Clinical performance of a levonorgestrel-releasing intracervical contraceptive device during the first two years of use

One-hundred-and-ninety-eight women used a levonorgestrel-releasing intracervical contraceptive device (LNG-ICD) designed to release 20 micrograms levonorgestrel/day. Clinical performance during the first two years of LNG-ICD use was evaluated. A total of seven pregnancies occurred during the study period, all of them during the first year. Six pregnancies were after unnoticed expulsion of the device. One pregnancy occurred in an epileptic women using carbamazepine, with the LNG-ICD remaining in situ. Eighteen spontaneous expulsions occurred, 16 during the first year and 2 during the second year. Three pelvic infections were observed, all of them during the first year. Bleeding problems, hormonal side effects and other medical reasons were the most common side effects resulting in removal of the device. The continuation rate was 72.6 per cent after one year and 57.1 per cent after two years.     

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.     

Five years' experience with a small intracervical/intrauterine levonorgestrel-releasing device

OBJECTIVE: A randomized study was performed to compare the efficacy, safety and acceptability of a new model of an intracervical/intrauterine contraceptive device (ICD) releasing 20 microg of levonorgestrel (LNG) per day. METHODS: The LNG-ICD was inserted in Group I into the cervical canal and in Group II into the uterine cavity. Group I included 151 women (age, 18-43 years) whereas Group II included 147 (age, 19-43 years). The number of nulliparous women was 145. RESULTS: The 5-year results are presented here. The results showed a total continuation rate of 50%; the continuation rate in the cervical group and that in the uterine group were 53.6% and 46.3%, respectively--the difference being statistically insignificant (p=.3593). The main reason for termination was a wish for pregnancy, which is explained by the relatively young age and degree of nulliparity of the study population. During the first year, two pregnancies occurred in both groups. Two of these were ectopic, one in each group. The other two occurred after unnoticed expulsions. Thereafter, no pregnancies occurred. The cumulative gross rate for pregnancy was 1.3 and the Pearl index at 5 years was 0.425. The total expulsion rate was relatively high (11.1%). Expulsions occurring during the first few months of the first year were related to insertion. Removals because of bleeding and because of amenorrhea were low, the combined gross rate being 5.7 and the Pearl rate 1.8 at 5 years. Also, the gross rate of infection was low (0.7). The continuation was high in spite of a high rate of removals for planning pregnancy (15.4). CONCLUSIONS: The method is safe and effective. There were only minor differences between the groups. There were no perforations and the incidence of infection was low. The device can also be used by young nulliparous women.     

Clinical experience with triphasic oral contraceptive (Triquilar) in 527 women in China

From October 1987 to May 1989, a total number of 527 women completed a total of 6,291 treatment cycles in 6 centers in China for the study of a triphasic oral contraceptive - Triquilar. The mean age of subjects was 30.21 +/- 2.84 years. There were 7 pregnancies during the study period. Among them, five were patient failures because of missed pill or incorrect intake; one had taken barbiturates along with Triquilar. Only one woman became pregnant in the 11th treatment cycle without any reason being found. In most cases, menstrual flow decreased and dysmenorrhea improved as treatment continued. Of the total treatment cycles, the incidence of missed withdrawal bleeding was 0.25%, spotting 0.97%, and breakthrough bleeding 0.48%. Nausea and vomiting was the most common side effect and accounted for 6.4% of the total treatment cycles. This was followed by breast tenderness (3.7%), dizziness (2.4%) and headache (1.6%). Most of the side effects occurred during the first few cycles and were alleviated later. By the end of one year, the total dropout was 64 cases. The reasons for discontinuing treatment were: pregnancy 1.33 (per hundred women), menstrual disturbances 0.76, side effects 3.80, other medical reasons 2.09, and personal reasons 4.18. The results confirm that Triquilar is an effective oral contraceptive with good cycle control and low incidence of side effects. No serious reaction has been reported. It has been well accepted by the Chinese women. However, due to the low dosage of steroids, it is of utmost importance to avoid errors in its use.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical results with subcutaneous implants containing 3-keto desogestrel

Eight healthy women using one Silastic implant of 30 mm length filled with 3-keto desogestrel, the active metabolite of desogestrel, were studied for 36-664 days. The release rate of 3-keto desogestrel was quite constant and around 30 micrograms/day. No ovulations occurred. One woman was amenorrheic, while the others had different bleeding patterns, often with periods of spotting. No other side effects were recorded. The mean plasma levels of 3-keto desogestrel were 0.9 nmol/l after 1 month and 0.5 nmol/l after 12 months. 3-Keto desogestrel was less effective than testosterone, estradiol or levonorgestrel in displacing 3H-dihydrotestosterone from SHBG. It is concluded that contraception with 3-keto desogestrel delivered through an implant is a promising method for further investigation. With a single implant we found a duration of at least one year.     

