Induction of puberty by prolonged pulsatile LRH administration.

Pubertal maturation was induced in a 17.7 year old hypogonadotrophic boy by pulsatile LRH treatment. LRH was administered in three periods. During period one 20 micrograms LRH pulses were given iv 16 times per day for 10 weeks; during period two 2 micrograms LRH pulses iv 16 times per day for 12 weeks. During period three 2 micrograms LRH pulses 16 times per day were given sc for 13 weeks. Treatment was interrupted for 6 weeks between period one and two. Rapid initiation of pubertal maturation was evidenced by an increase of penile length and testicular volume as well as by growth of pubic hair. After 21 weeks of treatment spermatozoa were observed in the ejaculate. Gonadotrophin levels increased from prepubertal values into the supranormal range in the beginning of period one, spontaneously declining to normal adult levels. A rapid increment of testicular volume during period one was also evidence for overstimulation. During period two gonadotrophin levels were in the normal range. Testosterone levels were normal during period one and two albeit higher during period one. We conclude that 1) pulsatile LRH treatment with 2 micrograms per pulse iv 16 times per day is an adequate and feasible way to induce puberty in hypogonadotrophic males with an intact pituitary. 2) Under pulsatile LRH treatment spermatogenesis takes place more rapidly than during normal puberty. 3) Testicular hormones exert a negative feedback action at the pituitary in the LRH treated hypogonadotrophic male. 4) The supranormal levels of LH and FSH during the first weeks of treatment may be caused by a delayed reaction of the testicles to gonadotrophin stimulation rather than to an overdose of LRH. 5) No evidence was found of a direct inhibitory action of LRH on testicular function.