Effects of Deslorelin on Testosterone Secretion and Testicular Volume in Male Rhesus Macaques (Macaca mulatta).

Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have potential consequences such as sperm granulomas and long recovery time. Deslorelin is a gonadotropin-releasing hormone agonist that temporarily and reversibly suppresses sex hormone secretion. Our goal in this study was to investigate the effects of deslorelin on testosterone secretion and testicular volume in male rhesus macaques (Macaca mulatta). Male macaques (n = 4) each received two, 4.7-mg deslorelin implants subcutaneously in the interscapular region. Serum testosterone and testicular volume were then monitored at specific time points until 10 mo after treatment. Testosterone suppression was defined as testosterone levels lower than 0.6 ng/mL for a sustained period of at least 30 d. After implantation, mean testicular volume was significantly reduced by day 121. Testosterone suppression was observed in all subjects. However, the time from implantation to testosterone suppression and duration of suppression varied. Two macaques were hormonally suppressed by day 26 after implantation and remained suppressed for at least 6 mo. The other 2 macaques were hormonally suppressed by 2 mo after implantation; of these two, one remained suppressed for 70 days while the other was suppressed for at least 245 days. We conclude that deslorelin can safely suppress testosterone secretion in male rhesus macaques, but individual variation in onset and duration of action should be considered when establishing reimplantation time points and potential return to reproductive activity.

Effect of the Prolactin Inhibitor Cabergoline and the Gonadotropin Releasing-Hormone Agonist Deslorelin in the Suppression of Plasma Prolactin Concentrations and Egg Laying in Quail (Coturnix japonica).

Egg binding and excessive laying frequently affect avian patients, and in many cases the treatment includes suppression of egg production. Currently, for the suppression of egg production in avian patients, a gonadotropin-releasing hormone agonist, in the form of a deslorelin implant, is often used. However, the commercially available deslorelin implants have an undesired delayed onset, as well as a potential brief increase in gonadotropin secretion after administration ("flare-up" effect) that can lead to oviposition before the actual suppression of gonadotropins. The objective of this study was to investigate whether the prolactin inhibitor cabergoline suppresses ovulation and whether it could be used to bridge the time until the onset of effect by the deslorelin implant. We measured the effect of cabergoline (30 µg/kg PO q24h × 14 days), deslorelin implants (4.7 mg SC), and a combination of both on egg laying and plasma prolactin concentrations in 37 quail (Coturnix japonica) over 6 weeks. Quail were divided into 4 groups: group DesCab (deslorelin implant and cabergoline oral; n = 9); group DesPlac (deslorelin implant and placebo oral; n = 9); group PlacCab (placebo implant and cabergoline oral; n = 9); and group PlacPlac (placebo implant and placebo oral; n = 10). Regular egg laying stopped in 100% (9/9) of birds in group DesCab and 78% (7/ 9) of birds in group DesPlac within 5 days of placing the deslorelin implant. No bird ceased egg production in group PlacCab (0/9), and 10% of birds ceased egg production intermittently in group PlacPlac (1/10). Treatment with the deslorelin implant (P < .001) and with cabergoline (P = .04) had a significant (negative) influence on plasma prolactin concentrations compared with the baseline. The interaction of deslorelin and cabergoline treatment, as well as time after initiation of treatment, did not have a significant effect on plasma prolactin concentrations. These results show that daily oral cabergoline has no significant influence on egg laying and only a minor biologically nonsignificant effect on lowering the relative plasma prolactin concentrations in quail.

Hormonal Suppression in Female Rhesus Macaques (Macaca mulatta) Implanted Subcutaneously with Deslorelin.

Providing effective contraception for nonhuman primates (NHP) is challenging. Deslorelin acetate is a commercially available gonadotropin-releasing hormone (GnRH) agonist that may provide a relatively noninvasive, long-lasting, and potentially reversible alternative to standard NHP contraception methods. This study evaluated the duration of suppression of progesterone and estradiol in 6 adult female rhesus macaques (Macaca mulatta) that received a single subcutaneous 4.7 mg deslorelin implant. We hypothesized that deslorelin would suppress production of these hormones for 6 mo with a correspond- ing cessation of menses. Prior to implantation, blood was collected over 1 mo for baseline hormone analyses. Macaques were sedated at the onset of the next menstrual cycle and a 4.7 mg deslorelin implant was placed in the interscapular region. Blood was collected over the subsequent month at the same intervals used for the baseline collection schedule, and then every 7 d thereafter. Results showed that estradiol and progesterone transiently increased 1 to 3 d after implantation, then fell to basal levels within 6 d of implantation. The duration of hormone suppression (progesterone <0.5 ng/mL) varied among animals. Two macaques returned to cyclicity by 96 d and 113 d after implantation, while hormones remained suppressed in the other 4 macaques at 6 mo after implantation. Cessation of menses correlated with hormone suppression except in 1 animal that continued to have sporadic vaginal bleeding despite progesterone remaining below 0.5 ng/mL. This study indicates that deslorelin is a noninvasive and long-lasting contraceptive method in female rhesus macaques. However, individual variation should be considered when determining reimplantation intervals.

