The Rapid Ovarian Secretory Response to Pituitary Stimulation by the Gonadotropin-Releasing Hormone Agonist Nafarelin in Sexual Precocity*

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Abstract
We evaluated a GnRH agonist (GnRHa) asa potential single stimulus to both pituitary and ovarian secretion i n 13 girls with true precocious puberty. We compared the GnRH agonist [6-D-(2-naphthyl)alanine]GnRH acetate (nafarelin, Syntex) administered as a single sc injection of 0.2μg/kg to GnRH infused iv in a dose ofμg/kg-h for3h and assessed the response of plasma steroid intermediates in estradiol (E2) bio synthesis. Although serum LH and FSH levels increased to similar peaks 3 h after commencing GnRH and nafarelin testing, they rose faster (Pvs. baseline), whereas the rise in E2 was inconsistent and averaged only one third (P < 0.02). However, plasma E2 increased later after nafarelin, but not after GnRH, rising from a baseline level of 30 ± 6 (±SEM) to 115± 13pg/ml at 24h (P < 0.001). The least E2 response to nafarelin at this time was 150%. This rise is probably an underestimate of the maximum E2 rise, since a 6-fold response to nafarelin was found at 12 h in patients sampled then. Measurement of steroid intermediates from progesterone and 17α-hydroxypregnenolone to E2 indicated that the response to nafarelin was typical of normal ovarian follicular secretion. That is, plasma levels of the intermediates in E2 biosynthesis rose less than 2-fold, and only the elevations in androstenedione, from 58 ± 10 to 78 ± 16 ng/dl (P < 0.05), and estrone, from 14 ± 3 to 38 ± 7 pg/ml (P < 0.02), at 24h were significant. The greater effectiveness of nafarelin than GnRH in stimulating E2 secretion appears to be related to the more prolonged gonadotropin response. The magnitude, consistency, specificity, and rapidity of the gonadotropin and E2 responses to nafarelin indicate that this is a promising agent for rapidly testing pituitary and ovarian function simultaneously. (J Clin Endocrinol MetabGS63: 1386, 1986)