Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.     

Norplant as a Contraceptive Device in Enugu, Eastern Nigeria

This paper is an evaluation of acceptability and use-experience with the contraceptive device Norplant at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria. Over a period of 36 months, 173 women (8% of the clinic population) accepted the implant. Use of Norplant was concentrated among high-parity women, and the proportion of Norplant users was highest among women aged 30–34 years. Comparing Norplant and IUD users, we found Norplant users to be significantly less highly educated with <1% of Norplant users having tertiary education compared to 25% of new IUD users. The continuation rate with Norplant was 89% at three years, suggesting this method has the potential for improving the low contraceptive prevalence in this region.     

三种皮下埋植避孕剂对农村妇女月经影响的比较性研究

采用随机方法在辽宁省北宁地区选择40岁以下健康经产妇女埋入国产Ⅰ型、Ⅱ型和Norplant皮埋剂各100例,按照统一标准随访,对于皮埋后主要副反应月经问题进行追踪观察和分析。结果:由于人们已经逐渐了解皮下埋植避孕法,尤其农村妇女对其引起不垫月经垫的出血的耐受力较强,主诉月经问题及月经日记分析的流血、滴血天数低于以往文献报道,主要是因平均滴血天数不同的原因。埋植者对月经稀发问题并不反对,对埋后闭经者约半数可接受。通过月经日记分析,在使用第一年约有70％妇女出现月经异常,与文献报道相符。对于典型的异常出血(包括年度内出现≥90天不出血者和出现持续出血≥14天者)对接受者体重并无影响,三组P>0.05。三组埋植者血红蛋白在正常范围内有增无减,至2年均有显著差异,P<0.01。本文提示皮下埋植后妇女可能改变既往传统的月经规律,只要不是长期不规则出血、出血期过长及出血过频较严重或过长的闭经则不必担心,也不需处置,良好的咨询及等待即可,一般可接受的异常出血对妇女健康并无影响,埋植剂一经取出,大部分在60天内恢复月经。     

Norplant contraceptive implants: a new contraceptive for women

This article summarizes current knowledge on the mechanism of action, side effects, and effectiveness of Norplant contraceptive implants. The most common side effect of the implant method is its disruption of the menstrual cycle, especially in the 1st few months of use. Long intervals without frank bleeding may occur and be misinterpreted as pregnancy in women who have not been counseled about this possibility. The average annual continuation rate was 84/100 in a study of 324 women from several countries who were followed for 5 years after Norplant implantation. The net cumulative pregnancy rate for the 5-year study period was 0.6/100. Reasons for method termination included menstrual problems, other medical problems (headache, depression, fatique), planning pregnancy, and other personal reasons (change in marital status, change in residence). To provide training for doctors, nurses, and counselors, the Population Council has established a network of 5 training institutions. Within the next few years, drug regulatory agencies are expected to approve use of Norplant implants in many countries. Although at present the method is available only in Finland and Sweden, Thailand and Indonesia are considering the method and clinical trials are underway in India, China, Brazil, and the US. A consulting committee of the World Health Organization has concluded that Norplant implants are a suitable contraceptive method for use in family planning programs.     

国产皮下埋植剂多中心研究

目的:评价两种国产皮下埋植剂的避孕效果、副反应和继续使用率。方法:分两期进行。第一期为国产Ⅰ型、Ⅱ型皮下埋植剂与Norplant进行前瞻性临床对比研究,各100例,共300例。第二期为国产皮下埋植剂扩大临床应用,接受合格对象Ⅰ型999例,Ⅱ型998例,共1997例。随访5年。结果:5年随访率为99.5％。第一期国产Ⅰ型、Ⅱ型皮下埋植剂和Norplant的5年累计妊娠率分别为0/百妇女、1.0/百妇女、0/百妇女,5年继续使用率分别为77％、80％、80％,差异均无统计学意义(P>0.05)。主要副反应为月经紊乱,月经卡分析显示3种埋植剂的出血模型相似。第二期国产Ⅰ型、Ⅱ型皮下埋植剂5年累计妊娠率分别为0.20/百妇女,2.10/百妇女,5年继续使用分别为84.47％、82.28％。使用埋植剂6个月Ⅰ型和Ⅱ型月经问题主诉发生率分别为50.88％、57.16％,差异有显著意义(P<0.01),但随着使用时间延长,月经紊乱主诉发生率逐渐下降,两组间无差异。结论:5年研究表明两种国产皮下埋植剂的避孕效果、副反应发生率和继续使用率与Norplant相似,也是一种高效,长效的避孕制剂。国产皮下埋植剂Ⅱ型使用至第5年避孕失败率明显增加,建议国产Ⅱ型皮下埋植剂使用期限在3～4年为好。     

Efficacy and side effects of Norplant use in Thai women above the age of 35 years.

