Objective The primary aim of this study was to investigate the contraceptive efficacy of a self‐assembling uterine device (iUPOD™) in the mare. In addition, the effects of iUPODs on oestrous cyclicity, uterine health and circulating concentrations of cortisol were evaluated. Methods Domestic mares underwent oestrous monitoring and artificial insemination. After subsequent ovulation, mares underwent either placement (n = 7) or sham placement (n = 7; controls) of an iUPOD device. Devices were left in place for at least 3 months. Pregnancy diagnoses were carried out 14 days post‐ovulation, with any pregnancies terminated at 28 days post‐ovulation. All mares underwent weekly blood sampling with or without reproductive examinations throughout the study. Towards the end of the study, multiple serum samples collected over three consecutive days were analysed for concentrations of cortisol. Endometrial biopsies were collected before artificial insemination and during the subsequent breeding season. Endometrial cytology and bacterial cultures were performed before device removal (iUPOD mares) or at the end of the study (control mares). Results Pregnancies were diagnosed in 0 of 7 iUPOD mares versus 7 of 7 control mares. Placement of iUPODs was associated with extended luteal phases and variable accumulations of intra‐uterine fluid. Bacterial culture results suggested that the mild endometritis associated with iUPODs was sterile in six of seven mares. Short‐term placement of iUPODs had no detrimental effects on endometrial architecture. Mean serum cortisol concentrations were significantly lower in iUPOD mares than control mares. Conclusion iUPODs represent a promising means of fertility control in the mare.

Background Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses. Hypothesis/Objective Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses. Animals Eight Standardbred geldings. Methods A PK study was performed followed by a placebo‐controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography‐mass‐spectrometry. PK indices were estimated by fitting a 2‐compartment model using nonlinear least squares regression. An oral glucose test (OGT) was conducted before and 4, 24, 72, and 144 hours after administration of sirolimus or placebo. Effects of time, treatment and animal on blood glucose and insulin concentrations were analyzed using mixed‐effects linear regression. Sirolimus was then administered to 4 horses with dexamethasone‐induced ID and an OGT was performed at baseline, after ID induction and after 7 days of treatment. Results Median (range) maximum sirolimus concentration was 277.0 (247.5‐316.06) ng/mL at 5 (5‐10) min and half‐life was 3552 (3248‐4767) min. Mean (range) oral bioavailability was 9.5 (6.8‐12.4)%. Sirolimus had a significant effect on insulin concentration 24 hours after a single dose: median (interquartile range) insulin at 60 min (5.0 [3.7‐7.0] μIU/mL) was 37 (−5 to 54)% less than placebo (8.7 [5.8‐13.7] μIU/mL, P = .03); and at 120 min (10.2 [8.4‐12.2] μIU/mL) was 28 (−15 to 53)% less than placebo (14.9 [8.4‐24.8] μIU/mL, P = .02). There was minimal effect on glucose concentration. Insulin responses decreased toward baseline in ID horses after 7 days of treatment. Conclusion and Clinical Importance Sirolimus decreased the insulinemic response to glucose and warrants further investigation.

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