Hormonal Control of the Estrous Cycle in Horses

The dopamine antagonists sulpiride (1 mg/kg, IM, every 24 hours until onset of ovulation, or a maximum of 21 days [1, 2]) or domperidone (1.1 mg/kg, PO, every 24 hours until onset of ovulation, or maximum of 21 days [2]) can shorten the interval to the onset of the ovulatory season in horses, particularly when used in combination with artificial lighting programs or photostimulation.

Treatment with dopamine antagonists has not been universally successful in stimulating ovarian activity in anestrus mares. It is potentially most effective in mares in transition, compared with those in deep anestrus (see The Reproductive Cycle of Horses for details).

Other hormone therapies that have been attempted for inducing seasonal cyclicity or advancement of the first ovulation of the year in horses have includedGnRH analogues such as buserelin (10–100 mcg, IM, every 12 hours) or deslorelin (25–125 mcg, IM, every 12 hours) when a dominant follicle of > 30 mm is present (3, 4, 5, 6), or the synthetic progestin altrenogest (0.044 mg/kg, PO, every 24 hours for 2–3 weeks [7, 8, 9]) alone or in conjunction with dopamine antagonists. As with dopamine antagonists, the response might vary; success is the most likely in mares in mid- to late transition, compared with those in anestrus.

Once a mare has begun cycling, manipulation of the estrous cycle for breeding management routinely consists of administering prostaglandin to cause luteolysis and shorten the period of diestrus, or ovulation induction agents to induce ovulation. Estrus can be induced in diestrous mares (having a corpus luteum that is 5 or more days postovulation) by treatment with natural prostaglandin F2alpha, PGF2alpha (dinoprost tromethamine, 5–10 mg, IM, once) or cloprostenol (250 mcg, IM, once) to lyse the corpus luteum (7, 10).

Mares should return to estrus in approximately 3 days and ovulate an average of 8–10 days after PGF2alpha treatment. The time to ovulation varies, however, depending on the size of the largest follicle in the ovary at the time of PGF2alpha administration. PGF2alpha causes numerous transient adverse effects in horses, including sweating, increased motility of the GI tract, colic, increased heart rate, muscle weakness, and possibly ataxia.

All adverse effects of PGF2alpha in mares typically begin within 15 minutes after administration and last up to 1 hour. The extent of adverse effects varies between individuals and with the type of prostaglandin used; some mares show less pronounced adverse effects with the synthetic prostaglandin cloprostenol.

Dosages of prostaglandin that are substantially lower than those administered in typical luteolytic protocols (cloprostenol at 25 mcg, IM, once; dinoprost tromethamine at 0.5 mg, IM, once or twice [11, 12, 13, 14]) have also been shown to effectively induce luteolysis in mares, while virtually eliminating the unwanted adverse effects of natural PGF2alpha. However, although cloprostenol is widely used in mares, it is labeled only for use in cattle. Prostaglandin causes luteolysis of a mature corpus luteum (> 5 days after ovulation), so it does not induce estrus in anestrous mares.

As part of routine breeding management, ovulation can be induced in mares with mature preovulatory follicles (> 35 mm in diameter) via administration of human chorionic gonadotropin (hCG; 2,500–5,000 IU, IV, once) (15, 16, 17, 18); compounded deslorelin acetate (1–2 mg, IM, once); or compounded histrelin (0.5–1 mg, IM, once) (19). Previously commercial available deslorelin is no longer available in the US.

Ovulation in mares occurs within 48 hours after administration of either hCG or a GnRH analogue, typically 36–48 hours after hCG (range 24–48 hours) or 40–44 hours after injectable deslorelin or histrelin. Repeated use of hCG over a long period is associated with antibody formation and can decrease the response to treatment; such an effect has not been observed with GnRH analogues.

Although they are not currently available in the US, GnRH implants (deslorelin, 2.1 mg, SC [15, 19]) can be used to induce ovulation in mares. The long-term use of a single deslorelin implant can cause anestrus due to downregulation of the hypothalamic-pituitary-gonadal axis has been associated with periods of anestrus in treated mares. For this reason, many veterinarians remove the implant after ovulation occurs; the implant can easily be removed if it is placed in the vulvar mucosa.

Ovulation can also be synchronized in mares via the simultaneous administration of progesterone in oil (150 mg) and estradiol 17-beta in oil (10 mg, IM) every 24 hours for 10 days, and of PGF2alpha (10 mg, IM, once) on the tenth day (7, 20). This protocol is most commonly used to synchronize embryo donors and small numbers of recipient mares ahead of intended fresh embryo transfer.

The combination of progesterone plus estradiol in a biorelease vehicle is available by prescription from a compounding pharmacy. Mares should come into estrus approximately 3 days after the end of treatment, and 85% of mares ovulate 9–13 days after the end of treatment (21).

Superovulation, as performed in ruminants (cattle or sheep and goats), is not as successful in horses.Treatments with purified equine follicle-stimulating hormone (FSH) from pituitary extracts, recombinant FSH, equine chorionic gonadotropin (eCG), and GnRH have been attempted, and some studies have shown an increase in the number of ovulations (22, 23, 24, 25, 26). However, increasing numbers of ovulations have been associated with a decreased embryo recovery rate per ovulation, compared with untreated mares (27).

Estrous behavior might be undesirable in performance horses and can be suppressed in mares by the administration of progestogens—either progesterone in oil (150–300 mg, IM, every 24 hours) or altrenogest (0.044 mg/kg, PO, every 24 hours) (28, 29). The duration of administration depends on the response; many mares remain on progestogen formulations for extended periods, such as the duration of a breeding season or even years.

Injectable administration of progestogen formulations may be associated with localized injection site reactions, tissue swelling, and pain (30). Progesterone in a biorelease vehicle is available by prescription from compounding pharmacies. This preparation(1.5 g/horse, IM) is administered once every 7–10 days (30). Although these preparations suppress estrous behavior, they might not effectively suppress follicle growth and ovulation in cyclic mares.

Oxytocin (60 IU, IM, every 24 hours for 30 days; or 60 IU, IM, every 12 hours for 7–14 days after ovulation) has been administered to prevent estrus in horses by prolonging the period of diestrus and corpus luteal function (31).

Behavioral estrus can be induced in anestrous or ovariectomized mares by administration of estradiol 17-beta in oil (5–10 mg, IM, periodically [3]) or estradiol cypionate (2–5 mg, IM, every 3 days–3 weeks, depending on receptivity [32]). Mares should show estrous behavior beginning 12–24 hours after injection. This estrus is not associated with follicular growth and is not fertile.

Treatment with estradiol cypionate is long-lasting; however, repeated or high doses can cause aggressive or defensive behavior in a mare when she is approached by a stallion.

Treatment with estrogen in the presence of progesterone (eg, in a cyclic mare in diestrus) does not induce estrous behavior.

• Moss C, Lu K. Hormonal manipulation of the estrous cycle in mares. Clin Theriogenology. 2025;17(special issue):49-63.

• Dasciano J, McCue P, eds. Equine Reproductive Procedures. 2nd ed. John Wiley & Sons; 2021.

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