To evaluate the effect of Norplant on lactation and the growth of the infant, a comparative study on lactating women using a cohort approach has been carried out in Klinik Raden Saleh, Department of Obstetrics and Gynaecology, University of Indonesia and Dr Cipto Mangunkusumo General Hospital, Jakarta. The recruitment of the study group took place between 1 November 1983 and 31 August 1984. The inclusion criteria, among others, were age 18-40 years, full term gestation, spontaneous delivery, 4-6 weeks after delivery and plans to breastfeed for at least 6 months. The study group consisted of 60 Norplant acceptors, while the control group consisted of 60 Cu-7IUD acceptors. The subjects had a free choice in deciding which form of fertility regulation they preferred. After 6 months of observation the following conclusions were drawn: Norplant use did not have any effect on maternal body weight, hemoglobin concentration or breastmilk production in comparison with IUD use. The development of infants breastfed by Norplant acceptors was not delayed compared to that of infants breastfed by IUD acceptors.

Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infant's circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.

Long-acting progestin contraceptives have been available in many countries for a number of years with a large number of women now using them. Although some improvements in delivery systems have been made, the major problem with progestin-only contraceptives remains unpredictable endometrial breakthrough bleeding (BTB), which is responsible for more than 50% of drop-outs from this form of contraception. Using hysteroscopy, endometrial petechiae and ecchymoses are a common finding among Norplant users, although these features do not always correlate with BTB. It has been postulated that epithelial and subepithelial tissues may provide a barrier to BTB, as long as epithelial integrity is maintained. The aim of this pilot study is to explore structural changes in the endometrial surface epithelium, and subepithelial collagen III fibres. Endometrial biopsies from noresthisterone-enanthate (NetEn) users (n = 6) and controls (n = 6) were assessed using routine haematoxylin and eosin staining and immunohistochemical staining for cytokeratins 8, 18 and 19, and collagen III. A conventional silver impregnation method was also used to identify subepithelial collagen III fibres. Most of the Net-En tissues showed reduced surface epithelial cell height compared controls (P = 0.002). Cytokeratin staining as weaker (P = 0.04) and distributed evenly between basal and apical parts of the cell in Net-En tissue, compared to more apically in controls. Both immunohistochemical and conventional silver staining methods revealed that the subepithelial collagen III meshwork remained unchanged in Net-En compared to control endometrium. Both staining methods identified collagen fibres with equal sensitivity. In conclusion, atrophic changes remain the dominant appearance for progestin-exposed endometrium, with reduced cytokeratin staining, but apparently there is little change in subepithelial collagen III expression.

Norplant is a hormonal, long term method of contraception requiring the sub-dermal placement of six flexible capsules containing levonorgestrel in the inner aspect of the upper non-dominant arm. This open, prospective, multicentre, parallel group study, comparing the acceptability of Norplant and a combined pill, was originally designed to follow 700 subjects for five years, but was discontinued early. The main outcome criteria were duration of use and reason for discontinuation if appropriate. This final analysis, concerning the 364 subjects who used the implant and 307 subjects who used a gestodene/ethinyloestradiol combined pill, shows a statistically significantly higher (p<0.001) continuation rate amongst the implant users at 83.4 per cent compared to the pill users at 64.4 per cent at one year and this difference decreased only slightly by two years. The most common reasons for discontinuation by the end of the study were adverse events in both groups (menstrual and then mood changes in the implant group and mood changes and then headaches in the pill group). From the whole cohort the proportion which were 'very satisfied' were higher in the implant group (28.5 per cent compared to 14.6 per cent). This study confirms, in the UK, a high continuation rate for implant users similar to other countries as reported in the literature. If acceptability and continuation rates are similar in the none study setting, then a substantial number of women will seek removal of the implant and possible reinsertion five years after the time of initial high popularity (ie 1999). Doctors need to be prepared for this possible high level of activity.

The objective of the study was to assess the possible differences in effects of Implanon and Norplant implants on carbohydrate metabolism. This is a 2-year open randomized study of 80 implant (Implanon and Norplant) acceptors. Oral glucose tolerance test (OGTT) was performed before implant insertion and at 6, 12, and 24 months after implant insertion. Glycosylated hemoglobin A(1)C was measured in fasting samples and plasma samples during OGTT were tested for glucose and insulin levels. There was a significant increase in the area under the curve for both glucose and insulin during OGTT within each group with increasing duration of use. However, there was no significant change in the fasting plasma glucose values. There was no significant difference in the carbohydrate parameters between the two groups during implant use, except for a minimal but statistically significant rise in fasting glycosylated hemoglobin A(1)C levels at 24 months in the Implanon group. Both implants appear to induce mild insulin resistance but no significant change in serum glucose levels. These alterations in carbohydrate metabolism should have no clinical significance in healthy women.

