Long term effects of administration of a gonadotropin releasing hormone superagonist analog in men with prostatic carcinoma

Administration of the superagonist analog of GnRH, D-Leu⁶-GnRH proethylamide, profoundly reduced plasma LH, FSH, testosterone, and dihydrotestosterone levels when given for 6–11 weeks to adult men with prostatic carcinoma. Since patients with prostatic carcinoma can be expected to receive this analog for as long as 3–4 yr, we questioned whether the same degree of reduction could be maintained during chronic administration. In 22 men who had received D-Leu⁶-GnRH proethylamide for at least 1 yr, LH and testosterone remained at the initial low levels. Plasma dihydrotestosterone concentrations, on the other hand, gradually fell further with long term administration. FSH levels reached a nadir of 5.7 ± 0.94 (± SEM) mlU/ml at 10–11 weeks. Unexpectedly, the plasma levels of this gonadotropin then gradually increased, and between 25 and 97 weeks were approximately 10–15 mlU/ml. This pattern occurred identically in patients receiving either 1 or 10 mg D-Leu6-GnRH proethylamide daily. These data indicate persistent suppression of LH and androgen levels during prolonged therapy and suggest that D-Leu⁶-GnRH-induced “medical castration” can be maintained with chronic administration.