scholarly journals Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

2018 ◽  
Vol 118 (11) ◽  
pp. 1940-1950 ◽  
Author(s):  
Nicholas Roetker ◽  
Richard MacLehose ◽  
Ron Hoogeveen ◽  
Christie Ballantyne ◽  
Saonli Basu ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Hormone Replacement ◽  
Plasma Concentrations ◽  
Cox Proportional Hazards ◽  
Sex Hormone Binding Globulin ◽  
Endogenous Hormones ◽  
Atherosclerosis Risk In Communities ◽  
Menopausal Women ◽  
Atherosclerosis Risk ◽  
Post Menopausal

AbstractExogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Abstract P012: Association Between Testosterone And Sex Hormone Binding Globulin And Risk Of Ischemic Stroke: The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Carin A Northuis ◽  
Erin Michos ◽  
Christie M Ballantyne ◽  
Ron C Hoogeveen ◽  
Pamela L Lutsey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Sex Hormones ◽  
Stroke Risk ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Atherosclerosis Risk In Communities ◽  
Menopausal Women ◽  
Atherosclerosis Risk ◽  
Post Menopausal

Background: Sex hormones are associated with obesity, diabetes mellitus, and other stroke risk factors; however, studies on sex hormones and stroke risk report inconsistent results. We assessed the associations of testosterone and sex hormone binding globulin (SHBG) with risk of ischemic stroke among men and post-menopausal women in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: A total of 4,349 men and 4,720 post-menopausal women who had SHBG and total testosterone measurements at visit 4 (1996-98) were followed through 2018 for the development of ischemic stroke. We examined log transformed SHBG and testosterone exposure as quartiles and as per 1 SD increment. We used Cox regression to estimate the hazard ratios (HR) for ischemic stroke, adjusting for demographic, behavioral and clinical variables. Analyses were stratified by sex and menopausal hormone therapy (HT) use. Results: Participants were aged 63±6 years at baseline, 52% were women (25% HT users), and 21% Black. There were 691 strokes over a median follow-up of 19.8 years. Mean log SHBG (nmol/L) and testosterone (nmol/L) were 4.3±0.7 and 3.1±0.5 for HT users, 3.6±0.7 and 3.2±0.5 for non-HT users, and 3.4±0.5 and 6.2±0.5 for men. Quartile 1 vs Q4 for SHBG and testosterone were ≤50.3 vs >121 and ≤16 vs >28 in HT users, ≤23.3 vs >55 and ≤17.9 vs >32.7 in non-HT users, and ≤23.3 vs >41.8 and ≤388 vs >657 in men. SHBG and testosterone were not significantly associated with stroke in any group (Figure). The HRs [95% confidence interval] for highest to lowest SHBG and testosterone quartiles were 1.04 [0.51-2.14] and 1.64 [0.85-3.17] in HT-users, 1.02 [0.70-1.48] and 1.16 [0.83-1.62] in HT non-users, and 0.96 [0.70-1.32] and 0.87 [0.63-1.21] in men, respectively. The HRs for stroke associated with 1 SD increase in SHBG and testosterone were 1.14 [0.88-1.46] and 1.19 [0.96-1.46] in HT users. Associations were also null among non-HT users and men. Conclusion: SHBG and testosterone were not associated with ischemic stroke risk in this cohort of older men and post-menopausal women.

Abstract MP75: Glycemia (Hemoglobin A1c) is Not Related to Incident Venous Thromboembolism in the Atherosclerosis Risk in Communities Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Elizabeth J Bell ◽  
Pamela L Lutsey ◽  
Vijay Nambi ◽  
Mary Cushman ◽  
Elizabeth Selvin ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Smoking Status ◽  
Cox Proportional Hazards ◽  
Self Report ◽  
Diabetes Diagnosis ◽  
Atherosclerosis Risk In Communities ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Diagnosed Diabetes

