Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men

Xie, Shao-Hua; Ness-Jensen, Eivind; Rabbani, Sirus; Langseth, Hilde; Gislefoss, Randi Elin; Mattsson, Fredrik; Lagergren, Jesper

doi:10.14309/ajg.0000000000000446

Cited by 23 publications

(21 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, there have been just two prospective studies of prediagnostic circulating sex hormones and risk of upper gastrointestinal cancers. Combined, these studies provide evidence for an inverse association between endogenous circulating testosterone and esophageal adenocarcinoma risk (13,14), but there was less evidence for inverse associations of estradiol, luteinizing hormone (LH), and dehydroepiandrosterone (DHEA) with esophageal adenocarcinoma (15). Meanwhile, no study has specifically investigated risk of esophageal squamous cell carcinoma or gastric cancer with respect to prediagnostic circulating sex hormones.…”

Section: Introductionmentioning

confidence: 99%

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank

McMenamin

Kunzmann

et al. 2020

Am J Gastroenterol

View full text Add to dashboard Cite

INTRODUCTION: Gastrointestinal cancers show an unexplained male predominance, but few prospective studies have investigated sex hormones and gastrointestinal cancer risk. This study aimed to determine the impact of circulating sex hormones on risk of esophageal, gastric, and colorectal cancers in men and women. METHODS: We included 219,425 men and 147,180 women from the UK Biobank. Sex hormones were quantified using chemiluminescent immunoassay. Gastrointestinal cancers were identified from cancer registry linkages. Sex hormone concentrations and risk of gastrointestinal cancers were investigated using Cox proportional hazards regression. RESULTS: During the 10 years of follow-up, 376 esophageal adenocarcinoma, 108 esophageal squamous cell carcinoma, and 333 gastric and 2,868 colorectal cancer cases were identified. Increased hazard ratios (HRs) were found for sex hormone–binding globulin (SHBG) and risk of gastric cancer in men (Q4 vs Q1 HR 1.43, 95% confidence interval [CI] 0.95–2.17, Ptrend = 0.01). Free testosterone was inversely associated with esophageal squamous cell carcinoma in women (Q4 vs Q1 HR 0.32, 95% CI 0.11–0.98, Ptrend = 0.05). For colorectal cancer, SHBG was associated with a reduced risk among men (Q4 vs Q1 HR 0.89, 95% CI 0.77–1.03, Ptrend = 0.04) and free testosterone concentrations was associated with a reduction in risk among women (Q4 vs Q1 HR 0.80, 95% CI 0.66–0.97, Ptrend = 0.01). No associations were found for esophageal adenocarcinoma. DISCUSSION: In this large prospective investigation of prediagnostic sex hormones and risk of gastrointestinal cancers, men with higher SHBG concentrations had higher gastric, yet lower colorectal, cancer risks, whereas women with higher free testosterone levels had a lower risk of esophageal squamous cell carcinoma and colorectal cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank

McMenamin

Kunzmann

et al. 2020

Am J Gastroenterol

View full text Add to dashboard Cite

show abstract

“…[19][20][21][22] We evaluated the following 12 sex hormone measures in serum samples: sex hormone-binding globulin (SHBG); the nine steroid sex hormones dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol and androstenedione; and finally calculated free testosterone index (testosterone × 10/SHBG) and testosterone:estradiol ratio. These hormone measures cover key points in the biosynthesis of sex hormones, 7,11,23 and are at detectable levels in serum in men with the available analytic methods.…”

Section: Hormone Level Exposuresmentioning

confidence: 99%

“…This striking male predominance may be explained by the differences in endogenous sex hormonal levels between the sexes 1,6 . Recent studies have reported associations between circulating sex hormone levels and the risk of developing EAC and its precursor Barrett's esophagus 7‐11 . Any procarcinogenic or anticarcinogenic effects of certain sex hormones could potentially influence treatment efficacy and risk of tumor recurrence after treatment of EAC.…”

Section: Introductionmentioning

confidence: 99%

Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma

Xie

Ness-Jensen

Langseth

et al. 2020

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.

show abstract

“…Testosterone plays a critical role in the metabolism of proteins, carbohydrates, and fat; therefore, de ciency can contribute to the development of functional disorders throughout the body [16]. Previous studies have reported the high incidence of testosterone de ciency among critically ill patients with condition such as myocardial infarction, acute respiratory failure, and esophageal adenocarcinoma [17][18][19]. Recent data have demonstrated that, among men with end-stage liver disease, low testosterone is associated with an increased risk of mortality regardless of the etiology of disease [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Low Testosterone Levels Predict Increasing Severity and Worse Outcomes of Hepatitis B Virus-related Acute-on-chronic Liver Failure in Males

Huang

Dong

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is more prevalent among males than females and has a high rate of short-term mortality, and low serum testosterone has been prevalent in critical illness such as acute respiratory failure and cirrhosis, we investigated the association between testosterone level and severity of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) in males remains unknown.MethodsThis single-center observational study involved patients with HBV-ACLF planned to undergo treatment with an artificial liver support system. Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. We assessed the relationships between androgen levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF.ResultsAmong 160 male subjects, 32 had early stage HBV-ACLF, 61 middle stage, and 67 end stage. Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among subjects than chronic hepatitis B patients and healthy controls, while androstenedione was higher. Low TT, SHBG, FTI and high androstenedione were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (<142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be a predictor for the composite outcome independent of age, BMI, SHBG, FTI, cortisol, and androstenedione.ConclusionLow serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease.

show abstract

Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men

Cited by 23 publications

References 27 publications

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank

Circulating Sex Hormones Are Associated With Gastric and Colorectal Cancers but Not Esophageal Adenocarcinoma in the UK Biobank

Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma

Low Testosterone Levels Predict Increasing Severity and Worse Outcomes of Hepatitis B Virus-related Acute-on-chronic Liver Failure in Males

Contact Info

Product

Resources

About