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Interaction of gonadal status with systemic inflammation and opioid use in determining nutritional status and prognosis in advanced pancreatic cancer

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Abstract

Purpose

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.

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Acknowledgements

R. J. E. S. performed data collation and data analysis. A. G. W. M., A. C. V. and J. A. R. were involved in conception of the study, patient recruitment and acquisition of data. K. S., C. M. S. and J. S. performed experimental analysis of volunteer blood. M. T. F. and R. A. A. were involved in data analysis. K. C. H. F. was chief investigator for the study. All authors were involved in manuscript preparation. We thank the Cancer Cachexia Study Group for their help in collecting the original data set: D. Gouma, R. van Geenen, N. Aaronson, M. Tisdale, P. Kind, A. Roy, P. Price, A. Giacosa, A. Makin, A. Siriwardena, B. Rolls, S. Ash, W. Davidson, S. Capra, D. Ataya, M. Ferguson, W. MacLean, K. Mayer, K. Ried, A. Wennberg, M. Barber, R. Richardson, B. Jones, T. Preston, M. McMahon, M. Larvin, J. Bauer, I. Martin, M. von Meyenfeldt, J. Maessen and A. van Gossum.

R. J. E. S. was supported by the Maurice Wohl Fellowship in Surgery from the Royal College of Surgeons of Edinburgh.

Conflict of interest statement

There are no conflicts of interest.

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Authors and Affiliations

  1. Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK

    Richard J. E. Skipworth, Alastair G. W. Moses, Kathryn Sangster, James A. Ross & Kenneth C. H. Fearon

  2. Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK

    Catharine M. Sturgeon

  3. Abbott Nutrition Research and Development, Abbott Laboratories, 625 Cleveland Avenue, Columbus, OH, 43215-1724, USA

    Anne C. Voss

  4. Department of Palliative Medicine, Edinburgh Cancer Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XR, UK

    Marie T. Fallon

  5. Division of Reproductive and Developmental Science, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

    Richard A. Anderson

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  1. Richard J. E. Skipworth
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  2. Alastair G. W. Moses
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  9. Kenneth C. H. Fearon
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Correspondence to Kenneth C. H. Fearon.

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Skipworth, R.J.E., Moses, A.G.W., Sangster, K. et al. Interaction of gonadal status with systemic inflammation and opioid use in determining nutritional status and prognosis in advanced pancreatic cancer. Support Care Cancer 19, 391–401 (2011). https://doi.org/10.1007/s00520-010-0832-y

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  • DOI: https://doi.org/10.1007/s00520-010-0832-y

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