Endogenous sex hormones and colorectal cancer survival among men and women.
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ABSTRACT:
SUBMITTER: Yang W
PROVIDER: S-EPMC7895324 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Project description:Breast density is a strong risk factor for breast cancer and reflects epithelial and stromal content. Breast tissue is particularly sensitive to hormonal stimuli before it fully differentiates following the first full-term pregnancy. Few studies have examined associations between sex hormones and breast density among young women.We conducted a cross-sectional study among 180 women ages 25 to 29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-up Study. Eighty-five percent of participants attended a clinic visit during their luteal phase of menstrual cycle. Magnetic resonance imaging measured the percentage of dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple-linear mixed-effect regression models were used to evaluate the association of sex hormones and sex hormone-binding globulin (SHBG) with %DBV, ADBV, and ANDBV.Testosterone was significantly positively associated with %DBV and ADBV. The multivariable geometric mean of %DBV and ADBV across testosterone quartiles increased from 16.5% to 20.3% and from 68.6 to 82.3 cm(3), respectively (Ptrend ? 0.03). There was no association of %DBV or ADBV with estrogens, progesterone, non-SHBG-bound testosterone, or SHBG (Ptrend ? 0.27). Neither sex hormones nor SHBG was associated with ANDBV except progesterone; however, the progesterone result was nonsignificant in analysis restricted to women in the luteal phase.These findings suggest a modest positive association between testosterone and breast density in young women.Hormonal influences at critical periods may contribute to morphologic differences in the breast associated with breast cancer risk later in life.
| S-EPMC4323882 | biostudies-literature
Project description:Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [β = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women <65 years of age, but not in those ≥65 years (p = 0.04). We did not see similar associations in men. Conclusions: A more androgenic SH profile of higher free testosterone and lower SHBG was associated with worse %FMD in postmenopausal women. Changes in SH with aging and menopause may result in vascular changes in women. Further studies are needed to assess longitudinal changes in SH levels and their association with vascular function.
| S-EPMC6645200 | biostudies-literature
Project description:Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone-binding globulin (SHBG) with biomarkers of inflammation, C-reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999-2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, -0.18; p-trend, 0.001) and calculated free (slope, -0.13; p-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (?3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (?3 mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2: slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, -0.03; p-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti-inflammatory effect in men.
| S-EPMC3812341 | biostudies-literature
Project description:BACKGROUND:Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results. OBJECTIVES:The authors assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline. METHODS:The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use. RESULTS:The mean age was 64.9 ± 8.9 years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the hazard ratio (95% confidence interval [CI]) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes. CONCLUSIONS:Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women's increased CVD risk later in life.
| S-EPMC5986086 | biostudies-literature
Project description:BackgroundThe risk of venous thromboembolism (VTE) in young women can predominantly be attributed to exogenous hormone use. The influence of (abnormalities in) endogenous sex hormones, as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI), on VTE risk is uncertain.ObjectivesTh assess the association between endogenous sex hormone levels and VTE risk.MethodsWomen aged ?45 years from the MEGA case-control study who provided a blood sample in the absence of exogenous hormone exposure or pregnancy were included. Sex hormone-binding globulin (SHBG), estradiol, follicle-stimulating hormone (FSH) and testosterone were measured. The free androgen index (FAI) and estradiol to testosterone ratio (E:T) were calculated. VTE risk was assessed according to quartiles (Qs) of levels and clinical cut-offs as proxies for PCOS (FAI > 4.5) and POI (FSH > 40 U/L). Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs).ResultsSix hundred and sixty-five women (369 cases; 296 controls) were eligible for the analyses. Testosterone and FSH levels, E:T and POI (FSH > 40 U/L vs FSH ? 40 U/L) were not associated with VTE risk. For estradiol, VTE risk was increased with levels in Q4 vs Q1 (OR 1.6; 95% CI 1.0-2.5). There was a dose-response relationship between SHBG levels and VTE risk, with the highest OR at Q4 vs Q1: 2.0 (95% CI 1.2-3.3). FAI > 4.5 (PCOS proxy) vs FAI ? 4.5 was associated with increased VTE risk (OR 3.3; 95% CI 0.9-11.8).ConclusionsEstradiol, SHBG and FAI were associated with VTE risk, suggesting a role for endogenous sex hormones in the pathophysiology of VTE in young women.
