Comparison of the efficacy of subcutaneous and nasal spray Buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer

The comparative efficacy of subcutaneous injections and intranasal spray in the maintenance of suppression of testicular function in men with advanced prostatic cancer treated with a gonadotropin-releasing hormone (GnRH) agonist, Buserelin, was evaluated in a nonrandomized clinical trial. After a common induction period of 1 week’s treatment with 500 µ g three times daily by subcutaneous injection, patients were allocated into one of two groups for maintenance therapy with either subcutaneous (200 µ g once daily) or intranasal (400 µ g nasal spray three times daily) Buserelin therapy. Plasma luteinizing hormone (LH) and sex steroid (testosterone [T], dihydrotestosterone [DHT], and estradiol [E 2 ]) patterns were studied before the start and at days 1, 7, and 14 and months 2, 4, 6, and 12 on maintenance regimens. During the maintenance therapy, age-adjusted T levels were markedly suppressed to near-castrate levels in both treatment groups. Despite this marked suppression, age-adjusted T levels were consistently lower in men treated with the subcutaneous regimen from the 2nd week to the 12th month of treatment in morning pooled specimens as well as in detailed sampling over a 24-hour period after 12 months of continuous treatment. A similar pattern of enhanced suppression by the subcutaneous regimen was also observed for age-adjusted DHT, but not E 2 , levels during the study. Neither the magnitude nor the time course of T suppression by GnRH analog treatment could be entirely explained by the nature of the decline in plasma LH levels, which fell much less and more gradually over a 12-month period. These results suggest the two maintenance regimens are not equivalent and that, in the regimens used, subcutaneous therapy produces more complete androgen suppression, presumably due to the suboptimal intranasal dose regimen, although pharmacokinetic route-dependent limitations cannot be entirely excluded.