Plamen Georgiev

Clinical efficacy of a GnRH-agonist implant containing 4.7 mg deslorelin, Suprelorin®, regarding suppression of reproductive function in tomcats

The aim of the present study was to test for the efficacy of a slow release GnRH-agonist implant (4.7 mg deslorelin, Suprelorin) in the male cat. Ten toms were implanted sc in the neck. Changes in testosterone (T) secretion, testicular size, body weight and behaviour (mounting, mating, urine marking) were monitored. T concentrations were significantly decreased (P < 0.0001) to basal levels (< 0.1 ng/mL) in 5 of 10 cats after 4 weeks and in all but one tom after 11 weeks (T < 0.1 ng/mL). In this respective tom only partial downregulation with T-values from 0.2 to 0.1 ng/mL was achieved until week 27. In weeks 28 and 32, T concentrations were below 0.1 ng/mL. Compared to pretreatment values, testicular volume was significantly decreased by about 60% in week 12 and about 73% after 36 weeks (P < 0.001). Penile spines disappeared 9.4 ± 1.0 weeks after treatment. Food intake was significantly increased during treatment period (P < 0.001). In all tomcats libido, mating behaviour and urine marking were significantly reduced (P < 0.0001) after an initial stimulation. In one tom, mating an oestrous queen on day 20 after implant administration resulted in pregnancy. Mating of another tom that had T-values between 0.1 and < 0.1 ng/mL since day 24 in week 8 revealed the presence of spermatozoa; however, this mating did not result in pregnancy. Subcutaneous implant administration was well tolerated by all tomcats without sedation or anaesthesia and no treatment related negative effects were observed. These results demonstrate the clinical efficacy of the 4.7 mg deslorelin implants (Suprelorin) in the tom inducing all castration related effects.

Treatment of queens in estrus and after estrus with a GnRH-agonist implant containing 4.7 mg deslorelin; hormonal response, duration of efficacy, and reversibility

Although slow release GnRH-agonist implants have been shown to effectively suppress the estrous cycle in queens, there are still several remaining questions about their use: if the probability and frequency of estrus induction because of initial stimulation is dependent on the stage of cycle when animals are treated, if all effects are reversible, and to what extent fertility is regained after the end of efficacy. The latter is of major interest to cat breeders who want temporary suppression of estrus in breeding animals. Twenty queens (14 with known fertility) were treated with a 4.7 mg deslorelin implant; hormonal changes (progesterone [P4], and estradiol [E2]) and behavioral changes with special respect to estrus signs and subsequent fertility were assessed. Group A cats (N = 10) were treated 3.2 ± 0.8 days after the beginning of estrus and estrus stopped 4.1 ± 2.5 days after treatment. Estrus induction was observed in one queen 6 days after treatment, and one queen showed estrous signs 138 and 155 days after treatment. Progesterone increased significantly after treatment in all animals until day 14, then slowly decreased reaching basal levels on day 56 without any further increase. Group B cats (N = 10) were treated 7 days after the end of estrus; nine cats had P4 > 1.5 ng/mL and basal E2, one cat (B10) had basal E2 and P4. In cat B10 estrus induction occurred after treatment, but in none of the others; however, E2 increased in all group B cats 1 day after treatment but reached pretreatment concentrations on Day 7 again and remained basal. The implant was still effective in one animal of the estrus group with a duration of efficacy >1102 days, in the others duration of efficacy varied between 483 and 1025 days. Eight queens were mated afterwards and gave birth to a healthy litter with 3.3 ± 1.5 kittens. This study proves that (1) the incidence of estrus induction-although very low-is highest after treatment in estrus or postestrus, (2) the duration of efficacy varies between 16 and 37 months, and (3) estrus suppression is reversible and animals remain fertile after the treatment effect has expired.

