Zhang Xinmei, Yuan Hong, Deng Lin, Hu Fuqiang, Ma Junyan, Lin Jun
Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, People's Republic of China.
Hum Reprod. 2008 Sep;23(9):2024-30. doi: 10.1093/humrep/den208. Epub 2008 Jun 14.
Danazol, a synthetic steroid with antigonadotrophic properties, has been widely used for the treatment of endometriosis and adenomyosis. However, the local application of danazol to the uterus to treat adenomyosis is controversial. The objective of this study is to develop an effective treatment for adenomyosis using danazol via intrauterine contraceptive device (IUCD) delivery.
An adenomyosis animal model was established using Institute for Cancer Research, Swiss-derived (ICR) mice, grafted with a single pituitary gland (n = 30). Four months after grafting, IUCDs with three different quantities of danazol were prepared and used to treat the ICR mice with adenomyosis. After 2 months of treatment with a danazol-loaded IUCD, the number of adenomyosis nodules and the hematoxylin-eosin staining scores were measured and compared with mice given daily oral danazol and controls (no adenomyosis).
As the danazol dose increased, the nodule number decreased reaching significance at a dose of 2.0 mg per 20 g body weight (P = 0.002). When compared with oral administration, the plasma danazol concentrations with IUCD delivery were low and stable.
These results suggest that an IUCD loaded with an appropriate dose of danazol may be an effective treatment for adenomyosis and that human trials are warranted.
达那唑是一种具有抗促性腺激素特性的合成类固醇,已广泛用于治疗子宫内膜异位症和子宫腺肌病。然而,将达那唑局部应用于子宫治疗子宫腺肌病存在争议。本研究的目的是开发一种通过宫内节育器(IUCD)递送达那唑来有效治疗子宫腺肌病的方法。
使用瑞士癌症研究所(ICR)小鼠建立子宫腺肌病动物模型,移植单个垂体(n = 30)。移植后4个月,制备含三种不同剂量达那唑的宫内节育器,用于治疗患有子宫腺肌病的ICR小鼠。在用含达那唑的宫内节育器治疗2个月后,测量子宫腺肌病结节数量和苏木精-伊红染色评分,并与每日口服达那唑的小鼠和对照组(无子宫腺肌病)进行比较。
随着达那唑剂量增加,结节数量减少,在每20克体重2.0毫克的剂量时达到显著水平(P = 0.002)。与口服给药相比,宫内节育器递送时血浆达那唑浓度较低且稳定。
这些结果表明,装载适当剂量达那唑的宫内节育器可能是治疗子宫腺肌病的有效方法,值得进行人体试验。