Evaluation of estrous activity in bitches treated with mibolerone and exposed to adult male dogs.

Over approximately a 16-month period, adult male dogs had no influence on estrous activity in bitches treated with an estrus prevention agent (mibolerone). In addition, there was no obvious effect on interestrous interval in untreated bitches.

Effects of mibolerone on conception, pregnancy, parturition, and offspring in the Beagle.

Mibolerone was administered to Beagle bitches at dose levels of 20 or 60 microgram/day, starting 1,3, or 6 days after the 1st breeding and continuing until the offspring were weaned. Adverse effects on conception, pregnancy, or parturition were not observed in the treated bitches. Female offspring were masculinized. There were no gross effects on the male offspring.

Serum concentrations of mibolerone in Beagle bitches as influenced by time, dosage form, and geographic location.

A radioimmunoassay was developed for the assay of mibolerone in the serum of adult bitches with a lower limit of detection of 0.5 ng of mibolerone/ml of serum. Serum concentrations in Beagle bitches given mibolerone were found to be dependent on concentration in and type of formulation. The type of formulation also influenced the time to reach peak serum concentrations of mibolerone. Serum concentrations were also different for the same animals treated at 2 geographic locations.

Clinical, morphologic, and clinicopathologic findings in Beagles treated for two years with melengestrol acetate.

Melengestrol acetate (MGA) was administered orally to groups of 10 female and 3 male Beagles at doses of 0, 1, 2, or 8 microgram/kg of body weight/day for 2 years. Treatment was continuous at the same dose rate in the first 3 groups, but in the 4th group, the dose for bitches was reduced to 4 microgram of MGA/kg/day during the 2nd year. Matings were made within MGA-dosage groups and among 10 additional bitches treated at 1 microgram of MGA/kg/day and the dogs treated at 8 microgram/kg/day. Doses of 8 and 4 microgram of MGS/kg caused progestational effects on the uterus resulting in expected histopathologic changes, dystocia, and pyometritis. Leukocytosis, normocytic, hypochromic anemia, and increased alkaline phosphatase values were the results of systemic and uterine effects consistent with the indirect and expected pharmacologic action of progestational agents in the bitch. Doses of 1 and 2 microgram of MGA/kg in dogs and bitches and 8 microgram/kg in dogs produced no significant differences in clinical observations, hematologic findings, blood chemical analysis, urinalysis, organ weights, or gross and microscopic observations at necropsy.

Biological evaluation of mibolerone in the female Beagle.

Mibolerone effectively inhibited estrous activity in immature or mature Beagle bitches given 60 and 200 microgram, respectively, daily for up to 730 days. A dose level of 20 microgram of mibolerone daily was 70% effective in preventing estrus. Effects of mibolerone included estrus inhibition prolongation of the interestrous interval in bitches given 20 microgram of the mibolerone daily, vaginal discharge, and a dose-related increase in clitoral size. A decrease in posttreatment conception rate was observed only in bitches receiving 20 microgram of mibolerone daily for 730 days. Pups born to bitches conceiving after mibolerone treatment were grossly normal.

Seasonal incidence of estrus and interestrous interval for bitches of seven breeds.

For 7 breeds of bitches (Toy Poodle, Cocker Spaniel, Basset Hound, Boston Terrier, German Shepherd Dog, Pekingese, and Beagle), estrous activity occurred in all seasons. Differences in seasonal incidence of estrus were not statistically significant when compared within the total group or within and between breeds. The German Shepherd Dog breed had the shortest interestrous interval (149 +/- 28.5 days), which was significantly different from that of the other breeds. Means interestrous interval in parous Beagle bitches was not significantly different from that in nonparous Beagle bitches. In Beagle bitches, the mean interval between fertile estrous periods was not significantly different from the mean interval between nonfertile estrous periods.

A 280-day tolerance-efficacy study with mibolerone for suppression of estrus in the cat.

Mibolerone, a synthetic anabolic steroid, prevented estrus in domesticated cats when orally given a daily dose of 50 microng over a 180-day period. Doses of 20 microng daily and 50 microng given once a week failed to prevent estrus. Treatment with the 50-microng dose each day for 6 months had no apparent effects on subsequent estrus, mating, queening, or litter size. Kittens born to queens which had been treated did not have obvious developmental defects. Systemic metabolic changes produced by treatment were detected only in thyroid function, as revealed in dose- and time-related changes in serum cholesterol concentrations, thyroid gland weights, and thyroid histology. Clinical evidence of thyroid dysfunction was not apparent during the 6 months of treatment. Clinical and microscopic evidence of slight masculinization was apparent in cats after 3 months of treatment with 20 or 50 microng per day. Masculinizing changes consisted of thickening of the cervical dermis and clitoral hypertrophy. Behavioral changes were not observed. The apparent mechanism of action of mibolerone in the cat is the suppression of the release of pituitary luteinizing hormone.

Effect of prostaglandin F2alpha-THAM in the bitch.

The subcutaneous median lethal dosage for prostaglandin F2alpha for the Beagle bitch was determined to be 5.13 mg/kg, using a sequential experimental design. Clinical signs and gross and histologic findings were consistent with a diagnosis of shock syndrome. It was concluded that prostaglandin F2alpha could be used to develop a pharmacologically controlled shock model.

Evaluation of selected compounds for estrus control in the bitch.

Steroidal and nonsteroidal compounds were evaluated for estrus inhibition in the bitch. Mibolerone, an anabolic steroid, was effective and appeared to be safe. The remaining compounds lacked efficacy or had extensive side effects, or both.

Effects of melengestrol acetate on reproduction in the Beagle bitch.

Melengestrol acetate orally given to bitches at dose levels of 200 mug or more each day effectively inhibited estrous activity for a treatment period of 243 days and a lapsed period of more than 400 days from the preceding estrous period. The 100-mug dose of the drug, given orally once a day, starting immediately after the bitches were bred or late in gestation, had no effect on conception, pregnancy, or parturition. Gestation was prolonged in bitches given melengestrol acetate starting 1 day after breeding. Drug-polymeric implants blocked reproductive activity, and the progestogen induced cystic endometrial hyperplasia.

Antigenicity of sodium carboxymethyl cellulose with or without 9-fluoroprednisolone acetate in the adult cow.

Multiple intramuscular injections of sodium carboxymethyl cellulose with or without 9-fluoroprednisolone acetate were not antigenic in the cow, as measured by anaphylactoid response or delayed hypersensitivity.

Histologic evaluation of gallbladder in progestogen-treated bitches.

Adverse histologic effects were not observed in the gallbladder mucosa of selected bitches with endometrial hyperplasia experimentally induced by administration of exogenous medroxyprogesterone acetate.