section name header

Basics

Outline


BASICS

Definition!!navigator!!

  • Estrus—period of sexual receptivity of the mare for the stallion
  • Abnormal estrus interval—mare displays sexual behavior for longer or shorter periods than normal
  • Abnormal interovulatory intervals result from altered estrus or diestrus lengths

Pathophysiology!!navigator!!

Mares are seasonally polyestrous with the ovulatory period in spring/summer:

  • Average estrous cycle is 21 days
  • Estrus length averages 5–7 days
  • Diestrus length more consistently 14–15 days

Key Hormonal Events in the Equine Estrous Cycle

  • FSH causes follicular growth
  • Follicular estradiol (E2) stimulates increased GnRH pulse frequency and LH secretion
  • LH surge causes ovulation
  • Progesterone (P4) (CL origin) rises from basal levels (<1 ng/mL) at ovulation to > 4 ng/mL by 4–5 days post ovulation
  • A second FSH surge in diestrus initiates another follicular wave
  • Endometrial PGF2α is released 14–15 days post ovulation, causing luteolysis and a decline in P4 levels

Sexual Behavior

  • Absence of P4 allows onset of estrus behavior even if E2 is present in small quantities
  • Conditions that eliminate P4 and/or > E2 concentrations are likely to induce estrus behavior (including bilateral ovariectomy)

Systems Affected!!navigator!!

Signalment!!navigator!!

  • Mares of any age/breed
  • Ponies have longer estrous cycles (average 24 days) than mares

Signs!!navigator!!

Historical Findings

  • Chief complaints—infertility, failure to show estrus, prolonged estrus, split estrus, or frequent estrus behavior
  • Reproductive history—review breeding/teasing records, previous foaling data, urogenital infections/treatments, pharmaceutical interventions
  • Seasonal influences—review time of year, individual variation (onset/duration/termination of cyclicity)
  • Have clients log behaviors in a journal for persistent estrus cases to identify patterns

Physical Examination Findings

  • Poor body condition/malnutrition or metabolic disease (pituitary pars intermedia dysfunction) may contribute to abnormal cyclicity
  • Poor perineal conformation can result in pneumovagina, ascending infections, and/or urine pooling, anestrus/infertility
  • Clitoral enlargement may relate to drug history (anabolic steroids) or intersex conditions
  • TRP and US are essential for evaluation. Rule out pregnancy. Assess uterine size/tone, ovarian size/shape/location, and cervical relaxation. Serial TRP may be needed to completely define status
  • Vaginal speculum examination to identify inflammation, urine pooling, cervical competency, conformational abnormalities

Causes!!navigator!!

Shortened Estrus Duration

  • Split heats often observed during transition periods (seasonality)
  • Silent heat—mare with normal cyclic ovarian activity but minimal or no overt sexual receptivity
  • Often behavior-based problem—nervousness, foal-at-side, maiden mare; possibly previous anabolic steroid use

Lengthened Estrus Duration

  • May appear as persistent estrus behavior or split heats
  • Persistent estrus behavior due to cystitis, vaginitis, urine pooling, ovarian neoplasia (GTCT), chromosomal abnormalities
  • Split heats often observed during transition periods (seasonality)
  • Up to 30% of bilaterally ovariectomized mares may show persistent estrus

Shortened Interestrus Interval

Premature luteolysis:

  1. endometritis
  2. endotoxemia (i.e. colic, colitis, laminitis)
  3. iatrogenic due to intrauterine infusions, biopsy, administration of PGF2α

Lengthened Interestrus Interval

  • Prolonged CL function—diestrus ovulation, persistent CL (due to idiopathic/spontaneous or uteropathic (pyometra) causes), pregnancy, early embryonic death after maternal recognition of pregnancy or endometrial cup formation, oxytocin treatment, placement of intrauterine marbles, use of deslorelin implants
  • Suppression of estrus behavior by treatment with altrenogest or natural P4
  • Induction of anestrus via GnRH vaccination or bilateral ovariectomy

Diagnosis

Outline


DIAGNOSIS

Differential Diagnosis!!navigator!!

Differentiating Conditions with Similar Symptoms

  • Behavior complaints must be investigated as to the inciting cause—physiologic, pathologic, or psychologic
  • All mares should be submitted for physical and urogenital examination including TRP, US, and vaginal speculum examination
  • Urinalysis, uterine culture, uterine cytology, and endometrial biopsy can provide specific diagnoses for persistent estrus behavior, endometritis
  • Serial examination may be required to differentiate silent heat, split heat, transitional period, prolonged CL function
  • GTCT may be suspected on US; confirm with serology
  • Karyotype to diagnose chromosomal disorders

CBC/Biochemistry/Urinalysis!!navigator!!

N/A

Other Laboratory Tests!!navigator!!

  • Serum progesterone
    • Basal < 1 ng/mL (no luteal tissue present)
  • GTCT panel
    • Nonpregnant mare—AMH < 3.8 ng/mL, inhibin < 0.7 ng/mL, testosterone 20–45 pg/mL
    • GTCT if AMH > 8.0 ng/mL, inhibin > 0.7 ng/mL, testosterone > 100 pg/mL
  • Karyotype

Imaging!!navigator!!

  • Transrectal US of reproductive tract
  • Hysteroscopy to diagnose uterine abnormalities

Other Diagnostic Procedures!!navigator!!

