Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue.
Six patients with advanced prostatic cancer were treated with a potent GnRH agonist analog (buserelin, Hoechst; 600 micrograms, intranasally, three times a day) for 6 months. The first 2-6 days of treatment were associated with a 50% elevation (P less than 0.01) in serum testosterone (T) and a simultaneous elevation of 20% (P less than 0.01) in serum prostate-specific acid phosphatase (PAP). Serum T fell to the castrate range (less than 1 nmol/liter) in all patients in 2-3 weeks, and PAP decreased concomitantly in five of the six patients. Serum LH progressively decreased by about 80% during the treatment, whereas a secondary rise of FSH levels occurred after the first month of treatment. The patients were orchiectomized after 6 months of treatment. No differences were found between the pre- and postsurgical levels of serum T or in comparison with those of six patients orchiectomized as the first therapeutic measure. Testicular endogenous T concentrations, LH and FSH receptors, and in vitro T production were measured in three testis samples and compared with those values in testis tissue obtained from five control patients. The endogenous levels and in vitro production of T were depressed by over 95% in testes from agonist-treated patients. The small residual T production responded to hCG stimulation as in control patients. Interestingly, no change was found in testicular LH receptor content, but FSH receptors decreased by 80%. The elevation in serum PAP at the beginning of the agonist treatment and the small residual testicular T production after 6 months may not be clinically important. However, they indicate the necessity of comparative long term studies between orchiectomy and GnRH agonists in the treatment of patients with prostatic cancer.
Huhtaniemi
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I
Nikula
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H
Rannikko
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S
D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D002064:Buserelin / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011962:Receptors, FSH; D011974:Receptors, LH; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood; D013997:Time Factors
D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011974:Receptors, LH; D013739:Testosterone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000135:Acid Phosphatase; D002064:Buserelin