-
The Canadian Veterinary Journal = La... Aug 2019Horses are long-day breeders and commence ovarian follicular activity during the spring. Evidence suggests that there is an endogenous circannual rhythm in mares, and it...
Horses are long-day breeders and commence ovarian follicular activity during the spring. Evidence suggests that there is an endogenous circannual rhythm in mares, and it is uncertain whether hormonal manipulation during or immediately following the fall transition induces follicular development. The current study was designed to test the hypothesis that both deslorelin and naltrexone induce follicular development in late fall transitioning or anestrous mares. Five of six mares treated with deslorelin, and 4 of 6 mares treated with naltrexone, developed a pre-ovulatory-sized follicle and were inseminated. Zero of three deslorelin-control mares and 1 of 3 naltrexone-control mares were inseminated. The number of mares bred in the deslorelin treatment group was significantly higher than in the corresponding control group ( < 0.05). Six of nine mares inseminated were pregnant 14 days after insemination. In conclusion, we were able to induce follicular development resulting in fertile ovulations during and shortly after the fall transition.
Topics: Anestrus; Animals; Female; Horses; Naltrexone; Ovulation; Pregnancy; Triptorelin Pamoate
PubMed: 31391602
DOI: No ID Found -
Animals : An Open Access Journal From... Sep 2022The search for an alternative approach of estrus control (induction or suppression) in dogs is an important issue and the use of slow GnRH agonist-releasing implants has... (Review)
Review
The search for an alternative approach of estrus control (induction or suppression) in dogs is an important issue and the use of slow GnRH agonist-releasing implants has been the subject of frequent research in recent years. Studies to date demonstrate that the short- and long-term effects of deslorelin implants applicated at different time points of the prepubertal period are similar to those of adult dogs; however, there are important differences. The age of the prepubertal bitch and the dosage appear to be the main determinants of the response to deslorelin, as well as the individual metabolism of the bitch. Recent studies reported that the deslorelin-mediated long-term delay of puberty does not have negative carry-over effects on subsequent ovarian functionality, serum steroid hormone concentrations, uterine health, and fertility; however, more molecular studies are needed to determine the effects of application time of GnRH agonists on hormone concentrations and peripheral receptor expression. Furthermore, the long-term effects of delay of puberty with deslorelin on joint health, tumor development, the immune system, and social behavior deserve further investigations.
PubMed: 36077986
DOI: 10.3390/ani12172267 -
Reproduction in Domestic Animals =... Sep 2022The behaviour of mares is often detrimental to their performance resulting in frequent demand for methods to suppress gonadal function. In addition, prevention of... (Review)
Review
The behaviour of mares is often detrimental to their performance resulting in frequent demand for methods to suppress gonadal function. In addition, prevention of unintended reproduction especially in feral horse populations may require methods for suppression of gonadal function. Surgical ovariectomy is a safe method but not an acceptable approach in feral mares and undesired in mares where future breeding is considered. There are different approaches for artificial prolongation of the luteal phase resulting in transient inhibition of oestrus and ovulation. Among those, treatment with natural or synthetic progestogens is considered the most common and successful method. Whereas application of intrauterine devices may result in prolongation of luteal function in non-pregnant mares, intrauterine insertion of glass balls is no longer recommended because of complications in individual mares. There are several safer alternatives that may be of interest, especially for population control in free-roaming horses. Treatment with long-acting deslorelin implants inhibited ovulation and oestrus behaviour in mares for limited and variable time intervals in a dose-dependent manner. The effect of GnRH vaccines varies considerably among individual mares, is age dependent, and oestrus-like behaviour may still occur. Contraception via immunization against native porcine or recombinant zona pellucida antigen is successful, but immunocontraception is as much a result of ovarian inactivity as an antibody-based block to sperm-oocyte binding. In conclusion, several treatments for suppression of gonadal function in mares are available, but there are advantages and disadvantages associated that have to be considered. The treatment of choice will thus differ with regard to the demands.
Topics: Animals; Contraception, Immunologic; Female; Gonadotropin-Releasing Hormone; Horses; Male; Ovulation; Reproductive Behavior; Semen; Swine
PubMed: 35467049
DOI: 10.1111/rda.14129 -
Animals : An Open Access Journal From... Dec 2020This article presents B-mode and color Doppler imaging of the prostate and testes in dogs suffering from benign prostate hyperplasia (BPH), and receiving deslorelin...
