Reproduction in Domestic Animals

160 J de Gier, NJ Beijerink, HS Kooistra and AC OkkensAndrogens can also be used for this purpose, butprimarily for short-term prevention. As androgens arenot currently registered for this use, they are notincluded in this paper.GnRH agonists or GnRH antagonistsGnRH agonists or GnRH antagonists may also be usedfor oestrus prevention. At this stage, the GnRHantagonists are unfit for clinical use, because ofeconomic and delivery problems for long-term use(Vickery et al. 1989). Gonadotrophin-releasing hormoneagonists administered at high dosages over a longperiod of time prevent oestrus by pituitary downregulation.However, the early stimulatory effect ofGnRH analogues may cause signs of oestrus, if administeredduring anoestrus and sometimes even if administeredduring the luteal phase. It is possible to preventthe occurrence of oestrus by administering a GnRHagonist in pre-pubertal bitches at approximately4 months of age, whereas implantation of a GnRHagonist at 7 months of age does not prevent theoccurrence of an oestrous cycle (Rubion et al. 2006;Trigg et al. 2006). However, in the latter dogs, oestrus isdelayed for a long time. Rubion et al. (2006) showedthat GnRH agonist implants administered beforepuberty prevented reproductive function for 1 year inpre-pubertal bitches. Following removal of the implant,oestrus occurred naturally in 7 of 10 bitches and wasinduced in three bitches after 1.2–14.3 months. Anotherstrategy to prevent oestrous induction during anoestrusafter implantation of a GnRH agonist is administrationof a progestagen before implantation. The efficacy ofthis initial treatment, however, appears to depend on theinterval between start of progestagen treatment andimplantation, the stage of anoestrus, the dosage of theused progestagen or the type of GnRH analogue(Wright et al. 2001; Sung et al. 2006). Furthermore,adding progestagens to prevent the initial stimulation ofGnRH agonists cancels the advantage of not administeringprogestagens for oestrous prevention. Additionally,it is sometimes a problem to remove these implants,because they cannot be found.ProgestagensThe mechanism of the contraceptive activity of progestagensis still unclear. In many species, there is evidencethat contraceptive progestagens reduce serum concentrationsof gonadotrophins. However, high doses ofmedroxyprogesterone acetate (MPA) administered tobeagle bitches for several months did not reduce theincreased circulating concentrations of LH in ovariectomizedbitches, nor did it lower LH concentrations inintact bitches (McCann et al. 1987). In another study,high contraceptive doses of megestrol acetate (MA) didnot suppress basal gonadotrophin secretion duringanoestrus, nor was the pituitary hypersecretion of LHand FSH that occurs in ovariectomized bitches suppressed(Colon et al. 1993). Beijerink (2007) examined 6-h plasma profiles of FSH and LH in five bitches beforeand 3, 6, 9 and 12 months after the start of MPAtreatment. The results of this study demonstrate thattreatment with MPA affects the hypothalamic-pituitaryovarianaxis. Oestrus, ovulation and a subsequent lutealphase did not occur in any of the bitches duringtreatment with MPA. However, the prevention ofoestrus by MPA could not be ascribed to a significantreduction in circulating levels of either FSH or LH. Onthe contrary, during the first months of MPA treatment,there was an increase in basal plasma FSH and LHconcentrations. This progestagen-induced increase ingonadotrophin concentration was not observed in thestudies of McCann et al. (1987) and Colon et al. (1993),and its recognition may be explained by the repeatedsampling employed in the studies by Beijerink (2007).The elevated plasma gonadotrophin levels during thefirst months of MPA treatment may be due to a directinhibitory effect of MPA at the ovarian level, resulting insuppression of the ovarian secretion of oestradiol orinhibin (Mann et al. 1992; Shupnik 1996).With continuing MPA treatment, basal plasmagonadotrophin concentrations returned to pre-treatmentlevels. In addition, the pituitary FSH response toGnRH stimulation decreased, suggesting that MPAtreatment attenuated pituitary FSH sensitivity to endogenousGnRH (Fig. 2) (Beijerink et al. 2007). PulsatileFSH and LH release was maintained during MPAtreatment, but there were indications that changesoccurred in the pulsatile release of the gonadotrophins.In general, LH pulses coincide with a FSH pulse, butduring MPA treatment several LH pulses were accompaniedby such small increases in FSH that theseincreases were not recognized as significant (Fig. 3)(Beijerink 2007).The progestagens most frequently used for oestrousprevention in the dog are proligestone and MPA. Thesingle subcutaneous injection dosage recommended byLH (µg/l)FSH (µg/l)12010080604020050403020100Before 2 5 8 11Months of treatmentBefore 2 5 8 11Months of treatmentFig. 2. Plasma LH and FSH responses (mean ± SEM) in five dogs ina combined anterior pituitary function test according to Meij et al.(1996) before and subsequently 2, 5, 8 and 11 months after the start ofthe treatment with MPA (10 lg ⁄ kg, every 4 weeks). Blood sampleswere collected at -15, 0, 5, 10, 20, 30 and 45 min following the injectionof the releasing hormones at 0 min (arrow) (Beijerink et al. 2007)Ó 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag