Efficacy and toxicity of estrogens commonly used to terminate canine pregnancy

Three groups of bitches were treated with diethylstilbestrol (75 micrograms/kg) orally for 7 days (n = 12), estradiol cypionate intramuscularly once (22 micrograms/kg; n = 12), or estradiol cypionate intramuscularly once (44 micrograms/kg; n = 12). Treatments commenced during late proestrus (n = 4/group), the fourth day of behavioral estrus (n = 4/group), or the second day of diestrus (n = 4/group). All bitches were bred on alternate days throughout estrus to stud dogs of known fertility. Ovariohysterectomies were performed on day 25 of diestrus to diagnose pregnancy and to assess any pathologic changes in the uterus. Eleven bitches treated with diethylstilbestrol, 6 bitches treated with the low dosage of estradiol cypionate, and 4 bitches receiving the high dosage of estradiol cypionate were pregnant at the time of surgery. Ten of the bitches treated with estrogens during proestrus, 6 treated during estrus, and 4 treated during diestrus were pregnant. The serum concentration of progesterone in 2 bitches treated with the high dosage of estradiol cypionate decreased to less than 2 ng/ml by day 25 of diestrus, suggesting premature luteal regression. Diethylstilbestrol appeared to have little efficacy in terminating pregnancy. Estradiol cypionate appeared to have greater efficacy when administered during estrus or early diestrus; however, pyometra developed in 2 bitches treated with this estrogen during diestrus.     

Concentration of receptors for estradiol and progesterone in canine endometrium during estrus and diestrus

Receptors for estrogen and progesterone were measured in cytosols prepared from specimens of canine endometrium obtained at late proestrus, day 4 of estrus, day 2 of diestrus, and at 10 day intervals from days 10 through 80 of diestrus. Twenty nine adult bitches were used, with 2 to 4 dogs used at each time point. Concentrations of estradiol receptors measured in endometrial cytosols from late proestrus through day 10 of diestrus were similar (mean +/- SEM: 9.9 +/- 2.2, 10.5 +/- 1.2, 16.3 +/- 1.6, and 16.2 +/- 2.9 pmol/g of tissue at proestrus, day 4 of estrus, days 2 and 10 of diestrus, respectively). As serum concentrations of progesterone increased during early diestrus, the concentration of estradiol receptors decreased and were significantly (P less than 0.05) lower on days 30 (4.9 +/- 1.3 pmol/g of tissue) and 40 (3.7 +/- 0.6 pmol/g of tissue) of diestrus. After day 40 of diestrus, when serum concentrations of progesterone were approaching basal concentrations, the concentration of estradiol receptors increased and remained significantly (P less than 0.05) higher from days 60 to 80 of diestrus (day 60, 13.4 +/- 2.9; day 70, 15.7 +/- 1.7; day 80, 19.8 +/- 2.4 pmol/g of tissue). As observed for estrogen receptors, the concentration of endometrial receptors for progesterone also gradually increased from late proestrus (4.9 +/- 1.3 pmol/g of tissue) to day 2 of diestrus (6.4 +/- 0.3 pmol/g of tissue).(ABSTRACT TRUNCATED AT 250 WORDS)     

Shortening of interestrous intervals with cabergoline in bitches: a clinical trial

Two consecutive interestrous intervals (n=46) were recorded in 23 bitches of different breeds. At varying times after day 100 from the onset of the second proestrus, cabergoline (5 microg/kg per os q 24 hours) was administered from early (n=11), mid- (n=10), and late (n=2) anestrus until 2 days after the beginning of the following proestrus. Interestrous intervals (IEI) were significantly shorter in the cabergoline-treated time periods when compared to the nontreated IEI (184+/-4.5 days versus 239+/-4.5 days; P<0.01). The mean number of days of cabergoline treatment until the onset of proestrus was 21.4+/-2.9 (least square means and standard error of the mean [LSM+/-SEM]). Mean cabergoline treatment durations beginning in early, mid-, and late anestrus were 27.4+/-3.7, 17.6+/-3.8, and 5+/-3 days (LSM+/-SEM), respectively. A significant correlation was found between the stage of anestrus in which the treatments began and the duration of the treatments required to induce estrus (0.51, P=0.01).     