Clinical use of Anti-Müllerian Hormone to monitor resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

OBJECTIVE: The use of deslorelin implants to control reproduction in cats is increasing but because of its prolonged duration, cat breeders often request implant removal before the end of the treatment. Assaying Anti Mullerian Hormone (AMH) concentrations might be useful to predict time of resumption of ovarian activity in deslorelin-treated queens following implant removal. In queens a minimum of 3 weeks during increasing photoperiod after implant removal has been described for resumption of ovarian activity but no information about AMH concentrations were observed for determining ovarian activity. ANIMALS: Sixteen queens in which deslorelin implants were surgically removed after 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively) were used in this study. PROCEDURES: A general and reproductive health check with a GnRH stimulation test were performed before the treatment. After implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection to assay AMH concentrations. RESULTS: AMH concentrations decreased significantly at the end of the treatment to ≤ 2.5 + 0.6 ng/ml (p ≤ 0.05) and reached a nadir at 1.9 ± 0.9 (p < 0.05) one-week post-removal. Following implant removal AMH concentrations started to rise reaching a value of 3.9 ± 0.7 ng/ml on the third week and were not different from pre-treatment levels on week 6 post-removal (5.8 ng/ml + 0.9, p ≥ 0.05). AMH values did not differ depending on duration of deslorelin treatment but were lower in adult queens (p < 0.05). CLINICAL RELEVANCE: AMH assay can be a useful tool to follow resumption of feline ovarian function following a deslorelin treatment.

Resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty-three queens were treated with a 4.7 mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre-treatment general and reproductive health check. Following implantation treatment, all queens in inter-oestrus-anoestrus at the time of treatment came in oestrus within 2-5 days. Starting 7-14 days following implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7 weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p < .05). In conclusion, at least 3 weeks post-removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7 mg deslorelin implant, while this time may increase up to 7 weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.

Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog.

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.

Long-term effect of repeated deslorelin acetate treatment in bitches for reproduction control.

Long-acting gonadotropin-releasing hormone (GnRH) analogs, which are approved for male dogs and ferrets, have been used off-label to suppress estrus in bitches predisposed to the side effects of spaying. Health data from the past 12 years were evaluated from bitches without progestogen pretreatment that received deslorelin acetate (DA) to suppress estrus for the first time before the age of 4.5 years. The study population included 32 client-owned bitches repeatedly treated with either 4.7 mg or 9.4 mg DA implants for a period of 5.3 ± 3.4 years (range 0.5-11.3 years). Follow-up information concerning immediate side effects of DA occurring within five months after the first DA treatment (n = 23) as well as long-term side effects of sustained gonadal suppression occurring after five months up to three years (n = 2), three years up to five years (n = 2) or more than five years (n = 8) were assessed through a questionnaire. Treatment was considered successful if no major side effects requiring medical treatment occurred, which applied to 26 out of 32 (81 %) bitches. In the six remaining bitches, the following major side effects led to treatment discontinuation: persistent urinary incontinence (n = 1), reoccurring induced heat (n = 1), uterine disease (n = 3) and/or ovarian tumor (n = 3). The bitches recovered completely after surgical spaying and/or DA implant removal. Minor side effects that did not require therapy or affect animal welfare included body weight changes (n = 18), subtle behavioral changes (n = 13), induced heat (n = 12), coat changes (n = 11), pseudocyesis (n = 6), transient urinary incontinence (n = 4), and/or temporary thickening of the uterine wall with little anechogenic content (n = 2). To examine a possible causal relationship between adverse side effects and DA treatment, further studies should compare the frequency of pathologies between groups of GnRH-treated, intact and spayed bitches of similar breeds and ages. Nevertheless, DA application before the age of 4.5 years may be a means of postponing surgical spaying for several years in breeds at high risk for developing urinary incontinence. Before DA is used in bitches, owners should be fully informed regarding possible side effects.

