Hormonal Control of Estrus in Horses

Estrous behavior may be undesirable in performance horses and can be suppressed in mares by administration of progestagens, either progesterone in oil (150–300 mg/day, IM) or altrenogest (0.44 mg/kg/day, PO). In the past, oral progestagen was preferable because of muscle irritation from the injectable preparation. However, progesterone in a biorelease vehicle is available by prescription from a compounding pharmacy. This preparation (1.5 g, IM) is administered once every 7–10 days. Treatment with progestagens for 15 days during the late transition season can advance the first ovulation of the year by ~10 days. Although these preparations suppress estrous behavior, they may not effectively suppress follicle growth and ovulation in cyclic mares.

Ovulation may be synchronized in mares by administration of progesterone in oil (150 mg) and estradiol 17β in oil (10 mg/day, IM, for 10 days) with prostaglandin F_2α (PGF_2α; 10 mg, IM) administered on the tenth day. Progesterone plus estradiol in a biorelease vehicle is also available by prescription from a compounding pharmacy. Mares should come into estrus ~3 days after the end of treatment, and 85% of mares ovulate 9–13 days after the end of treatment.

Estrus may be induced in diestrous mares (having a corpus luteum that is 5 or more days postovulation) by treatment with PGF_2α (10 mg, IM) or cloprostenol (250 mcg, IM) to lyse the corpus luteum. Mares should return to estrus in ~3 days and ovulate an average of 9–10 days after prostaglandin treatment. The time to ovulation is variable, however, depending on the size of the largest follicle on the ovary at the time of prostaglandin administration. PGF_2α causes numerous transient adverse effects in horses, including sweating, colic, and trembling. Greatly reduced doses of cloprostenol (25 mcg) also effectively induce luteolysis in mares while virtually eliminating the unwanted adverse effects of PGF_2α. However, although widely used in mares, cloprostenol is labeled only for use in cattle. Prostaglandin causes luteolysis of a mature corpus luteum and so does not induce estrus in anestrous mares.

Behavioral estrus may be induced in anestrous or ovariectomized mares by administration of estradiol 17β in oil (1–10 mg, IM) or estradiol cypionate (0.5 mg, IM). Mares should show estrus 12–24 hr after injection. This estrus is not associated with follicular growth and is not fertile. Treatment with estradiol cypionate is longlasting, but repeated or high doses may cause aggressive or defensive behavior when the mare is approached by a stallion. Treatment with estrogen in the presence of progesterone (eg, in a cyclic mare in diestrus) will not induce estrous behavior.

Ovulation may be induced in mares with mature preovulatory follicles (>33 mm diameter) by administration of human chorionic gonadotropin (hCG), 2,500 IU, IV; by administration of a deslorelin implant, 2.2 mg, SC; or by administration of deslorelin, 1–2 mg, IM, in a biorelease vehicle. Ovulation is seen in 85% of mares within 48 hr, typically 36–42 hr after hCG or injectable deslorelin treatment or 40–44 hr after treatment with a deslorelin implant. Repeated use of hCG over a long period is associated with antibody formation and may decrease response to treatment; this has not been seen with deslorelin. Use of deslorelin in implant form has been associated with periods of anestrus in treated mares, especially if the corpus luteum of ovulation is lysed with prostaglandin. For this reason, many veterinarians remove the implant after ovulation is seen; this is easily performed if the implant is placed in the vulvar mucosa.

Mares do not superovulate in response to equine chorionic gonadotropin (eCG), and they do not respond well to follicle-stimulating hormone (FSH) derived from other species, but they may be superovulated (average of three to four follicles ovulated) by treatment with equine FSH (no longer commercially available in the USA). GnRH given at 2–20 mcg/hr (by infusion pump) throughout ~10 days induced normal follicular growth and ovulation in anestrous mares; the larger dose induces superovulation (average of three follicles). Cyclicity has also been induced in anestrous mares by treatment with 200 mcg GnRH every 6 hr, 500 mcg GnRH every 12 hr, or by administration of a GnRH agonist, buserelin (10 mcg, SC), every 12 hr plus hCG (2,500 IU, IV) once a follicle has reached 35 mm in diameter. The dopamine receptor antagonist domperidone (1.1 mg/kg/day, PO) alone or in combination with GnRH (250 mcg, SC, qid) has also been used to stimulate follicular development in mares with quiescent ovaries.