Introduction— Diabetes has been inconsistently associated with increased risk of venous thromboembolism (VTE). Glycemia is positively associated with coagulation activation and hypofibrinolysis, resulting in a procoagulant state. However, there is little direct evidence on associations of glycemia with VTE. Hypothesis— Glycemia, as measured by hemoglobin A 1c (A 1c ), is positively associated with incident VTE over a follow-up period of 15 years. Methods— The Atherosclerosis Risk in Communities (ARIC) study is a population-based cohort study of middle-aged adults followed for 15 years after visit 2, when A 1c was measured. Because A 1c is affected by treatment in diagnosed diabetics, separate analyses were conducted for individuals with diagnosed diabetes. Diagnosed diabetes was defined as taking diabetes medication or a history of diabetes (self-report). We assessed the relation between A 1c and incident VTE during follow-up using Cox proportional hazards models, controlling for potential confounders: age, sex, race, smoking status and amount, hormone use, body mass index, and waist-to-hip ratio. Results— The cohort free of VTE and/or anticoagulant use in 1990-1992 included 11,976 participants without a diagnosis of diabetes (317 VTE events) and 1,040 participants with a diagnosis of diabetes (45 VTE events). As shown in the figure, the adjusted hazard ratio estimates, using participants with an A 1c < 5.70 % and without diagnosed diabetes as the referent, were close to 1, regardless of A 1c level and diabetes diagnosis status. Further, there was no relation in analyses conducted by VTE type (provoked and unprovoked) or in participants with diabetes (both diagnosed and undiagnosed) relative to those without diabetes. Conclusions— In conclusion, although a modest association cannot be ruled out, our findings do not support an association between A 1c and VTE.

scholarly journals 1191Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K Reeves ◽  
Timothy J Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Proportional Hazards ◽  
Menopausal Status ◽  
Cox Proportional Hazards ◽  
Sex Hormone Binding Globulin ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. We investigated the associations between serum concentrations of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1) and oestradiol (pre-menopausal women only) and the risk of invasive breast cancer using data from UK Biobank. Methods We included 30,565 pre-menopausal and 133,294 post-menopausal women in this analysis. Hormone concentrations were measured in serum collected between 2006 and 2010, and incident cancer cases were identified through linkage to cancer and death registries. Multivariable Cox proportional hazards models were used, and hazard ratios (HRs) were corrected for regression dilution bias using repeat measures collected in about 5,000 women four years after recruitment (except for oestradiol). Results During a median follow-up of 7.1 years, 527 pre-menopausal and 2,997 post-menopausal women were diagnosed with invasive breast cancer. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in premenopausal women (pheterogeneity=0.03), and with IGF-1 (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity=0.2), and inversely associated with SHBG (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity=0.4). Oestradiol was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone. Key messages Breast cancer risk was positively associated with testosterone and inversely associated with SHBG in post-menopausal women, and positively associated with IGF-1 in both pre- and post-menopausal women.

Oestrogens, gonadotrophins and SHBG during oral and cutaneous administration of oestradiol-17β to menopausal women

1982 ◽  
Vol 101 (4) ◽  
pp. 592-596 ◽  
Author(s):  
Lars Fåhraeus ◽  
Ulf Larsson-Cohn
Keyword(s):  
Plasma Concentrations ◽  
Sex Hormone Binding Globulin ◽  
Clinical Effects ◽  
Routes Of Administration ◽  
Menopausal Women ◽  
Before And After ◽  
The Mean ◽  
Post Menopausal ◽  
Cutaneous Administration ◽  
The Given