DESLORELIN (SUPRELORIN®) USE IN NORTH AMERICAN AND EUROPEAN ZOOS AND AQUARIUMS: TAXONOMIC SCOPE, DOSING, AND EFFICACY.

The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin®), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.

The past, present and future of hormonal contraceptive use in managed captive female tiger populations with a focus on the current use of deslorelin acetate.

Tigers (Panthera tigris spp.) are endangered in the wild; ensuring sustainable insurance populations requires careful planning within zoological collections. In captive situations, contraceptives are often used to control breeding and ensure genetically viable populations that contain manageable numbers of animals; reversible contraceptives are ideal because they offer flexibility for breeding management. Historically, synthetic progestins, such as melengestrol acetate implants, were used in female tigers, but these are associated with an increased risk of reproductive pathology and subsequent infertility. Recent management advice to ex-situ collections has been to transition to the use of gonadotropin-releasing hormone agonists, such as deslorelin acetate implants, which do not appear to have a similar risk of reproductive pathology but are associated with highly variable reversal times in exotic felids. Using data from 917 contraceptive records in female tigers captured by the Association of Zoos and Aquariums Reproductive Management Center and the European Association of Zoos and Aquaria Reproductive Management Group's joint Contraception Database and from supplementary surveys, this study reviews the changing use of contraceptives in captive female tigers. The aim was to describe the historical and current use of contraceptives and provide a comprehensive assessment on the use of deslorelin implants, including data on product protocols, efficacy, pathology, and reversibility. This study determined that current dose, frequency, reversibility, and anatomical placement sites of deslorelin implants are highly variable, indicating that specific, readily available, unified, evidence-based recommendations on the use of deslorelin would be useful for future contraceptive use in managed tiger populations.

Transient suppression of ovulatory ovarian function in pony mares after treatment with slow-release deslorelin implants.

Behavior during the estrous cycle of mares can affect their performance and therefore inhibition of cyclical ovarian activity is indicated. We hypothesized that implants containing the GnRH analog deslorelin downregulate GnRH receptors and inhibit ovulation in mares. The estrous cycles of Shetland mares were synchronized with 2 injections of a PGF2α analog. One day after the second injection (day 0), mares received 9.4 (group D1, n = 6) and 4.7 mg deslorelin (D2, n = 5) as slow-release implants or 1.25 mg short-acting deslorelin as a control (C, n = 5). Ultrasonography of the reproductive tract and ovaries and observation of estrous behavior and collection of blood samples for analysis of progesterone and LH concentrations were performed every second day until day 10 and thereafter at 5-d intervals. Stimulation tests with the GnRH-agonist buserelin were performed on days 10 and 45. Until day 50, there were less spontaneous ovulations in group D1 (P < 0.01) and estrous behavior was reduced in groups D1 and D2 compared with group C (P < 0.05). The time until first ovulation (D1 62.0 ± 8.6, D2 44.2 ± 14.1, C 22.2 ± 3.1 d, P < 0.05) and the number of days with estrous behavior (P < 0.05) differed among groups. On day 10 after treatment, a GnRH stimulation test revealed interactions between group and time (P < 0.001) in plasma LH concentration that were no longer detectable on day 45 after treatment. In conclusion, long-acting deslorelin implants result in a transient downregulation of pituitary GnRH receptors that is associated with inhibition of ovulation and estrous behavior in Shetland mares.

[GnRH agonist implants in small animal practice - what do we know 13 years following EU registration?] / GnRH-Agonisten in der Kleintierpraxis ­ Was wissen wir 13 Jahre nach der EU-Zulassung?

