title: Interaction of gonadal status with systemic inflammation and opioid use in determining nutritional status and prognosis in advanced pancreatic cancer.
abstract: OBJECTIVE
  Hypogonadism has been linked with systemic inflammation and opioid use in males with advanced cancer. We aimed to investigate the interaction of gonadal status with systemic inflammation and opioids in determining nutritional status and prognosis in advanced pancreatic cancer.
  
  
  METHODS
  One hundred and seventy-five patients (92 males, 83 postmenopausal females) with unresectable pancreatic cancer were studied. Serum sex steroids (total testosterone [TT], calculated free testosterone [cFT], oestradiol, sex hormone binding globulin), gonadotropins (follicle-stimulating hormone and luteinising hormone) and pro-inflammatory mediators (C-reactive protein [CRP], interleukin-6 [IL-6], soluble tumour necrosis factor receptor 75 [sTNFR75]) were measured, and nutritional assessment and opioid use recorded.
  
  
  RESULTS
  Seventy-three percent of males were hypogonadal (by cFT definition). cFT correlated positively with BMI (r (2) =0.349; p< 0.001) and grip strength (r (2) = 0.229; p = 0.034) and inversely with weight loss (r (2) = -0.287; p = 0.007), CRP (r (2) = -0.426; p < 0.001) and IL-6 (r (2) = -0.303; p = 0.004). CRP (p= 0.007), opioid dosage (p = 0.009) and BMI (p = 0.005) were independent determinants of cFT on ANOVA. Hypogonadal males demonstrated worsened survival compared with eugonadal patients (TT: OR of death = 2.87; p < 0.001; cFT: OR = 2.26; p = 0.011). Furthermore, male opioid use was associated with decreased TT (p < 0.001) and cFT (p < 0.001) and worsened survival (OR = 1.96; p = 0.012). In contrast, 18% of postmenopausal females exhibited premenopausal ("hyperoestrogenic") oestradiol levels. Oestradiol correlated positively with sTNFR75 (r (2) = 0.299; p = 0.008). CRP (p < 0.001) was an independent determinant of oestradiol. Hyperoestrogenic females demonstrated worsened survival compared with eugonadal patients (OR = 2.43; p = 0.013).
  
  
  CONCLUSIONS
  In males with pancreatic cancer, systemic inflammation and opioid use are associated with hypogonadism. Male hypogonadism and female hyperoestrogenism are associated with shortened survival in advanced pancreatic cancer.
authors.affiliation: Clinical and Surgical Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK.
authors.forename: Richard J E
authors.initials: RJ
authors.lastname: Skipworth
authors.forename: Alastair G W
authors.initials: AG
authors.lastname: Moses
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sangster
authors.forename: Catharine M
authors.initials: CM
authors.lastname: Sturgeon
authors.forename: Anne C
authors.initials: AC
authors.lastname: Voss
authors.forename: Marie T
authors.initials: MT
authors.lastname: Fallon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000150:complications*; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D017698:Postmenopause; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000701:Analgesics, Opioid; D004958:Estradiol