Sexual behavior and serum testosterone concentration in stallions treated with slow-release implants of deslorelin acetate

The objective of this study was to determine the long-term effects of the administration of 4.7-mg slow-release deslorelin implant on stallions' plasma testosterone concentrations and sexual behavior. Five control animals received a subcutaneous dose of saline solution, whereas treated animals (n = 11) received a subcutaneous implant of 4.7-mg deslorelin acetate (Suprelorin; Virbac SA, Carros, France). Testosterone plasma concentrations were monitored from April to September every week for the first 30 days, then every 2 weeks until the end of the study (98 days in total). A stimulation test using human chorionic gonadotropin was performed before and 70 days after implant administration. Behavior was assessed by asking owners to fill out a questionnaire before treatment, weekly during the study, and then at 7 months after treatment. In treated stallions, an acute increase in testosterone concentration was evident within 7 days after treatment, which was followed by a gradual decline to below basal values over the next 42 days. Results of this study support that deslorelin is biologically active in the stallion. The answers to the questionnaires showed a significant decrease (P = 0.03) in the rearing up behavior at week 3 and 4 after treatment. At the end of the study, of 11 owners, 5 asked their stallions to be reimplanted. Lacking side effects, deslorelin could be considered, in some instances, in the treatment of some behavioral problems in stallions, although there are individual variations in response, which deserve further investigations.     

Sustained-release deslorelin acetate implants disrupt oestrous cyclicity in the mare

There is a need for a safe, effective and practical method of oestrus suppression in the mare. The aim of this study was to monitor ovarian activity in mares exposed to either 9.4 or 28.2 mg deslorelin acetate, a GnRH agonist, in the form of a sustained-release implant. Following oestrus synchronisation, mares were randomly assigned to one of three groups (n = 4 per group) and administered either one (Des1 group; 9.4 mg) or three (Des3 group; 28.2 mg) implants of deslorelin acetate (Suprelorin-12, Virbac Australia) or one blank implant (Control group; Virbac Australia). Mares underwent weekly blood sampling for 12 weeks following implant placement (Day 0–Day 84), with transrectal palpation and ultrasonography of the reproductive tract at all sampling timepoints except Days 56, 70 and 77. All mares showed baseline serum progesterone concentrations (SPC; ≤1.3 nmol/L or 0.4 ng/ml) on Day 0. Cycling Control mares showed typical oestrous cyclicity characterised by peaks and troughs in SPC over time. Four of eight treated mares demonstrated a sustained elevation in SPC after the initial ovulation after implant placement; SPC declined to baseline levels (Des1 group; 2 mares) or remained elevated (Des3 group; 2 mares) at the final sampling timepoint on Day 84. Oestrous cyclicity was erratic in three of the remaining four treated mares. In total, 87.5% (7 of 8) of treated mares showed atypical oestrous cyclicity after implant placement. These results suggest that deslorelin acetate disrupts oestrous cyclicity in the mare, which warrants further research.     

Effect of deslorelin acetate on gonadotropin secretion and ovarian follicle development in cycling mares

OBJECTIVE: To evaluate gonadotropin secretion and ovarian function after administration of deslorelin acetate to induce ovulation in mares. DESIGN: Randomized controlled trial. ANIMALS: 16 healthy mares with normal estrous cycles. PROCEDURE: 8 control mares were allowed to ovulate spontaneously, whereas 8 study mares received deslorelin to induce ovulation when an ovarian follicle > 35 mm in diameter was detected. Follicle development and serum concentrations of gonadotropins were monitored daily during 1 estrous cycle. Pituitary responsiveness to administration of gonadotropin-releasing hormone (GnRH) was evaluated 10 days after initial ovulation. RESULTS: Interovulatory intervals of mares treated with deslorelin (mean +/- SD, 25.6 +/- 2.6 days) were longer than those of control mares (22.9 +/- 1.8 days). Diameter of the largest follicle was significantly smaller during 2 days of the diestrous period after ovulation in deslorelin-treated mares than in control mares. Concentrations of follicle-stimulating hormone (FSH) were lower in deslorelin-treated mares on days 5 through 14 than in control mares. Concentrations of luteinizing hormone were not different between groups during most of the cycle. Gonadotropin release in response to administration of GnRH was lower in mares treated with deslorelin acetate than in control mares. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of deslorelin was associated with reduction in circulating concentrations of FSH and gonadotropin response to administration of GnRH during the estrous cycle. Low concentration of FSH in treated mares may lead to delayed follicular development and an increased interovulatory interval.     