N/A

Treatment

TREATMENT

  • Serial monitoring of the mare's reproductive tract by TRP and US
  • For persistent estrus:
    • Treat underlying endometritis, cystitis, vaginitis, urine pooling
    • Correct poor perineal conformation (Caslick's vulvoplasty, Gadd procedure, Pouret procedure)
  • For prolonged diestrus:
    • Rule out pregnancy
    • Treat pyometra or other uterine disease, if present
    • PGF2α treatment
    • Remove marble or deslorelin implant
  • For anestrus:
    • Identify if mare is cyclic or truly anestrus
    • If cyclic, modify teasing/breeding management schemes. Breed based on TRP and US, if possible
    • Ovariectomy if GTCT diagnosed
    • If anestrus during the breeding season, identify and treat inciting cause, if possible
    • Consider artificial lighting schemes or pharmaceuticals to advance the vernal transition period in broodmares

Medications

Outline


MEDICATIONS

Drug(s) of Choice!!navigator!!

  • To induce luteolysis—PGF2α (dinoprost tromethamine, Lutalyse (Pfizer) 10 mg IM) or analogs
  • To induce ovulation in estrus—deslorelin 1.8 mg IM: ovulation within 48 h if follicle(s) > 30 mm; hCG 2500 IU IV: ovulation within 48 h if follicle(s) > 35 mm
  • To hasten vernal transition:
    • Altrenogest (0.044 mg/kg PO daily 15 days) if follicles > 20 mm are present and mare is exhibiting behavioral estrus. PGF2α is given on day 15
    • Combination P4/E2 treatments followed by PGF2α are also used
    • Dopamine antagonists—domperidone 1.1 mg/kg PO daily or sulpiride 1.0 mg/kg or 200 mg/mare IM daily; often used in combination with artificial photoperiod
    • FSH—used experimentally
  • To suppress estrus:
    • Oxytocin 60 IU IM daily 7–14 days post ovulation or for 29 days at any time during the cycle
    • Altrenogest 0.044 mg/kg PO daily
    • Natural P4—available in several injectable formulations (short- or long-acting)

Contraindications!!navigator!!

PGF2α and analogs—contraindicated with equine asthma/bronchoconstrictive disease.

Precautions!!navigator!!

  • Horses
    • PGF2α causes sweating/colic-like symptoms due to stimulation of smooth muscle. Symptomatic treatment if not resolved in 1–2 h
    • Antibodies to hCG can develop:
      • Limit use to < 2 or 3 times per breeding season
      • Half-life of antibodies is 1 to several months
    • Deslorelin implants are associated with prolonged interovulatory periods in nonpregnant mares, if not removed soon after ovulation has been confirmed. Not available in the USA
    • Progesterone supplementation may be contraindicated in mares with a history of uterine infection
  • Humans
    • PGF2α should not be handled by pregnant women or persons with asthma/bronchial disease
    • Altrenogest should not be handled by pregnant women or persons with thrombophlebitis, thromboembolic disorders, cerebrovascular/coronary artery disease, breast cancer, estrogen-dependent neoplasia, undiagnosed vaginal bleeding, or tumors that developed with use of oral contraceptives or estrogen-containing products

Possible Interactions!!navigator!!

N/A

Alternative Drugs!!navigator!!

Cloprostenol sodium (Estrumate (Schering-Plough Animal Health) 250 μg/mL IM) is a PGF2α analog. This product is used in similar fashion to dinoprost tromethamine and has been associated with fewer side effects. While it is not currently approved for use in horses, it is in broad use in the absence of an alternative.

Follow-up

Outline


FOLLOW-UP

Patient Monitoring!!navigator!!

The mare should be examined serially until normal cyclicity or pregnancy is determined.

Possible Complications!!navigator!!

Undesirable behavior, infertility, prolonged nonpregnant intervals.

Miscellaneous

Outline


MISCELLANEOUS

Pregnancy/Fertility/Breeding!!navigator!!

PGF2α administration to pregnant mares can cause luteolysis and abortion. Definitively rule out pregnancy before administering this drug or its analogs.

Synonyms!!navigator!!

  • Persistent estrus
  • Prolonged CL function

Abbreviations!!navigator!!

  • AMH = anti-Müllerian hormone
  • CL = corpus luteum
  • E2 = estradiol
  • FSH = follicle-stimulating hormone
  • GnRH = gonadotropin-releasing hormone
  • GTCT = granulosa–theca cell tumor
  • hCG = human chorionic gonadotropin
  • LH = luteinizing hormone
  • P4 = progesterone
  • PGF2α = prostaglandin F2α
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading

Aurich C. Reproductive cycles of horses. Anim Reprod Sci 2011;124:220228.

Ball BA, Almeida J, Conley AJ. Determination of serum anti-Müllerian hormone concentrations for the diagnosis of granulosa-call tumours in mares. Equine Vet J 2013;45:199203.

Coffman EA, Pinto CR. A review on the use of prostaglandin F2a for controlling the estrous cycle in mares. J Equine Vet Sci 2016;40:3440.

Schulman ML, Botha AE, Muenscher SB, et al. Reversibility of the effects of GnRH-vaccination used to suppress reproductive function in mares. Equine Vet J 2013;45:111113.

Vanderwall DK, Parkinson KC, Rigas J. How to use oxytocin treatment to prolong corpus luteum function for suppressing estrus in mares. J Equine Vet Sci 2016;36:14.

Author(s)

Author: Lisa K. Pearson

Consulting Editor: Carla L. Carleton

Acknowledgment: The author and editor acknowledge the prior contribution of Carole C. Miller.