Original Research
Evaluation of Injectable Sustained Release Progestin Formulations for Suppression of Estrus and Ovulation in Mares

https://doi.org/10.1016/j.jevs.2008.11.007Get rights and content

Abstract

Thirty-one mares were used in an experiment to evaluate the effectiveness of three sustained-release injectable formulations of altrenogest and one formulation of medroxyprogesterone acetate (MPA) for long-term suppression of estrus and ovulation. Luteolysis was induced by injection of prostaglandin-F (Lutalyse) on day 0 (6th day after the previous ovulation) and was immediately followed by treatment with 1) no injection (controls; n = 7), 2) 1.5 mL of an altrenogest solution in sustained-release vehicle (LA 150, 1.5 mL; 225 mg altrenogest; n = 6), 3) 3 mL (450 mg altrenogest) of the same solution (n = 6), 4) 500 mg altrenogest in lactide-glycolide microparticles suspended in 7-mL vehicle (MP 500; n = 6), or 5) 1.0 g MPA as a 5-mL suspension. Mares were checked for estrus daily, and their ovaries scanned every other day until a 25-mm or greater follicle was detected, after which they were scanned daily. Control mares returned to estrus an average of 3.9 days after Lutalyse administration; all the single-injection altrenogest formulations increased (P < .05) the days to return to estrus, with the greatest increase occurring in mares receiving MP 500. Return to estrus was not affected by MPA treatment. Time of ovulation was determined by serial ultrasound scans and confirmed by daily plasma luteinizing hormone (LH) and progesterone concentrations. Control mares ovulated an average of 8.8 days after Lutalyse administration. Treatment with 1.5 or 3 mL of LA 150 increased (P < .05) the mean days to ovulation to 16.5 and 21.2 days, respectively; MP 500 increased (P < .05) the days to ovulation to 33.5 days. Administration of MPA did not affect (P > .1) days to ovulation relative to control mares. The MP 500 treatment provided long-term suppression of estrus and ovulation and could prove useful for that purpose. Treatment with the LA 150 solutions provided shorter-term suppression, and a relatively tight grouping of the individual mares around the mean days to ovulation; these one-shot formulations could be useful for synchronizing ovulation in cyclic mares and inducing normal estrous cyclicity in vernal transitional mares exhibiting erratic, anovulatory estrous periods.

Introduction

Progestins are frequently used to prevent the expression of estrus in race, show, and broodmares for periods of weeks and up to months or longer. Daily administration can be an impractical method for administration of altrenogest or progesterone to mares, being inconvenient and time consuming. Recent advances in biodegradable, controlled-release drug delivery systems offer the potential for single-administration products to replace prolonged daily treatment protocols, resulting in reduced labor, less handling stress, and greater flexibility for veterinarians in maintaining effective compliance rates on farms and show barns with wide varieties of management systems. The primary objective of the current experiment was to evaluate the effectiveness of three sustained-release injectable formulations of altrenogest, a progestin that along with progesterone is known for its efficacy for pregnancy maintenance and inhibition of estrus behavior and ovulation in the mare.1, 2, 3, 4, 5, 6, 7, 8, 9 Medroxyprogesterone acetate, a synthetic progestin that is widely prescribed but not documented in controlled experiments to affect estrus or ovulation, was included for comparison.

Section snippets

Materials and Methods

Thirty-one mares of light horse breeds, maintained on native grass pasture at the Louisiana State University Agricultural Center horse farm in Baton Rouge, LA, were used in this study. They were in good body condition (scores of >610) and ranged in age from 5 to 16 years. Verification of normal reproductive cyclicity was determined by transrectal ultrasound scanning of the ovaries, estrus detection with a vigorous stallion, and serial radioimmunoassay of plasma progesterone concentrations.

The

Results

Control mares returned to estrus an average of 3.9 days after Lutalyse administration (Table 2). All the single-injection altrenogest formulations increased (P < .05) the days to return to estrus, with the greatest increase occurring in mares receiving MP 500. Four of the six mares receiving the altrenogest MP 500 formulation did not display estrus around the time of their first ovulation; when removed from the experiment because of ovulation, they had gone 28, 34, 47, and 49 days without

Discussion

With a few exceptions, the estimation of days to first ovulation (based on ultrasound scanning, LH concentrations, and progesterone concentrations) were in good agreement, and each was highly correlated to days to first estrus (r > 0.8 in all cases). One exception was a control mare that evidently ovulated a mid-cycle follicle in response to the Lutalyse injection on day 0. That ovulation (4 days later) was not detected by the ultrasound technician, even though LH and progesterone indicated

Acknowledgment

The authors thank A. F. Parlow and the National Institute of Diabetes and Digestive and Kidney Diseases, National Hormone and Pituitary Program, Harbor-University of California Los Angeles Medical Center, Torrance, CA, for reagents.

References (13)

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Approved for publication by the Director of the Louisiana Agric. Exp. Sta. as manuscript no. 2008-230-1610.

Refereed

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