Efficacy and toxicity of tamoxifen citrate for prevention and termination of pregnancy in bitches

Five groups of bitches were given tamoxifen citrate (1 mg/kg of body weight) orally twice daily for 10 days. Drug administration commenced during late proestrus, day 4 of estrus, day 2 of diestrus, day 15 of diestrus, or day 30 of diestrus (n = 4/group). Nineteen of the bitches accepted natural mating by 1 or more of 3 stud dogs of known fertility (1 bitch did not). Twenty days after cessation of drug administration, ovarian, uterine, and hepatic specimens were obtained from each bitch in 4 of the groups. Pregnancy proceeded to natural termination in bitches of the remaining group (diestrous day 30). Pregnancy was not detected in any bitch of the proestrus, estrous, or early diestrous groups. Of 4 bitches of each of the remaining groups (diestrous day 15 and diestrous day 30), 2 aborted fetuses and/or resorbed placental remnants; the other 2 bitches in each of these groups had normal-appearing fetuses (diestrous day-15 group) or clinically normal pups (diestrous day-30 group). Of the 20 bitches given tamoxifen citrate, 5 developed endometritis with or without pyometra, and 4 of these had ovarian cysts. Although tamoxifen citrate is effective for preventing or terminating pregnancy in the bitch, the regimen used in the study reported here was associated with high frequency of pathologic changes in the reproductive tract.     

Concentrations of testosterone in canine serum during late anestrus, proestrus, estrus, and early diestrus

Serum testosterone concentrations in samples collected daily from 6 bitches for at least 60 days before the onset of diestrus were determined by radioimmunoassay. Mean serum concentrations (+/- SEM) of testosterone ranged from 31 +/- 11 to 141 +/- 63 pg/ml during late anestrus. Mean testosterone concentrations during proestrus ranged from 106 +/- 29 to 239 +/- 113 pg/ml, with the highest concentration (526 +/- 225 pg/ml) occurring the day of the preovulatory surge of luteinizing hormone. Although the ovaries may be sites of production during late anestrus, proestrus, estrus, and early diestrus, further investigation is necessary to determine whether testosterone has an important physiologic or endocrinologic function in the bitch (ie, sexual behavior, vaginal hypertrophy, and luteinizing hormone surge).     

Use of pulsatile intravenous administration of gonadotropin-releasing hormone to induce fertile estrus in bitches

The pulsatile IV administration of gonadotropin-releasing hormone (GnRH) was evaluated as a method to induce fertile estrus in 8 anestrous Beagle bitches. Bitches received 1.25 micrograms of GnRH every 90 minutes for 11 to 13 days. Gonadotropin-releasing hormone was delivered by use of an automatic pump. Reproductive history was known for all bitches, 4 of which, on the basis of 3 or 4 preceding cycles, had an interestrous interval of 219 +/- 14 days (mean +/- SEM). Estrus induction was attempted during early anestrus in 6 bitches (ie, 148 +/- 10 days since the preceding estrus) and late anestrus in 1 bitch (ie, 260 days since the preceding estrus); another bitch had not had an estrous cycle for nearly 2 years before GnRH administration. Signs of estrus were seen within 16 days after the start of GnRH administration in the bitches with regular estrous cycles (group 1, n = 7), and within 23 days in the bitch (group 2) with prolonged anestrus. All bitches were bred, and 7 of 8 (87.5%) became pregnant, with a mean litter size of 4.5 +/- 0.75. A normal hormonal response pattern was observed in group-1 bitches--a peak increase in plasma estrogen concentration of 22.3 +/- 2 pg/ml immediately before the onset of estrus. Peak plasma progesterone concentration (17.3 +/- 3 ng/ml) was observed 1 to 14 days after the onset of diestrus in the group-1 bitches that ovulated, and adequate plasma progesterone concentration was maintained throughout gestation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uterine motility during the estrous cycle: studies in healthy bitches

Natural and drug-induced uterine motilities (UM) were recorded via uterine-implanted catheter-tip pressure transducers in 5 bitches during proestrus and estrus and in 6 bitches during early (30 days) and late (60 days) diestrus. The UM was monitored in unanesthetized bitches for 2 days after the estrous-cycle stage had been determined by vaginal cytologic findings. Natural UM, expressed as Alexandria units (pressure X frequency X duration of contractions), was greatest during estrus, moderate during proestrus, and appreciably decreased or lacking during early and late diestrus. During proestrus and estrus, prostaglandin F2 alpha (5 micrograms/kg of body weight, IV) induced intrauterine pressures of 107 and 115 mm of Hg, respectively, and oxytocin (0.05 USP units/kg, IV) induced pressures of 106 and 116 mm of Hg, respectively. In contrast, the intrauterine pressure values induced by prostaglandin F2 alpha given IV during early and late diestrus were 61 and 58 mm of Hg, respectively, and for oxytocin, were 61 and 51 mm of Hg, respectively. Prostaglandin F2 alpha given IM (50 micrograms/kg) also induced a greater intrauterine pressure during proestrus and estrus than during diestrus. We concluded that in the bitch, natural and drug-induced UM are decreased during early and late diestrus.     

