Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy.

OBJECTIVE: To compare the effects of intrauterine and subdermal administration of levonorgestrel on control of bleeding and on the endometrium in postmenopausal hormone replacement therapy. INTERVENTIONS: Nineteen women started continuous oral E2 valerate therapy (2 mg daily) together with continuous parenteral progestin therapy. The subjects randomly received either a subdermal levonorgestrel-releasing implant (n = 9) or an intrauterine device (IUD) releasing levonorgestrel (n = 10). MAIN OUTCOME MEASURES: Serum concentrations of estrone, E2, FSH, sex hormone-binding globulin (SHBG) and levonorgestrel were followed. Endometrial biopsies and transvaginal ultrasonography were used to evaluate the endometrium. The subjects kept daily records of bleeding. The observation time was 1 year. RESULTS: Serum concentrations of the hormones mentioned above and SHBG were similar in both groups during the observation time, but the patterns of bleeding differed. In the IUD group there were 0.9 days (mean, range 0 to 4 days) of spotting and no days of bleeding during the last month of the follow-up year. In the implant group there were 8 days (mean, range 0 to 25 days) of spotting and 3.4 days (mean, range 0 to 14 days) of bleeding. In histological examination there was uniform atrophy in the endometrial samples from the IUD group, and a weak or absent progestin effect in the implant group. CONCLUSIONS: In spite of similar serum levonorgestrel concentrations, local intrauterine administration of levonorgestrel resulted in better control of bleeding and in more effective endometrial suppression than subdermal administration.

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.

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

PIP: Gynecologists accepted 288 women aged 30-49 from six different clinics in Finland into a clinical trial of a new biphasic oral contraceptive (OC) containing natural estradiol and cyproterone acetate (manufactured by Leiras Oy, Turku, Finland). They aimed to determine the contraceptive efficacy, safety, cycle control, and acceptability of this OC. 24% of the women smoked cigarettes. Gastrointestinal upset in one woman led to failure to take the fourth and fifth tablets at the beginning of the second treatment cycle. She became pregnant (pregnancy rate = 0.35%). 9.3% and 13.3% of women missed pills at the 3-month and 12-month follow-up visits, respectively. 95% of the women had serum progesterone values lower than 9 nmol/l, indicating ovulation suppression. OC use reduced excessive menstrual bleeding (30% before study vs. 3% after 13 cycles; p 0.0005). It also reduced dysmenorrhea (14% vs. 2%; p 0.0005). No one had any serious side effects. The minor side effects (breast tension, edema, headache, and depression) subsided with time. The 12-month continuation rate was 63%. The main reason for discontinuation was side effects (25.9%). Total serum cholesterol and HDL-cholesterol levels did not change significantly, while serum triglyceride levels increased from 0.92 to 1.14 mmol/l (p = 0.02). Even though serum potassium and creatinine levels changed significantly, the 13-month levels fell within the normal range. These findings show that this new OC is an effective contraceptive for premenopausal women. The absence of adverse effects on the blood coagulation system and lipoprotein metabolism make this new OC safe for smokers.

An analysis of the corrosion process of the Nova-T IUD.

OBJECTIVE: To measure the copper from Nova-T IUDs that have been used for up to 9 years. To examine the composition and extent of surface deposits on these used IUDs. DESIGN: Nova-T IUDs were randomly collected at normal replacement or removal. The copper, silver and calcium content was quantified by X-ray fluorescence; surface topography and analysis was by scanning electron microscopy and X-ray dispersive analysis. RESULTS: Copper loss slowly increased at an exponential rate over the study period but the copper was stabilized by the silver core and did not show increased fragmentation with extended use. No corrosion of the silver core was detected. Calcium- and sulfur-containing surface deposits built up on the copper but did not modify the rate of copper release. CONCLUSIONS: The mean rate of copper loss was 0.25 mumol/day during the first 40 months of use, which is not significantly different from that of similar IUDs without a silver core. The silver core of the copper coil on the Nova-T IUD prevented its fragmentation. Surface deposits containing calcium and sulfur that built up on the IUD did not affect the rate of copper loss.

Sustained-release subdermal estradiol implants: a new alternative in estrogen replacement therapy.

