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letter
. 2016 Mar 2;18(3):248–249. doi: 10.1177/1098612X16631235

Use of megestrol in cats

Gary D Norsworthy, Stefano Romagnoli
PMCID: PMC11148908  PMID: 26936496

Dear Editors – I read with great interest Dr Romagnoli’s comments on the use of megestrol in his recent JFMS review on progestins to control feline reproduction. 1 This is a drug, under the trade name Ovaban, that I started using in the 1970s for canine contraception. We went off-label and used it for feline contraception as he described. Its long-term use serendipitously uncovered that megestrol has powerful soft tissue anti-inflammatory properties in cats that are not found in dogs. It came to be used widely for atopy, flea allergic dermatitis, lymphoplasmacytic stomatitis, vomiting due to inflammatory bowel disease (or ‘idiopathic vomiting’ as it was then called), eosinophilic keratitis, rodent ulcers, eosinophilic granulomas and dysuria due to idiopathic cystitis. We reached a point where we said humorously that no cat should be allowed to die without a test dose of Ovaban; it was called the ‘feline silver bullet’.

However, its widespread use eventually uncovered some notable side effects that I would like to list for the benefit of veterinarians who may wish to use this drug for feline contraception. The most common doses were 5 mg/cat 1–3 times per week.

  • Increased appetite and weight gain. This is the most consistent side effect. Megestrol can produce significant weight gain in just a few months. Conversely, it has been used to stimulate the appetite of cats (and humans) with anorexia due to severe illness, especially neoplasia.

  • Personality changes. Aggressive cats can become very calm and docile; very laid-back cats can become aggressive.

  • Mammary hyperplasia. This can be very severe. Discontinuation of the drug can cause reversal, but some cats require mastectomy.

  • Mammary adenocarcinoma. This occurs very infrequently, but when it does occur it is usually fatal.

  • Onset of diabetes. This is the most dramatic of the common side effects. During the 1980s we thought that megestrol caused diabetes since it impairs glucose metabolism. In retrospect, it is more likely that the onset of diabetes was only in cats that were borderline diabetics already. Those cats would have become diabetic within a few months, even if megestrol had not been given. Most of the megestrol-associated diabetics went into diabetic remission if the drug was promptly withdrawn. However, those cats usually became diabetic again because they had impaired insulin secretion prior to the use of megestrol.

These side effects, especially diabetes, gave the drug a very bad reputation in the 1980s and 1990s. Many condemned its use and those who prescribed it. My contact with US graduates in the past 5 years tells me that it is no longer even discussed in veterinary schools. Therefore, I am writing this to give new graduates an understanding of the history of this drug. I still use it occasionally, and only short-term, for situations that are not well treated with other drugs. However, I am still in the hope that another ‘silver bullet’ will emerge so I no longer feel that I have to use megestrol.

Gary D Norsworthy, DVM, DABVP (Feline)
San Antonio, Texas, USA

letter J Feline Med Surg. 2016 Mar 2;18(3):248–249.

The author responds – The very interesting letter of Dr Norsworthy gives a historical perspective and throws more light on the reasons for the negative reputation that progestins, particularly megestrol acetate (MA), have unjustifiably gained over the past 40 years thanks to erroneous use. As Dr Norsworthy remarks, MA ended up being frequently used for reproductive and non-reproductive indications at dosages of 5 mg/cat 1–3 times/week for months (the so-called ‘feline silver bullet’). For a 4.0 kg cat, a 5.0 mg/cat/week dosage is equivalent to 1.25 mg/kg/week, which is an extremely high dosage (see box on ‘Dosing of MA’ on page 745 of my article 1 ) when considering that satisfactory control of reproduction with almost no side effects can be obtained in queens using half that dose, or 0.625 mg/kg/week. Efficacy and safety of half the feline silver bullet dose were reported in two papers published in 1977.2,3 Unfortunately, neither paper was given the attention it deserved and, instead, use of MA at extremely high dosages became commonplace, particularly because of the anti-inflammatory properties MA displays in cats when given at high dosages. Overdosing is responsible for a number of reproductive and endocrine side effects, which were widely reported in the world literature during the 1980s and 1990s. This led to the bad reputation of MA, as I noted in my article (in the aforementioned box on ‘Dosing of MA’) and as Dr Norsworthy rightly underlines.

In my opinion, MA’s poor reputation among feline practitioners is unfounded and veterinarians who may wish to use this drug for contraception should be convinced that MA can be very safe for cats provided it is used properly. As explained in my article, 1 not only is half the feline silver bullet dosage (0.625 mg/kg/week) effective and fairly safe, but dosages as low as one-tenth (or 0.11 mg/kg/week) can effectively and safely control feline reproduction based on anecdotal reports by North American cat colony managers as well as my personal experience (unpublished observations). Side effects of MA used at one-tenth the feline silver bullet are absent provided that treatment length is appropriate and the right candidates are chosen (see box on ‘Evaluation of queens prior to progestin treatment’ on page 748 of my article 1 ).

It is regrettable that so many cats had to suffer unnecessarily over the years with drug-induced conditions such as mammary hyperplasia, mammary adenocarcinoma, pyometra and even diabetes, all of which could have been avoided simply by reading and debating the literature. With regard to diabetes, I am not aware of any study showing that diabetes would develop following the use of MA in cats that were already borderline diabetics at the time of treatment. Glucose intolerance and diabetes reliably develops in cats treated with the feline silver bullet (0.625 mg/kg q48h for >2 weeks), but then regresses once treatment is discontinued,4 –10 while it does not regress when the same dosage is administered for months or years.11 –13

Stefano Romagnoli, DVM, MS, PhD, Dipl ECAR
University of Padova, Italy

References

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