Megestrol acetate for estrus postponement in the bitch.

Megestrol acetate was given orally to 389 bitches in early proestrus, at a dosage of 2.2 mg/kg (1 mg/lb) per day for 8 days. Estrus was suppressed in 357 (92%) of the bitches. Additionally, 119 bitches in anestrus were given the drug at the rate of 0.55 mg/kg (0.25 mg/lb) per day for 32 days. Estrus was suppressed in 115 (98%) of these bitches. Adverse effects were minimal. Pyometra developed in 3 (0.8%) of the 389 bitches treated in early proestrus. The drug also was given to 19 bitches at the rate of 0.55 mg/kg/day for 32 days, regardless of the stage ofting at the 1st posttreatment estrus and 4 after mating at the 2nd posttreatment estrus. Litter size, success in rearing pups, and sex ratios were not significantly different from these factors in 53 litters from untreated bitches.     

Expression and regulation of Enpp2 in rat uterus during the estrous cycle

Ectonucleotide pyrophosphatase/phosphodiestrase 2 (Enpp2) isolated from the supernatant of human melanoma cells is a lysophospholipase D that transforms lysophosphatidylcholine into lysophospatidic acid. Although multiple analyses have investigated the function of Enpp2 in the hypothalamus, its role in the uterus during the estrous cycle is not well understood. In the present study, rat uterine Enpp2 was analyzed by RT-PCR, Western blotting, and immunohistochemistry. Quantitative PCR analysis demonstrated that uterine Enpp2 mRNA was decreased during estrus compared to proestrus and diestrus. To determine whether uterine Enpp2 expression is affected by sex steroid hormones, immature rats were treated with 17β-estradiol (E2), progesterone, or both on postnatal days 14 to 16. Interestingly, the expression of Enpp2 mRNA and protein were down-regulated by E2 in the uterus during estrus but not during proestrus or diestrus, suggesting that Enpp2 may play a role in uterine function during estrus. Enpp2 is primarily localized in the stromal cells of the endometrium during proestrus and estrus. During diestrus, Enpp2 was highly expressed in the epithelial cells of the endometrium. Taken together, these results suggest that uterine Enpp2 may be regulated by E2 and plays a role in reproductive functions during female rat development.     

Estrus cycle effect on muscle tyrosine kinase activity in bitches

Estrus cycle is a well recognized cause of insulin resistance in bitches. The insulin receptor (IR) as well as the insulin-like growth factor-I receptor belong to the same subfamily of tyrosine kinase (TK) receptors. The objective of this study was to evaluate basal TK activity in muscle tissue of bitches during the estrus cycle. Twenty-four bitches were used in the study (7 in anestrus, 7 in estrus, and 10 in diestrus). Muscle samples, taken after spaying surgery to determine TK activity, were immediately frozen in liquid nitrogen and then stored at −80°C until the membranes were prepared by sequential centrifugation after being homogenized. TK activity was determined by Poly (Glu 4:Tyr 1) phosphorylation and expressed in cpm/μg of protein. TK activity was significantly lower (P < 0.001) in the animals in estrus (104.5 ± 11.9 cpm/μg of protein) and diestrus (94.5 ± 16.9 cpm/μg of protein) when compared with bitches in anestrus (183.2 ± 39.2 cpm/μg of protein). These results demonstrate, for the first time, lower basal TK activity in the muscle tissue of female dogs during estrus and diestrus, which may represent lower insulin signaling capacity, opening a new field of investigation into the molecular mechanisms of insulin resistance in dogs.     

Temporal sequence of events in the estrous cycle of the bitch.

