Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: A review

Over the last 10 years, new drugs have been applied to canine reproduction, widening the spectrum of therapeutic possibilities for diseases that were previously surgically treated, and facilitating better control of the estrous cycle and fertility. Some are not approved for use in dogs; their use is experimental and further clinical trials are necessary. Dopamine agonists such as cabergoline, bromocriptine or metergoline are ergoderivative alkaloids that exert an anti-prolactinergic effect via stimulation of D₂ pituitary receptors or inhibition of central serotoninergic ones. Their main indication is suppression of lactation. Anti-prolactinergic compounds have also been successfully used for pregnancy termination and shortening of interestrous intervals. Anti-progestins, (e.g. mifepristone and aglepristone) are synthetic steroids that bind with high affinity to progesterone (P₄) receptors, preventing P₄ from exerting its biological effects. Anti-progestins have been indicated in P₄-dependent conditions, such as pregnancy termination, induction of parturition and the medical treatment of pyometra. Several groups of drugs have been described to have anti-androgenic properties through different mechanisms of action: progestins, receptor binding anti-androgens (e.g. flutamide), competitive enzyme inhibitors (e.g. finasteride), aromatase inhibitors, and GnRH agonists. Their main application is medical treatment of benign prostatic hyperplasia. Long-term release formulations of GnRH agonists (e.g. leuprolide or deslorelin acetate) postponed puberty and reversibly suppressed reproductive function in male and female dogs for periods exceeding 1 year. Anti-estrogens (e.g. clomiphene and tamoxifen citrate) are synthetic non-steroidal type I anti-estrogenic compounds that competitively block estrogen receptors with a combined antagonist-agonistic effect. In dogs, their action is more agonistic than antagonistic.

Hormonal state and effects of the use of an antiprogestin in bitches with pyometra.

The pathogenic significance of progesterone in pyometra in bitches was investigated by evaluating the stages of the oestrous cycles of 369 bitches with pyometra. Concentrations of progesterone and oestradiol were determined in 100 bitches with pyometra before ovariohysterectomy. Six bitches with pyometra with progesterone > 5 ng ml-1 and oestradiol < 25 pg ml-1 were treated with the antigestagen RU 46534 (6 mg kg-1, s.c.) twice on day 1 and once on days 2, 3 and 4; ovariohysterectomy was performed on day 6. Six control bitches that met the same criteria were ovariohysterectomized and uterine morphology was compared with that of the treated bitches. The effects of treatment were monitored by hormone, ultrasonographic imaging and histomorphological studies. The results confirm that pyometra may occur at any stage of the reproductive cycle and that most animals are in the phase of dioestrus. Uterine mass (g kg-1 bodymass) with versus without content was not different in treated bitches and was significantly lower (P < 0.01) than in the control bitches. In all six dogs general clinical conditions improved during the observation period; 23.5 +/- 11.1 h after the start of antiprogestin treatment a profuse, purulent vulval discharge was observed. The effusion was nearly complete at day 6. The maximal detectable uterine lumen varied between 23 and 39 mm in diameter, it was no longer detectable on day 6. Oestradiol concentrations remained constant while progesterone decreased with distinct individual variations. Morphometrical examination of the endometrium revealed no differences between groups. The data suggest that antigestagen treatment is a promising approach for treatment of pyometra in bitches.