Pituitary responsiveness to GnRH in mares following deslorelin acetate implantation to hasten ovulation

The present experiment characterized the pituitary responsiveness to exogenous GnRH in the first 10 d after ovulation following commercially available deslorelin acetate implantation at the normal dosage for hastening ovulation in mares. Twelve mature, cyclic mares were assessed daily for estrus and three times weekly for ovarian activity starting May 1. Mares achieving a follicle at least 25 mm in diameter or showing signs of estrus were checked daily thereafter for ovarian characteristics. When a follicle >30 mm was detected, mares were administered either a single deslorelin acetate implant or a sham injection and then assessed daily for ovulation. On d 1, 4, 7, and 10 following ovulation, each mare was challenged i.v. with 50 microg GnRH, and blood samples were collected to characterize the LH and FSH responses. The size of the largest follicle on the day of treatment did not differ (P = 0.89) between groups. The number of days from treatment to ovulation was shorter (P < 0.001) by 2.0 d for the treated mares indicating a hastening of ovulation. The size of the largest follicle present on the days of GnRH challenge was larger in the treated mares on d 1 (P = 0.007) but smaller on d 10 (P = 0.02). In addition, the interovulatory interval was longer (P = 0.036) in the treated mares relative to controls by 4.4 d. Concentrations of FSH in plasma of the treated mares were lower (P < 0.05) than control concentrations from d 3 to 12; LH concentrations in the treated mares were lower (P < 0.05) relative to controls on d 0 to 5, d 7, and again on d 20 to 23. Progesterone values were the same (P = 0.99) for both groups from 2 d before ovulation though d 23. There was an interaction of treatment, day, and time of sampling (P < 0.001) for LH and FSH concentrations after injection of GnRH. Both the LH and FSH responses were suppressed (P < 0.009) in the treated mares relative to controls on d 1, 4, and 7; by d 10, the responses of the two groups were equivalent. In conclusion, deslorelin administration in this manner increased the interovulatory interval, consistently suppressed plasma LH and FSH concentrations, and resulted in a complete lack of responsiveness of LH and FSH to GnRH stimulation at the dose used during the first 7 d after the induced ovulation. Together, these results are consistent with a temporary down-regulation of the pituitary gland in response to deslorelin administered in this manner.     

Interovulatory intervals in mares receiving deslorelin implants in Ireland (2009 to 2010)

Deslorelin acetate implants, recently licensed in Ireland and the UK for ovulation induction in mares, have been associated with prolonged interovulatory intervals in USA studies, leading to the practice of removing implants postovulation. Trial data in Australia indicate a less pronounced effect on interovulatory intervals, suggesting possible geographical variation. Objectives of the current study were to assess the effect of deslorelin implants, with and without removal on oestrous cycle length in Irish- and UK-based Thoroughbred broodmares. Data were collected retrospectively from 88 oestrous cycles. A statistically significant difference (P=0.02) was found between interovulatory intervals in mares in which the deslorelin implant was not removed, compared with administration and removal of the implant or the use of human chorionic gonadotrophin. The results suggest that implant removal when possible is advisable. The delay in subsequent ovulations was less marked than that reported in some studies from the USA. This information is useful in deciding when to schedule subsequent breeding for mares which received a deslorelin implant during the previous oestrous period and provides evidence to counter-concerns that mares treated with deslorelin implants may experience a long delay in return to oestrus if the implant is not removed.     

Clinical and endocrine responses to treatment with deslorelin acetate implants in ferrets with adrenocortical disease

OBJECTIVE: To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate. ANIMALS: 15 ferrets with ACD. PROCEDURE: Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically. RESULTS: Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk.     