Serum concentrations of luteinizing hormone (LH), estradiol-17 beta, and progesteron were compared with the onset of diestrus in Beagle bitches. The LH peak occurred 8.0 (standard error (SE), 0.3) days before the onset of diestrus. Vaginal cytologic characteristics during proestrus were studied, and vaginal cornification was complete 12.1 (SE,0.2) days before the onset of diestrus. A time sequence of hormonal, vaginal cytologic, and developmental events was outlined during proestrus, estrus, and early diestrus.     

Effect of sex and reproductive status on sucrose preference, food intake, and body weight of dogs

In a study of preferences for diets containing 1% to 20% sucrose over a bland diet, both female and male dogs preferred the diets containing sucrose over a bland diet, but female dogs had a significantly (P less than 0.05) greater preference for 1% sucrose than did males. Differences between sexes were not observed at the higher concentrations. Mean daily caloric intake was calculated for 12 bitches fed ad libitum during metestrus, estrus, and anestrus, as determined from metachrome-stained vaginal smears. Mean daily caloric intake was lowest during estrus (149 +/- 17 kcal/kg of body weight), was higher during metestrus (159 +/- 8 kcal/kg of body weight), and was highest (175 +/- 9 kcal/kg of body weight) during anestrus. Ovariohysterectomized bitches gained significantly (P less than 0.01) more weight (1.3 +/- 0.3 kg) in the first 10 days after surgery than did sham operated controls (0.3 +/- 0.1 kg). Food intake also was significantly greater ( less than 0.01) in the ovariohysterectomized bitches (1,708 kcal/day) than in the sham operated controls (1,423 kcal/day). Depth of subcutaneous fat in shoulder, rib, and rump areas of ovariohysterectomized bitches was not significantly different from that of intact bitches.     

Vascular Endothelial (VEGF) and Epithelial Growth Factor (EGF) as Well as Platelet‐Activating Factor (PAF) and Receptors are Expressed in the Early Pregnant Canine Uterus

The aim of this study was to investigate the course of expression of platelet‐activating factor (PAF), PAF‐receptor (PAF‐R), epidermal growth factor (EGF), EGF‐R, vascular endothelial growth factor (VEGF), VEGF‐R1 and VEGF‐R2 in uterine tissue during canine pregnancy. For this purpose, 20 bitches were ovariohysterectomized at days 10–12 (n = 10), 18–25 (n = 5) and 28–45 (n = 5) days after mating, respectively. The pre‐implantation group was proven pregnant by embryo flushing of the uterus after the operation, the others by sonography. Five embryo negative, that is, non‐pregnant, bitches in diestrus (day 10–12) served as controls. Tissue samples from the uterus (placentation sites and horn width, respectively) were excised and snap‐frozen in liquid nitrogen after embedding in Tissue Tec^®. Extraction of mRNA for RT‐PCR was performed with Tri‐Reagent. In the embryos, mRNA from all factors except VEGF was detected. In the course of pregnancy, significantly higher expression of PAF and PAFR as well as VEGF and VEGFR2 during the pre‐implantation stage than in all other stages and a strong upregulation of EGF during implantation were characteristic. The course of EGF was in diametrical opposition to the course of the receptor. These results point towards an increased demand for VEGF, EGF and PAF during the earliest stages of canine pregnancy.     

Cytoplasmic estrogen and progesterone receptors in canine endometrium during the estrous cycle

Estradiol and progesterone receptors (ER, PR) were characterized and measured in cytosols from canine endometrium, using saturation and sucrose-gradient centrifugation radioassays. Both receptors were demonstrated to be steroid- and tissue-specific saturable proteins, which bound the respective steroids with high affinity (dissociation constant [Kd] approximately 10(-9)M). Serum estradiol, progesterone, and endometrial cytosol receptor concentrations and receptor-binding affinity were measured for 25 bitches from which samples were obtained at 5 stages of the estrous cycle (5 bitches each): anestrus (A), the 3rd day of proestrus (P3), the 3rd day of estrus (E3), the 12th day after onset of estrus (E12), and the 28th day after onset of estrus (E28). Mean (+/- SEM) serum estradiol concentrations were 17.0 +/- 2.2 (A), 55.4 +/- 5.0 (P3), 89.4 +/- 24.9 (E3), 41.0 +/- 5.9 (E12), and 50.6 +/- 3.9 (E28) pg/ml. Mean (+/- SEM) serum progesterone concentrations were 0.4 +/- 0.1 (A), 1.5 +/- 0.2 (P3), 17.3 +/- 7.5 (E3), 41.6 +/- 9.5 (E12), and 25.8 +/- 3.2 (E28) ng/ml. Concentrations of ER increased significantly from 1.06 pmol/g of uterus during stage A to a peak concentration of 6.18 pmol/g of uterus at E12, followed by a gradual decrease to 0.69 pmol/g of uterus by E28. The PR concentrations increased from 3.01 pmol/g of uterus in stage A to 17.32 pmol/g of uterus at P3; PR concentrations, thereafter, decreased gradually to 1.85 pmol/g of uterus by E28. Dissociation constants were significantly higher at E12 for the ER (Kd = 2.6645 X 10(-9)M) and at P3 for the PR (Kd = 5.8282 X 10(-9)M) than at the other stages examined, indicating a decrease in receptor affinity during the periods of high receptor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of estrus in greyhound bitches with prolonged idiopathic anestrus or with suppression of estrus after testosterone administration