The availability of GnRH agonist implants offers the possibility of a reversible, temporary downregulation of endocrine and germinative testicular function in male dogs and hobs. This review provides an overview of the registered indication, the induction of temporary infertility in healthy, intact, sexually mature male dogs (4.7 and 9.4 mg deslorelin) and hobs (9.4 mg deslorelin) as well as various off-label indications. Off-label use requires strict indications, informed consent from the owner and a lack of licensed medication (safe and optimum effect). Off-label indications in the male dog include sexual-hormone dependant (disturbing) behavior, benign prostatic hyperplasia, small adenomas of the hepatoid glands and alopecia X. Successful use of deslorelin implants for estrus suppression in jils, but also for the treatment of hyperadrenocorticism in ferrets in general have been described. Similarly, hormonal castration can be induced in tomcats and queens. The variable time to onset of effect and its duration (extremely variable in some animals) represent a challenge for breeders. No (sufficient) contraceptive activity was identified in male rabbits and male guinea pigs; however, treatment did successfully suppress the estrus cycle in female individuals of these species, as well as reproductive activity in male and female rats. Regarding the use in birds and reptiles, significant species-specific differences exist with regard to efficacy, time until onset of effect and duration of downregulation. In birds, the implant is efficient to fully suppress egg laying in chicken, Japanese quail and psittacids. In doves, egg laying is only significantly reduced. Successful treatment of reproduction-associated (unwanted) behaviour patterns (feather picking, aggression) has also been described. In some male birds, namely zebrafinch and Japanese quail, the deslorelin implant is suitable to reduce testosterone levels. Successful treatment of hormone-dependent tumours (Sertoli-cell tumorus) in budgerigars has been described as well as the modulation of specific behavior in turkeys and an efficacy in facilitating their keeping (i. e. reduction of aggression). In reptiles, only the successful use of deslorelin in iguana has been demonstrated to date.

[Development of a large intraprostatic cyst following the use of a GnRH agonist-implant in a male dog with benign prostatic hyperplasia]. / Entwicklung einer großen intraprostatischen Zyste nach Einsatz eines GnRH-Agonist-Implantats bei einem Rüden mit benigner Prostatahyperplasie.

A male dog with benign prostatic hyperplasia and several small intraprostatic cysts was treated with a GnRH-agonist implant containing 4,7 mg deslorelin (Suprelorin®). Within 2 weeks after the implantation, the prior urethral bleeding worsened. A large intraprostatic cyst was detected sonographically. The patient was subsequently treated with osaterone acetate (0.4 mg/kg p. o. once a day for 7 days) and enrofloxacin (5 mg/kg p. o. once a day for 21 days). The clinical symptoms receded within 10 days. Within one month, the cyst regressed completely. The mechanisms of cyst enlargement are discussed.

Timed Artificial Insemination by Combining Estrous Behavior Observation With Deslorelin Treatment in Jennies.

The purpose of this study was to determine the optimal time for ovulation induction and artificial insemination (AI) based on the relationship between estrous behavior and ovulation in jennies. Thirty-two jennies were teased by one jackass for 1 hour per day during 46 days and estrous behaviors were recorded, while the follicular development and ovulation was examined by ultrasound. Furthermore, another 31 jennies were teased by one jackass as the teasing group (group T), which were injected with Deslorelin at 2 and 4 days after the onset of estrus, and AI was performed at 8 hours after each injection. Moreover, Ultrasound was performed on the follicle development of 23 jennies as the ultrasonography group (group U). Injection with Deslorelin when the follicle diameter ≥ 30 mm, and AI was performed at 8 hours later. The results showed that mouth clapping was the specific estrous behavior of jennies and indicated the beginning of estrus. The mean time for jennies to develop dominant follicles (≥30 mm) after the onset of estrus was 3.5 ± 1.3 days, and the mean time between the onset of estrus and ovulation was 5.1 ± 1.5 days. Estrous behaviors ended 0.5 ± 1.2 days after ovulation. After AI, there were no significant differences in ovulation (96.8% vs. 91.3%) and conception rates (40.0% vs. 38.1%) between group T and U. The optimal breeding time of jennies can be determined by jackass teasing and hastening ovulation by Deslorelin injection.

Effect of GnRH agonist deslorelin implant on spermatogenesis and testosterone concentration in Guinea pigs (Cavia aperea porcellus).

Guinea pigs are social animals that are often kept in groups regardless of their gender. Due to reproduction control and male aggressiveness prevention, surgical castration is commonly required. In the present study, we evaluated the effect of GnRH agonist implant (4.7 mg deslorelinum) on the serum testosterone concentration (T) and spermatogenesis in male guinea pigs. Twenty-four animals were divided into two groups. All animals in the first group were neutered (Group 1), animals in the second group (Group 2) were administered the implant subcutaneously and then neutered in one-month intervals. A histological examination was performed when cross sections of seminiferous tubules were assessed. Subsequently, these tubules were divided based on the most developed germ cell observed: spermatogonia, spermatocytes, round spermatids, elongating spermatids and elongated spermatids. The anticipated decrease in testosterone concentration and cessation of spermatogenesis was not achieved. Thus, the results obtained proved the inefficacy of the deslorelin implant in male guinea pigs so the alternative methods of contraception remain the methods of choice.

