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Mechanism of action of intrauterine devices: biochemical changes.

The mechanism of action of intrauterine devices varies from one type of device to another, although the principle of action is the same, namely, to interfere with the physiology of reproduction at the endometrial level. The biochemical changes of the endometrial tissue and the composition of the uterine fluid have been reviewed in relation to the use of inert, copper-medicated and steroid-releasing IUDs. All IUDs, whether inert or medicated, provoke a significant increase in the number of neutrophils, mononuclear cells and plasma cells, the presence of which is unrelated to the tissue infiltration of inflammatory cells occurring pre-menstrually of the normal menstrual cycle. The increase of leucocytes in IUD-users is compatible with a foreign body reaction which may be related to the antifertility effect. The addition of copper to an inert IUD has been shown to significantly alter the metabolism of the endometrial cells, e.g. the enzymatic activity and the DOVA-synthesis. The steroid-medicated IUDs represent a new approach to intrauterine contraception where the morphology of the endometrium is considerably altered, showing massive decidual changes, atrophic glands and sometimes atrophy of the whole functional layer. In addition, there is an important foreign body reaction, similar to that of the inert IUDs. The enzymatic activity, as well as the proliferative activity was significantly altered in the endometrium of these IUD-users. Changes in the endometrial fibrinolytic activity in IUD-users have been demonstrated to be related to the presence of irregular bleeding. Micro-traumata of the endometrium and the increased fibrinolytic activity may also interfere with the protective processes present in the physiologically normal endometrium. Further studies on the factors influencing the fertilizing ability of the spermatozoa in the female genital tract, as well as on the conditions of the human endometrium required for the implantation of a blastocyst, may yield important information for the improvement of intrauterine contraception.

Endometrium↗

The intrauterine device in the present and future.

Good counseling and better selection of candidates would result in the intrauterine device's (IUD) safer use. Age and parity of the IUD acceptor do not seem to be associated with an increased risk of pelvic inflammatory disease (PID). The newer generation of copper- and hormone-releasing IUDs are associated with improved safety and efficacy.

Aftercare↗

Early chorionic activity in women bearing inert IUD, copper IUD and levonorgestrel-releasing IUD.

Early chorionic activity was assessed in the premenstrual days by means of serum HCG beta-fraction. As control, a group of women with no contraceptive use was studied; early chorionic activity was detected in 31.8% of the cycles. In the group bearing an inert IUD the incidence was 20%, which did not differ from the control; while in the medicated IUD groups (Cu-IUD and LNG-IUD) the incidences were 4.8% and nil, respectively. Both medicated IUD groups showed a significant difference when compared with the control, as well as the inert IUD groups. The meaning of these findings, pointing out differences in the main mechanism of action between inert and medicated IUDs, is discussed.

Adult↗

Factors associated with actinomyces-like organisms on Papanicolaou smear in users of intrauterine contraceptive devices.

To determine the factors associated with the presence of actinomyces-like organisms on cervicovaginal Papanicolaou smears in users of the intrauterine contraceptive device (IUD), we carried out a case-control study. Among about 80,000 Papanicolaou smears examined in one year in a large cytology laboratory, actinomyces-like organisms were identified on 107 smears; all but three smears were from IUD users. Compared with IUD users who did not have actinomyces-like organisms on Papanicolaou smears, those with actinomyces-like organisms had used the IUD for more years. An increased risk of actinomyces-like organisms on Papanicolaou smear was not apparent until 7 years of IUD use, however. No significant association of actinomyces-like organisms with the type of IUD was found after controlling for differences in duration of use between users of various IUDs. The percentage of women reporting gynecologic symptoms (vaginal discharge, pelvic pain, abnormal bleeding) also did not differ significantly between IUD users with and without actinomyces-like organisms on Papanicolaou smear (p = 0.5).

Actinomyces↗

The effects of intrauterine contraceptive devices on the ultrastructure of the endometrium in relation to bleeding complications.

The effects of inert (Lippes Loop D and Dalkon Shields) and medicated (copper 7, copper T, and Progestasert) intrauterine contraceptive devices (IUDs) on the ultrastructure of the endometrium were studied in intact human uteri. The most striking morphologic changes induced by the inert and copper-bearing devices were erosion of the surface epithelium and extensive microthrombosis in stromal capillaries of the endometrium in contact with the device. These abnormalities were associated with extravascular thrombi, erythrocytes, and fibrin deposition in the adjacent stroma. Capillary microthrombosis and leukocyte infiltration into the uterine cavity were most extensive around the active part of the copper-bearing devices. With the Progestasert erosion of surface epithelium was rarely seen, but the intact epithelial lining had fewer ciliated cells with flattened and shortened cilia. Large dilated venules were a common finding below the surface epithelium adjacent to the active part of the Progestasert; capillary microthrombosis was found only below the inert arms of the Progestasert. The vascular response of the endometrium to IUDs appears, therefore, to be directly related to the type and proximity of the device. The morphologic changes induced in both surface epithelium and the microvasculature of the endometrium are the likely explanation of the uterine bleeding problems associated with IUDs but are probably intrinsic to the mode of action of the IUD in interfering with implantation.

