Abstract
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.
Highlights
In analyses stratified by surgery, higher sex hormone-binding globulin (SHBG) levels were associated with decreased disease-specific mortality in nonoperated patients, while no such decrease was found in operated patients (Table 3)
Higher SHBG levels were associated with decreased all-cause mortality in esophageal adenocarcinoma (EAC) patients
Our study indicated an increased disease-specific mortality with lower SHBG levels and higher follicle-stimulating hormone (FSH) levels in male EAC patients without surgical treatment
Summary
Predominant histologic type of esophageal malignancy in many Western countries.[1] The overall 5-year survival rate in EAC is below 20%, with tumor stage at diagnosis as the strongest prognostic factor.[1,2,3,4] Surgical resection (esophagectomy) alone or combined with chemotherapy or chemoradiotherapy is the main curative treatment in most patients.[2]. Studies have found expression of sex hormone receptors in EAC and correlations between the status of estrogen receptor beta and more advanced tumor stage at EAC diagnosis.[12,13] Yet, no study has far examined whether endogenous sex hormone levels influence the survival in EAC patients.
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