ジエチルスチルベストロール
ジエチルスチルベストロール（DES）は合成非ステロイド性エストロゲンであり、獣医療では主に避妊済み雌犬の**エストロゲン反応性尿失禁**の管理に使用されます。また、雄犬の良性前立腺肥大症や発情誘起にも使用されてきました。 > **臨床のポイント：** 重篤な骨髄毒性（致命的な再生不良性貧血）のリスクがあり、潜在的な発がん性および催奇形性物質に分類されているため、産業動物への使用は厳格に禁止されています。 人間の健康への懸念と市場からの撤退により、DESはFDA承認の市販製品としては入手できなくなり、獣医用調剤薬局を通じて入手する必要があります。現代の臨床では、括約筋機能不全の第一選択薬として、エストリオール（Incurin）やフェニルプロパノールアミン（PPA）などのより安全な代替薬が好まれることが多くなっています。
作用機序: DES acts as a potent agonist at **estrogen receptors (ER-α and ER-β)**. Upon binding, the receptor-ligand complex translocates to the cell nucleus, where it binds to estrogen response elements (EREs) on DNA, altering mRNA transcription and subsequent protein synthesis. * **Urinary Incontinence:** Estrogens upregulate the expression and sensitivity of **α-adrenergic receptors** in the internal urethral sphincter. This increases the sphincter's responsiveness to endogenous norepinephrine, thereby increasing resting urethral closure pressure and preventing urine leakage. * **Reproductive/Systemic Effects:** Promotes growth and development of female sex organs, increases cervical/vaginal mucosal thickness, and causes endometrial proliferation. It also accelerates epiphyseal closure, increases calcium deposition in bone, and inhibits pituitary gonadotropin release via negative feedback.
動物種別の用量
- Estrogen-responsive incontinence (females) · 0.1-1 mg (total dose) PO once daily for 5 days, then 1 mg once a week · PO · Once daily for 5 days, then weekly · Long-term maintenance · Doses of 2.2 mg/kg per day have caused death in cats secondary to bone marrow toxicity.
- Primary sphincter mechanism incompetence (Option A) · 0.1-1 mg (total dose) per dog PO for 5 days followed by maintenance of 1 mg/week or a maximum of 0.1 mg/kg/week. Minimum effective dose should be used for maintenance. Do NOT give more than recommended. · PO · Once daily for 5 days, then weekly · Long-term maintenance · As an alternative to phenylpropanolamine.
- Primary sphincter mechanism incompetence (Option B - females) · 0.1-1 mg (total dose) PO once daily for 5 days, then 1 mg once a week · PO · Once daily for 5 days, then weekly · Long-term maintenance
- Primary sphincter mechanism incompetence (Option C) · 0.5-1 mg (0.02 mg/kg; maximum dose of 1 mg) for 3-5 days as an induction dose and then periodically decreased to every other day and then to the lowest dose that will maintain continence. · PO · Daily initially, then tapered · Long-term maintenance · In difficult cases, may be used with phenylpropanolamine. Note: Conjugated estrogens (e.g., Premarin) are sometimes used as a substitute (e.g., 20 mcg/kg PO every 4 days).
- Estrus induction · DES at 5 mg/day for a tentative 7 days. The first day of vulvar swelling is designated as Day 1. Continue DES on DAY 1 and Day 2. If no effect is seen in 7 days, give DES at 10 mg/day for another tentative 7 days. If vulvar swelling and bleeding detected, DES is continued on Day 1 and Day 2. If no effect seen in these 14 days, discontinue and restart in 30 days. Once proestrus initiated, on Day 5 give 5 mg of Luteinizing hormone (LH) if obtainable. If LH unavailable, give GnRH 3.3 micrograms/kg IM and FSH 10 mg IM in its place. Bitch is bred on Day 13. · PO · Daily · 7-14 days · Adjust dosages of LH and FSH for animal size-the above dosages are for a dog weighing 50-60 lbs.
投与経路
禁忌
- Food-producing animals (FDA prohibited)
- Pregnancy (teratogenic; causes fetal genitourinary malformations)
- Patients with preexisting anemias or leukopenias
- Females with estrogen-sensitive neoplasms
有害事象
- Bone marrow suppression (thrombocytopenia, leukopenia, fatal aplastic anemia)
- Cystic endometrial hyperplasia
- Pyometra (in intact females)
- Mammary neoplasia
- Feminization (in males)
- Signs of estrus (in females)
- Pancreatic, hepatic, and cardiac lesions (reported in cats)
- Malignant ovarian adenocarcinomas (experimental)
薬物相互作用
- Azole Antifungals (itraconazole, ketoconazole, etc.) · May increase estrogen levels
- Cimetidine · May decrease metabolism of estrogens
- Corticosteroids · Enhanced glucocorticoid effects may result; estrogens may alter protein binding or decrease metabolism of corticosteroids
- Erythromycin, Clarithromycin · May decrease the metabolism of estrogens
- Warfarin · Oral anticoagulant activity may be decreased; increases in anticoagulant dosage may be necessary
- Phenobarbital · May decrease estrogen concentrations
- Phenytoin · May decrease estrogen concentrations
- Rifampin · May induce hepatic microsomal enzymes and decrease estrogen levels
モニタリング
- Packed Cell Volumes (PCV)
- White blood cell counts
- Platelet counts
- Liver function tests (at baseline, one month after therapy begins, and repeat 2 months after cessation if abnormal)
過量投与
Acute overdosage in humans with estrogens has resulted in nausea, vomiting, and withdrawal bleeding in females. In veterinary patients, acute overdose information is limited, but **chronic overdosage or high doses** are well-documented to cause severe, potentially fatal **bone marrow suppression** (aplastic anemia, thrombocytopenia, neutropenia). Doses of 2.2 mg/kg per day have caused death in cats. Treatment of overdose should involve immediate discontinuation of the drug and aggressive supportive care (e.g., blood transfusions, broad-spectrum antibiotics for neutropenia).
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。