Gonadotropin-releasing hormone analog and testosterone synergistically inhibit spermatogenesis

We recently demonstrated that superactive gonadotropin-releasing hormone (GnRH) analogs and testosterone synergistically suppress gonadotropin secretion in castrate rats. We proposed that these two classes of agents used in combination would lead to enhanced suppression of spermatogenesis by synergistically inhibiting gonadotropin secretion. This hypothesis was tested in the present study in which synergistic inhibition of spermatogenesis was produced by combined analog and testosterone treatment. The mechanism of the synergistic action observed differed from that hypothesized in that the analog had both primary inhibitory actions directly on the testis and effects at a pituitary level. The addition of testosterone to the regimen further inhibited spermatogenesis by decreasing the secretion of gonadotropins thereby attenuating the compensatory rise in LH and FSH secretion expected with direct analog inhibition of the testis. These studies demonstrate the potential of combined GnRH analog and testosterone administration as a male contraceptive agent and indicate the complexity of their synergistic interactions.