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.

Effects of various IUDs on the composition of cervical mucus.

The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage.

PIP: Earlier studies have suggested that the effects on the composition of cervical mucus varies by IUD type. To further investigate this finding, the amount of mucin, albumin, and immunoglobulin (IG) G was measured in 27 healthy parous women who received either an inert, copper-bearing, or levonorgestrel-releasing Nova-T IUD. To enable each women to serve as her own control, cervical mucus parameters were measured before IUD insertion as well as in the 3 cycles following insertion. There were no significant differences in estradiol levels before or after treatment or among women in the 3 study groups. Luteal phase progesterone levels were significantly lower in users of a levonorgestrel-releasing device, however, than in women with a copper-bearing IUD. During the pretreatment month, there were no differences between the 3 groups of women in cervical mucus content changes. The inert IUD caused a significant decrease in mean mucin content and a significant increase in albumin, but had no effect on IgG levels or the wet weight of the mucus. The copper-containing IUD produced significant increases in mucin, albumin, and IgG, but did not affect wet weight of cervical secretions. Finally, the levonorgestrel-releasing device had no effect on the mucin, albumin, and IgG contents, but did induce a significant decrease in wet weight. There was no correlation between mean serum levels of levonorgestrel and the weight of cervical mucus.

Modern trends in contraception.

Substantial improvements have been made in oral contraceptives, a new injectable contraceptive (Norplant), and the intrauterine device (IUD). Major risks with oral contraceptives have declined substantially, and a number of noncontraceptive health benefits have been discovered. Norplant is probably the first new contraceptive in recent years, and offers long-term contraception with high efficacy and modest risks. The IUD, by carefully selecting users, is a safe and efficacious contraceptive method. The major risk, pelvic inflammatory disease (PID), is far less common if one avoids use in the presence of risk factors for PID.

PIP: Oral contraceptives (OCs, long-acting progestins (LAPs), and IUDS are reviewed in terms of new information on safety and efficacy. OC formulations are described and their mechanism of action and efficacy indicated. Reports are provided for thromboembolism, hemorrhagic and thrombotic stroke, ischemic heart diseases, alterations in lipid and hypoprotein and carbohydrate metabolism, hypertension, coagulation changes, breast and cervical cancers, and such minor side effects as menstrual irregularities, nausea, headaches, weight gain, premenstrual syndrome effects, and mood and libido changes. Noncontraceptive health benefits and clinical considerations are discussed. Norplant, as the only long acting progestin available in the US is described in terms of its formulations, mechanism of action, sequelae and metabolic effects, menstrual irregularities, metabolic effects, nuisance side effects, candidates for insertion, method of insertion and removal, and continuation rates. 2 IUD types are identified as the only ones available in the US, Progestasert T and T-Cu-380A (Paragard). Mechanism of action, efficacy, candidates, major sequelae such as salpingitis, infertility, and uterine perforation, minor sequelae such as metrorrhagia and dysmenorrhea, and other considerations are indicated. OCs in the US contain an average of 35 mg of ethinyl estradiol and assorted progestins e.g.s, ethynodiol diacetate, norethindrone acetate, nortestosterone derivatives with a complex mechanism of action. The failure rate for use effectiveness is 6 pregnancies/100 woman years. Modern formulations have combined rates of no more than 50 to 100 adverse events/100,000 users. Some of the effects are indicated as follows: Thromboembolism accounts for 60% of adverse effects and appears to be declining along with hemorrhagic and thrombotic stroke, however, modern use studies are only partially available. Myocardial infarction related to OC use may be embolic, and has a low risk at 7/100,000 users. Low-dose contraceptives substantially reduce the associated risks. Those with risk factors need close monitoring. Norplant is useful for those not wanting to take a daily regimen and is commonly accompanied by menstrual irregularity and sometimes headaches. Continuation is 80% after the 1st year and 40% after 5 years. Candidates for IUDs are parous women in monogamous relationships, who are not at risk for salpingitis, which is related to IUD use, or sexually transmitted diseases. Continuation is 70% after 1 year compared with 50% of OC users.