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Prolonging Function of the Corpus Luteum to Suppress Estrus in Mares

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Prolonging Function of the Corpus Luteum to Suppress Estrus in Mares IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY Prolonging Function of the Corpus Luteum to Suppress Estrus in Mares Dirk K. Vanderwall, DVM, PhD, Diplomate ACT The orally active synthetic progestin altrenogest is widely considered to be the “gold-standard” method of inhibiting estrous behavior in mares. However, its expense, need for long-term daily administration, safety concerns for personnel during handling, and increased public scrutiny regard- ing the use of exogenous steroids in performance horses have collectively prompted interest in the development of practical methods of prolonging corpus luteum (CL) function, which allows continued secretion of endogenous progesterone to keep mares out of heat naturally. Placement of an intra- uterine glass ball has been the most widely used method of prolonging CL function, but variable efficacy and the potential for deleterious consequences associated with them (if not eventually removed), have stimulated interest in alternative methods of prolonging CL function. Currently, oxytocin treatment appears to be the most practical and efficacious alternative method of prolonging CL function. Additional methods include inducing a late-diestrus ovulation, intrauterine infusion of plant oils, and establishment of pregnancy followed by manual reduction of the conceptus after day 16 of gestation. Author’s address: Department of Animal, Dairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84322; e-mail: [email protected]. © 2013 AAEP. 1. Introduction necessarily associated with estrus. In addition, it A common complaint of horse owners, trainers, and is important to note that some behaviors displayed veterinarians is variable performance of mares that by mares that are thought to be associated with is related to the estrous cycle.1,2 In a survey of estrus are in fact not estrous behaviors. They are more than 750 veterinarians, approximately 90% instead signs of 1) submissive behavior, 2) urogen- 3,4 had the clinical impression that the estrous cycle ital discomfort, or 3) stallion-like behavior. Of affected the performance of mares, and the most these, submissive behavior may be most easily con- frequently reported clinical sign associated with an fused with estrous behavior. Submissive behavior effect of the reproductive cycle on performance was includes leaning away from perceived threats, attitude change, whereas other signs included tail- swishing/ringing the tail, and actively squirting swishing, difficulty to train, squealing, “horsing,” urine, which collectively can give the impression of excess urination, kicking, and a decrease in perfor- estrus, whereas true estrous behavior is manifested mance.1 As the preceding list of objectionable be- by leaning toward the stallion (or other stimulus), a haviors suggests, not all problematic behaviors are relaxed, lifting motion of the tail, stationary/squat- NOTES 342 2013 ր Vol. 59 ր AAEP PROCEEDINGS IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY ting stance, and passive urination (full stream or ated with hormone secretion from the adrenal cor- small amounts in dribbles).4 Urogenital discomfort tex.11,12 The intensity of this type of may be the result of cystitis or renal disease, “unseasonable” estrous behavior can be equivalent whereas stallion-like behavior may be associated to the behavior intact cycling mares display during with neoplasia of the ovaries or administration of the initial and terminal days of estrus but is gener- exogenous anabolic steroids. ally less intense than the behavior displayed near Because numerous factors (both reproductive and ovulation.11 It has been postulated that behavioral nonreproductive) can adversely affect performance, receptivity to a stallion outside the breeding/ovula- when evaluating an owner/trainer complaint of an tory season that is independent of ovarian estrogen estrous cycle-related behavior/performance problem secretion may have developed as a means of main- in a mare, the first step is to determine if the prob- taining social bonds between a harem stallion and lematic behavior is or is not related to a specific his mares.11,13 This phenomenon has important phase of the estrous cycle. To thoroughly evaluate implications for the clinical management of estrous the mare, additional expertise may be needed in the behavior in mares, since simply suppressing ovarian form of consultation with or referrals to behavior follicular activity or removing the ovaries may not and/or reproduction experts, because a systematic ensure complete elimination of estrous behavior. team approach to evaluating and solving the prob- lem may be most successful.5 2. Exogenous Progesterone/Progestins If