OBJECTIVE: This trial was a therapeutic and pharmacokinetic dose-finding study with subdermal implants that showed a constant in vitro daily release rate of estradiol. The aim was to find the daily release rate of estradiol that produces serum estradiol concentrations comparable with those obtained with transdermal estradiol at 0.05 mg/day. STUDY DESIGN: The study was an open crossover comparison of transdermal and subcutaneous delivery systems. Thirty-six postmenopausal (serum follicle-stimulating hormone concentration > 30 IU/L before commencing the study) were treated with transdermal estradiol for 4 weeks. Immediately after this transdermal estradiol delivery was replaced by either one or three estradiol implants. The serum concentrations of estrone, estradiol, follicle-stimulating hormone, and sex hormone-binding globulin were followed up for 8 weeks on implant therapy and compared with those during transdermal estrogen administration. To oppose the estrogen effect on the endometrium, each patient received an intrauterine device releasing a progestin, levonorgestrel. RESULTS: The serum estradiol concentrations achieved with three implants were comparable with those during transdermal administration of estradiol at 0.05 mg/day. Suppression of follicle-stimulating hormone was also better maintained with three implants compared with one. CONCLUSIONS: This study shows that constant release profiles can be achieved with nonbiodegradable estradiol implants. The results suggest that a single application should give sufficient estrogen substitution for more than a year.

Clinical experiences with intrauterine devices inserted with and without tail.

Nova T and TCu 200 Ag IUDs were inserted with or without a tail in order to study the possible role of the thread on the occurrence of PID. The five-year gross cumulative termination rate for infection was 3.7 in the group with a tail and 1.3 in the group without a tail. The results indicate a lower risk of genital infection if the device is inserted without the tailstrings.

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 micrograms 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 less than .001), demonstrating the levonorgestrel IUD's 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 less than .013). This significantly lowered incidence of pelvic inflammatory disease may help to solve one of the major concerns associated with intrauterine contraception.

A controlled study with taltrimide and sodium valproate: valproate effective in partial epilepsy.

Taltrimide was compared with valproate and placebo in 17 patients with intractable epilepsy being on carbamazepine monotherapy. Taltrimide (400 mg/day), valproate (1000 mg/day) or placebo were added to the treatment for periods of 3 months using a randomized cross-over design. Serum carbamazepine concentrations remained within the therapeutic range throughout the trial. Thirteen patients completed the study. In partial epilepsy of 7 the seizure frequency was reduced by 27% during valproate (p less than 0.05), compared with placebo, while no improvement was found during taltrimide. In 6 with primary generalized epilepsy, the number of seizures was reduced by 49% during taltrimide and by 38% during valproate, but neither effect was significant, compared with placebo. Headache was reported by 3 patients while on taltrimide. One with hypersensitivity history developed petecchiae and nasal bleeding during taltrimide and, therefore, the treatment was stopped. The three other interruptions were independent of taltrimide. Thus, the only statistically significant effect in this study was that of valproate in partial epilepsy.

Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-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.

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.

Erythromycin ethylsuccinate, base and acistrate in the treatment of upper respiratory tract infection: two comparative studies of tolerability.

The efficacy and tolerability of erythromycin ethylsuccinate, erythromycin base and erythromycin acistrate were studied in two separate randomized studies in 80 and 82 primary health care patients with upper respiratory tract infections. In Study I, the patients were given either ethylsuccinate 666 mg tid or base 500 mg qid for ten days. Possible side-effects, abdominal pain, nausea, diarrhoea and vomiting, were recorded daily by the patient. Study II followed the same design as Study I with the exception of the side-effect evaluation method. Patients were given in a randomized fashion ethylsuccinate 666 mg tid, or acistrate 400 mg qid. Side-effect evaluation was based on a 10-cm analogue visual scale to record abdominal pain, while nausea, vomiting and diarrhoea were recorded as daily frequencies. These studies indicated that erythromycin ethylsuccinate caused significantly less abdominal pain than the base form (chi 2-test), but there were no significant differences in tolerance between the ethylsuccinate and acistrate forms. Other tolerance parameters revealed no real differences. The clinical response was good with all erythromycin preparations at the doses used in this study.

Patterns of bleeding and body iron stores during the use of a levonorgestrel-releasing intracervical device.

