Antifertility effects of an LH-RH analogue in male rats and dogs.

The antifertility effects of a highly active LH-RH analogue, D-Ser(Bu)6-LH-RH(1-9)nonapeptide-ethylamide (buserelin) were studied in male rats and dogs. Pituitary-testicular function was not impaired by a "physiological" dose of 5 ng/rat; this dose gave reproducible LH release during chronic administration. At higher dose testicular LH receptors and responsiveness to HCG were diminished in intact prepubertal and adult rats. Pituitary inhibition was independent of gonadal or adrenal steroid feedback, and hypothalamic LH-RH as well as pituitary LH and FSH were reduced by 4 weeks treatment of castrate/adrenalectomized rats with 50 ng buserelin. In male dogs, a dose of 2.5 micrograms/kg sc reduced serum testosterone to 6% of controls within 8 weeks of treatment. Treatment was continued for 6 months and testicular involution was found to be reversible within 8 weeks of stopping treatment. LH-RH analogues at "supraphysiological" doses can be used as antifertility agents, but suppression of sexual activity in male dogs under treatment indicates that loss of libido will be a problem.