A prospective study of Norplant implant use in women aged above 35 years was conducted in Bangkok, Thailand. The purposes of this study were to evaluate the efficacy, menstrual patterns, and side effects of Norplant use in these women. A total of 100 women were recruited in a 1-year clinical study. Their mean age was 39.7 years. Most acceptors had completed secondary school. No accidental pregnancy occurred throughout the 1 year of use in this study. The most common menstrual pattern in these acceptors was amenorrhea followed by irregular bleeding. The major side effect was irregular bleeding. There was no significant change in systolic and diastolic blood pressure during the 1 year follow-up period. Thus, Norplant implant use in older women is a safe and effective contraceptive method. This should become another choice for contraception in women aged above 35 years who have contraindications for oral contraceptive use.     

Racial differences in Norplant use in the United States

The introduction of the contraceptive implant Norplant has focused attention on how social factors may affect contraceptive use. In the United States, race is a central category of social organization which may impact Norplant use. I use data from the 1995 National Survey of Family Growth to answer three main questions. (1) Are women of color more likely to use Norplant? (2) To what extent can racial differences in Norplant use be explained by a structural bias in the provision of medical care? (3) To what extent can racial differences in Norplant use be explained by life circumstances which may affect individual women's contraceptive decisions? I find that African American and Native American women are more likely than white or Asian American women to be recent Norplant users. There are no differences in recent use by Hispanic origin. Both a structural bias in the provision of care and differences in life circumstances account for the disparity in Norplant use between African Americans and whites. However, none of the factors examined here explain Native American women's high rate of use. Concerns about health risks for Norplant use are also discussed. These findings point out the importance of examining structural, individual and health status factors in studies of the use of health services.     

国产皮下埋植剂因月经异常停用的影响因素分析

长效单纯孕激素皮下埋植剂上市20多年来,因其高效、安全、方便、长效、可逆等优点,受到广大育龄妇女的欢迎,但单纯孕激素引起的月经紊乱问题成为限制其可接受性的主要因素[1]。本文通过5年的随访研究,采用COX多元逐步回归方法分析中国经产妇使用国产皮下埋植剂后因月经异常停用     

皮下埋植避孕剂用于临床避孕的疗效研究

目的:对皮下埋植剂避孕剂避孕的临床疗效及安全性进行研究,对其临床应用的前景进行展望。方法:对2007年4月～2008年4月在东台市计划生育指导站实行避孕术的妇女进行回顾性分析,选取98例符合标准者,观察组使用皮下埋植避孕剂进行避孕,对照组使用宫内节育器进行避孕。对两组研究对象避孕效果、术后阴道出血、月经情况、放置率、患者满意率等临床数据进行比较。结果:术后对患者随访5年,观察组有效率为97.9%,较对照组91.3%有优势。观察组出现不良反应4例,不良反应率为8.5%;对照组出现不良反应11例,不良发应率为23.9%,观察组不良反应率低于对照组(P<0.05)。观察组在放置率及患者满意率明显优于对照组。结论:皮下埋植避孕剂在临床避孕的使用中,具有避孕率高,不良发应少,放置率高等优势,受到临床医患的认可,适于推广使用。     

Norplant皮下埋植避孕150例临床研究

目的:探讨Norplant皮下埋植避孕的效果。方法:选择Norplant皮下埋植避孕妇女150例作为治疗组,以宫内节育环避孕妇女150例作为对照组,比较两组使用情况、避孕效果和月经紊乱情况。结果:5年后随访,治疗组因不适取出32例,取出率为21.33%,其余118例全部达到避孕效果,有效率100.00%;期间出现月经紊乱58例,发生率为49.15%;对照组因不适取出或自行脱出10例,取出率为6.67%,其余140例中达到避孕效果115例,有效率82.14%,出现月经紊乱33例,发生率为23.57%。两组避孕效果、月经紊乱和不适失败率比较均具有统计学差异(P<0.01)。结论:对生育期要求避孕妇女行皮下Norplant埋植避孕手术可达到有效的避孕效果,但月经紊乱发生率相对较高,宫内节育环避孕有效率较皮下Norplant埋植避孕手术低,但月经紊乱发生率亦较治疗组低。使用Norplant埋植避孕如何减少月经紊乱,仍是今后值得探讨的一个问题。     