Twelve anestrous adult Greyhound bitches were used to study a regimen for induction of estrus. Once daily, 7 bitches were given diethylstilbestrol (DES; 5 mg, PO) until sanguineous vaginal discharge and vulvar edema were observed (designated as day 1 of proestrus) and for 2 days thereafter. If no response was elicited after 7 days, a doubled DES dose was given for up to an additional 7 days. Luteinizing hormone (5 mg, IM) was given on day 5 of proestrus, and follicle-stimulating hormone (10 mg, IM) was given on days 9 and 11 of proestrus. Bitches were bred once on day 13. Five bitches were used as a control group; they were given candy tablets for 7 days (first day on tablets, treatment day 1) and 0.9% NaCl (1.0 ml, IM) on treatment days 12, 16, and 18. The 7 bitches treated with DES had a mean proestrus period of 7.7 days and a mean estrus period of 5.7 days up to the day of mating. After mating, they had a mean gestation interval of 64 days and delivered a mean of 4 pups/litter. In 5 bitches, initial treatment with 5 mg of DES/day induced proestrus within 7 days; however, in 2 bitches, additional treatment with 10 mg of DES/day was needed for 5 and 6 days, respectively. Serum estradiol-17 beta and progesterone concentrations remained at base line during the period of DES treatment. Concentrations of both hormones increased after injection with luteinizing hormone and remained high for the next 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term study of aerobic bacteria of the genital tract in breeding bitches.

The aerobic bacterial flora of the genital tract was characterized in 59 bitches in an 18-month study. The bitches represented 4 breeds and were from 3 kennels. Collection of vaginal swab specimens for bacterial culturing was performed every month, except during estrus when specimens were collected every week (n = 826). The capsule of the swab containing transport media was broken before specimen collection to moisten the tip, which helped to reduce the number of negative cultures. All bitches helped at least once during the study and, thus, had known reproductive functions. Pregnancy rates, litter sizes, and pup mortality were within normal limits. Pasteurella multocida, beta-hemolytic streptococci group G, and Escherichia coli were the most common bacteria isolated. Although these species generally were isolated from mixed cultures, pure cultures were obtained from 18% of the specimens. There was a tendency for the various breeds to differ in their vaginal bacterial flora. The flora also varied during the reproductive cycle. Pasteurella multocida was isolated significantly more often during proestrus, estrus, metestrus, and pregnancy, than during anestrus and the postpartum period, and beta-hemolytic streptococci were isolated significantly more often during proestrus than during estrus, pregnancy, or the postpartum period. Staphylococcus intermedius was almost exclusively found after parturition. Culture results were negative for only 5.2% of specimens cultured. On the basis of our findings, bacterial culturing of vaginal swab specimens from bitches without signs of genital disease is of little value.     

Recovery and light microscopic evaluation of follicular oocytes of swine and relationship between the degeneration rate of oocytes and the estrus phase

