Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

Keywords:
Estrogen, Liver cancer, Sex hormone binding globulin, Testosterone
1.
Wilson JD, Foster DW, Kronenberg HM, Larsen PR: Williams Textbook of Endocrinology, ed 9. Philadelphia, Saunders, 1999, p 846.
2.
Madersbacher S, Grunberger T, Maier U: Andrological status before and after liver transplantation. J Urol 1994;151:1251–1254.
3.
Madersbacher S, Ludvik G, Stulnig T, Grunberger T: The impact of liver transplantation on endocrine status in men. Clin Endocrinol 1996;44:461–466.
4.
Lampropoulou-Karatzas C, Goritsas P, Makri MG: Low serum testosterone: A special feature of hepatocellular carcinoma. Eur J Med 1993;2:23–27.
5.
Kew MC, Kirschner MA, Abrahams GE, Katz M: Mechanism of feminization in primary liver cancer. N Engl J Med 1977;296:1084–1088.
6.
Aabo K, Dimitrov NV: Feminization in hepatocellular carcinoma corrected by chemotherapy: A case report. Med Pediatr Oncol 1980;8:275–280.
7.
De Besi L, Zucchetta P, Zotti S, Mastrogiacomo I: Sex hormones and sex hormone binding globulin in males with compensated and decompensated cirrhosis of the liver. Acta Endocrinol 1989;120:271–276.
8.
Wang YJ, Lee SD, Lin HC, Hsia HC, Lee FY, Tsai YT, Lo KJ: Changes of sex hormone levels in patients with hepatitis B virus-related postnecrotic cirrhosis: Relationship to the severity of portal hypertension. J Hepatol 1993;18:101–105.
9.
Wang YJ, Wu JC, Lee SD, Tsai YT, Lo KJ: Gonadal dysfunction and changes in sex hormones in postnecrotic cirrhotic men: A matched study with alcoholic cirrhotic men. Hepatogastroenterology 1991;38:531–534.
10.
Kaymakoglu S, Okten A, Cakaloglu Y, Boztas G, Besisik F, Tascioglu C, Yalcin S: Hypogonadism is not related to the etiology of liver cirrhosis. J Gastroenterol 1995;30:745–750.
11.
Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, Trichopoulos D, Stuver S: Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 2000;85:498–502.
12.
Kuper HE, Tzonou A, Kaklamani E, Hadziyannis S, Tasopoulos N, Lagiou P, Trichopoulos D, Stuver S: Hepatitis B and C viruses in the etiology of hepatocellular carcinoma: A study in Greece using third generation assays. Cancer Causes Control 2000;11:171–175.
13.
Stuver SO, Kuper H, Tzonou A, Lagiou P, Spanos E, Hsieh CC, Mantzoros C, Trichopoulos D: Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men. Int J Cancer 2000;87:118–121.
14.
Trichopoulos D, Hsieh CC, Macmahon B, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S: Age at any birth and breast cancer risk. Int J Cancer 1983;31:701–704.
15.
Miettinen OS: Theoretical Epidemiology. New York, Wiley, 1985.
16.
Chopra IJ, Tulchinsky D, Greenway FL: Estrogen-androgen imbalance in hepatic cirrhosis. Studies in 13 male patients. Ann Intern Med 1973;79:198–203.
17.
Baker HW, Burger HG, de Kretser DM, Dulmanis A, Hudson B, O’Connor S, Paulsen CA, Purcell N, Rennie GC, Seah CS, Taft HP, Wang C: A study of the endocrine manifestations of hepatic cirrhosis. Q J Med 1976;45:145–178.
18.
Santen R: The testis: Function and dysfunction; in Yen SSC, Jaffe RB, Barbieri RL (eds): Reproductive Endocrinology, ed 4. Philadelphia, Saunders, 1999, pp 632–668.
19.
Goldberg MJ, Kaplan MM, Mitamura T, Anderson CL, Matloff DS, Pinn VW, Agnello V: Evidence against an immune complex pathogenesis of primary biliary cirrhosis. Gastroenterology 1982;83:677–683.
© 2001 S. Karger AG, Basel
2001
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