Reactive oxygen intermediates and reactive nitrogen intermediates in copper intrauterine device users.

The mechanism of action of copper in copper intrauterine devices (Cu IUD) as an antimicrobial agent is not well understood. Copper and iron are supposed to be responsible for release of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), which are very active in the presence of infection. The copper in a copper IUD could be responsible for limiting pelvic inflammatory disease. The present study was composed of 20 IUD seekers in whom ROI and RNI were studied before insertion of Cu IUD and then at 1, 4, and 12 weeks afterward. ROI showed a rise after insertion, whereas RNI showed a steady decline. Hence, it is presumed that the rise in ROI could be responsible for both the bactericidal effect of Cu IUD and also for the fall in RNI.

PIP: There is evidence of an increase in the number of polymorphonuclear leukocytes in the endometrium after insertion of a copper IUD. When activated, these macrophages secrete two groups of toxic metabolites that interact with each other: reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). The mechanism of action of the copper in copper IUDs as an antimicrobial agent is not well understood. The present study measured ROI and RNI levels in 20 copper IUD users from Chandigarh, India, before and 1, 4, and 12 weeks after insertion. A statistically significant decrease in RNI levels was observed at each postinsertion time. In contrast, ROI levels showed an initial fall at 1 week postinsertion followed by a rise at 4 and 12 weeks. Control of infection has been found to be associated with this pattern of a rise in ROI and fall in RNI. (The initial fall in ROI at 1 week observed in the present study is assumed to be an anomaly related to the introduction of microbials during IUD insertion.) The copper in a copper IUD could be responsible for limiting pelvic inflammatory infection.

[Copper IUDs (author's transl)]. / Dispositifs intra-uterins au cuivre.

PIP: Following initial development of the Grafenberg ring in the 1920's, IUDs fell into disuse until the late 1950s, when plastic devices inserted using new technology began to gain worldwide acceptance. Further research indicated that copper had a significant antifertility effect which increased with increasing surface area, and several copper IUDs were developed and adapted, including the Copper T 200, the Copper T 220C, and the Copper T 380 A, probably the most effective yet. The Gravigard and Multiload are 2 other copper devices developed according to somewhat different principles. Copper devices are widely used not so much because of their great effectiveness as because of their suitability for nulliparous patients and their ease of insertion, which minimizes risk of uterine perforation. Records of 2584 women using Copper IUDs for 7190 women-years and 956 women using devices without copper for 6059 women-years suggest that the copper devices were associated with greater effectiveness and fewer removals for complications. Research suggests that the advantages of copper IUDs become more significant with increased duration of use. Contraindications to copper devices include allergy to copper and hepatolenticular degeneration. No carcinogenic or teratogenic effect of copper devices has been found, but further studies are needed to rule out other undesirable effects. Significant modifications of copper devices in recent years have been developed to increase their effectiveness, prolong their duration of usefulness, facilitate insertion and permit insertion during abortion or delivery. The upper limit of the surface area of copper associated with increased effectiveness appears to be between 200-300 sq mm, and at some point increases in copper exposure may provoke expulsion of the IUD. The duration of fertility inhibition of copper IUDs is usually estimated at 2-3 years, but recent research indicates that it may be 6-8 years, and some devices may retain copper surface for as long as 20 years. Shorter and smaller versions of standard copper IUDs have been tested as they permit easier insertion, but high rates of pregnancy, expulsion, and removal have prevented their wider use. The discovery that the size of the uterine cavity is more important than its length has prompted the development of some promising uterine measuring instruments. Attempts to develop a device appropriate for postpartum use have been disappointing, and expulsion rates remain high. A few promising new forms of copper IUDs have been developed but not yet tested clinically.^ieng