This article presents B-mode and color Doppler imaging of the prostate and testes in dogs suffering from benign prostate hyperplasia (BPH), and receiving deslorelin acetate (Suprelorin) or osaterone acetate (Ypozane). The study was planned as a controlled clinical trial, dogs were divided into negative control (healthy dogs, = 10), positive control (dogs with BPH, = 10), and study groups, III ( = 15), receiving deslorelin acetate (DA), and IV ( = 10), receiving osaterone acetate (OA). The B-mode appearance of the prostate parenchyma improved in all investigated dogs from the DA group, and in 60% of OA dogs. Prostate volume was reduced more quickly with OA (from D14), but lasting for a shorter time (on average up to week 20), compared to DA that reduced the prostate volume more slowly (>8 weeks), but the reduction remained longer (>24 weeks). The systolic peak velocity (SPV) and mean velocity (Vmean) were higher in all dogs diagnosed with BPH, compared to Control Group I. The indices did not change in both Control Groups I and II, whereas in study Groups III and IV they decreased throughout the study period compared to day 0 and Control Group II. In Group III the highest reduction was noted from day 21 to week 8, whereas in Group IV the lowest Vmean was recorded before day 21. Testicular parenchyma and volume changed significantly in Group III receiving DA, and the velocity of blood flow in the testicular artery correlated positively with testicular volume only in this group (III). The present study proved the usefulness of B-mode and color Doppler US imaging techniques for diagnosis and progress assessment of dogs suffering from BPH. The blood flow kinetics (mainly SPV) demonstrated a time association between the blood flow changes registered in the prostatic artery, and the subsequent volumetric and sonographic improvement of the prostate parenchyma. The reduction in flow indices was noted prior to the reduction in prostate volume, suggesting that the sonographic recovery of the prostate tissue, occurs secondarily to the regression of the prostate vascular system. Both investigated medications (osaterone acetate and deslorelin acetate) led to a significant sonographic improvement. Deslorelin acetate reduced prostate volume more slowly, but its effect lasted longer than for osaterone acetate.
PubMed: 33322633
DOI: 10.3390/ani10122379 -
Journal of Feline Medicine and Surgery Sep 2022The literature is full of papers reporting side effects of progestogens in cats; however, they are, in fact, safe drugs, as discussed in this article.... (Review)
Review
BACKGROUND
The literature is full of papers reporting side effects of progestogens in cats; however, they are, in fact, safe drugs, as discussed in this article. Gonadotropin-releasing hormone (GnRH) agonists and melatonin are additionally a practical solution for controlling cyclicity in queens, but they also have some contraindications and need to be used carefully.
CLINICAL RELEVANCE
Mastering the use of reproductive drugs allows feline practitioners to handle many more clinical situations than can be solved using surgery. It is not necessary to be a specialist in reproduction to be able to halt cyclicity in a valuable breeding queen using hormones.
EQUIPMENT AND TECHNICAL SKILLS
A sound knowledge of appropriate dosages and criteria for patient selection for all reproductive drugs currently used in feline reproduction is the best guarantee of owner satisfaction and of ensuring the queen's health. Availability of a serum progesterone assay, either in-house or via an external laboratory, is also important, in order to confirm a queen is at an appropriate stage of the reproductive cycle for treatment.
AUDIENCE
This article is aimed principally (but not exclusively) at veterinarians working with cat breeders and whose clientele is increasingly interested in alternative methods of controlling reproduction in pet queens. Surgery is no longer the only choice, and practitioners who manage to keep abreast of new developments will be able to address clients' needs in a modern, professional way.
EVIDENCE BASE
This review draws on a vast body of scientific evidence-based literature. Previously, personal (and sometimes misinformed) opinions, such as the proposed dangerous side effects of progestogens, have been perpetuated in the scientific literature. The papers cited in this review have therefore been carefully scrutinised to distinguish reliable information based on controlled studies from non-evidence-based information.
Topics: Animals; Cats; Contraception; Humans; Melatonin; Periodicity; Progestins; Reproduction
PubMed: 36002142
DOI: 10.1177/1098612X221118754 -
Frontiers in Veterinary Science 2020At present, only surgical sterilization is available for veterinarians and pet owners seeking suppression of fertility in male dogs, in most countries. An alternative... (Review)
Review
At present, only surgical sterilization is available for veterinarians and pet owners seeking suppression of fertility in male dogs, in most countries. An alternative contraceptive alternative approach is GnRH releasing implants that desensitize the pituitary to the stimulatory effects of GnRH and thereby block testicular function (testosterone and sperm production). Two GnRH agonists (deslorelin and azagly-nafarelin) have been researched in controlled release formulations for this purpose. A deslorelin-releasing biodegradable implant, marketed under the name Suprelorin®, has been available in Australia and New Zealand since 2007, the European Union (EU) since 2008, and received regulatory approval in China and Mexico in late 2019. Two versions of the implant are available, one labeled for a minimum of 6 months of fertility suppression in male dogs, and the other for a minimum of 12 months in male dogs. Another GnRH agonist (azagly-nafarelin) was also included in a solid implant (Gonazon®). Research results showed it delivered 6-months to 1 year of suppressed fertility; however, it is not commercialized. This review paper summarizes research on the mechanism of action for these technologies and compiles and interprets the research on efficacy and safety. New findings on usage of the deslorelin releasing implant in countries where veterinarians and pet owners have this option is shared. Research on off-label use of the product in male dogs is also reviewed. This review aims to aid in the evaluation of the deslorelin releasing implant as an adjunct or alternative for surgical sterilization of male dogs.
