Effect of d-tryptophan-6-luteinizing hormone-releasing hormone on the tumoral growth and plasma sex steroid levels in cirrhotic patients with hepatocellular carcinoma

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Abstract
Certain evidence suggests androgen dependence of hepatocellular carcinoma in cirrhotic patients. Consequently, it was postulated that antiandrogen therapy might be effective in the treatment of hepatocellular carcinoma. d-Tryptophan-6-luteinizing hormone-releasing hormone is a potent agonist analog of luteinizing hormone-releasing hormone which, when chronically administered, inhibits the pituitary gonadal axis and testicular androgen secretion in man. We studied the effects of d-tryptophan-6-luteinizing hormone-releasing hormone on tumoral growth in 17 male cirrhotic patients with hepatocellular carcinoma. After 3 to 6 months of therapy, no tumoral response was observed. Furthermore, measurements of plasma levels of testosterone, dihydrotestosterone, androstenedione, estradiol, estrone and sex hormone-binding globulin were performed before and 3 months after initiation of the antiandrogenic treatment. Before treatment, hypoandrogenism and hyperestrogenism were present; d-tryptophan-6-luteinizing hormone-releasing hormone induced a fall in plasma testosterone and dihydrotestosterone levels. Only a moderate decrease in estradiol and no modification of plasma estrone and sex hormone-binding globulin were found, indicating that the hyperestrogenemia of cirrhotic patients could be attributed to an increase in peripheral aromatization of androgens of adrenal origin. The inability of d-tryptophan-6-luteinizing hormone-releasing hormone to reduce the growth of hepatocellular carcinoma is not totally in disagreement with the concept of androgen dependence of hepatocellular carcinoma since d-tryptophan-6-luteinizing hormone-releasing hormone does not inhibit the production of androgens of adrenal origin.