A levonorgestrel-releasing intracervical device (LNG-ICD) was inserted in 198 women. The subjects registered bleeding and spotting days on special cards, which were analyzed after one year of treatment. Bleeding and spotting days gradually declined from sixteen during the first month to seven during the seventh month, and they remained under that level until the end of the first year. There were more days of spotting than bleeding. Eleven per cent of the subjects experienced at least 90 days non-bleeding interval during the first year of LNG-ICD use. There were no significant changes in blood hemoglobin concentrations during the first four years of LNG-ICD use. The mean serum ferritin concentration increased from 38 micrograms/l at the beginning to 97 micrograms/l at the end of the fourth year.

Clinical experience with intrauterine contraceptive devices (IUDs) inserted with and without tail.

Between 1982 and 1984, two comparative clinical trial for testing new types of IUDs, were initiated at the Family Planning Center (Debrecen, Hungary) in collaboration with the Leiras Research Laboratories (Turku, Finland). 685 Nova T and 500 TCu 200Ag IUDs with and without tail were inserted in a randomized manner in order to study the possible role of the thread of the device in generating pelvic inflammatory disease (PID). Because there were no statistically significant differences between the corresponding rates of the devices, the data regardless of the type of the IUD, were pooled, then separated into two new groups: the study group (IUD without tail) consisted of 581 cases, while the control population (IUD with tail) included 602 insertions. The age and parity distribution was the same in both groups (mean age 29.4, mean parity 1.9). In the study group 300 patients completed the two-year follow-up, and 9675 womanmonths of use were evaluated. The corresponding figures for the control population were 304 and 9935, respectively. The two-year gross cumulative termination rates for the study and the control group were as follows: pregnancy 4.4 and 4.6; expulsion 1.9 and 2.9; bleeding/pain removals 6.3 and 6.0, removal for infection 0.2 and 2.7; removal for other medical reason 2.1 and 1.9; removal for planning pregnancy 4.6 and 6.6; removal for other personal reason 1.6 and 0.6. The pregnancy, expulsion and removal rates, except infection, were almost the same in both groups. There was a statistically significant difference only between the rates of removals for PID (p less than 0.05): during the two-year period of use 12 devices were removed for infection and out of these only 1 was inserted without tail! Although these findings are promising, to draw a final conclusion more cases and a longer follow-up are needed.

Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers.

1. The hypokalaemia-inducing effects of two widely used inhaled antiasthmatic beta 2-adrenoceptor agonists, fenoterol and salbutamol, were compared in six healthy male volunteers. 2. Each drug was administered in three different doses, 400, 600 and 800 micrograms, which were repeated three times with 30 min intervals (total doses 1200, 1800 and 2400 micrograms in 1 h). The treatments were given at 1 week intervals in random order in a single-blind fashion. 3. The concentration of potassium in plasma was dose-dependently reduced by both drugs with peak effects 75-90 min after the first inhalations. The hypokalaemic effect of fenoterol was significantly greater than that of equal doses of salbutamol (average +/- s.d. reductions of 1.13 +/- 0.32 and 0.67 +/- 0.25 mEq l-1, respectively, after the highest doses, P less than 0.05). Concomitantly, decreases were noted in the amplitude of the T-wave on the ECG. 4. The concentration of cyclic AMP in plasma was measured and used as an indicator of systemic beta 2-adrenoceptor agonistic effects of the drugs. Increases in cAMP were a close mirror image of the drugs' effects on potassium in plasma. 5. Plasma renin activity, noradrenaline in plasma and heart rate were also dose-dependently increased by the treatments, whereas blood pressure remained unaltered. 6. While the clinical significance of hypokalaemia induced by inhaled beta 2-adrenoceptor sympathomimetics still is a matter of debate, our results point to possible differences between therapeutically equipotent doses of fenoterol and salbutamol in their propensity to cause hypokalaemia and other acute non-bronchial effects.

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.

PIP: The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levon ISZ orgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized comparative mulicenter 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 (0.1/100 women) was significantly lower than that with the Nova T (0.9/100). Removal rates for menstrual problems and/or pain were similar for the 2 methods (net rates 7.5 and 8.7 respectively). The 12-moth 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 highly effective contraceptive method which reduced menstrual bleeding. It it a promising alternative for women desiring a highly-effective method for long-term use.

A comparison between Nova T and Copper T 200 Ag in Hungary.

