Circulating Sex Hormone Levels and Risk of Esophageal... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ARTICLE: Esophagus

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

Xie, Shao-Hua BMed, PhD1; Ness-Jensen, Eivind MD, PhD1,2,3; Rabbani, Sirus PhD1; Langseth, Hilde MSc, PhD4; Gislefoss, Randi E. MSc, PhD4; Mattsson, Fredrik BSc1; Lagergren, Jesper MD, PhD1,5

1Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;

2HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway;

3Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway;

4Cancer Registry of Norway, Institute of Population-based Cancer Research, Department of Research, Oslo, Norway;

5School of Cancer and Pharmaceutical Sciences, King's College London, the United Kingdom.

Correspondence: Shao-Hua Xie, BMed, PhD. E-mail: [email protected].

SUPPLEMENTARY MATERIAL accompanies this paper at https://links.lww.com/AJG/B308

Abstract

OBJECTIVES:

Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma.

METHODS:

This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones.

RESULTS:

Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22–0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19–0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30–0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR = 0.56, 95% CI 0.27–1.13 for testosterone; OR = 0.46, 95% CI 0.23–0.91 for testosterone:estradiol ratio; OR = 0.55, 95% CI 0.29–1.08 for luteinizing hormone). No associations were observed for sex hormone–binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OH progesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest vs lowest quartile = 0.60, 95% CI 0.38–0.97), whereas no associations were identified for androstenedione, sex hormone–binding globulin, estradiol, or testosterone:estradiol ratio.

DISCUSSION:

Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.