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Hum. Reprod. Advance Access originally published online on June 14, 2008
Human Reproduction 2008 23(9):2024-2030; doi:10.1093/humrep/den208
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Evaluation of the efficacy of a danazol-loaded intrauterine contraceptive device on adenomyosis in an ICR mouse model

Xinmei Zhang1, Hong Yuan2, Lin Deng1, Fuqiang Hu2, Junyan Ma1 and Jun Lin1,3

1 Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, People's Republic of China 2 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310006, People's Republic of China

3 Correspondence address. Tel: +86-571-87061501/2131; Fax: +86-571-87061878; E-mail: xinmei6{at}yahoo.com

BACKGROUND: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.

Key words: danazol/adenomyosis/mouse/animal model/intrauterine contraceptive device

Submitted on November 15, 2007; resubmitted on February 21, 2008; accepted on March 28, 2008.


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