In a comparative use-effectiveness study, 855 Nova T and 883 TCu 200 Ag devices were inserted in a randomised sequence. By the end of the first year the gross rate of unplanned pregnancy was 1.1 per 100 users of Nova T and 2.1 per 100 users of TCu. After 2 years the pregnancy rates for Nova T and TCu were 3.1 and 4.8 per 100 users, respectively. Although there was no statistically significant difference between the rates for the two devices, they suggest a higher contraceptive efficacy for Nova T.

PIP: Between February 1982 and February 1983, 2 family planning clinics in Hungary enrolled 1738 subjects for a study comparing contraceptive efficacy and clinical performance of 2 types of IUD. In the comparative use-effectiveness study, 855 Nova T and 883 TCu 200 Ag devices were inserted in a randomized sequence. Subjects were advised to return to the clinic for a check-up at 1, 3, 6, 12, and 24 months after insertion. 40% of the women were IUD users before entering the study. By the end of the 1st year the gross rate of unplanned pregnancy was 1.1/100 users of Nova T and 2.1/100 users of TCu. After 2 years the pregnancy rates for Nova T and TCu were 3.1 and 4.8/100 users, respectively. Although there was no statistically significant difference between the rates for the 2 devices, they suggest a higher contraceptive efficacy for Nova T. In different age categories of Nova T users the pregnancy rate varied from 3.5 among those under 25 to 1.7 in those over 35. For Copper T users, these figures were 9.3 (under 25) and 3.3 (over 35). Over the 2 year period 88 women terminated the study due to pain and/or bleeding. Rate of removal of the device was the same for both types of device.

A randomized comparative trial of Nova-T and TCu200Ag in Yugoslavia.

The contraceptive efficacy and clinical performance of Nova-T and TCu200Ag were studied in a randomized comparative study with 819 interval acceptors. The 1- and 2-year gross termination rates were evaluated by means of the life-table method. The 12-month pregnancy rates were 1.0 per 100 women with Nova-T and 3.0 per 100 women with TCu200Ag. The preliminary 2-year rates were 1.7 and 5.5 per 100 respectively (p = 0.037). Rates of expulsion, medical and personal removals were not significantly different for the two devices. Continuation rates for the first year were 89.4 and 90.5 per 100 respectively.

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.

[Copper-silver T: The classic T resuscitated]. / T Cuivre-argent--le T classique ressuscite.

PIP: Tests of the contraceptive efficacy of different amounts of copper have indicated that effectiveness is proportional to surface area, but the improvement achieved with more than 200 sq mm of copper is minimal. Rates of release of copper vary considerably in different women. IUDs removed because of bleeding had a significantly higher release of copper. 1 consequence of variations in release of copper is unequal dissolution of copper leading to fragmentation of the copper thread. The Nova-T IUD has 200 sq mm of copper and a flexible body which is able to maintain correct placement in the uterus. A new device with a wire of silver coated with copper was designed to avoid the fragmentation of the copper and thus increase the duration of use. The new copper silver T was compared to the Nova-T in a randomized study in Scandinavia. The pregnancy rate after 1 year was under 1% in users aged 30 and over. Cumulative rates after 5 years of use of the Nova-T and copper silver T respectively for women under 25 were 3.0 and 7.1 for pregnancy, 8.2 and 12.5 for expulsion, 27.1 and 30.2 for removal for pain and bleeding, 42.7 and women 25-29 the cumulative rates were 2.6 and 9.0 for pregnancy, 12.3 and 5.8 for expulsion, 26.1 and 21.8 for removal for pain and bleeding, 25.3 and 29.1 for removal for other reasons, and 33.6 and 34.2 for continuation. For women 30-34 cumulative rates were 1.1 and 2.2 for pregnancy, 5.9 and 3.4 f expulsion, 27.4 and 20.6 for removal for pain and bleeding, 17.5 and 22.0 for removal for other reasons, and 48.0 and 51.7 for continuation. Among women 35 and over cumulative rates were .8 and 2.1 for pregnancy, 10.9 and 3.7 for expulsions, 25.0 and 17.6 for removal for pain and bleeding, 18.8 and 12.0 for removal for other reasons, and 44.5 and 64.7 for continuation. Cumulative pregnancy rates were better for the Nova-T after 1, 3, and 5 years of use, but differences diminished with age and parity. After age 30 the pregnancy rate with the copper silver T is particularly appropriate for women whose cervical canals permit insertion of a larger device.^ieng