A 2-year longitudinal study was undertaken to investigate the effects of the implantable contraceptive Norplant on lipid and lipoprotein metabolism. A group of 177 Norplant implants acceptors was recruited in five centers (Bangkok, Jakarta, Mexico City, Singapore, and Stockholm) and monitored during one baseline menstrual cycle and 3, 5, 11, 16, and 22 months after implant insertion. They were compared with a group of 174 copper intrauterine (IUD) device users who had blood sampling performed at comparable time points. Lipid changes were greatest 3 months after implant insertion and a slow reversal of these trends towards baseline was observed during the next 19 months. The main changes observed at 3 months were a 10% drop in total cholesterol, and an 11% drop in high-density lipoprotein (HDL)-cholesterol and apolipoprotein AI levels, together with a 19% decline in serum triglycerides. Variations in low-density lipoprotein (LDL)-cholesterol and apolipoprotein B levels were not significantly different from those observed in the group of IUD users. There was consistency in these findings between centers in that the changes were in the same direction but of different magnitude in different centers. It is concluded that lipid changes induced by Norplant implants will probably not affect the risk of atherosclerotic disease in women who use this contraceptive method.

One of the methods to establish the safety and risk profile of hormonal contraceptives is employing a study on their metabolic effects. In order to evaluate the effect of Norplant implants on serum lipids, a cross-sectional study was undertaken at Klinik Raden Saleh, Jakarta. The subjects recruited were divided into 8 groups depending on the length of Norplant use, i.e. before insertion, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months and one week after the removal of Norplant. Blood samples were collected from the subjects after an overnight fast. The parameters studied were triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol. There were no significant differences between the groups regarding the triglycerides and HDL-cholesterol (p greater than 0.05). There were significant differences between the groups regarding the total cholesterol and LDL-cholesterol (p less than 0.01).

The Norplant subdermal implants system is rapidly becoming acceptable as a contraceptive system all over the world. Earlier studies in Singapore indicated that the implants do not appear directly contributory to cardiovascular risk. However, extraneous environmental effects could have contributed to the observed changes. In this study, when nonsteroid copper intrauterine device (IUD) users were used as control, we have shown that the findings are in concordance with the results of the earlier studies. There was a decrease in serum triglycerides, total cholesterol, and HDL and LDL cholesterol over the period of study. However, despite these changes the HDL cholesterol/total cholesterol ratio remained stable and was above 0.200. As regards apolipoprotein, there was generally a significant full in apolipoprotein AI, AII, and B. As a result, the apolipoprotein AI/AII ratio showed a significant decrease in the first 3 months before increasing close to its preinsertion value at 2 years. Similarly, the apolipoprotein AI/B ratio also stabilized at the end of 2 years. This study thus confirms our earlier findings that Norplant implants do not appear directly contributory to cardiovascular risk.

This open, randomized study was intended to assess the effects of the new single-rod contraceptive implant (Implanon) containing etonogestrel on lipid metabolism in Indonesian women, in comparison with the six-rod implant Norplant, containing levonorgestrel. The effects of both products were compared with a control group using an intrauterine device (IUD) over a 3-year period. A total of 135 healthy volunteers of childbearing potential, aged 22 to 41 years, were enrolled in Jakarta, Indonesia. Ninety volunteers were randomized to use Implanon (n = 45) or Norplant (n = 45), and a nonrandomized group of 45 Multiload Cu 250 IUD users served as a control. Serum concentrations of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein AI, apolipoprotein AII, and apolipoprotein B were measured. The ratios of HDL cholesterol to total cholesterol, of HDL to LDL cholesterol, and of apolipoprotein AI to apolipoprotein B were determined. Lipid and lipoprotein determinations were done at screening and after 3, 6, 12, 18, 24 and 36 months. Contraceptive efficacy and insertion and removal times were also recorded. Mean changes from baseline in the lipid and apolipoprotein parameters, although occasionally statistically significant, were small in all groups (less than 1 standard deviation of the mean concentration at baseline) and clinically not significant. Statistically significant differences between the Implanon and Norplant groups were only occasionally observed. In both implant groups, total mean cholesterol, LDL cholesterol, and apolipoprotein AI concentrations tended to decrease during the study, but statistically significant changes from baseline were only occasionally observed, suggesting that drug-related factors are not involved. The mean ratios of HDL/total cholesterol and the HDL/LDL cholesterol showed very little change over time in both implant groups; slight and statistically nonsignificant increases were noted at most time points. Similar changes were seen in the group of IUD users. It can be concluded that changes from baseline in the lipid and apolipoprotein parameters tested were generally small and did not differ between Implanon and Norplant.