Long-term experience with Norplant contraceptive implants in Finland

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 124 women. During five years of use no accidental pregnancy occurred. The first year continuation rate was 90% and the five-year continuation rate was 54%, including terminations for wish to become pregnant. The medically relevant continuation rate was 68% after five years. Menstrual irregularities were the most frequent reason for termination, but only in the first two years. 70% of the terminations for that reason occurred during the first two years. Terminations for other steroid-related reasons were infrequent. The follow-up will continue up to the end of the seventh year. Seven of seventeen women who requested removal of the implants because they wanted to become pregnant conceived during the first two cycles and only three were not pregnant one year after removal.     

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.     

Contraceptive rings; self-administered treatment governed by bleeding

In an attempt to overcome bleeding problems and reduce the risk of ovulation during treatment, a new treatment schedule for contraceptive Silastic intravaginal rings (IVR) was studied in 16 women. The IVRs released about 300 μg of d-norgestrel (d-Ng) per day. They were used continuously and removed for five days only when bleeding occurred or after several days of spotting. A total treatment period of 2279 days was studied corresponding to 81 28-day cycles. After an initial peak, the height of which was correlated with the plasma sex hormone binding globulin capacity (SHBGc), the d-Ng concentrations in plasma decreased and stabilized at mean concentrations between 0.8 and 2.2 ng/ml. The mean d-Ng concentration correlated well with the body weight of the women. Follicular activity was depressed during treatment as judged by plasma estradiol concentrations and no ovulations occurred. Four women were amenorrheic for treatment periods between 101 and 197 days. In most of the other women the incidence of bleeding and spotting was less than would have been expected during a comparable period without treatment. Systemic side effects in the form of aggressiveness, weight gain, acne and headache were noted by some of the subjects. No local side effects were obsered and no pregnancy occurred.     

Early puerperal insertions of Copper-T-200

The Copper-T-200 (CuT-200) was inserted after delivery at term in 197 women on the day preceding discharge from the hospital. The majority of the insertions were done on day 5 or 6 after delivery. Every subject in the study was followed more than 12 months. The insertions were well tolerated; no perforations or serious side effects occurred. During the first year of use, only 9 infections were recorded. The first segment pregnancy rate (7.2) and expulsion rate (14.8) were significantly higher and the continuation rate, 69.5, lower than that obtained with the same device inserted in postmenstrum women. The expulsions were mainly partial (11.1), and were discovered during the first and second months postpartum. The postpartum insertions were found to be safe and well accepted. The high pregnancy and expulsion rates make the CuT-200 an unsuitable IUD in postpartum programs where follow-up is not adequate and early removals of partially expelled or displaced devices is not possible.     

Long-term follow-up of women treated with NORPLANT implants

This report describes the long-term follow-up of 376 women who received NORPLANT^R implants in the period October 1974 through May 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set.

The average levonorgestrel plasma levels declined steadily through eight years of use of NORPLANT^R capsules (r = −.937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area.

Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first 5 years of NORPLANT^R implants use was 0.63. No pregnancy has occurred in 4194 woman-months observed during treatment with a second set of capsules.

Fifty-six women (14.9%) out of 376 acceptors of the first implant and 10 (9.1%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly bleeding problems and side effects commonly associated with hormonal contraception. Two women died while using NORPLANT^R implants, one of a cardiac arrest after surgery for a gallbladder disease and one because of endocranial hypertension originating from the rupture of an aneurism of the median cerebral artery.

The bleeding pattern observed in the three months after NORPLANT^R capsules replacement was similar to that observed in the 90 days before replacement and different from that experienced by the same women in the first 90 days of implant use. This finding can be interpreted as an indicator of adaptive changes experienced by the target organs during long-term continuous administration of levonorgestrel. The prompt recovery of fertility after removal of NORPLANT^R implants suggests that these changes are reversible.     

A three-year clinical trial with levonorgestrel silastic implants

Silastic implants containing the progestin, levonorgestrel, were tested as long-term contraceptives in 101 women. After three full years of exposure and 2,998 woman-months of use, no pregnancies had occurred. The continuation rates were 87% at 12 months, 79% at 24 months and 66% at 36 months. The most important side effect was excessive or irregular bleeding during the first year. No treatment was offered for this side effect other than vitamins and iron or change of method, with the exception of 3 cases where ethinyl estradiol was used one time for 2 weeks each. Bleeding disturbances led 8 patients to ask for removal of implants. Other side effects were headache, acne and lower abdominal pain. Blood and urine analysis tested 17 different parameters and all but plasma cortisol remained within normal limits throughout the study. A general tendency toward lowered Cortisol values was observed and two subjects had more than one value below the normal limit for the population during the study. Glucose tolerance tests during the second year were abnormal in two women with familial diabetes but they returned to normal values spontaneously at the next test.

