酢酸メゲストロール
酢酸メゲストロールは、強力な合成**プロゲスチン**であり、顕著な抗エストロゲン作用および内因性グルココルチコイド特性を持っています。 歴史的に、特に猫の皮膚疾患や行動問題に広く使用されてきましたが、重篤で不可逆的な副作用（重度の副腎皮質抑制や医原性糖尿病など）のリスクが高いため、**現在では猫への使用は大幅に減少しています**。 犬においては、メスの発情延期および偽妊娠の軽減としてFDAに承認されており、オスでは良性前立腺肥大（BPH）に適応外使用されます。人間医学では、食欲増進剤や進行性乳がん・子宮内膜がんの緩和ケアとして利用されています。
作用機序: Megestrol acetate exerts its effects through multiple receptor pathways: * **Progesterone Receptors**: Binds to progestin receptors → provides negative feedback to the hypothalamus and pituitary → inhibits the release of **GnRH**, **LH**, and **FSH** → suppresses estrus and ovulation. * **Glucocorticoid Receptors**: Possesses significant intrinsic glucocorticoid activity → binds to glucocorticoid receptors → 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.
動物種別の用量
- Suppression of estrus (in anestrus) · 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) · PO · q7-14d · Variable
- Suppression of estrus (in proestrus) · 5 mg/cat per day for 4 days, then 5 mg PO every 2 weeks. · PO · q24h then q14d · Variable
- Suppression of estrus (behavioral estrus) · 5 mg/day PO until estrus stops (generally within 3-5 days), then 2.5-5 mg PO once weekly for 10 weeks · PO · q24h then q7d · 10+ weeks
- Postponement of estrus (started during diestrus) · 2.5 mg PO daily for 8 weeks · PO · q24h · 8 weeks
- Postponement of estrus (started during anestrus) · 2.5 mg PO once weekly for up to 18 months. · PO · q7d · Up to 18 months · Recommend allowing cat to have a cycle (unmedicated) before beginning another treatment cycle.
- Prevention of estrus · 5 mg daily PO for 3 days as soon as behavioral signs of estrus are seen · PO · q24h · 3 days · Next estrus period will occur in approximately 4 weeks.
- Idiopathic feline miliary dermatitis · 2.5-5 mg once every other day, followed by weekly maintenance dosages. · PO · q48h then q7d · Variable · Reserve use for severe cases; explain risks to owner and do not exceed 2.5 mg per week during maintenance phase.
- Appetite stimulant · 0.25-0.5 mg/kg q24h for 3-5 days, then q48-72h · PO · q24h then q48-72h · Variable
- Alternative treatment for immune-mediated skin diseases · 2.5-5 mg PO once daily for 10 days, then every other day · PO · q24h then q48h · Variable
投与経路
禁忌
- 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)
有害事象
- 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)
薬物相互作用
- Corticosteroids · Concurrent long-term use may exacerbate adrenocortical suppression and increase the risk of diabetes mellitus.
- Rifampin · May decrease progestin activity due to microsomal enzyme induction, resulting in increased progestin metabolism.
モニタリング
- 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
過量投与
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.
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