Prolonged use of reformulated and the original 2-rod Norplant implants showed similar changes in most hemostatic parameters studied. Raised hemoglobin concentration and hematocrit values with not enhanced platelet activation or significant changes in platelet numbers were seen. Factor VII showed an increase from 18 months compared to the first 12 months of original Norplant implant use, while with reformulated Norplant implant, the level at 36 months was significantly higher than the first 24 months of implant use. Fibrinogen levels were significantly elevated by 36 months of both implant use. No evidence of enhanced activation of coagulation, fibrinolysis/inhibitor were observed during prolonged implant use. Overall, no significant changes in tissue plasminogen activator (t-PA) levels were observed but urokinase-like plasminogen activator (u-PA) levels were significantly reduced, indicating no enhancement of tissue breakdown. Plasminogen activation inhibitor (PAI-1) antigen levels were significantly reduced from 12 to 36 months with original Norplant implant use compared to the pre-insertion levels, while a nonsignificant decreased trend was seen with prolonged reformulated Norplant implant use. The increased levels of fibrinogen and FVII at the end of 36 months of implant use require further observation as these factors are known markers of hypercoagulation and associated with increased arteriosclerotic and cardiovascular risks. This study is on-going to evaluate the effects of levonorgestrel-containing subdermal reformulated Norplant implants on hemostasis after five years of use.

A large scale, phased investigation of NORPLANT contraceptive systems was conducted in the People's Republic of China. The first phase comprehended 1,200 women in four cities. Expanded trials included 11,918 women at 12 major centers and at sub-centers by 31 May 1987. At that date 4,676 NORPLANT capsule subjects and 1,089 rod subjects had completed one year of use, 1,381 capsule acceptors had completed two years as had 197 rod users. Gross pregnancy rates were less than 0.1 per 100 for each implant type both at one and at two years. Continuation rates were 94 per 100 for each implant type at one year, and were 82.0 and 83.6 per 100 among users of NORPLANT capsule and rod implants, respectively, at two years. Disruption of menstrual function was the dominant reason for termination, but mean hemoglobin levels increased in each of the nine centers reporting values at admission and at one year. First year gross cumulative termination rates for medical reasons were 1.2 to 1.3 per 100, reaching 3.8 and 5.6 per 100 for capsule and rod implants, respectively, at two years. Microdose contraception with these levonorgestrel-releasing implants appears to be a highly acceptable and effective modality suitable for Chinese women. NORPLANT implants are now approved by the national drug regulatory agency for general use in China.

From November 1988 to December 1994, a total of 567 female volunteers were enrolled in Norplant implant studies at the National Taiwan University Hospital. After a median follow-up of 29 months, only 3 of the 529 available cases became pregnant (a cumulative rate of 1.2 pregnancies per 100 users over 5 years). Chromosome analysis of 2 of the 3 abortuses revealed 46,XX/46,XX,inv(3) and 46,XX. Menstrual problems were the most common adverse effects and were also the main reason for discontinuation (65%, 108/166). The continuation rate was 90%, 78%, 70%, 61%, and 42% at the end of 1, 2, 3, 4, and 5 years after insertion, respectively. In the 21 patients who wished to become pregnant, fertility recurred soon after removal of the Norplant implants. The data suggested that the Norplant implants system is a highly effective, safe, and long-acting method of reversible contraception. It would be worthwhile to introduce this contraceptive system to Taiwan's family planning program.

One-hundred-thirty of 178 women who received Norplant-2 implants were followed prospectively for 4 years. Menstrual disorders were the most common reason for discontinuation. Only one patient conceived, for a failure rate of 0.6%.

An analysis of 350 users of Norplant contraceptive subdermal implants from six centers in two African countries (Ghana and Nigeria) indicates that method acceptability remained high among the women who used the method for five years. Overall, 90.1% of the 155 five-year users in these countries reported having a very favorable experience and 9.9% a favorable experience with Norplant implants. Ease of use was cited by 56.1% and duration of use by 13.6% of the women as the most liked characteristics of the method at study completion after five years. Menstrual disturbance was the least liked aspect, by 41.9% of the women. On average, women who discontinued early from the study had fewer living children and were more likely to desire additional children at method adoption than those who completed five years of use; the differences were statistically significant. Differences in level of education and previous use of contraception were not found to be statistically significant between completers and non-completers. Differences in age were not significant in Nigeria, but were marginally significant in Ghana, with completers being older than non-completers. Of the clients who completed this study, 79.2% indicated a desire to continue with contraception and 43.9% planned to have a second set of implants inserted. These findings have important implications for counseling, method access and service sustainability in African countries.