| S-EPMC6852478 | biostudies-literature
Project description:Sex hormones, adipokines, and ghrelin have been implicated in central control of appetite, energy homeostasis, maintenance of fat mass, and inflammation. Women tend to gain weight after menopause and adipose tissue is a major source of sex steroid postmenopause. Understanding the dynamics of these analytes are of particular importance in postmenopausal women, who are at greater risk for cardiometabolic diseases.This study sought to evaluate the associations of adipokines and ghrelin with sex hormone concentrations in postmenopausal women.We conducted a cross-sectional analysis of baseline clinical trial data.The parent trial was conducted at a university clinical research facility.Baseline data from 634 postmenopausal women participating in the Early vs Late Intervention Trial with Estradiol (ELITE). PARTICIPANTS had no history of chronic illness in the past 5 years and were not taking exogenous hormone therapy.Serum levels of estrone (E1), total estradiol (E2), free estradiol (FE2), free testosterone (FT), total testosterone (T), and sex hormone-binding globulin (SHBG).Adjusted for age, race, time since menopause, and body mass index (BMI), leptin concentrations were significantly positively associated with E1, E2, FE2, and FT and inversely associated with SHBG levels. Only the associations of adiponectin with FE2 (inverse) and SHBG (positive) remained significant after controlling for BMI. The inverse associations of adiponectin with E1, E2, and FT were substantially mediated by BMI. Associations of ghrelin with E1, E2, FE2, and SHBG were not independent of BMI. Waist-to-hip circumference ratio was not a mediator in any of the associations.In postmenopausal women, leptin and adiponectin concentrations are substantially correlated with sex hormone and SHBG concentrations regardless of obesity status.
| S-EPMC4318897 | biostudies-literature
Project description:BackgroundSex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown.MethodsWe retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P?<?0.005 was considered statistically significant.ResultsDuring 20?years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend <?0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (??10?mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend?=?0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend?=?0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend?=?0.03, respectively).ConclusionsThe findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.
| S-EPMC7841996 | biostudies-literature
Project description:Sex steroid hormone concentrations and insulin-like growth factor (IGF) proteins have been independently associated with risk of cancer, chronic diseases, and mortality. However, studies that evaluated the inter-relation between the sex hormones and IGF pathways have provided mixed results. We examined the association between endogenous sex hormones and sex hormone-binding globulin (SHBG) with IGF-1 and IGF-binding protein 3 (IGFBP-3) in a population-based sample of US men.Data from 1,135 men aged 20 years or older participating in the third National Health and Nutrition Examination Survey (NHANES III) were analyzed. Weighted linear regression was used to estimate geometric means and 95 % confidence intervals for IGF-1 and IGFBP-3 concentrations by sex steroid hormones and SHBG after adjusting for age, race/ethnicity, body mass index, waist circumference, alcohol consumption, cigarette smoking, physical activity, diabetes, and mutually adjusting for other sex hormones and SHBG.No significant association was observed between sex steroid hormones, SHBG, and IGF-1 concentrations. Total estradiol (% difference in Q5 - Q1 geometric means -9.7 %; P-trend 0.05) and SHBG (% difference -7.3 %; P-trend 0.02) were modestly inversely associated with IGFBP-3. Total testosterone was modestly inversely associated with IGFBP-3 (% difference -6.2 %; P-trend 0.01), but this association disappeared after adjustment for total estradiol and SHBG (% difference 2.6 %; P-trend 0.23). Androstanediol glucuronide was not associated with IGFBP-3.These findings suggest that there may be inter-relationships between circulating total estradiol, SHBG, and IGFBP-3 concentrations. Future research may consider these inter-relationships when evaluating potential joint effects of the sex hormones and IGF pathways.
| S-EPMC4332790 | biostudies-other
Project description:BackgroundPostmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.MethodsThe relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided.ResultsComparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend = .001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ? .0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend = .08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ? .0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend < .0001). Progesterone was not associated with colorectal cancer risk.ConclusionEndogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.
| S-EPMC5964717 | biostudies-literature
Project description:To determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife.249 Pre- or early peri-menopausal women (42-57 years) from the Study of Women's Health Across the Nation (SWAN) were followed for up to 9 years (median = 3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity.In final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression (P = 0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression (P = 0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression (P = 0.003). T and SHBG were not associated with progression or level of AD.Independent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife.
| S-EPMC3478422 | biostudies-literature