Prevention of pregnancy in cats using aglepristone on days 5 and 6 after mating

The aim of this study was to test for the efficacy of aglepristone treatment for prevention of early pregnancy in the cat. Eleven cats (Gr. 1) were treated with 10 mg/kg aglepristone on days 5 and 6 after mating, 17 cats (Gr. 2) were used as untreated controls. Blood samples for progesterone (P4) determination were collected from 6 cats of Gr. 1 and 9 cats of Gr. 2, respectively. Ultrasound examination on day 25 revealed no pregnancy in any of the treated cats. In both groups, P4 concentrations increased from day 5 (before treatment) to day 20 (P < 0.01). In Gr. 1, the interval between aglepristone treatment and the subsequent estrus ranged from 5-299 d [18.5 (5.2) d]. Mean interestrus interval was 205 +/- 72 d in Gr. 2. Mean duration of subsequent estrus was not different to duration of estrus before treatment in Gr. 1 and in Gr. 2, respectively. Mean time between treatment and next pregnancy was 56.4 (4.7) d, ranging from 5-325 d. Pregnancy rates after the next estrus following treatment were 64 and 82% after the first and second estrus, respectively. No major treatment-related side effects were observed. In conclusion, treatment was found to be highly effective for prevention of early pregnancy.

Suppression of fertility in adult cats.

Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific and clinical options are available for the suppression of fertility in adult cats and the decision as to which should be chosen - independent of the legal registration of any state - depends on different facts: (i) feral or privately owned animal? (ii) temporary or permanent suppression of fertility wanted/needed? (iii) sex of the animal? New effective and available methods for hormonal contraception include melatonin implants for short-term post ponement of oestrus in adult queens and slow-release GnRH-agonist implants containing deslorelin (Suprelorin(®) ) for short- and long-term contraception in male and female companion and breeding cats.

Basal testosterone concentrations after the application of a slow-release GnRH agonist implant are associated with a loss of response to buserelin, a short-term GnRH agonist, in the tom cat

Slow-release GnRH agonist implants are considered an effective, reversible alternative to surgical castration in male tom cats. Individual differences exist regarding the onset of efficacy and might be delayed in some animals. Single measurements of testosterone (T) might result in basal concentrations also in intact male cats. Consequently, GnRH stimulation tests are performed to measure T increase in intact animals and to differentiate castrated from intact male cats. In this study, five tom cats were treated with a 4.7-mg deslorelin implant and GnRH stimulation tests using buserelin were performed before treatment and at 4-week intervals afterward until Week 20. After the last test in Week 20 all animals were castrated. Four of five animals had basal T after 4 weeks and-in contrast to pretreatment-application of buserelin did not result in any further T increase. In one animal, T was low after implant insertion, but not basal; however, a GnRH stimulation test induced a slight increase of T in Week 8 and 16 only and no response in Weeks 4, 12, and 20. Testicular volume was significantly decreased and penile spines disappeared in all cats. Testicular histology showed mixed atrophy, but also fully elongated spermatids in three of five male cats making infertility questionable. Because of the loss of the stimulatory effect of short-term GnRH application (buserelin), it can be assumed that long-term GnRH agonists also act by some mechanisms of downregulation of pituitary GnRH receptors in the tom cat.

Treatment with Suprelorin in a pregnant cat

Suppression of oestrus is of major interest in feral cat populations, but also in breeding queens temporarily not intended for breeding. Slow release gonadotropin-releasing hormone (GnRH) agonist implants are a new off-label approach for reproduction control in cats. However, initially, oestrus induction may occur and no data exist regarding what happens if previously mated queens are treated. This case report presents a queen mismated 9 and 8 days before treatment with a 4.7 mg deslorelin implant. The queen delivered four healthy kittens 66 days after mismating, but showed no interest in the kittens and lactation was not adequate. Progesterone and oestradiol concentrations were monitored and the queen was followed until the return of oestrus and subsequent breeding. The next oestrus was observed 498 days after treatment and the queen was mated in the second oestrus afterwards, became pregnant and delivered two healthy kittens, both of which were raised successfully by the queen. This case report clearly shows that pregnancy following a GnRH-agonist implant may go to term, but maternal care might be influenced owing to hormonal changes induced by treatment. In addition, this is the first report demonstrating reversibility of effects induced by long-term treatment with a deslorelin implant (return to oestrus, fertility and normal maternal care).