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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Failure of mare to show estrus. Can be physiologic or pathologic.

Pathophysiology!!navigator!!

Mares are seasonally polyestrus with the ovulatory period in spring/summer; primarily regulated by photoperiod:

  • Increasing day length decreases melatonin secretion (pineal gland), allowing increased production and release of GnRH, stimulating gonadotropin release (FSH and LH)
    • FSH promotes folliculogenesis
    • D2 dopamine likely regulates ovarian function locally
  • When sufficient LH is produced by dominant follicle(s), ovulation occurs, initiating cyclicity
  • Average estrous cycle is 21 days; defined as the interval between 2 ovulations with progesterone > 1 ng/mL. Repeatable in individual mares
  • Key hormonal events of equine estrous cycle:
    • FSH causes follicular growth
    • Follicular E2 stimulates increased GnRH pulse frequency and LH secretion
    • LH surge causes ovulation
    • 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 decline in P4 levels

Systems Affected!!navigator!!

Signs!!navigator!!

Historical Findings

  • Chief complaint—failure of mare to show estrus or accept stallion
  • Inadequate teasing
  • Seasonal influences
  • Reproductive history—estrous cycle length, teasing response, prior breeding/foaling data, previous genital tract injuries/infections
  • Pharmaceuticals interfering with normal estrous cycle

Physical Examination Findings

  • Poor body condition/malnutrition or metabolic disease (PPID)
  • 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 and US may be needed to completely define status
  • Vaginal speculum examination to identify inflammation, urine pooling, cervical competency, conformational abnormalities

Causes!!navigator!!

Normal Physiologic

  • Winter anestrus—≈30% of mares cycle year-round; most enter a period of anestrus
  • 2 transitional phases occur yearly—fall transition (ovulatory to anestrus) and vernal transition (anestrus to cyclicity). Behavior and ovarian activity varies during transition
  • Behavioral anestrus (silent heat)—mare has normal cycle but fails to demonstrate estrus
  • Pregnancy
  • Persistent endometrial cups—early embryonic death after formation of endometrial cups results in persistent CL activity
    • eCG (by endometrial cups, 35–150 days of pregnancy) is luteotropic, maintaining primary CL and formation of secondary CLs
  • Postpartum anestrus—most mares reestablish cyclicity ≤ 20 days postpartum. Some fail to continue cycling after their first postpartum ovulation, due to ovarian factors, seasonal factors (foaling late in winter without artificial light supplementation), or lactational anestrus/poor body condition
  • Age—puberty occurs at 12–24 months and mares > 25 years may develop ovarian senescence

Congenital Abnormalities

  • Gonadal dysgenesis—no functional ovarian tissue; can result in anestrus, erratic estrus, or prolonged estrus
    • Behavioral estrus may be due to adrenal-origin steroid production and absence of progesterone
    • Typically flaccid, infantile uterus, hypoplastic endometrium, small, nonfunctional ovaries
    • Most common chromosomal defect—XO monosomy; most common intersex condition—XY sex reversal

Endocrine Disorders

  • PPID—destruction of FSH/LH-secreting cells and/or overproduction of glucocorticoids
  • Increased adrenal-origin androgens can suppress normal hypothalamic–pituitary–ovarian axis

Ovarian Abnormalities

  • Ovarian hematoma, hemorrhagic anovulatory follicle, or ovarian abscess
  • Ovarian neoplasia (most common—GTCT)

Uterine Abnormalities

Pyometra—can prevent formation and release of PGF2α, prolonging diestrus.

Iatrogenic/Pharmacologic

  • GnRH vaccination—prevents ovarian activity
  • Bilateral ovariectomy—although up to 30% of mares show constant estrus
  • Drugs causing behavioral anestrus:
    • Anabolic steroids
    • Progesterone/progestins—inhibition of estrus behavior
    • Oxytocin treatment to prolong CL lifespan
  • Placement of intrauterine marbles to prolong CL lifespan

Risk Factors!!navigator!!