problematic behavior is consistently associated Historically, the use of exogenous progesterone/pro- with estrus, it is necessary to determine if the un- gestins has been the most widely used method of derlying cause is physical or behavioral. Some suppressing estrous behavior in mares. It was first mares that exhibit performance problems during es- demonstrated in the 1960s that daily intramuscular trus may be having pain in the periovulatory period administration of 0.2 mg/kg progesterone in oil ef- that can vary from sensitivity to weight and/or ma- fectively suppressed signs of estrus in mares.14 nipulation of the back (caused by tack and/or rider) Although progesterone in oil is available from com- to overt colic-like symptoms.6–9 Mares that have pounding pharmacies, the need for daily administra- back pain and/or colic-like symptoms in the peri- tion and the potential for soreness at the site of ovulatory period may benefit from the use of an injection are limitations to its use. An alternative ovulatory agent to reduce the time a large pre-ovu- to daily administration of progesterone in oil is a latory ovarian follicle is present or complete sup- compounded long-acting injectable formulation of pression of cyclical reproductive activity. In progesterone containing a total dose of 1.5 g proges- contrast to mares with an underlying physical cause terone that will maintain blood levels of progester- of performance issues during estrus, some mares one above 1.0 ng/mL for approximately 10 days,15 display such profound signs of estrus that the be- which is a sufficient level of progesterone to block havior itself impairs performance. For example, estrous behavior14,16; however, the potential for even under saddle, some mares may “break down” soreness at the injection site is a limitation to its use and show estrus in response to being around other in performance horses. horses and/or other stimuli.4 For these mares, sup- In contrast to native progesterone, the orally ac- pression of estrus is clearly warranted. In other tive synthetic progestin altrenogesta,b is approved mares, the condition may be much more subtle, for suppressing estrus in mares and is widely con- causing owners and trainers to report that the mare sidered the “gold-standard” method of inhibiting es- is less cooperative or attentive during estrus, trous behavior. Daily oral administration of prompting them to pursue estrus suppression.2 altrenogest at a dose of 0.044 mg/kg is very effica- It is also common to suppress estrus when the signs of cious for suppressing estrus in mares17,18; however, estrous behavior are simply perceived to be associated its expense, need for long-term daily administration, with performance problems or to preemptively block and safety concerns for personnel during handling the behavior to preclude the possibility of an adverse and administration19 are drawbacks to its use. effect of estrus on performance. When suppression As an alternative to oral administration, it was re- of estrous behavior is desired, the following general cently reported that intramuscular administration methods have been used in mares: 1) administra- of a compounded preparation containing 225 mg or tion of exogenous progesterone or synthetic proges- 450 mg of altrenogest in a sustained-release vehicle tins, 2) extending the duration of corpus luteum blocked estrous behavior for approximately 12 and (CL) function, 3) downregulating ovarian follicular 15 days, respectively, and administration of 500 mg activity, and 4) ovariectomy (for complete review, altrenogest in microparticles suppressed estrous be- see Vanderwall and Nie10). havior for approximately 30 days.20 Veterinarians When discussing methods of suppressing estrus, it should use FDA approved products for this indica- is important to note that mares are unique among tion. Certain compounded products can vary sig- domestic animals, because in addition to ovarian- nificantly in potency and stability. Consequently derived estrogen-induced signs of estrous behavior, results may vary substantially. There can also be many seasonally anovulatory and ovariectomized legal and ethical issues with using a compounded mares exhibit paradoxical estrous behavior associ- product when there are FDA approved products AAEP PROCEEDINGS ր Vol. 59 ր 2013 343 IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY available in the appropriate dosage form and for the normal duration after placement of the glass ball appropriate indication. before CL function was prolonged. Therefore, on a Although there have been anecdotal reports on “per-cycle” basis, the incidence of prolonged CL func- the use of synthetic progestins other than altreno- tion was only 11% (7/62 cycles) in the mares that gest for estrus suppression in mares, none have been received a glass ball compared with 8% (4/50 cycles) found to be efficacious
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