己烯雌酚
己烯雌酚 (DES) 是一種合成的非類固醇雌激素，在獸醫學中主要用於治療已結紮母犬的**雌激素反應性尿失禁**。它也曾被用於公犬的良性前列腺肥大和誘導發情。 > **臨床要點：** 由於具有嚴重的骨髓毒性（致命性再生不良性貧血）風險，且被歸類為潛在的致癌物和致畸胎物，DES 嚴禁使用於經濟動物。 基於人類健康考量和市場撤出，DES 目前在美國已無 FDA 核准的市售成藥，必須透過獸醫調劑藥局取得。在現代臨床實務中，通常更傾向使用較安全的替代藥物，如雌三醇 (Incurin) 或苯丙醇胺 (PPA) 作為括約肌機能不全的第一線治療。
作用機制: 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.
各物種劑量
- 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.
給藥途徑
禁忌症
- Food-producing animals (FDA prohibited)
- Pregnancy (teratogenic; causes fetal genitourinary malformations)
- Patients with preexisting anemias or leukopenias
- Females with estrogen-sensitive neoplasms
不良反應
- 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)
藥物相互作用
- 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
監測
- 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
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).
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