It is concluded that levonorgestrel implants offer effective protection against pregnancy during the first three years of continuous use. Their acceptability and few side effects justify larger trials, especially if treatment of bleeding irregularities is introduced.     

Plasma levonorgestrel levels and ovarian function during the use of a levonorgestrel-releasing intracervical contraceptive device

Levonorgestrel, estradiol and progesterone plasma concentrations were measured over four years of use of a 20 micrograms/day levonorgestrel-releasing intracervical device (LNG-ICD). The mean levonorgestrel concentration showed a slight decline, being 142 + 46 (SD) pg/ml in the third month and 81 +/- 22 pg/ml in the 48th month of LNG-ICD use. However, considerable interindividual variation in levonorgestrel plasma levels between study subjects was observed. In 77% of the monitored cycles, ovulation or a luteinized follicle was observed when judged by a plasma progesterone elevation of over 5 ng/ml. Some follicular function was also noted in anovulatory cycles. Inhibition of ovulatory ovarian function is not the mode of contraceptive action of the LNG-ICD.     

Use effectiveness of the prentif cervical cap in private practice: A prospective study

Of two-hundred-sixty women seeking cervical cap contraception, exactly half subsequently used the Prentif cavity rim cap as their sole method of contraception. The one year continuation rate for these exclusive cap users was 56.7 per hundred. No major side effects related to the use of the Prentif cap were observed in the course of this study, involving 918 women-months in year 1. Pregnancy and dislodgement of the cap during use were the principal reasons for discontinuation of exclusive use, with gross rates of 19.1 and 12.9 per 100 at one year, respectively.     

A multicentered clinical trial of the long-acting injectable contraceptive Depo Provera in Chinese women

This study was an open trial where 1994 subjects each received Depo Provera injectable contraceptive every three months for one year and were observed a total of 20,294.3 woman months. At the time of observation, only one accidental pregnancy had occurred giving a use-effectiveness rate of 99.94% and a cumulative continuation rate of 72.87%. There were no significant adverse effects on weight and blood pressure. The main side effects were spotting, prolonged bleeding, and amenorrhea and these were also the main reasons of discontinuation. Complaints related to bleeding problems gradually decreased and complaints of amenorrhea increased with continued use. In lactating women, side effects occurrence rate was lower and continuation rate was higher in comparison with non-lactating women. Users did not report any effect on milk secretion. The results of this study confirm that Depo Provera is a very effective contraceptive method. With appropriate counseling and medical support, high acceptability and continuation rate can be achieved. Depo Provera is especially suitable for lactating women and could become a popular contraceptive method for lactating Chinese women.     

Postmenopausal hormone use following a 3-year randomized clinical trial

Postmenopausal women often discontinue estrogen therapy within the first year. No studies have examined reasons why women continue or discontinue hormone replacement therapy (HRT) after several years of use, when hormone side effects have subsided. We wanted to identify determinants of estrogen use after participation in a 3-year randomized placebo-controlled trial. The Postmenopausal Estrogen/Progestin Intervention (PEPI) study compared the effects of estrogen alone or in combination with one of three progestogens with placebo. Post-PEPI use of hormone therapy was ascertained 1-4 years after the trial in 775 (90%) of the originally enrolled women. Potential correlates of treatment decisions were identified from sociodemographic characteristics, medical histories, and clinical measures ascertained at baseline and during and after the trial. Among women who had been assigned to placebo during PEPI, post-PEPI hormone use was significantly less common in women who were adherent to placebo during PEPI, older, or of non-Caucasian ethnicity. Hormone use was positively associated with hysterectomy. Among women assigned to an active regimen during PEPI, post-PEPI hormone use was significantly more common in women who used hormones before PEPI and in women who were adherent to hormones during PEPI. Older age, less education, and being non-Caucasian predicted less hormone use. Post-PEPI hormone use was highest in San Diego and lowest in Iowa City. Women on placebo who lost more bone mineral density (BMD) were more likely to begin hormones than women with less bone loss. Lipids, blood pressure, and other cardiovascular risk factors had relatively little influence on hormone use. The main predictors of post-PEPI hormone use were those associated with use in the general population (education, ethnicity, geographical region, hysterectomy, and prior use/adherence).     