Abstract. Thirty-eight post-menopausal women were randomly allocated to 6 months of treatment with either 2–4 mg of micronized oestradiol-17β taken orally or 3 mg of oestradiol-17β applied cutaneously. The plasma concentrations of oestrone, oestradiol, LH, FSH and sex hormone binding globulin (SHBG) were determined twice before and after 2,4 and 6 months of treatment. In both groups the clinical effects were satisfactory. During treatment the mean oestradiol levels showed similar increases in the two groups while the oestrone concentration was markedly raised only among those taking oestradiol orally. The mean LH and FSH concentrations were significantly lowered in both groups. SHBG was increased with both treatments although more marked in the group on oral medication. Doubling of the oral dose from 2 mg to 4 mg gave significant changes of the LH, FSH and oestrone concentrations. Thus, in the given doses, the two routes of administration seemed to have similar effects on post-menopausal symptoms and on the plasma concentrations of gonadotrophins and oestradiol. However the plasma oestrone and SHBG levels became significantly higher during the oral than during the cutaneous treatment.

Abstract 020: NT-proBNP, hs-Troponin T and Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Pamela L Lutsey ◽  
Vijay Nambi ◽  
Mary Cushman ◽  
Susan R Heckbert ◽  
Christopher R DeFilippi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Proportional Hazards ◽  
General Trend ◽  
Troponin T ◽  
Volume Overload ◽  
Race Model ◽  
Cox Proportional Hazards ◽  
Atherosclerosis Risk In Communities ◽  
Diabetes Status ◽  
Atherosclerosis Risk

Background: NT-pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (TnT) are important biomarkers for CHD and HF risk, but whether they are related to incidence of venous thromboembolism (VTE) is unknown. NT-proBNP is a marker of volume overload; volume overload may contribute to VTE risk via increased stasis and thrombogenesis. TnT might relate to VTE indirectly, as a marker of vascular inflammation or endothelial dysfunction. Hypotheses: NT-proBNP and TnT are associated positively with risk of incident VTE. Methods: Data from visit 4 (1996-1998) of the prospective population-based Atherosclerosis Risk in Communities study (n = 10,735; 53-74 yrs) were used. VTE events through 2005 were identified and validated by medical record review. Cox proportional hazards regression was used to explore the relation between the biomarkers and VTE. Model 1 adjusted for age, sex, and race. Model 2 additionally adjusted for HRT use, diabetes status, BMI, eGFR, CRP, aPTT and factor VIII. Results: A total of 227 incident VTE cases accrued over a median follow-up of 8.0 yrs. Relative to participants in the lowest quintile of NT-proBNP (≤26.7 pg/mL), those in the highest quintile (≥151.3 pg/mL) were at 2.28 (95% CI: 1.47-3.54) times greater risk of incident VTE (p-trend = 0.0002), adjusted via Model 1. This association was only slightly attenuated after adjustment in Model 2 [HR: 1.98 (95% CI: 1.25, 3.13); p-trend = 0.003]. The general trend was present for both unprovoked [HR: 1.62 (95% CI: 0.70, 3.75)] and provoked VTE [HR: 2.22 (95% CI: 1.28, 3.84)] in the fully-adjusted models, though power was low when stratifying by VTE type. Participants in the highest category (≥0.014 ug/L) of TnT were also at modestly greater risk of incident VTE in Model 1 [HR: 1.99 (95% CI: 1.23, 3.21); p-trend = 0.0002] and Model 2 [HR: 1.52 (95% CI: 0.89, 2.60); p-trend = 0.03], relative to those with undetectable TnT. The association was, however, present for only provoked VTE, with no evidence of a relation for unprovoked VTE. Discussion: In this large prospective cohort, both NT-proBNP and TnT were positively associated with risk of incident VTE. For NT-proBNP, the general trend was present for both provoked and unprovoked events, while for TnT the relation was isolated to provoked VTE events. Additional research is warranted to evaluate whether NT-proBNP and TnT are related to risk of VTE, or if the associations observed were the result of uncontrolled confounding.

