anti-Mullerian Hormone and Breast Cancer Risk: A Study in Ten Prospective Cohorts

Ge, Wenzhen; Clendenen, Tess V; Afanasyeva, Yelena; Koenig, Karen L; Agnoli, Claudia; Brinton, Louise A; Dorgan, Joanne F; Eliassen, A Heather; Falk, Roni T; Hallmans, Göran; Hankinson, Susan E; Hoffman-Bolton, Judith; Key, Timothy J; Krogh, Vittorio; Nichols, Hazel B; Sandler, Dale P; Schoemaker, Minouk J; Sluss, Patrick M; Sund, Malin; Swerdlow, Anthony J; Visvanathan, Kala; Liu, Mengling; Zeleniuch-Jacquotte, Anne
A strong positive association has been observed between circulating anti-Mullerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles < 0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top versus bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4-Q1 = 1.96, 95% CI = 1.46-2.64, ptrend <0.0001; ER+/PR-: ORQ4-Q1 = 0.82, 95% CI = 0.40-1.68, ptrend = 0.51; ER-/PR+: ORQ4-Q1 = 3.23, 95% CI =0.48-21.9, ptrend = 0.26; ER-/PR-: ORQ4-Q1 = 1.15, 95% CI = 0.63-2.09, ptrend = 0.60. The association was observed for both pre- (ORQ4-Q1 = 1.35, 95% CI= 1.05-1.73) and post-menopausal (ORQ4-Q1 =1.61, 95% CI = 1.03 - 2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.
PMID: 29315564
ISSN: 1097-0215
CID: 2906472

Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study

Clendenen, Tess V; Hertzmark, Kathryn; Koenig, Karen L; Lundin, Eva; Rinaldi, Sabina; Johnson, Theron; Krogh, Vittorio; Hallmans, Goran; Idahl, Annika; Lukanova, Annekatrin; Zeleniuch-Jacquotte, Anne
Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; >/=55 years, n = 110 cases). Among women who were >/=55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged >/=55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.
PMID: 26925952
ISSN: 1868-8500
CID: 2009252

Serum Taurine and Stroke Risk in Women: A Prospective, Nested Case-Control Study

Wu, Fen; Koenig, Karen L; Zeleniuch-Jacquotte, Anne; Jonas, Saran; Afanasyeva, Yelena; Wojcik, Oktawia P; Costa, Max; Chen, Yu
BACKGROUND: Taurine (2-aminoethanesulfonic acid), a conditionally essential sulfur-containing amino acid, is mainly obtained from diet in humans. Experimental studies have shown that taurine's main biological actions include bile salt conjugation, blood pressure regulation, anti-oxidation, and anti-inflammation. METHODS: We conducted a prospective case-control study nested in the New York University Women's Health Study, a cohort study involving 14,274 women enrolled since 1985. Taurine was measured in pre-diagnostic serum samples of 241 stroke cases and 479 matched controls. RESULTS: There was no statistically significant association between serum taurine and stroke risk in the overall study population. The adjusted ORs for stroke were 1.0 (reference), 0.87 (95% CI, 0.59-1.28), and 1.03 (95% CI, 0.69-1.54) in increasing tertiles of taurine (64.3-126.6, 126.7-152.9, and 153.0-308.5 nmol/mL, respectively). A significant inverse association between serum taurine and stroke risk was observed among never smokers, with an adjusted OR of 0.66 (95% CI, 0.37-1.18) and 0.50 (95% CI, 0.26-0.94) for the second and third tertile, respectively (p for trend = 0.01), but not among past or current smokers (p for interaction < 0.01). CONCLUSIONS: We observed no overall association between serum taurine and stroke risk, although a protective effect was observed in never smokers, which requires further investigation. Taurine, Stroke, Epidemiology, Prospective, Case-control study, NYUWHS.
PMID: 26866594
ISSN: 1932-6203
CID: 1948722