Hyperoestrogenism is a disorder that specifically affects the female ferret (jill) and consists of oestrogen-induced bone marrow toxicity. This disorder is the consequence of the peculiar reproductive cycle of the jill, which includes ovulation induced and influenced by the photoperiod. Exposed to a natural photoperiod, jills enter oestrus in February-March; this phase of the sexual cycle terminates only if the animal mates or at the end of the reproductive season in August-September. For the whole duration of oestrus, which can last several months, there are high levels of oestrogens in the circulation which can have severe toxic effects on the bone marrow, with depression of the production of all cells lines (red blood cells, white blood cells and platelets). The myelotoxicity may appear within 1-3 months of the start of oestrus, causing the death of the animal from irreversible bone marrow failure, an event that occurs in 50% of jills with prolonged oestrus.
Although hyperoestrogenism is typically a disease of sexually intact female ferrets (jills), it may also develop in spayed ferrets (sprites) if a fragment of ovary is accidentally left in situ during the operation (residual ovary syndrome).
CLINICAL SIGNS
The clinical picture of hyperoestrogenism is characterized initially by vulvar hyperplasia and bilateral, symmetrical, non-pruritic alopecia, with intact skin. As the disease progresses, clinical signs secondary to anaemia, leucopenia and thrombocytopenia appear: weakness of the hind quarters (inability to maintain the trunk arched), depression, anorexia, pale mucosae, petechiae and ecchymoses, haemorrhages, melaena and increased incidence of bacterial infections (pyometra or uterine stump pathology, pneumonia, septicaemia).
DIAGNOSIS
Hyperoestrogenism should always be considered in jills which have been in oestrus for more than 1 month and also in sprites with vulvar hyperplasia.
A full blood count should always be performed to evaluate the presence of non-regenerative anaemia, leucopenia and thrombocytopenia. The haematocrit in affected animals decreases to a variable extent and can reach levels lower than 5% before death. The normal haematocrit is 46-61%, but it tends to decrease within a few minutes following gaseous anaesthesia and after prolonged exposure may decrease by 40% which should be taken into consideration when interpreting laboratory values.
The presence of alopecia and vulvar hyperplasia should raise the differential diagnosis of adrenal disease. Hyperoestrogenism, whether in the jill or in the sprite with residual ovarian tissue, always occurs in the spring following birth (in practice at the time of the first oestrus) and, therefore, within about the age of 10 months. Adrenal disease is frequently observed around 3 to 4 years of age, or later, but an early onset within 1 year of life cannot be excluded. In doubtful cases, an attempt can be made to induce ovulation pharmacologically (as described below): in the case of hyperoestrogenism the vulva returns to normal within a few days, whereas in the case of adrenal disease there are no changes.
PREVENTION AND TREATMENT
Ovulation can be induced in the jill in heat, thereby terminating oestrus, by administering gonadotropin-releasing hormone (GnRH; 20 mg i.m. per jill) or human chorionic gonadotropin (hCG; 100 IU i.m. per jill). In order to be effective the treatment must be given at least 10 days after the start of oestrus (evaluated by the appearance of evident vulvar hyperplasia). If the oestrus is not terminated following the first dose, the treatment can be repeated after 2 weeks. In the absence of a response, adrenal disease should be suspected and an abdominal ultrasound examination proposed. Megestrol acetate is contraindicated because it predisposes to the development of pyometra. Another method of inducing ovulation is to mate the female with a hoblet (vasectomised male), if available (difficult, in practice) or a sexually intact hob if the owner wants the jill to reproduce.
If the ferret is brought for examination within a couple of weeks of starting oestrus, surgical sterilisation or asportation of the residual ovary can be performed immediately after a full blood count has been checked to determine that the platelet count and haematocrit are adequate. If the haematocrit is greater than 30%, the operation can be carried out immediately, otherwise a blood transfusion should be given or medical treatment used to terminate the oestrus while awaiting for the animal’s condition to stabilise. If the haematocrit is less than 15% the prognosis is poor and, besides medical therapy to terminate the oestrus, repeated blood transfusions and supportive therapy (rest, heat, assisted feeding, administration of vitamins and iron and antibiotics in the case of infection) are required. Euthanasia should be considered for animals with very low haematocrit levels. Once oestrus has been terminated, the bone marrow suppression can take months to recover and repeated transfusions are needed if the haematocrit is low. In rare cases the bone marrow suppression is permanent. The efficacy and safety of stanozolol (an anabolic steroid) have not been evaluated in the ferret. Jills with complications, such as pyometra, pneumonia and thrombocytopenia often do not respond well to medical treatment and are not good candidates for surgery.
Hyperoestrogenism is easily prevented by sterilising jills within the spring after their birth; if the animals’ haematological values are good, there are no contraindications to operating on jills already in oestrus. Alternatively, chemical sterilisation can be achieved by implanting deslorelin.