PubMed: 32923467
DOI: 10.3389/fvets.2020.00483 -
Theriogenology Nov 2021The 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...
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.
Topics: Animals; Anti-Mullerian Hormone; Biomarkers; Dogs; Down-Regulation; Insulin; Insulins; Leydig Cells; Male; Peptides; Proteins; Testis; Testosterone; Triptorelin Pamoate
PubMed: 34534687
DOI: 10.1016/j.theriogenology.2021.08.017 -
Animals : An Open Access Journal From... Jun 2022Benign prostatic hyperplasia (BPH) is one of the most common problems in older male dogs that often has a huge impact on their health and welfare. This article presents...
Benign prostatic hyperplasia (BPH) is one of the most common problems in older male dogs that often has a huge impact on their health and welfare. This article presents a comparison between osaterone acetate (Ypozane; Virbac)(OA) and deslorelin acetate (Suprelorin; Virbac)(DA), medications that are the main therapeutic alternative to castration in dogs with BPH. Forty dogs were divided into four groups: I-negative control (five dogs without BPH); II-positive control (10 individuals diagnosed with BPH); III-15 dogs treated with DA, and IV-10 individuals treated with OA. Semen fractions were collected on days 0 (day of treatment), 7, 14, and 21, and weeks 8, 12, 16, and 20. Macroscopic, microscopic and CASA analyses were performed. Both DA and OA significantly affected the properties of the canine ejaculate. The DA lead to the lack of libido and had lesser effects to the sperm function before it caused azoospermia, whereas OA had no effect on libido and only temporary reduction in seminal plasma volume was observed, which resulted in temporary deterioration in the percentage of motile and progressive spermatozoa.
PubMed: 35739884
DOI: 10.3390/ani12121548 -
Journal of the American Association For... Nov 2023Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have...
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 (). Male macaques ( = 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.
Topics: Male; Animals; Testis; Gonadotropin-Releasing Hormone; Macaca mulatta; Testosterone; Semen; Drug Implants; Triptorelin Pamoate
PubMed: 37844997
DOI: 10.30802/AALAS-JAALAS-22-000116 -
Animals : An Open Access Journal From... Jan 2023This multicenter-controlled, double-masked randomized European study was conduc-ted to confirm both the efficacy and safety of a deslorelin implant in controlling...
This multicenter-controlled, double-masked randomized European study was conduc-ted to confirm both the efficacy and safety of a deslorelin implant in controlling fertility and sexual behavior in a large population of tom cats over a 12-month period. Among the 225 screened individuals, a total of 205 privately owned indoor intact male cats, aged 3 months of age or older, were randomly allocated to a deslorelin implant (n = 154) or to a negative control group (n = 51). After the screening visit performed between day (D)-14 and D-7, six additional visits were sche-duled on D0, D45, D93, D186, D279 and D372. Effects on testosterone, sexual behaviors, penile spines, testicular volume and intact male cat urine odor were assessed at every visit under masked conditions as regards to the treatment group. In addition, phone calls from the investigators to the owners were scheduled on D7 and then on a monthly basis whenever no visit was scheduled. Success was defined as an individual serum testosterone concentration below or equal to 0.10 ng/mL and was 77.9% at D45, 83.1% at D93, 84.4% at D186 and D279, and 61.7% at D372 in the deslorelin group, and 3.9% at D45, 5.9% at D93, 3.9% at D186, 7.8% at D279 and 3.9% at D372 in the negative control group. Testing for superiority was made stepwise from D45 to D372 upwards; the difference in success rates was significant from D45 to D372 ( < 0.001 for each time point). The mean testosterone concentration dropped from baseline in the deslorelin group, remaining below the set threshold of 0.1 ng/mL until D372. From D7 onwards, the mean sum score for sexual behaviors (including vocalization, urine marking, aggression and intact male cat urine odor) was significantly lower at each observation time point in the deslorelin group compared to the control group, where no decrease in scores was observed. The mean percent change to baseline of the testicular volume and the percentage of cats with a decreased visibility and adult appearance of penile spines were significantly lower in the deslorelin group as soon as D45. No relevant safety concerns were reported during the course of the study. The deslorelin implant Suprelorin 4.7 mg (Virbac, Carros, France) is a safe and effective neutering option, inducing infertility over a 12-month period when administered to intact male cats aged between 3 months of age and 11 years of age. The implants also successfully reduced sexual behaviors (i.e., vocalization, urine marking, aggression), intact male cat urine odor, testicular volume and penile spine score for 1 year (372 ± 5 days).
PubMed: 36766268
DOI: 10.3390/ani13030379