Deslorelin acetate implant induces transient sterility and behavior changes in male olive baboon (Papio anubis): A case study.

This case study evaluates the effects of a 4.7 mg deslorelin acetate implant on one male olive baboon (Papio anubis). Implantation induces transient azoospermia after which the subject was able to conceive again. Behavior was also impacted with a decrease in our proxies of aggressiveness and sexual arousal.

Deslorelin subcutaneous implants in Oryx dammah males for reproductive control.

The aim of this study was to assess the effects of the deslorelin subcutaneous implant as a temporary contraceptive method in the Oryx dammah male. For this purpose, deslorelin at different doses, i.e. 14.1 mg and 9.4 mg, was subcutaneously implanted in three males (Phase 1) and one male (Phase 2) adult Oryx dammah, respectively. Quantitative behavior evaluation and androgen concentrations in feces and plasma were assessed before and after implant application. Fecal androgen concentrations observed in treated males were compared with those measured in one orchiectomized male and two females. Fecal androgen concentrations increased up to 15 days after the implant application, then progressively decreased, reaching the basal level at day150 in Phase 1. In Phase 2, levels remained high until day 60 and returned to basal level on day 120. Plasma testosterone concentration was higher on the day of implant application than three months later, but with variable ranges among males. A general increase of activity levels and hierarchical changes were observed after treatment, in accordance with hormonal variations. Despite males cohabiting with two fertile females during the observation period, no births were recorded. However, between the end of Phase 1 and the beginning of Phase 2, i.e. about 10-11 months after the first deslorelin implant, a fertile mating occurred leading to the birth of a calf. Therefore, we can hypothesize a contraceptive effect up to 10 months after the implant. Testicular histology performed on one male at the end of the Phase 2 showed no spermatogenetic activity. Our results suggest that deslorelin implant can be used to temporarily control reproduction in the Oryx dammah male. Behavior and fecal androgen measurements were useful and repeatable, non-invasive methods to monitor response.

Contraceptive implants used by cat breeders in France: a study of 140 purebred cats.

OBJECTIVES: Deslorelin 4.7 mg and melatonin 18 mg subcutaneous implants were studied in purebred male and female cats, via questionnaires sent to French cat breeders, to assess breed, age, duration of the contraceptive effect, fertility after use, changes in behaviour and side effects. METHODS: Reproductive data were collected in 57 tom cats and 41 queens implanted with deslorelin 4.7 mg, and 42 queens implanted with melatonin 18 mg, for a total of 140 purebred cats, from 38 different catteries, representing 18 breeds. RESULTS: Using deslorelin (Suprelorin 4.7 mg; Virbac), sexual behaviour in males was inhibited for a mean ± SD of 13.4 ± 3.2 (range 8-21) months in 37/57 cats. Of these, 24/37 mated successfully and produced litters at a mean of 15.5 ± 3.6 (range 9-20) months. Inhibition lasted 11 ± 1.1 (range 9-12; n = 6), 13.2 ± 2.4 (range 12-18; n = 6) and 15 ± 3.5 (range 9-18; n = 6) months in Norwegian Forest Cat, Singapura and Ragdoll males, respectively. In 26/41 females implanted with deslorelin 4.7 mg, oestrus was inhibited for a mean of 16.0 ± 5.7 (8-38) months; 12/26 went on to produce a litter. Of the side effects specific to females: two presented persistent oestrus, leading to the removal of the implant; two developed lactation; one had fibroadenomatosis; and one was sterilised owing to cystic endometrial hyperplasia. Using melatonin (Melovine 18 mg; Ceva), 33/42 females had oestrus inhibited for a mean of 86 ± 50 (range 21-277) days after implantation with a peak return to oestrus in March, and 12/33 had a subsequent litter. No side effects were reported. CONCLUSIONS AND RELEVANCE: This study is the first to collect a large amount of field data, in 140 purebred male and female cats where a deslorelin 4.7 mg or a melatonin 18 mg implant was used. These field results may allow for more accurate clinical advice and open up new avenues of research.

Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of Central precocious puberty (CPP): a retrospective study.

