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 different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks; Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration; this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared, FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but 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.