LONG-TERM GNRH-AGONIST ADMINISTRATION REVEALED A GNRH-INDEPENDENT MECHANISM STIMULATING FSH DISCHARGE IN HUMANS

The present study evaluated the FSH and LH episodic discharge in diffe rent physiopathological conditions undergoing chronic GnRH-agonist adm inistration. Four girls with true precocious puberty and five postmeno pausal women were administered GnRH-agonist (3.73 leuprolide acetate e very 4 weeks: Takeda Italia, Rome, Italy) for at least 4 months. Plasm a LH and FSH secretory profiles were assessed before and under GnRH-ag onist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, w ith blood sampling intervals of 10 min. Pubertal and postmenopausal pa tients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration; this co-secretion disappeared in both gro ups after 21 and 120 days of treatment. Moreover, while LH concentrati ons decreased to almost undetectable levels and LH episodic release di sappeared, FSH plasma levels were only partially reduced and FSH episo dic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH bu t not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.