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

RADIOIMMUNOASSAY FOR 2-METHOXYOESTRONE IN HUMAN PLASMA

1979 ◽  
Vol 91 (1) ◽  
pp. 158-166 ◽  
Author(s):  
Günter Emons ◽  
Peter Ball ◽  
Gertrud v. Postel ◽  
Rudolf Knuppen
Keyword(s):  
Human Plasma ◽  
Plasma Concentrations ◽  
Cross Reactivity ◽  
Elderly Men ◽  
Specific Antibodies ◽  
Assay Procedure ◽  
Menopausal Women ◽  
Bovine Serum Albumin Conjugate ◽  
Post Menopausal

ABSTRACT A bovine serum albumin conjugate of 2-methoxyoestrone was used for the preparation of highly specific antibodies in rabbits. Cross-reactivity for catecholoestrogens and monophenolic steroids was below 0.3 %. Only 2-methoxyoestradiol cross-reacted with 44 %. An assay procedure for the determination of unconjugated and conjugated 2-methoxyoestrone in human plasma is described. The following mean plasma concentrations (pg/ml) were found (unconjugated/conjugated): children 61/1130, young men 74/1320, elderly men 109/1260, cycling women 131/1040, post-menopausal women 102/1420, and pregnant women 3980/5850.

Abstract 47: Atrial Fibrillation is Associated With Increased Risk of Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Pamela L Lutsey ◽  
Faye L Norby ◽  
Alvaro Alonso ◽  
Mary Cushman ◽  
Lin Y Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Case Reports ◽  
Time Dependent ◽  
Atherosclerosis Risk In Communities ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Shared Risk

Background: It is well-established that atrial fibrillation (AF) is associated with thrombus formation in the left atrium, which can lead to ischemic stroke. Case reports, autopsies, and transesophageal echo data have indicated that clot formation also occurs in the right atrium (i.e. right-side intracardiac thrombosis) of AF patients, which could lead to pulmonary embolism (PE). However, it is unclear whether this occurrence is common. Objective: Test the hypotheses that individuals with incident AF are at elevated risk of developing venous thromboembolism (VTE), and that the association will be stronger for those presenting with PE alone versus PE and deep vein thrombosis (DVT) or DVT alone. Methods: A total of 15,205 Atherosclerosis Risk in Communities (ARIC) study participants, aged 45-64 years, were followed from baseline (1987-1989) to 2011 for incidence of AF and VTE (median follow-up 19.8 years). Incident AF and VTE events were identified via active surveillance and defined by relevant hospital discharge ICD codes. VTE events were validated by medical record review. Multivariable-adjusted Cox proportional hazards regression models were used, with AF modeled as a time-dependent covariate. We also evaluated separately risk of PE without evidence of DVT, DVT without PE, and events presenting with both PE and DVT. Results: At baseline participants were on average 54 years old, 55% female and 26% black. In the absence of AF there were 678 VTE events, for an incidence rate of 2.6 per 1000 person-years. After an AF diagnosis there were 77 events, with an incidence rate of 7.1 per 1000 person-years. In multivariable-adjusted models, having AF (versus no AF) was associated with a greater risk of incident VTE; the HR (95% CI) was 2.10 (1.65-2.68) after adjustment for demographics, 1.82 (1.42-2.32) additionally accounting for numerous AF and VTE risk factors, and 1.97 (1.53-2.53) after further adjusting for time-dependent anticoagulant use. When we restricted to PE events without evidence of DVT there were 188 events in total, of which 19 occurred following a diagnosis of AF. The HR for AF (versus no AF) was 1.53 (0.92-2.56) in fully adjusted models. For DVT alone there were 384 events in total, of which 48 occurred after AF diagnosis; the HR for AF was 2.43 (1.77-3.33). Among the 116 events presenting with both DVT and PE, 10 occurred after AF diagnosis, and the HR for AF was 1.36 (0.67-2.75). Conclusions: Diagnosis with AF was associated with a nearly 2-fold increased risk of incident VTE. The association was not stronger when isolated to those with PE without DVT, suggesting that higher risk of VTE among AF patients may be due to either the coagulation abnormalities that accompany AF, or shared risk factors that were not fully accounted for in this analysis.

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