3种常用避孕节育技术对已婚育龄妇女生活质量的影响

目的:分析比较育龄妇女使用元宫铜300宫内节育器(IUD)、复方甲地孕酮避孕针和两根型皮下埋植剂3个月后生活质量的变化情况。方法:2007年7月～2008年12月在我国8个省的20所县级计划生育服务站开展多中心临床研究。以在每所服务站就诊要求使用上述3种避孕方法的健康育龄妇女为研究对象,采用SF-36量表调查妇女使用避孕措施前和使用后3个月时的生活质量状况。结果:20个研究中心共纳入1356例已婚育龄妇女,其中446例使用元宫铜300IUD、610例使用皮下埋植剂、300例使用避孕针避孕。使用避孕措施3个月后,IUD组和避孕针组生活质量总得分较基线得分略增加,而使用皮下埋植剂组生活质量总得分略下降。调整基线得分、所在地区、职业、收入、产次及末次使用避孕方法,使用皮下埋植剂和避孕针组生活质量得分增加值略低于元宫铜组。结论:3种避孕方法对妇女生活质量的影响均较小,使用元宫铜300IUD者生活质量改善情况略优于使用避孕针和皮下埋植剂者。     

Timing of onset of contraceptive effectiveness in Norplant implant users. II. Effect on the ovarian function in the first cycle of use.

The objective of this study was to time the onset of contraceptive effectiveness in Norplant implant users, when the capsules were inserted beyond the first 7 days of the cycle, based on the immediate effect on the ovarian activity. A total of 42 healthy women requesting Norplant implant contraception were enrolled at clinics in Santo Domingo, Dominican Republic, and in Baltimore, Maryland. Implants were inserted on days 8-13 of the menstrual cycle. Blood samples for estradiol (E2), progesterone (P), luteinizing hormone (LH) (in a subset of 12 women), and levonogestrel (LNG) assay, were taken at 0 h and at 6, 12, 24, 72, and 168 h postinsertion. Ovulation, as defined by P > 2.5 ng/mL, occurred in 40% of subjects. A short lasting, frequently blunted, LH peak occurred within 12 h postinsertion, in all these subjects. The remaining subjects had anovulatory cycles with two distinct E2 profiles: continuously increasing E2 levels to a high mean of 414.3 pg/mL (28%), or no sustained increase in E2 (32%). Most cycles (86%) in which Norplant was inserted with high E2 levels (> 175 pg/mL) were ovulatory, whereas none were ovulatory with low E2 (< 100 pg/mL) at insertion. Based on the endocrine effects of Norplant implant insertion in the midadvanced follicular phase, in which ovulation will either occur within 48 h of insertion or will be impaired, additional contraceptive protection is necessary only for 3 days.     

国产Ⅰ型、Ⅱ型埋植剂与Norplant使用第1年阴道出血模式的观察与比较

为了解两种国产埋植剂对阴道出血模式的影响,并与Norplant进行比较,对自1993年11月1日～1994年5月31日随机接受的857例埋植剂使用者记录的月经卡(其中国产Ⅰ型288份,国产Ⅱ型292份,Norplant277份),采用WHO推荐的参考时段法进行统计分析。结果:各项统计指标三组间差异均无显著意义;总出血天数和滴血天数各参考时段均有减少,自第3参考时段起差异有显著意义;各种出血类型的发生率三组间无差异,有基本正常出血类型的人数自第2参考时段明显增加,为30％～35％;出血不规则的发生率自第2参考时段明显减少,为34％～41％,但仍为各种异常出血的首位;再次使用埋植剂者的总出血天数和出血天数均少于首次使用者,差异有显著意义。初步认为两种国产埋植剂在使用后第1年中对阴道出血模式的影响与Norplant相似,阴道总出血天数随滴血天数的减少而缩短;与使用初期相比,使用三种埋植剂后三个月,有基本正常出血类型的人数明显增加,出血不规则的发生率明显减少,出血不规则是埋植剂使用后月经紊乱的主要表现;再次使用者的出血情况好于初次使用者。     

A longitudinal study of changes in endometrial microvascular density in Norplant implant users.

This study aimed to investigate the effects of the subdermal levonorgestrel contraceptive implant Norplant on endometrial vascular density at different durations of exposure, and the relationship between endometrial histology, vascular density, and bleeding patterns. A prospective controlled trial of Norplant implant users compared endometrial vascular density in biopsies taken before and after Norplant implant insertion. A total of 34 women with regular menstrual cycles requesting long-term contraception were recruited at the Sydney Centre for Reproductive Health Research, Australia. A significant increase in mean endometrial microvascular density was observed from as early as 3 weeks after insertion of Norplant implants. Vascular density was increased from a control secretory phase value of 189.6 (7.0 vessels/mm2 (+/- SEM) to 253.80 +/- 7 vessels/mm2 at 2-13 weeks of Norplant implant exposure (t ratio = 2.08, p = 0.01) and 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks of exposure (t ratio = 2.03, p = 0.02). In those with atrophic endometrium, or in whom myometrium and basalis only were found in biopsies (20 of 66, 30%), mean endometrial vascular density was increased at 273.1 +/- 16.1 vessels/mm2 compared with 210.9 +/- 11.7 vessels/mm2 in other histological groups (F ratio = 9.74, p = 0.0028). Bleeding and spotting in the previous 30 days were less common in those with this histological appearance at a mean of 4.95 days compared with 8.22 days. This is the first study to assess endometrial vascular density in the early months of Norplant implant use. The findings suggest that the endometrial vasculature is profoundly altered in the early months of Norplant implant exposure when bleeding problems are most common.     