Foaling in late winter; poor body condition at foaling.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Differentiating Causes

  • Review history/breeding/foaling records—medical/reproductive history, teasing methods
  • Physical examination, serial TRP and US to determine reproductive status, cyclicity, uterine/ovarian abnormalities
  • Vaginal examination

Other Laboratory Tests!!navigator!!

  • Serum progesterone
    • Basal < 1 ng/mL
  • 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
  • Serum eCG—diagnosis of persistent endometrial cups
  • PPID testing
  • Karyotype

Imaging!!navigator!!

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

Other Diagnostic Procedures!!navigator!!

Uterine cytology/culture/biopsy for diagnosis, treatment, and to monitor progression of pyometra/endometritis.

Treatment ⬆ ⬇

TREATMENT

  • Alter management/teasing techniques to elicit a response from a mare and/or base timing of artificial insemination on TRP and US
  • Advancement of the vernal transition:
    • Artificial lighting—expose mare to 14.5–16 h light/day or to additional 1–2 h light at 10 h after dusk (flash lighting). Duration of transition remains unchanged. Minimum of 60–90 days is needed to achieve cyclicity
    • Pharmaceuticals—combinations of FSH, dopamine antagonists, and P4/E2
  • Mare due to foal in late winter—add supplemental lighting 2 months prior to parturition to improve postpartum cyclicity and decrease potential for anestrus
  • Ovarian tumors
    • Removal of GTCT removes inhibin suppression of contralateral ovary, allowing cyclicity, often with longer interovulatory period. The time to cycle is affected by season:
      • If in winter, following the solstice, cyclicity resumes as day length increases
      • If in spring or summer, cyclicity may not resume until fall and significant decreases in day length
    • Some mares fail to cycle again
  • Pyometra/endometritis—specific intrauterine therapies based on diagnostic testing

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • To induce luteolysis:
    • PGF2α (Lutalyse 10 mg IM) or analogs
  • To induce ovulation in estrus:
    • Deslorelin 1.8 mg IM—ovulation usually 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

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 is recommended if it fails to resolve in 1–2 h
    • Antibodies to hCG can develop. Limit use to < 2 or 3 times per breeding season
    • Deslorelin implants are associated with FSH suppression in diestrus with prolonged interovulatory period in nonpregnant mares
    • Progesterone supplementation can decrease uterine clearance; use 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

Alternative Drugs!!navigator!!

Cloprostenol sodium (Estrumate 250 μg/mL IM) is a PGF2α analog. This product is used in similar fashion to natural PGF2α and has been associated with fewer side effects. Not currently approved for use in horses.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Serial TRP and US—establish diagnosis for etiology of anestrus
  • Mares with persistent endometrial cups will return to cyclicity upon regression of endometrial cups, as eCG decreases (up to 150 days post ovulation)

Possible Complications!!navigator!!

Infertility may result from intractable persistent anestrus.

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Age-Related Factors!!navigator!!

Postpartum anestrus occurs more often in old mares.

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!!

  • Gonadal dysgenesis
  • Gonadal hypoplasia
  • Lactational anestrus
  • Postpartum anestrus

Abbreviations!!navigator!!

  • AMH = anti-Müllerian hormone
  • CL = corpus luteum
  • E2 = estradiol
  • eCG = equine chorionic gonadotropin
  • 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
  • PPID = pituitary pars intermedia dysfunction
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Aurich C. Reproductive cycles of horses. Anim Reprod Sci 2011;124:220–228.

Donadeu FX, Watson ED. Seasonal changes in ovarian activity: lessons learnt from the horse. Anim Reprod Sci 2007;100:225–242.

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;36:1–4.

Williams GL, Thorson JF, Prezotto LD, et al. Reproductive seasonality in the mare: neuroendocrine basis and pharmacologic control. Domest Anim Endocrinol 2012;43:103–115.

Author(s) ⬆

Author: Lisa K. Pearson

Consulting Editor: Carla L. Carleton

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