Immediate postabortal insertion of a levonorgestrel-releasing IUD

Experimental IUDs releasing only 10 μg levonorgestrel per day and established copper-releasing IUDs (Nova-T) were inserted in 60 women in connection with legal first-trimester abortion. Bleeding and spotting and other events were recorded during the first year. Restoration of the menstrual cycle was studied. Blood samples were collected twice a week over a three-month period from five women receiving a levonorgestrel-releasing IUD to determine plasma levels of estradiol, progesterone, levonorgestrel, LH and FSH. FSH showed an increase approximately ten days (range 4–19) after abortion. LH/hCG concentrations reached a plateau approximately 24 days (range 9–42) after abortion. Initially, levonorgestrel concentrations were two-fold compared with concentrations of 90 pg/ml after four weeks. After four weeks the plasma levonorgestrel concentrations were stable. All five women had an ovulatory menstrual cycle. The first periods occurred 35 days after operation in the levonorgestrel-IUD group and 30 days after operation in the Nova-T group. The median duration of bleeding and spotting after the insertion was 12 days (range 3–26) in the Nova-T group and 12.5 days (range 3–93) in the levonorgestrel-IUD group. The difference was not statistically significant. From the second month on, menses-like bleeding was more common in the copper-releasing IUD group than in the levonorgestrel-IUD group. The difference was statistically significant (p < 0.001). After one year 75 percent of the patients continued with their IUDs in both groups. One pregnancy occurred in the experimental levonorgestrel-IUD group. One total expulsion was noticed in both groups, and one partial expulsion in the levonorgestrel-IUD group. Two levonorgestrel-IUDs and four Nova-Ts were removed because of bleeding and/or pain. One infection was noticed in the whole group six days after the operation. In the levonorgestrel-IUD group 74 percent of the women had a regular cycle after one year, while all Nova-T patients had a regular cycle. Twelve percent (7 women) were lost to follow-up at one year. The results of this study suggest that a levonorgestrel-releasing IUD can be inserted after legal first-trimester abortion and the results are comparable with those of previous studies that have been made using copper-releasing IUDs.     

狄波-普维拉长效避孕针在上海市育龄妇女中的应用

为验证每三个月注射一次的醋酸甲孕酮避孕针(狄波-普维拉),是否适于中国妇女应用,1995年10月起在上海市区(县)7家医院试用,共接纳451例,其中哺乳期208例,非哺乳对象243例,共使用3708妇女月,有效率100％,一年期因症停用率39％,因社会因素停用15.7％,早期副反应以滴血及少量不规则出血为主,后期闭经发生率上升,以90天为月经记录参照时期,第一至第四参照时期出血(滴血)过长,人数由65.8％降至23.3％,闭经人数由6.2％升至45.2％,未发生严重并发症;哺乳期或35岁以下妇女副反应发生率低于非哺乳或年龄≥35岁者(P<0.05),证明醋酸甲孕酮为高效、长效、安全、方便的避孕措施,尤其适宜于产后42天妇女使用,可减少产后早期及哺乳期人工流产,更适用于反复避孕失败的年轻妇女。     

3种宫内节育器临床使用12个月避孕效果比较分析

目的:比较育龄妇女月经间期放置3种宫内节育器(IUD)的使用效果.方法:对2008年1月～2010年5月在本中心、青海红十字医院和乐都县计划生育服务站放置GyneFix330、TCu380A和MLCu375IUD共799例妇女进行1年随访,比较使用1年的临床效果和副反应.结果:GyneFix330、TCu380A和ML...     

Clinical experience with the uterine progesterone system (Progestasert R).

The results of a joint project from Sweden and Denmark, in which a T-shaped IUD was selected for study is reported. The drug delivery system was developed to release progesterone at 65 mcg/day for 1 year. 150 women from 3 clinics, of whom 115 were multiparous and 35 nulliparous, were studied for 1598 woman-months. In 36% of the multiparous women, insertions were made 2-3 months after parturition. Increases in the duration of menstrual flow were noted after 6 and 12 months. Dsymenorrheic pains were decreased after use of the uterine progesterone system. Continuation rates were 84.4 for multipara and 80.2 for nulliparas. The most frequent reasons for removal were spotting and bleeding. After 1 year of use 3 pregnancies occurred 2 of them ectopic, a rate of 2.1/100 woman-years. Pelvic inflammatory disease was found in 4 patients. Endometrial biopsies in 10 cases, taken after 12 months of exposure, showed early decidual changes, gland suppression, and vascular variations. 4 patients were lost to follow-up. The Progestasert is considered a favorable alternative to other bioactive IUDs. Further studies are recommended.     

Reasons for Brazilian women to switch from different contraceptives to long-acting reversible contraceptives

Objectives

Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort.

Study Design

Women of 18–50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013.

Results

Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was “fear of becoming pregnant” while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~ 95.0/100 women/year for the three methods.

Conclusions

Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.