Hyperestrogenism in Ferrets | Vetlexicon
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Hyperestrogenism

ISSN 2398-2985

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Synonym(s): Estrogen toxicity

Introduction

  • Cause: persistent estrus, adrenocortical disease, ovarian abnormalities, eg neoplasia, cystic disease.
  • Signs: may be non-specific, eg lethargy, weakness, reduced food intake, pale mucous membranes, petechial or ecchymotic hemorrhages on skin and/or mucous membranes, melena, vulval swelling and discharge, bilaterally symmetrical dorsal and/or flank alopecia.
  • Diagnosis: an appropriate clinical history together with identification of anemia, leukopenia and thrombocytopenia is usually sufficient for a preliminary diagnosis in order to commence treatment. Additional investigations such as abdominal ultrasonography and elevation in serum estradiol may be indicated in some cases.
  • Treatment: supportive care, blood transfusion if anemia and/or thrombocytopenia is significant, remove source of estrogen, eg terminate estrus and induce ovulation in ferrets with persistent estrus. Prevent recurrence, eg neuter female ferrets.
  • Prognosis: guarded to fair depending on the clinical status of the animal.
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Presenting signs

  • Non-specific signs: lethargy, weakness, reduced food intake.
  • Pale mucous membranes.
  • Petechial and/or ecchymotic hemorrhages on skin and/or mucous membranes.
  • Melena.
  • Vulva swelling and discharge.
  • Bilaterally symmetrical dorsal and/or flank alopecia.

Acute presentation

  • Complications associated with hyperestrogenism typically occurs over time (weeks), however, some less observant owners may report sudden collapse or weakness if evidence or significance of estrus was missed.

Geographic incidence

  • Worldwide.

Age predisposition

  • Hyperestrogenism associated with persistent estrus can affect any intact female ferrets (jills) that are reproductively active.
  • Hyperandrogenism in ferret adrenocortical disease is typically identified in ferrets over 3 years of age.

Cost considerations

  • Although in most cases a tentative diagnosis can be reached through clinical history and examination alone, animals that are significantly compromised can require extensive medical stabilization followed by treatment that can become costly.

Special risks

  • Bone marrow depression can occur through prolonged estrogen exposure. Anemia, leukopenia and thrombocytopenia are typical clinicopathologic findings, and can range from mild to severe.
  • Significant hemorrhage can potentially result from benign handling and diagnostic investigative procedures.
  • Should anesthesia and surgery be indicated as part of the treatment plan, eg surgical neutering, this should only be performed once the animal is stabilized medically, eg blood transfusion, fluid therapy.

Pathogenesis

Etiology

  • Persistent seasonal estrus Prolonged estrus:
    • Female ferrets are induced ovulators; coital stimulation is required to induce ovulation.
    • Majority of reproductively active female ferrets will remain in estrus until mated or artificially stimulated to ovulate.
    • Persistent estrus over one month in duration typically results in hyperestrogenism.
  • Other causes:

Predisposing factors

General

  • Entire reproductively active females.
  • Breeding season, ie during periods with an increasing photoperiod (late winter and spring under natural conditions).

Specific

  • Female ferrets: persistent estrus caused by lack of coital stimulation to induce ovulation.
  • Ferret adrenocortical disease: early surgically neutered female pets ferrets exposed to prolonged photoperiods.

Pathophysiology

  • Estrogens (specifically estradiol) is primarily secreted by ovarian follicles in healthy reproductively active mammals, and to a lesser extent in extragonadol tissues such as the kidney, adipose tissue and brain.
  • Adrenocortical disease in ferrets is typically associated with hyperadrogenism. Serum estradiol concentrations are frequently elevated in affected animals compared with neutered animals.
  • Estrogen under normal physiologic conditions in results in vulval swelling (particularly noticeable in ferrets), uterine development, increased sexual receptivity and changes in vaginal cell types.
  • Prolonged estrogen exposure (usually accepted as ≥1 month) leads to bone marrow suppression and hypoplasia through all blood cell lines:
    • Secondary infection, eg bacterial pneumonia has occasionally been reported.
    • Bleeding diathesis, prolonged clotting times.
  • Estrogens, like other androgenic hormones, play a role in the hair cycle and hair follicle structure. Bilaterally symmetrical alopecia is frequently described in animals with androgenic hormonal disorders, although it is difficult to attribute this solely to hyperestrogenism.

Timecourse

  • Adverse effects of hyperestrogenism are typically associated with exposure to elevated levels of estrogen ≥1 month.

Epidemiology

  • Female ferrets are reflex ovulators and will remain in constant estrus during the breeding season if mating does not occur. All entire female ferrets that are kept in single-sexed groups or kept singly are therefore predisposed to the development of hyperestrogenism during the breeding season.
  • Adrenocortical disease in ferrets have been attributed to early surgical neutering which results in the loss of negative feedback in the hypothalamopituitary-gonadal axis. Additionally, artificially prolonged photoperiods in indoor pet ferrets, and a possible genetic component.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Schoemaker N J (2018) Gonadotrophin-releasing hormone agonists and other contraceptive medications in exotic companion animals. Vet Clin North Am Exot Anim Pract 21 (2), 443-464 PubMed.
  • Jekl V & Hauptman K (2017) Reproductive medicine in ferrets. Vet Clin Exotic Anim Pract 20 (2), 629-663 PubMed.
  • Goericke-Pesch S & Wehrend A (2012) The use of a slow release GnRH-agonist implant in female ferrets in season for oestrus suppression. Schweizer Archiv Fur Tierheilkunde 154 (11), 487 PubMed.
  • Rosenthal K L & Peterson M E (1996) Evaluation of plasma androgen and estrogen concentrations in ferrets with hyperadrenocorticism. J Am Vet Med Assoc 209 (6), 1097-1102 PubMed.
Other sources of information
  • Di Girolamo N & Huynh M (2020) Disorders of the Urinary and Reproductive Systems in Ferrets. In: Ferrets, Rabbits and Rodents - E-Book: Clinical Medicine and Surgery. 4th edn. Eds: Quesenberry K, Mans C, Orcutt C & Carpenter J W. Elsevier, USA.
  • Fox J G & Bell J A (2014) Diseases of the Genitourinary System. In: Biology and Diseases of the Ferret. Eds: Fox J G & Marini R P. Wiley & Sons, USA.