A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant.

To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.     

皮下埋植避孕妇女血清左炔诺酮含量影响因素分析

目的：测定使用Norplant皮下埋植剂妇女血清中左炔诺酮（LNG）水平,分析影响血清LNG水平的因素。方法：应用液相色谱－串联质谱法测定血清中LNG水平。结果：随着使用Norplant时间延长,血清LNG均值缓慢降低;体重〈60kg组血清LNG水平高于体重≥60kg组（P〈0．05）;不规则出血组血清LNG水平明显高于出血规则组（P〈0．01）。多因素分析显示,埋植时间、体重和月经类型是影响血清左炔诺酮水平的独立因素。结论：皮下埋植后妇女血清左炔诺酮含量与皮下埋植时间、体重和月经类型密切相关。     

Long-acting steroid contraceptive technology

Long-acting steroid contraceptive technologies that have either been recently approved or are currently under study are reviewed and the status of contraceptive research in the US is noted. The benefits and drawbacks, as well as the duration and possible cost, of each method are discussed. Approved by the Food and Drug Administration on December 10, 1990, Norplant is reportedly the first new contraceptive technology available to women in the US since the 1960s. This implant delivery system, which lasts up to 5 years, is cheaper than the pill and nearly as effective as sterilization. Study is currently under way on other multiyear, nonbiodegradable and biodegradable implants. Although already used by 4 million women worldwide, the long-acting injectable Depo-Provera has yet to be approved for use in the US. 5 new types of injectables are being developed. Steroid-containing IUDs have been in the market for some time, and current research is attempting to increase their contraceptive life beyond 1 year. Contraceptive developers are also exploring transdermal delivery systems, vaginal rings, and buccal and sublingual delivery. It is considered misleading to call Norplant the first new contraceptive introduced since the pill. Over the past 20 years, virtually every contraceptive has been significantly improved, developments that have enhanced the contraceptive options of couples. Because new contraceptive technologies are increasingly complex, their development is much slower. Consequently, it is concluded that in the foreseeable future, the demand for more acceptable contraceptives will be met through improvements of currently available technologies.     

Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction

In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R)-2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive.     

Implantable contraceptives for women: effectiveness, discontinuation rates, return of fertility, and outcome of pregnancies

Progestogen-only contraceptive implants are highly effective. In most studies, 5-year cumulative pregnancy rates are less than 1.5/100 women for Norplant and Norplant II. No study has yet reported any failures with Implanon. Weight over 70 kg and age at insertion under 25 years both increase the failure rate of Norplant and Norplant II; however, data are as yet lacking for Implanon. The effectiveness of other progestogen-only implants for which there are as yet few data are unlikely to be any different. Continuation rates are high compared with other hormonal methods and with the intrauterine device. In most cohorts at least 35% of women, and often many more, are still using Norplant by the end of 5 years. Rates vary according to a number of factors, including population studied, age, and parity. Menstrual disturbance is by far the most common reason for discontinuation, with headache, acne, weight gain, and desire for pregnancy accounting for other common reasons for implant removal. Fertility returns rapidly following implant removal, and pregnancy rates (76-100% 1 year after removal) are usually no different from those following discontinuation of any other contraceptive method. There is no increase in the risk of ectopic pregnancy, fetal malformation, or impaired infant health in pregnancies conceived either during implant use or after removal.     

Hormonal implants: the next wave of contraceptives

It will soon be possible for a woman who does not want to become pregnant to have a Norplant system implanted under the skin of her arm; it provides a 5-year supply of continuous hormonal contraceptive protection. Failure rates have been consistently below 1 pregnancy/100 users/year, and the system has generally shown continuation rates at least as good as IUDs. As with other contraceptives using progestins alone, the implant tends to disrupt menstrual patterns; a large proportion of women who stop using the method do so because of abnormal bleeding. However, menstrual disturbances appear to subside toward the end of the 1st year of use. The system consists of 6 separate capsules about 1.3 inches long and .1 inches in diameter made of silastic packed with 36 mg of levonorgestrel. Every day about 30 mg. of this hormone are released. The capsules are inserted in a fan-shaped pattern after a .2 inch incision is made; the entire operation, including preparing the patient and administering a local anesthetic, requires 10-15 minutes. Removing the implants is somewhat more complicated as the layer of fibrous tissue that forms around them must 1st be cut open. This procudure may take up to 20 minutes. The return of fertility does not appear to be compromised by the use of the implant. The 6-capsule Norplant system may be replaced in a few years by a more advanced 2-rod version that is now undergoing clinical trials.