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.

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:
  • Estrogen-secreting ovarian remnant Ovarian remnant syndrome.
  • Ovarian neoplasia Ovarian neoplasia.
  • Hyperadrenocortical disease Hypoadrenocorticism.

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

Treatment

Prevention

Outcomes