Contraceptive effect and potential side-effects of deslorelin acetate implants in rats (Rattus norvegicus): Preliminary observations

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study.     

Comparison of two dosage regimens of the GNRH agonist deslorelin acetate on inducing ovulation in seasonally anestrous mares

This study investigated the efficacy of two dosage regimens of a potent GnRH analogue (GnRHa), deslorelin acetate, in inducing ovulation in seasonally anestrous mares. Forty-five seasonally anestrous mares were randomly assigned according to follicular size to one of three treatment groups: control, increasing GnRHa dose, and constant GnRHa dose. Treatment began on February 28 and continued until ovulation or for a maximum of seven treatments. Mares were palpated every other day until a 35 mm follicle was detected, then every day until ovulation or regression of the follicle occurred. Blood samples were taken from five randomly chosen mares in each treatment group and analyzed for LH levels.Twenty percent of mares in both deslorelin treatment groups ovulated, while no control mares ovulated during the treatment period. There was no difference in the number of mares that ovulated between treatment groups. Four of the six mares that ovulated were in transitional anestrus at the initiation of treatment, while only two were in deep anestrus.Concentrations of LH were greater (p=0.0008) in both GnRH-treated groups than in the control mares. Concentrations of LH did not differ between the two GnRH-treated groups until day 12 of treatment, when mares treated with a constant dosage had higher (p=0.0358) levels of LH than those treated with an increasing dosage. It is possible that administration of larger amounts of the GnRH agonist lowered the sensitivity of the pituitary to stimulation by GnRH.Deslorelin acetate did stimulate follicular growth and ovulation in a limited number of anestrous mares. Further investigation into the potential of this short-term implant to shorten the onsent of the breeding season is recommended.     

Efficacy of the gnrh agonist deslorelin acetate for inducing ovulation in mares relative to age of mare and season

Deslorelin acetate (Ovuplant™, Fort Dodge), a GnRH agonist, is commonly used to induce ovulation in cycling mares. Although its efficacy in hastening ovulation has been previously reported, the effects of age of mare and month of administration on percent of mares responding and interval to ovulation have not been studied.Data was gathered from reproduction records of 376 mares receiving deslorelin acetate at the Equine Reproduction Laboratory, Colorado State University, from 1995 to 1999. Age of mare, date of administration, size of largest follicle at treatment, and interval to ovulation were recorded. Age of mare was categorized into five groups: 2–4, 5–9, 10–14, 15–19, and greater than or equal to 20 years. Date of administration was divided into four groups: March and April, May and June, July and August, and September and October.A higher (p < 0.05) percentage of mares aged 10–14 (98.5%) ovulated in response to deslorelin acetate than mares aged 2–4 or 5–9 (90.2% or 91.0%, respectively) or mares aged 15–19 or ≥ 20 (87.9% or 83.8%, respectively). Mares ≥ 20 had the lowest ovulation rate (83.8%). However, mares ≥ 20 that responded to deslorelin acetate had a shorter (p < 0.05) interval from treatment to ovulation (1.7 ± 0.1 days) than mares 2–4 and 5–9 years of age (1.9 ± 0.1 and 1.9 ± 0.0 days, respectively).Deslorelin acetate was more effective in inducing ovulation in the July and August (95.4%) (p < 0.01) and September and October (95.7%) (p = 0. 04) than in the March and April (81.1%). Mares treated in May through October also experienced shorter (p < 0.05) intervals to ovulation than mares treated in March and April.     

Responses of cortisol and prolactin to sexual excitement and stress in stallions and geldings

