EAAM Veterinary Working Group Advisory Comment- Megestrol Acetate Megestrol acetate is a synthetic progestin with glucocorticoid-like activity. Its primary clinical indication in human medicine is for the palliative treatment of advanced carcinoma of the breast or endometrium (recurrent, inoperable, or metastatic disease) and as an appetite stimulant for cachexia in advanced cancer (off-label). Indicated use in dogs and cats is for the control of estrus behavior and alleviation of false pregnancy1. The use of megestrol carries certain risks. Based on drug formulary warnings2, adrenal suppression and respiratory infections are possible with its use. Administration of megestrol acetate resulting in decreased ACTH (adrenocorticotropin) production and subsequent adrenal gland atrophy has been demonstrated in cats3. Megestrol acetate is an effective appetite stimulant in bottlenose dolphins, and has been used in the past as a contraceptive and to reduce inter-male aggression. Megestrol is not an effective means of contraception as male dolphins can, and have, bred successfully while on the medication. On the other hand, there have been also reported cases (personal communications) of irreversible sterility in breeding males under treatment, and although unpublished, worth mentioning. Recent reports4,5 have shown that megestrol acetate can have additional counterproductive and harmful secondary effects in bottlenose dolphins, similar to those reported for humans and other mammals. It is important that veterinarians and animal care specialists working with this species are aware of the secondary effects on the hypothalamic-pituitary-adrenal axis and all possible consequences. Accordingly, the use of megestrol acetate to reduce inter-male aggression is generally discouraged, and long term use for any reason should be avoided. Megestrol acetate must be prescribed by a veterinarian according to his/her judgment of the animal’s health status and needs, and, as with any other drug, the use of this drug should be evaluated carefully. 1 Plumb, Veterinary Drug Handbook 3rd Edition pp 461-464. 2 From: http://online.factsandcomparisons.com/MonoDisp.aspx?monoID=fandc- hcp12777&quick=495365%7c5&search=495365%7c5&isstemmed=True&NDCmapping=-1&fromTop=true#firstMatch Adrenal suppression: Glucocorticoid activity of megestrol acetate has not been fully evaluated. Clinical cases of new onset diabetes, exacerbation of preexisting diabetes, and Cushing syndrome have been reported in association with the use of megestrol acetate. Cases of adrenal insufficiency have also been reported in patients receiving or being withdrawn from chronic megestrol acetate therapy in the stressed and non-stressed state. Adrenocorticotropin (ACTH) stimulation testing also has revealed the frequent occurrence of asymptomatic pituitary- adrenal suppression in patients treated with megestrol acetate chronically. The possibility of adrenal suppression should be considered in any patient taking or withdrawing from chronic megestrol acetate therapy who presents with symptoms of adrenal insufficiency such as hypotension, nausea, vomiting, dizziness, or weakness. Laboratory evaluation for adrenal insufficiency and replacement or stress doses of a rapidly acting glucocorticoid may be indicated for such patients. Failure to recognize inhibition of the hypothalmic-pituitary-adrenal axis may result in death. In patients who are receiving or being withdrawn from chronic megestrol acetate, consider use of empiric therapy with stress doses of a rapidly acting glucocorticoid during stress or serious intercurrent illness (e.g. surgery, infection). Animal toxicology: Long-term treatment with megestrol acetate may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts and increased neutrophil counts was observed in a 2-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats. 3 Norsworthy GD, editor. The Feline Patient. 4th ed. Ames, Iowa: Blackwell Publ; 2011. pp. 265–266. 4 IAAAM 2010 Manire, The use of megestrol acetate in bottlenose dolphins. 5 IAAAM 2013 Champagne et al, The Progestin Megestrol Acetate Suppresses the HPA Axis in the Bottlenose Dolphin, Tursiops truncatus .