Megestrol Acetate
Megestrol acetate is a potent, synthetic **progestin** with significant anti-estrogenic and intrinsic glucocorticoid properties. Historically, it was widely used in veterinary medicineโparticularly in catsโfor a variety of dermatological and behavioral conditions. However, **its use in felines has drastically declined** in modern practice due to the high risk of severe, sometimes irreversible adverse effects, including profound adrenocortical suppression and iatrogenic diabetes mellitus. In dogs, it remains FDA-approved for the postponement of estrus and alleviation of false pregnancy in females, and is used off-label for benign prostatic hypertrophy (BPH) in males. In human medicine, it is utilized as an appetite stimulant and for the palliative treatment of advanced breast or endometrial carcinomas.
Mechanism: Megestrol acetate exerts its effects through multiple receptor pathways: * **Progesterone Receptors**: Binds to progestin receptors โ provides negative feedback to the hypothalamus and pituitary โ inhibits the release of **GnRH**, **LH**, and **FSH** โ suppresses estrus and ovulation. * **Glucocorticoid Receptors**: Possesses significant intrinsic glucocorticoid activity โ binds to glucocorticoid receptors โ causes profound suppression of the **hypothalamic-pituitary-adrenal (HPA) axis** and induces insulin resistance. * **Anti-estrogenic Activity**: Modifies target tissue response to estrogens. *Clinical Pearl*: Unlike some other progestins, megestrol acetate does not possess significant anabolic or masculinizing effects on the developing fetus.
Dosing by species
- Suppression of estrus (in anestrus) ยท 5 mg/cat PO every 2 weeks or 2.5 mg/cat per week (better if divided into 2 doses given every 3.5 days) ยท PO ยท q7-14d ยท Variable
- Suppression of estrus (in proestrus) ยท 5 mg/cat per day for 4 days, then 5 mg PO every 2 weeks. ยท PO ยท q24h then q14d ยท Variable
- Suppression of estrus (behavioral estrus) ยท 5 mg/day PO until estrus stops (generally within 3-5 days), then 2.5-5 mg PO once weekly for 10 weeks ยท PO ยท q24h then q7d ยท 10+ weeks
- Postponement of estrus (started during diestrus) ยท 2.5 mg PO daily for 8 weeks ยท PO ยท q24h ยท 8 weeks
- Postponement of estrus (started during anestrus) ยท 2.5 mg PO once weekly for up to 18 months. ยท PO ยท q7d ยท Up to 18 months ยท Recommend allowing cat to have a cycle (unmedicated) before beginning another treatment cycle.
- Prevention of estrus ยท 5 mg daily PO for 3 days as soon as behavioral signs of estrus are seen ยท PO ยท q24h ยท 3 days ยท Next estrus period will occur in approximately 4 weeks.
- Idiopathic feline miliary dermatitis ยท 2.5-5 mg once every other day, followed by weekly maintenance dosages. ยท PO ยท q48h then q7d ยท Variable ยท Reserve use for severe cases; explain risks to owner and do not exceed 2.5 mg per week during maintenance phase.
- Appetite stimulant ยท 0.25-0.5 mg/kg q24h for 3-5 days, then q48-72h ยท PO ยท q24h then q48-72h ยท Variable
- Alternative treatment for immune-mediated skin diseases ยท 2.5-5 mg PO once daily for 10 days, then every other day ยท PO ยท q24h then q48h ยท Variable
Routes of administration
Contraindications
- Pregnancy
- Uterine disease (e.g., pyometra, endometritis)
- Diabetes mellitus
- Mammary neoplasias
- Prior to the first estrous cycle in dogs
- Anestrus therapy in dogs with abnormal cycles
- During diestrus or in the presence of uterine hemorrhage
- Treatment of pseudopregnancy in bitches (per manufacturer, though off-label protocols exist)
Adverse effects
- Profound adrenocortical suppression (especially in cats)
- Transient or permanent diabetes mellitus
- Cystic endometrial hyperplasia (CEH) and pyometra
- Mammary hypertrophy and neoplasia
- Increased appetite and weight gain
- Polydipsia and polyuria (PU/PD)
- Lethargy and personality changes
- Hepatotoxicity (rare)
- Acromegaly (dogs)
- Lactation (rare)
Drug interactions
- Corticosteroids ยท Concurrent long-term use may exacerbate adrenocortical suppression and increase the risk of diabetes mellitus.
- Rifampin ยท May decrease progestin activity due to microsomal enzyme induction, resulting in increased progestin metabolism.
Monitoring
- Body weight
- Blood glucose (draw baseline before therapy)
- Mammary gland development and appearance (nodules/hypertrophy)
- Adrenocortical function (ACTH stimulation test if indicated)
- Liver enzymes (especially with long-term treatment)
- Clinical efficacy
Overdose
Acute toxicity from overdosage has not been reported. In humans, massive doses (up to 800 mg/day) caused no observable acute adverse reactions. **Chronic Toxicity in Dogs**: * Dosages of 0.1-0.25 mg/kg/day PO for 36 months yielded no gross abnormalities, but histologically, **cystic endometrial hyperplasia (CEH)** was noted (resolved when therapy was discontinued). * Dosages of 0.5 mg/kg/day PO for 5 months caused reversible uterine hyperplasia. * Dosages of 2 mg/kg/day demonstrated early cystic endometritis within 64 days.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.