Sexual stimulation induces rapid secretion of cortisol and prolactin (PRL) in stallions. Experiment 1 was designated to determine whether stallions associated location and(or) procedure with previous sexual stimulation in that location. After a control period on d 1, four stallions were exposed to an estrous mare for 5 min on d 2. On d 3, 4, 5, and 6, the same procedure was followed with no mare present. Concentrations of PRL and cortisol increased (P less than .05) after mare exposure on d 2 but did not vary (P greater than .05) on d 1, 3, 4, 5, or 6. In Exp. 2, six stallions were used to determine the short-term effects of 1) sexual stimulation, 2) acute physical exercise, 3) restraint via a twitch (twitching), 4) epinephrine administration, and 5) no stimulation on plasma concentrations of PRL and cortisol. Stallions received one treatment per day separated by 2 d of no treatment. Concentrations of cortisol increased (P less than .05) within 10 min after sexual stimulation, exercise, twitching, and epinephrine administration but not during control bleedings. Concentrations of PRL increased (P less than .05) immediately after sexual stimulation, exercise, and twitching but not after epinephrine administration or during control bleeding. In Exp. 3, the same five treatments were administered to six geldings. Concentrations of cortisol increased (P less than .05) after epinephrine administration, exercise, and twitching but not after sexual stimulation or during control bleedings. Concentrations of PRL increased (P less than .05) after exercise and sexual stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormone therapy for control of reproduction in mares and stallions

Because the reproductive performance of mares is lower than that of any other domesticated species, hormone therapy is important in ensuring fertility and proper management of pregnancy. Current techniques of hormone therapy are discussed.     

An outbreak of paresis in mares and geldings associated with equid herpesvirus 1

An outbreak of paresis occurred on a small isolated stud farm in July 1980. Of the 42 horses on the stud, infection was confined to a group of nine in-foal mares and their foals and eight other horses which were either housed together at night or grazed adjacent pastures. Eight mares and two geldings developed ataxia or paresis and one mare died. Equid herpesvirus 1 was isolated from 17 animals and serological studies confirmed that 24 of 26 animals sampled had experienced infection.     

Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares

The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin increased from the first to the second dose of the multiple dose oral study and then remained unchanged through 72 h. At 84 h after the first dose (i.e. 12 h after the final dose) the rifampin concentration was significantly decreased ( P = 0.001). The harmonic mean of the half-life of rifampin decreased significantly from 13.3 h after a single oral dose of 7.99 h after the seventh oral dose. The mean serum protein binding of rifampin over the concentration range of 2–20 μg/ml was 78%. Mean trough serum concentrations of unbound rifampin after multiple oral doses ranged from 0.67 μg/ml at 24 h to 0.40 μg/ml at 72 h. The mean unbound serum rifampin concentration at 84 h (i.e., 12 h after the final dose) was 0.30 μg/ml. Trough concentrations and the 84-h sample concentration of unbound rifampin exceeded the minimum inhibitory concentration for most gram positive bacterial isolates from horses reported in this study. All organisms with minimum inhibitory concentrations less than 0.125 μg/ml were considered susceptible.
Based on the pharmacokinetics of rifampin after p.o. administration, we concur with the current dosage recommendation of 10 mg/kg twice a day by mouth. At this dose, most streptococci, Rhodococcus equi , and coagulase-positive staphylococci would be considered susceptible to rifampin.     

Embryo transfer in competition horses: Managing mares and expectations

Embryo transfer (ET) is an accepted and successful technique for obtaining foals from mares without interrupting their competition careers. Recent research, however, suggests that the potential of factors including heat, exercise, repeated embryo flushing and repeated manipulation of the reproductive cycle using exogenous hormones to have a negative impact on fertility may have been underestimated. This paper reviews the evidence base for involvement of these factors in repeated failures to recover embryos from nongeriatric competition mares without obvious clinical or pathological indications of reproductive abnormalities. It concludes that, for some mares at least, a cessation of exercise for the periovulatory period and the period between ovulation and embryo flushing, combined with careful management of flushing‐induced endometritis, and minimal hormonal manipulation of the reproductive cycle, may be necessary to optimise embryo recovery rates. Mare owners may have been encouraged to request ET for their mares following high‐profile examples in the media of elite mares that have produced foals by ET whilst competing. The veterinarian should educate mare owners about the multiple factors that may affect the chances of recovering an embryo from their mares, and should manage the expectations of mare owners so that they do not approach ET programmes in the expectation that there will be no disruption to their training and competition plans.     

