Hannu Allonen

Protective effect of intrauterine release of levonorgestrel on pelvic infection: three years comparative experience of levonorgestrel- and copper-releasing intrauterine devices.

A randomized, multicenter comparison of two intrauterine contraceptive devices (IUDs) was carried out. Nine hundred thirty-seven women were fitted with a copper-releasing IUD, the Nova-T, and 1821 women with an IUD that releases 20 jug of levonorgestrel daily. After 36 months, the cumulative gross rates of amenorrhea and hormonal side effects were significantly higher in the levonorgestrel-IUD users. The cumulative 36-month gross pregnancy rate was 3.7 for the Nova-T and 0.3 for the levonorgestrel IUD (P<.001), demonstrating the levonorgestrel IUDs high contraceptive efficacy. For the first time, a protective effect of the levonorgestrel IUD against pelvic inflammatory disease as compared with the Nova-T was seen statistically. The cumulative 36-month gross rate of pelvic inflammatory disease was 2.0 in Nova-T- and 0.5 in levonorgestrel-IUD users (P<.013). This significantly lowered incidence of pelvic inflammatory disease may help to solve one of the major concerns associated with intrauterine contraception.

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

Five years' experience with levonorgestrel-releasing IUDs

Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.

Pharmacokinetic and pharmacodynamic studies of levonorgestrel-releasing intrauterine device

Intrauterine devices releasing 20 micrograms/day levonorgestrel were inserted in 10 women (ages 25-34). Bleeding and spotting patterns were recorded on a menstrual card during one year of follow-up. Blood samples were collected for radioimmunoassays of LH, estradiol (E2), progesterone (P) and levonorgestrel (LNG) and for sex hormone binding globulin (SHBG) 3 times a week during the 1st month of use, and twice a week during the 6th and 12th treatment months. Among the 10 women, two experienced irregular cycles with prolonged intermenstrual spotting, four had amenorrhea in the latter part of treatment months, while the other four had regular cycles. According to the serum levels of E2 and P, the hormone profiles were divided into four types of reaction: A) anovulatory, B) anovulatory but with high follicular activity, C) ovulatory but with luteal insufficiency, and D) ovulatory. Among the 29 treatment cycles, there were 10 D-type, 3 C-type, 13 B-type and 3 A-type of ovarian reactions: 44.8% of the cycles were ovulatory (C + D) and 55.2% were anovulatory (A + B). In general, serum levels of levonorgestrel were low in ovulatory cycles and were high in anovulatory cycles. The difference was statistically significant. There were marked individual differences. The decline of serum LNG from the 1st (492 pmol/l) to the 6th (320 pmol/l) treatment months was 34.9% on average. The amenorrheic cycles coincided mostly with the hormonal profile of ovulatory types, which indicated that the cause of amenorrhea is due to the local effect of levonorgestrel on the endometrium. The levonorgestrel levels were significantly correlated with serum SHBG, r = 0.8856, p less than 0.001, and with E2, r = 0.4661, p less than 0.05.

Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy

OBJECTIVE Efficacy and acceptability of continuous combined parenteral hormone replacement consisting of subdermal estradiol delivery and intrauterine progestin delivery was studied. STUDY DESIGN Thirty-six volunteer postmenopausal women seeking treatment for climacteric symptoms participated in this open, randomized study. The subjects received either one or three subdermal implants with a controlled daily release of estradiol in vitro. Progestin therapy was carried out with a levonorgestrel-releasing intrauterine device. Climacteric symptoms and serum concentrations of estrone, estradiol, follicle-stimulating hormone, and sex hormone-binding globulin were followed up for 1 year. The subjects kept daily records of bleeding. RESULTS Serum estradiol concentrations with the set of three implants were stable during the follow-up period; the range of mean serum estradiol concentrations was 45 to 57 pg/ml. Four women, all from the group with one implant, discontinued the study after 6 months because of the return of climacteric symptoms. In spite of different daily estradiol doses, the patterns of bleeding were similar in both groups. At the end of the follow-up year 72% of the women had had no bleeding or spotting in the previous 3 months. CONCLUSION Our results suggest that by combining subdermal and intrauterine steroid delivery systems postmenopausal hormone replacement therapy can be carried out successfully without daily effort and with minimal or no bleeding.

