Background: Cancer-related fatigue is a common symptom in patients with renal cell carcinoma (RCC) and can be similar to the fatigue found in late-onset hypogonadism (LOH). The aim of this study was to investigate the prevalence of LOH in patients with localized RCC (loRCC) and metastatic RCC (mRCC) disease under targeted therapy (TT) and compare the results to findings of epidemiologic studies. Methods: A total of 51 mRCC patients under TT and 33 patients with loRCC undergoing nephrectomy were included. Total testosterone (tT) levels and clinical signs of LOH were recorded (testicular volume, body-mass index (BMI), hip-to-waist ratio, International Index of Erectile Function, IIEF-5, Androgen Deficiency in the Aging Male, ADAM, and quality of life questionnaire-C30). LOH was defined according to current guidelines. Results: Morning tT and calculated free testosterone levels showed no significant difference in patients with mRCC and loRCC (p = 0.551 and p = 0.430). A significant difference was found for clinical signs and symptoms including the ADAM score (p = 0.003), hip-to-waist ratio (p = 0.017) and testicular volume (p < 0.001). IIEF-5 score and BMI were not significantly different. The prevalence of LOH according to the current EAU definition was 13.7 and 15.2% for the mRCC and loRCC cohort, respectively (p = 0.302). Conclusions: LOH was present in a significant proportion of RCC patients. Prevalence rates of LOH were higher in patients with RCC compared to patients without cancer.

Keywords:
Metastasis, Hypogonadism, Testosterone deficiency, Fatigue syndrome, Metastatic renal cell carcinoma, Targeted therapy
1.
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, et al: Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013;369:722-731.
2.
Lindblad P: Epidemiology of renal cell carcinoma. Scan J Surg 2004;93:88-96.
3.
Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C: Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 2008;34:193-205.
4.
Mills EJ, Rachlis B, O'Regan C, Thabane L, Perri D: Metastatic renal cell cancer treatments: an indirect comparison meta-analysis. BMC Cancer 2009;9:34.
5.
Thompson Coon JS, Liu Z, Hoyle M, Rogers G, Green C, Moxham T, Welch K, Stein K: Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma: a systematic review and indirect comparison of clinical effectiveness. Br J Cancer 2009;101:238-243.
6.
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, et al: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115-124.
7.
Mock V, Atkinson A, Barsevick A, Cella D, Cimprich B, Cleeland C, Donnelly J, Eisenberger MA, Escalante C, Hinds P, et al: NCCN practice guidelines for cancer-related fatigue. Oncology (Williston Park) 2000;14:151-161.
8.
Curt GA: Impact of fatigue on quality of life in oncology patients. Semin Hematol 2000;37(4 suppl 6):14-17.
9.
Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, McKinlay JB: Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab 2008;93:3870-3877.
10.
Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, et al: Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363:123-135.
11.
Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S, Punab M: Guidelines on Male Hypogonadism. EAU Guidelines, 2015.
12.
Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, et al: Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 2009;55:121-130.
13.
Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB: Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2004;89:5920-5926.
14.
Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C: Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006;60:762-769.
15.
Vermeulen A, Verdonck L, Kaufman JM: A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666-3672.
16.
Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P, McCready D, Perry HM 3rd: Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000;49:1239-1242.
17.
Zarotsky V, Huang MY, Carman W, Morgentaler A, Singhal PK, Coffin D, Jones TH: Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men. Andrology 2014;2:819-834.
18.
Afshar M, Clarke H, Porfiri E: Hypogonadism in men treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) as a clinical biomarker of response. J Clin Oncol 2014;32.e15610.
19.
Wolter P, Wildiers H, Vanderschueren D, Dumez H, Clement P, Schoffski P: Hypogonadism in Male Cancer Patients Treated with the Tyrosine Kinase Inhibitors Sunitinib (SUN) or Sorafenib (SOR). ASCO Annual Meeting Proceedings, 2009, p 3565.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.