Reproductive efficiency of Flatrace and National Hunt Thoroughbred mares and stallions in England

REASONS FOR PERFORMING STUDY: Previous surveys of reproductive efficiency in British Thoroughbreds included only mares and stallions standing on studfarms in and around Newmarket. The present study was widened to compare Flatrace (FR) (Group A) and National Hunt (NH) (Group B) mares and stallions on studfarms throughout England. OBJECTIVES: To assess the influences of mare type, status and age, and veterinary manipulations on reproductive efficiency parameters. To compare the inherent fertility of stallions, based on singleton and twin pregnancy rates and pregnancy loss rates, in Groups A and B Thoroughbred breeding stock. METHODS: Managers of 24 FR and 9 NH public studfarms were asked to complete a questionnaire for each mated oestrous cycle shown by 2321 Group A and 1052 Group B mares throughout the 2002 mating season. Parameters such as per cycle singleton and twin pregnancy rates, and pregnancy loss rates were noted, and the success of hormone treatments to induce oestrus and ovulation assessed. The number of matings per oestrus and per pregnancy were recorded, together with the incidence and effectiveness of uterine and other veterinary treatments. The inherent fertility of 84 Group A and 43 Group B stallions in the study, as measured by the singleton and twin early pregnancy rates and the pregnancy loss rates recorded in the mares they mated, was also estimated. RESULTS: Per cycle early pregnancy (Days 13-16) was 63.2% for Group A and 65.3% for Group B mares; and 10.3% and 13.1%, respectively, of those pregnancies were twins or triplets. Early, middle and late pregnancy loss rates were 7.2% vs. 8.0% (Days 15-42), 3.6% vs. 6.1% (Days 42-1st October) and 2.7% vs. 2.1% (October-foaling), respectively. Matings per oestrus and per early pregnancy were significantly higher in Group B vs. Group A mares. For stallions that mated > or = 30 mares, overall early pregnancy rates per cycle in mares mated ranged from 30-89% across the 2 groups. CONCLUSIONS: No major differences in reproductive efficiency were identified between FR and NH mares and stallions. Increasing mare age was the single biggest limiting factor to an otherwise high rate of fertility in well-managed English Thoroughbreds. POTENTIAL RELEVANCE: This study identified factors that influence reproductive efficiency in the Thoroughbred.     

Prevalence of mycoplasmas in the semen and vaginal swabs of Danish stallions and mares

The reproduction rate of horses is one of the lowest within domestic livestock despite advances the veterinary medicine. Infertility in horses may be due mainly to the lack of suitable selection criteria in the breeding of horses. However, acquired infertility due to genital, bacterial infections may occur. Mycoplasmas have been implicated in genital disorders and infertility of many species including humans and horses. However, their role as commensals or pathogens of the genital tract of horses is still not determined. Bacteriological examinations made on the fossa glandis, urethra, penis and semen of stallions, showed the presence of different Mycoplasma species. Therefore our study aimed to find the prevalence of Mycoplasma species and a possible association with fertility problems in Danish riding horses. Eighty semen samples from stallions and 19 vaginal swab samples from mares were tested by PCR for presence of mycoplasmal DNA. The vaginal swab samples were also cultured in the Mycoplasma specific medium. None of the samples were positive for presence of genital mycoplasmas during the screen. The lack of genital mycoplasmas observed in this study may be due to a very extensive use of artificial insemination of modern sport horses.     

The effect of the age of stallions and mares on their fertility

The study was based on the documentation of the Napajedla Stud Farm of the English Thoroughbred horse for 1888-1972. Evaluating the effect of the age of stallions on their fertility (leaving aside the variability of the age of their mothers), such an effect was found to be significant only in four out of the 26 studs evaluated. In 65% of the selected stallions, the correlation coefficients were found to be negative, but without statistical significance. However, the objective of the study was to evaluate stallions and mares parallelly as to their age variability and fertility. The relationships of the effect of the age of the stallion and of the mare on fertility were evaluated by different modificatons of the value chi2. The prerequisite for the analyses of the effect of different stallion age at a constant age of mares was the calculation of the global chi2 used jointly for the evaluation of the variable age of stallions and mares. The result are varied and report on the individuality of the effect of stallions, giving no clear basis for generalizing any fertility-decreasing tendency with the higher age of the parents. The problem is analyzed from the physiological viewpoint.