The
Nal-Glu gonadotropin-releasing hormone (
GnRH) antagonist, when given in daily subcutaneous (SC) doses of 5 mg or higher, maximally suppresses serum
luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) levels to near undetectable levels and induces
azoospermia in normal men; lower doses (1.5 and 3.0 mg) are less effective. Cost and convenience are important considerations in
contraceptive development. Studies with
GnRH agonists suggest that constant delivery is more effective in suppressing gonadal function than equal doses by single daily injection. In this study, we examined whether the constant infusion (CI) of a submaximal suppressive dose (1.5 mg) of
Nal-Glu would be more effective in suppressing the pituitary-gonadal axis than its repeated single daily
injections (SDI). This (1.5 mg) dose was selected because the 5 mg dose given once daily SC for 21 days led to maximal suppression of LH, FSH, and
testosterone (T) levels, whereas 1.5 mg once daily for 21 days gave only partial suppression. It was felt that if continuous infusion was considerably more effective than intermittent administration of this submaximal dose, then the development of long-acting sustained release delivery systems for
contraceptives based on
GnRH antagonist analogs would allow both reduced cost and enhanced convenience. One and a half mg of
Nal-Glu was administered SC either as a SDI or CI over 24 hours for 21 days to two groups of five normal men. Three measurements of serum LH, FSH, and T were performed before antagonist injection and 1, 2, 4, 8, 12, 16, and 24 hours after
Nal-Glu injection on days 0, 1, 7, 21.(ABSTRACT TRUNCATED AT 250 WORDS)