Patrick M. McCue, Ryan A. Ferris
Hormone Therapy in Equine Reproduction
A variety of hormone therapies is used to stimulate follicular development in noncycling mares, induce ovulation of a dominant follicle, lyse a corpus luteum to shorten the luteal phase, promote uterine contractions to evacuate uterine fluid, stimulate lactation, manage retained placenta, and manage multiple other clinical scenarios in equine reproductive medicine. The most common use of hormonal agents is in breeding management, to either induce a timed ovulation or to short-cycle a mare.
Gonadotropin-Releasing Hormone and Gonadotropin-Releasing Hormone Agonists
Gonadotropin releasing hormone (GnRH) is a 10–amino-acid peptide hormone produced in the hypothalamus. Agonists of GnRH, such as deslorelin, buserelin, and historelin, are administered to stimulate follicular activity in anestrous mares and induce ovulation in cycling mares. Substitutions in the amino acid sequence of native GnRH result in increased potency.
When a 1999 U.S. Food and Drug Administration (FDA)-approved implant1 containing 2.1 mg of deslorelin acetate is administered to mares that are in estrus that have uterine edema and a follicle greater than or equal to 35 mm in diameter, approximately 85% to 95% ovulate within 48 hours (average time to ovulation, 42 hours). Prolonged secretion of deslorelin by the implant may cause downregulation of pituitary gonadotropin secretion, suppression of ovarian follicular development, and a delayed return to estrus in some mares, but these effects can be prevented by removal of the implant 48 hours after insertion. The deslorelin implant is no longer commercially available in the United States, but an injectable solution2 has been approved by the FDA for ovulation induction. Administration of this deslorelin solution (1.8 mg, IM) to a mare in estrus with a follicle greater than or equal to 35 mm in diameter and uterine edema induces ovulation in approximately 90% of mares within about 40 hours (Table 162-1). Deslorelin may be used to induce ovulation in mares that do not ovulate in response to human chorionic gonadotropin (hCG), and repeated deslorelin use over multiple estrus cycles does not elicit an immune response or result in decreased efficacy.
TABLE 162-1
Comparison of Responses in Mares Receiving Deslorelin or Human Chorionic Gonadotropin Treatment to Induce Ovulation
| Group | Number of Cycles | Age (yr) | Follicle Size at Time of Treatment (mm) | Edema Score at Time of Treatment | Interval to Ovulation (days) | Percentage of Mares Ovulating Within 48 Hours |
| Deslorelin | 168 | 11.5 ± 5.1 | 39.9 ± 4.5* | 1.7 ± 0.6 | 2.2 ± 0.8 | 89.9% (151/168)* |
| Human chorionic gonadotropin | 134 | 10.8 ± 4.5 | 41.3 ± 4.3† | 1.6 ± 0.7 | 2.1 ± 0.7 | 82.8% (111/134)† |
*,† Different superscripts within a column indicate values are significantly (P < .05) different.
From Ferris RA, Hatzel JN, Lindholm ARG, et al. Efficacy of deslorelin acetate (SucroMate) on induction of ovulation in American Quarter Horse mares. J Equine Vet Sci 2012;32:285-288.
Administration of a low dose of buserelin or deslorelin (10 to 125 µg, IM, every 6 to 12 hours) stimulates follicular development in seasonally anestrous mares. Mares in spring transition (i.e., that have follicles ≥25 mm in diameter) are more likely to respond than mares in deep winter anestrus (follicles <20 mm in diameter). Mares in deep winter anestrus that respond to low-dose GnRH agonist administration are more likely to revert back to anestrus after treatment is discontinued than mares initially treated during spring transition.
Human Chorionic Gonadotropin
Human chorionic gonadotropin is a large glycoprotein hormone with inherent luteinizing hormone (LH)-like biologic activity. The commercially available hormone3 is used primarily to induce maturation and ovulation of a dominant follicle. Induction of ovulation with hCG is most effective when a mare is in estrus, a follicle greater than or equal to 35 mm is present, and uterine edema is visible on ultrasound. Ovulation usually occurs 36 hours after administration of hCG (1500 to 2500 units, IV or IM). Efficacy at inducing a timed ovulation may be reduced if hCG is given repeatedly during the same breeding season.
An hCG stimulation test may also be given as part of diagnostic testing to determine whether testicular tissue is present in colts or geldings suspected of being cryptorchid. A blood sample is collected immediately before administration of hCG (10,000 units, IV), and a second blood sample is collected between 1 and 24 hours after hCG administration. A true gelding will have low (<50 pg/mL) testosterone concentrations in both samples, whereas an intact stallion will have a high concentration of testosterone (>1000 pg/mL) in the first sample and an even higher level in the second. In a cryptorchid horse, the LH-like biologic activity of hCG causes an increase in testosterone production from Leydig cells of the testes, if they are present. In this type of horse, the moderately low testosterone concentration in the first sample increases in the second blood sample.
Follicle-Stimulating Hormone
Follicle-stimulating hormone (FSH) is administered to mares to advance the first ovulation of the year in seasonally anestrous mares, stimulate follicular development in postpartum acyclic mares, and induce ovulation of multiple follicles in cycling mares. Multiple FSH products have been tested, including porcine FSH, recombinant human FSH, equine pituitary extract, purified equine FSH, and recombinant equine FSH. Porcine and recombinant human FSH have limited efficacy in the horse.
Administration of recombinant equine FSH (reFSH) to mares in seasonal anestrus or postpartum anestrus usually stimulates follicular development if mares are in transition rather than deep anestrus, and FSH is administered twice rather than once daily. Administration of reFSH (0.65 mg, IM, every 12 hours) will stimulate follicular development in approximately 80% to 90% of anestrous mares within 7 to 10 days, but administration of hCG (1500 to 2500 units, IV or IM) is required to induce ovulation. Mares initially treated during deep anestrus that respond and ovulate may revert to anestrus following a normal luteal phase.
Superovulation of cycling mares can be accomplished by administration of 0.65 mg of reFSH twice daily for 3 to 7 days. Superovulation therapy for cycling mares will be most successful if (1) endogenous FSH initially stimulates a cohort of follicles to develop before the onset of exogenous FSH therapy (this reduces the number of FSH treatments required), (2) twice-daily FSH therapy is used, and (3) there is a 36-hour interval between the last FSH treatment and hCG administration. This interval may be beneficial in allowing the follicle or follicles to mature and likely improves the ovulation rate.