Adult↗

The effects of three different regimens of oral contraceptives and three different intrauterine devices on the levels of hemoglobin, serum iron and iron binding capacity in anemic women.

The effects on hemoglobin, iron and iron binding capacity (IBC) in 150 moderately anemic women of 1) a 21-day low-dose combined pill, 2) the same low-dose combined pill for 21 days, followed by 7 days of an iron-containing pill, 3) the same low-dose combined pill administered for 63 consecutive days, followed by 7 days of no pill intake, 4) Lippes IUD, 5) TCu 220C and 6) Progestasert were studied. The three pill regimens were associated with an increase in hemoglobin and serum iron after 12 months. However, the iron pill and 63-day schedule groups produced an increase in hemoglobin and iron at the 6th month ans a diminution of IBC at 12 months. The Lippes and TCu 220C groups did not show any change in hemoglobin, iron or iron binding capacity after 12 months. The Progestasert group showed an increase in hemoglobin and iron levels at 6 and 12 months, and a diminution of IBC at 12 months. The pill and Progestasert have advantages as contraceptives in anemic women.

Adolescent↗

Anaemia and menstrual blood loss studies in women using multiload Cu250 and progestasert IUDs.

Two to 9 months following insertion of the ML Cu250 (n = 54) and Alza T (n = 30) IUDs, mean menstrual blood losses (MBL) were 46.3 ml and 32.7 ml, respectively (p less than 0.005). Significantly more of the Alza T users had losses below 40 ml and they also perceived their menses to be lighter. Based on a haemoglobin level of 12gm/dL, the upper normal limit of MBL was about 40 ml. These findings are consistent with earlier observations that during the first year, ferritin levels fall in ML Cu250 users whereas they are unaltered in Alza T users.

Adult↗

Effectiveness of IUDs: a review.

Large, multicenter, randomized trials of IUDs conducted between 1970 and 1986 encompass more than 50,000 woman-years of experience in the two-year interval following device insertion. Taken singly and collectively, these trials demonstrate that IUD failure rates are strongly affected by the age of participants, notably by the proportion of women under age 25 admitted to the studies. Individual trials and overall comparisons indicate further that: 1. Non-medicated devices such as the Mahua steel ring and Lippes loop D have pregnancy rates above 2 per 100 woman-years. 2. The first approved copper IUDs, the Copper 7 and the TCu 200, do not markedly differ in pregnancy rates from standard plastic devices with rates significantly above 2 per 100 woman-years. 3. Five more recent, widely used copper IUDs have had failure rates significantly below 2 per 100 woman-years in multicenter trials. The point estimate of the failure rate was less than 1 pregnancy per 100 woman-years for three of these IUDs. One copper-bearing device had a failure rate significantly below 1 per 100 woman-years. 4. Devices releasing either 25 mcg/day of progesterone or 2 mcg/day of levonorgestrel have had significantly higher failure rates than the more effective copper-releasing IUDs; however, devices releasing 20 mcg/day of levonorgestrel appear at least as effective as the most effective copper IUDs. Long-term IUD failure rates derived from straight assignment as well as randomized trials indicate 4-year gross cumulative failure rates do not exceed 10 per 100 for any of the standard copper devices or the Lippes loop D. Point estimates of the four-year gross cumulative pregnancy rates have been below 5 per 100 users in studies of the TCu 220C, the Nova T, the TCu 380A, and the MLCu 375.

Adolescent↗

An evaluation of the levonorgestrel-releasing IUD: its advantages and disadvantages when compared to the copper-releasing IUDs.

The levonorgestrel-releasing IUD (LNG-IUD-20), providing a daily dose of 20 ug, has recently been approved for marketing in Finland. The IUD's high efficacy in preventing accidental pregnancy and other numerous positive features make it a promising contraceptive device for worldwide use, just like the currently available T-shaped copper-releasing (TCu) IUDs. This paper reviews published reports comparing the LNG-IUD-20 and the currently used TCu IUDs. The merits and disadvantages of the steroid-releasing IUD are evaluated in terms of its performance and other special features relative to the TCu IUDs. Also, a number of future studies with medical and programmatic importance are proposed. A broader understanding about these two IUD families will facilitate their use in a complementary way for family planning programs.

Drug Evaluation↗