Clinical performance of a new levonorgestrel-releasing intrauterine device. A randomized comparison with a Nova-T-copper device

The clinical performance of two levonorgestrel-releasing intrauterine devices (IUDs) with different release rates was studied and compared with a copper-releasing Nova-T device in a randomized partly double-blind multiclinical trial. Special attention was given to patterns of bleeding, hormonal side-effects, blood pressure and body weight. The clinical acceptability of the levonorgestrel IUDs was as good as that of the copper-releasing IUD. A highly significant decrease in the amount of menstrual blood loss was seen with the levonorgestrel-IUDs, the users of which experienced fewer days of bleeding than prior to insertion. Patients suffering from dysmenorrhea experienced relief from this symptom after insertion of a levonorgestrel-IUD. Some side-effects, usually referred to as hormonal, increased during the levonorgestrel-IUD use, but did not result in higher termination rates than with the Nova-T device. No changes in body weight were recorded for the levonorgestrel-IUDs and a slight decrease in both systolic and diastolic blood pressure was found after one year of use. No infections were recorded.

Return of fertility after the removal of Nova T or Copper T 200

The return of fertility after removal of Nova T or Copper T 200 IUDs was studied in 150 women who had a removal for planning pregnancy in a study performed for the comparison of the clinical performance of these IUDs in Denmark, Finland, and Sweden. There was no significant difference in the return of fertility of women having used either device. The cumulative probability of pregnancy per 100 women after the removal of the IUD, as a net rate, was 77.3 at one year, 88.9 at two years and 92.4 at three years. The return of fertility was analyzed separately for those women who had used their IUD for less than two years and for two or more years. The duration of the use had no significant effect on the return of fertility. The outcome of pregnancy, the birth weight, the condition at delivery and the sex ratio of the newborns were normal in the participating countries.

COMPARISON OF THE CLINICAL PERFORMANCE, CONTRACEPTIVE EFFICACY AND ACCEPTABILITY OF LEVONORGESTREL-RELEASING IUD AND NORPLANTR-2 IMPLANTS IN CHINA

The levonorgestrel-releasing IUD (LNG-IUD, 20 micrograms/d) and the Norplant-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant-2. In the LNG-IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant. Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG-IUD and 8.3 for the Norplant-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant-2 are highly effective, safe, long-acting, and well accepted by the Chinese women.

Combined and national experience of postmenstrual IUD insertions of Nova-T and Copper-T in a randomized study

A randomized comparative study between Nova-T and Copper-T-200 was performed simultaneously in Denmark, Finland and Sweden. The results of 741 postmenstrual insertions with Nova-T and 780 with Copper-T are reported. The pregnancy rate of Nova-T was lower in every age and parity group. The pregnancy rate of Copper-T-200 varied in participating countries, whereas the pregnancy rate of Nova-T was equally low in every country. The termination rate because of expulsion with Nova-T was less affected by age and parity than that of Copper-T. Significant differences in the continuation rates with the same device were found between countries. Removals because of infection showed that women below 25 years of age had a high risk for infection regardless of parity.

Two-year rates for Nova T and Copper T in a comparative study.

A random assignment comparative study between Nova T and Copper T 200 after two years of use revealed that the Nova T resulted in a significantly lower pregnancy rate than the Copper T. The study was performed simultaneously in Denmark, Sweden and Finland. The pregnancy rate in Nova T users was lower than in Copper T users in every country and in every age and parity group. There was no clinic effect in the pregnancy rate of Nova T users. The other termination rates of these two devices were not significantly different. The first segment continuation rates at two years of postmenstrual insertions were 64.7 for Nova T and 65.5 for Copper T 200. It seems that Nova T is an improved copper-releasing IUD.