An analysis of 1,882 Asian acceptors of Norplant implants indicates that method acceptability remained high among the 882 women who used the method for five years. Women who discontinued early from the study were, on average, younger than those who completed five years of use. Also, they had fewer live births and were more likely to desire additional children. Overall, about 70% of the women in these countries found the Norplant implant method to be very favorable. The majority >> 40%) of the women found the ease and duration of use of the method to be most attractive, while menstrual disturbances were the least-liked aspect of the method. Although it was apparent that there are still some potential obstacles to Norplant implant acceptance, most noticeably concerns about menstrual irregularities, interest in continuing the method after five years of use is high. Further research of issues related to Norplant implant acceptability may improve continuation rates and overall client satisfaction.

OBJECTIVE

This study examined correlates of Norplant selection and satisfaction among low-income women.

METHODS

Interviews were completed in family planning clinics in 4 Florida counties with 1152 Norplant users and 1268 nonusers, with follow-up interviews with a subsample up to 1 year later. Logistic regression models estimated the associations of socio-demographic and medical characteristics with Norplant selection and method satisfaction.

RESULTS

Odds ratios for Norplant selection were significantly greater among women who planned to have children in 5 or more years, those who were "offered" Norplant, those who lived in Palm Beach County, those who were using drugs, and those who were Medicaid clients. Women younger than 17 and those who learned about Norplant from a friend were twice as likely as others to select Norplant. Ninety-two percent of Norplant users were satisfied with the method; women with side effects and those who felt pressure to select a method were significantly less likely than others to be satisfied.

CONCLUSIONS

Norplant provides an acceptable and satisfying method of birth control for many low-income women. Proper counseling about all methods of birth control and about Norplant's side effects remains critical to the appropriate delivery of this method.

Norplant is a long-acting contraceptive that has been introduced into family planning programs all over the world. Its efficacy, safety and acceptability in the introductory phases have been widely tested, and most studies point to the need for good provider training in insertion and removal; good client counseling on side effects, suitable client selection to limit early removal, and attention to client access to removal services. Some problems with the method in the developed world, and a belief that it is too costly for developing countries, have led to a waning of support by international donors. Few studies have examined how service delivery expansion in the developing world can minimise and address potential problems as well as maintain Norplant's cost-effective edge against other methods. We examine the expansion of Norplant services in Kenya between 1992 and 1996, specifically in relation to client access to services, removal issues, and cost. Well-supervised and careful expansion has resulted in quality services being provided at more than 70 sites in the country. Early removal is limited, removals seem to have posed few problems, and Norplant offers a welcome and cost-effective addition to the family planning method mix.

In a longitudinal study involving 100 Singaporean women, results indicate that the acceptors persist in having a possibly increased predisposition to thrombosis, as evidenced by a significant increase in platelet count and aggregability. Furthermore, the shortened prothrombin time and activated partial thromboplastin time, together with changes in vitamin K factors, still indicate the possible enhanced potential for hypercoagulation.

All 133 women who began using the Norplant contraceptive implant between August and December of 1991 at a Planned Parenthood clinic in Baltimore were compared with a sample of 112 women who obtained prescriptions for the pill at the same clinic during the same time period. A multivariate analysis found that women of Medicaid are significantly more likely than those who are self-paying to select the implant rather than the pill. Similarly, compared with women who have had no children, those who have had two or more are also significantly more likely to choose the implant. However, adolescents and women who have had an abortion are no more likely than other women to select the implant.

This was a comparative study of users of Norplant contraceptive, Subdermal implants and LA Minilap, in rural, urban and peri-urban sites in Kenya during 1991-1993. Both methods are very well accepted by well counselled women seeking long-term, continuous, convenient, highly effective contraception. Norplant users had a mean age of 27.3 years, an average of 2.6 living children and 25.3 per cent were unmarried, while 32.9 percent had completed their families. This compares with 31.3 years, 6.2 living children, 0.6 percent unmarried and 100 percent completed families respectively for LA Minilap. Norplant acceptance rates have continued to rise over the few years since programme inception, and now stand at 5.4 percent of all new acceptors. LA Minilap acceptance trends shows a plateau or moderate down-turn at 21.6 percent of new acceptors. The possible reasons and implications of these observations, along with user characteristics are discussed.