Cumulus-oocyte complexes were recovered from 25 gilts by aspiration of follicular fluid or cutting of follicles from all Graafian follicles of greater than or equal to 3 mm in diameter during diestrus, proestrus or estrus. In 5 gilts the oocytes were collected post ovulation by flushing of oviducts. The recovery rate of follicular oocytes differed between 75.5% during the late diestrus (days 13-17) and 43.5% during the proestrus (days 18-21). During the proestrus and on day 1 of the estrus the recovery of oocytes was more difficult as a result of the higher viscosity of follicular fluid and the mucification of cumulus-oocyte complexes. The degeneration rate of oocytes was high during the diestrus with a peak at the time of regression of corpora lutea. From diestrus to the estrus the degeneration rate decreased. Following degeneration rates were found in the oocytes during the cycle: days 7-12: 38.8%, days 13-17: 50.0%, days 18-21: 29.6%, day 1 of the estrus: 10.8%, day 2 of the estrus ante ovulation: 11.8%, day 2 of the estrus post ovulation: 6.2%. Signs of degeneration were: Loss of cumulus cells (during diestrus and proestrus), damaged zona pellucida, enlargement of perivitelline space, deformation of oocyte, alteration of structure of the ooplasm, diameter of vitellus less than 100 microns. It was concluded that the selection of dominant follicles takes place in pigs during a long time of the cycle, especially during the diestrus. There were not any indications of a 2-wave hypothesis of follicular growth during the cycle in pig.     

Pregnancy rate in beef heifers after synchronization to either random or programmed estrous cycles

We hypothesized that heifers in diestrus at the beginning of a Syncro-Mate-B (SMB) regimen would have higher pregnancy rates to AI than heifers not in diestrus and that administration of a PGF2alpha analogue 11 d before a SMB regimen would increase pregnancy rates to AI. In both replicate years of Exp. 1, heifers (n = 150) were classified by stage of the estrous cycle at the beginning of a SMB regimen (d 0). Following implant removal (d 9), heifers were artificially inseminated 12 h after the onset of estrus (95.5% in estrus by 72 h). Blood samples were collected for progesterone (P4) analysis on d 0, 9, and 20. Pregnancy rates did not differ between yr 1 and 2. Pregnancy rate for heifers classified in diestrus (53.6%; n = 69) was higher (P = 0.06) than for heifers in metestrus (43.7%; n = 48). Pregnancy rate for proestrus (44.4%; n = 18) heifers was not different from that for heifers in the metestrus or diestrus groups. Mean plasma P4 concentration was affected by both treatment and day. Pregnancy rate was higher (P < 0.01) for heifers with P4 > 1 ng/mL plasma (51.6%; n = 120) than for heifers with P4 < or = 1 ng/mL plasma (23.3%; n = 30) on d 0. In Exp. 2, beef heifers (Santa Cruz; n = 195) were allotted to two treatments. Heifers (n = 98) in the control group were administered a conventional SMB treatment. Heifers (n = 97) in the PGF group were injected with PGF2alpha 11 d (d -11) before a SMB regimen. Progesterone concentration was determined from blood samples collected on d -11, -2, 0, and 9. All heifers were artificially inseminated 48 to 50 h after implant removal. At the beginning of the SMB regimen (d 0), a greater (P < 0.05) percentage of PGF (74.2%) than of control heifers (59.2%) were in diestrus (P4 > 1 ng/mL). Mean P4 concentration was not affected by treatment or day x treatment but differed (P < 0.05) among days. Pregnancy rate of cycling heifers was similar for PGF (36%) and control heifers (35.9%). Pregnancy rate was higher (P < 0.01) for heifers with P4 > 1 ng/mL plasma (37.6%) than for heifers with P4 < or = 1 ng/mL plasma (18.5%) on d 0. These results support the hypothesis that fertility is enhanced when a progestin synchrony regimen is initiated during diestrus, but methods to program estrous cycles to increase fertility warrant investigation.     

Use of cabergoline to treat primary and secondary anestrus in dogs

OBJECTIVE: To determine whether cabergoline would be safe and effective for induction of estrus in dogs with primary or secondary anestrus. DESIGN: Prospective case series. ANIMALS: 6 privately owned otherwise healthy pure-bred dogs with primary or secondary anestrus. PROCEDURE: Dogs were treated with cabergoline (5 microg/kg [2.3 microg/lb], p.o., q 24 h) until 2 days after the onset of proestrus. Follicular development was assessed by means of cytologic examination of vaginal smears; ovulation was assessed by measuring serum progesterone concentration 3 weeks after the onset of estrus. Five bitches were mated during behavioral estrus. RESULTS: All dogs had normal estrus periods, and all 5 dogs that were mated whelped normal litters. Mean duration of cabergoline treatment was 16 days. None of the dogs had any adverse effects associated with cabergoline administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of cabergoline is safe and effective for treatment for primary and secondary anestrus in dogs.