Long-term endocrine effects of administration of either a non-steroidal antiandrogen or a luteinizing hormone-releasing hormone agonist in men with prostate cancer.
The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of D-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising from a mean (SEM) of 17.5 +/- 1.6 to a maximum of 56.6 +/- 6.9 kU/l (p < 0.001), while mean testosterone and 17 beta estradiol-concentrations rose only by about 50% and 70% over pretreatment values, testosterone levels reaching a plateau after 1 month of treatment. In the subjects treated with the LHRH agonist, 6 months after discontinuation of long-term administration the mean (+/- SEM) LH had risen to 36.9 +/- 6.8 IU/l while mean testosterone levels were still as low as 1.7 +/- 0.7 and rose only to a maximum of 4.2 +/- 1 nmol/l after high-dose human chorionic gonadotropin loadings.(ABSTRACT TRUNCATED AT 250 WORDS)
Decensi
A
A
Department of Medical Oncology II, National Institute for Cancer Research, Genoa, Italy.
Torrisi
R
R
Fontana
V
V
Marroni
P
P
Padovani
P
P
Guarneri
D
D
Minuto
F
F
Boccardo
F
F
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D004702:Endocrine Glands / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D010907:Pituitary Hormones / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D013256:Steroids / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000627:therapeutic use*
D000726:Androgen Antagonists; D007093:Imidazoles; D048289:Imidazolidines; D010907:Pituitary Hormones; D013256:Steroids; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C021277:nilutamide