The aim of this study is to compare the clinical and biochemical outcomes of triptorelin acetate (TPA) versus triptorelin pamoate (TPP) treatment in girls with central precocious puberty. A total of 60 patients with idiopathic CPP were retrospectively recruited. Thirty girls were treated with triptorelin acetate 3.75 mg/month (TPA group) and thirty girls in a second group received triptorelin pamoate 3.75 mg/4 weeks (TPP group). Patient follow-up at 12 and 24 months included GnRH Test at 12 months and baseline LH at 24 months. Patients were monitored with pelvic ultrasound, X-Ray of the hand and wrist and anthropometric evaluations. A total of 60/60 girls showed a good response to both formulations. Significant reductions in basal and LH peaks, estradiol values, breast pubertal stage, progression of bone age and growth velocity rate after 12 months treatment were obtained in both groups, demonstrating the equivalence of the two formulations in regulating the hypothalamic-pituitary-gonadal (HPG) axis. Triptorelin pamoate provided a more effective and significant reduction in LH peak after 12 months in comparison with triptorelin acetate more effective in reducing ovarian volume and endometrial thickness. Both formulations were equivalent, even though the LH peak was significantly lower in girls treated with triptorelin pamoate.

Attempts to downregulate ovarian function in the bitch by applying a GnRH agonist implant in combination with a 3ß-hydroxysteroid-dehydrogenase blocker; a pilot study.

Approaches to downregulate ovarian function in the sexually mature bitch by applying slow release GnRH agonist implants are hampered by the initial stimulation of folliculogenesis (flare up) and the resulting side effects. The present pilot study was designed to test to what extent these effects can be suppressed by simultaneous treatment with the 3ß-hydroxysteroid-dehydrogenase (HSD3B) blocker trilostane (T). Treatment with T in 6-h intervals completely blocked adrenal cortisol production. However, in parallel and concomitant with the increase of LH, progesterone and estradiol levels increased, ending up in pro-estric steroid levels in two of the three dogs. Hormonal changes were reflected in the respective clinical symptoms. During the whole observation period the course of LH concentrations did not indicate downregulation of pituitary function as a result of treatment with the GnRH-agonist Suprelorin®, 4.7 mg. The incomplete inhibitory effect of T on the follicular production of sex steroids could be explained by an insufficient transfer of T into the follicular compartment or the existence of a HSD3B isoform in the dog ovary different from the adrenal enzyme. Concerning the lack of downregulation and when accounting for published data different pharmacodynamics/pharmacokinetic activities of GnRH-agonists should be taken into account.

Chronic use of a GnRH agonist (deslorelin) or immunization against GnRH: effects on testicular function and sperm quality of bucks.

Chronic use of GnRH agonists and immunization against GnRH have been used as reversible contraceptive methods. The aim of this study was to compare the effectiveness of both treatments to inhibit reproductive function of adult bucks, in terms of strength and duration of the effects. We used 9 control untreated bucks (CON), 7 bucks treated chronically with a GnRH agonist (subcutaneous implants with 7.4 mg of deslorelin, Suprelorin, Virbac) (AGO), and another 7 bucks were immunized against GnRH (dose of 2 mL of Improvac-Zoetis with 300 µg of a synthetic incomplete analog of natural GnRH; 300 mg of diethylaminoethyl-dextran; and 2.0 mg of chlorocresol) (IMM). Testicular and sperm evaluations, testosterone concentrations, and male odor were determined from 4 wk before applying the treatments until 17 mo of their application. Scrotal circumference of CON (21.0 ± 0.1 cm) and IMM (21.2 ± 0.2 cm) was greater than that of AGO bucks (19.9 ± 0.2 cm) (P < 0.05 for each), without difference between CON and IMM bucks. Pixels' color intensity of testicular ultrasound images was not affected by treatment (general mean ± SEM: 116.0 ± 1.8). Testosterone concentration was greater in CON than AGO and IMM in months 3 and 4, greater in CON and IMM than AGO bucks in months 15 and 16, and greater in IMM than CON and AGO bucks in month 17 (P < 0.05 for all comparisons). Male odor was greater in CON (1.5 ± 0.0) than IMM bucks (1.3 ± 0.0) and greater in IMM than AGO (1.1 ± 0.0) bucks (P < 0.05 for each). Treatment negatively affected all the sperm variables: the total number of sperm in the ejaculate, sperm motility, sperm with normal morphology and sperm with integral membrane function. It was concluded that both treatments were effective in inhibiting the reproductive axis; however, neither of them produced azoospermia or decreased testosterone concentrations to undetectable levels. With both treatments, there were individual males exhibiting characteristics of fertility in all periods of the study. However, chronic use of a GnRH agonist seemed to be the most effective treatment in terms of duration and strength.