A longitudinal study of hemostatic function was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraception. The results at the end of three years indicate a possible increased predisposition to thrombosis, as evidenced by significant increases in platelet count and aggregability. The prothrombin time (PT) and activated partial thromboplastin time (APTT) continued to remain shortened at the end of three years of use. There was also a general fall in most of the vitamin K coagulation factors. There is thus still an indication of a possible enhanced potential for hypercoagulation at the end of three years of Norplant-2 rod use.

A longitudinal study of coagulation parameters was carried out on 100 Singapore acceptors using the levonorgestrel subdermal implants Norplant-2 rods for contraceptive purposes. At the end of 1 year of use, results from this on-going study indicates that these acceptors have an enhanced potential for hypercoagulation with a significant shortening of their prothrombin time and activated partial thromboplastin time. They also have an increased predisposition to thrombosis as evidenced by significant increases in platelet count and aggregability. A number of other parameters achieved statistically significant differences by the end of one year but since the results were within the normal accepted range, they were therefore unlikely to be of much clinical importance.

Implanon, a novel contraceptive implant containing the progestogen, etonogestrel (68 mg), provides highly effective, well-tolerated contraception for up to 3 years. Its single-rod design, semi-rigid polymer base and convenient pre-loaded presentation mean that Implanon has potential insertion and removal advantages over the six-capsule Norplant implant. Insertion of Implanon is simple: the applicator needle is positioned subdermally and the cannula is withdrawn, leaving the implant rod in place. Implanon is removed using the 'pop out' technique, involving a 2-mm incision. A meta-analysis of data from seven open-label, randomized studies in 1,378 women compared the ease of insertion and removal of the Implanon and Norplant implants and the frequency of associated complications. It was approximately four times quicker to insert and remove Implanon than Norplant (mean insertion times 1.1 vs. 4.3 min, respectively; mean removal times 2.6 vs.10.2 min, respectively). Insertion complications were very rare with both Implanon (0.3%) and Norplant (0.0%). However, Implanon was associated with a significantly lower frequency of removal complications (0.2 vs. 4.8% with Norplant; p < 0.001). Implant site abnormalities were uncommon. The simplicity of the insertion and removal procedures with Implanon may have significant implications for contraceptive implant training programs and user counselling.

Norplant implantable contraceptives were developed mainly for use in Third World countries, but first were approved for marketing in Finland in 1983 and in Sweden in 1985. Since then Norplant has been approved in more than 40 countries, most of them in the Third World. The authors analyzed the clinical documentation submitted to the Finnish and Swedish drug control authorities, and the assessments made of the data. The Finnish review process lasted for three years, and the number of data increased substantially during that time. The authors have not been allowed to publish the clinical data submitted in Finland, but a reconstruction from the Swedish data showed that the clinical data were of poor quality and were mainly focused on assessing efficacy. Side effects, acceptability, and requirements of the health care system for proper use of Norplant were poorly studied. This example of Norplant licensing in Finland shows that licensing of drugs in industrialized countries is insufficient for guaranteeing their safety in Third World countries.

This paper analyzes data from a population-based survey fielded in Sri Lanka, which showed that almost half of the women interested in using Norplant contraceptive subdermal implants were actually those who wanted to limit childbearing, a pattern also found in international Norplant clinical studies. A comparison between recently sterilized women and professed limiters of potential Norplant users showed the limiters to be socio-economically and demographically a significantly different group of women from those sterilized. Among several variables analyzed, the most important factor distinguishing the two groups was their relative economic status. Further comparison of the limiters with professed spacers interested in using Norplant showed that the spacers were yet another distinct category of women, the most important characteristic distinguishing between the two groups being the total number of living children. The preliminary results suggest that the Norplant implants system is not necessarily a substitute for sterilization; it appears potentially a popular method among those who want no more children but are not ready to accept sterilization. These findings that the potential Norplant implant users represent different gradients of women in the population have implications for provider counseling and user satisfaction as well as continuation.

UNASSIGNED

Frequency of sex, contraceptive use and HIV infection are key determinants of fertility. Use of an effective family planning (EFP) method (injectable, oral, intra-uterine contraceptive device (IUCD), or Norplant) potentially eliminates women's concerns of unintended pregnancy. We report the association between EFP and frequency of sex among HIV-infected and HIV-uninfected non-pregnant African women.

UNASSIGNED

Prospective fertility intentions study nested within a phase 3 randomized double-masked placebo-controlled trial (2003-2005) to treat genital tract infections in HIV-infected and HIV-uninfected non-pregnant women. Enrollment of study participants was stratified by HIV infection status. Data on demographics, family planning and sexual history were obtained at baseline and at 3, 6, 9 and 12 months. Chi square and Wilcoxon Rank-Sum tests were used to compare categorical and continuous variables, respectively. Generalized Estimating Equations method was used to estimate relative risk (RR) of frequent sex (≥ 2 acts/week) among users of different EFP methods (injectable, oral, implant or intra-uterine contraceptive device).

UNASSIGNED

After adjusting for age, current health status, and fertility intentions, EFP use was significantly associated with frequent sex among HIV-infected women (RR 1.32; 95% Confidence Interval [CI] 1.14-1.52); this association was not statistically significant among HIV-uninfected women (RR 1.10; 95% CI 0.96-1.24). Fertility intentions among HIV-infected, and education among HIV-uninfected womenwere independent predictors of sex frequency.

UNASSIGNED

These data suggest that the association between EFP use and frequency of sex among women varies by HIV infection status. Service-delivery of diverse EFP methods should be integrated within HIV counseling, testing and treatment facilities.

UNASSIGNED

Registration number NCT00140764 under the clinicaltrials.gov, first Posted: September 1, 2005, last Update Posted: August 10, 2011.

Norplant contraceptives are manufactured in Finland, but the majority of Norplant users live in the Third World. The objective of this study was to study Finnish family planning physicians experience with and attitudes towards Norplant contraceptives. Three data sources were used: (1) review of articles published in non-commercial Finnish medical journals between 1980 and 1990, (2) a sample of eleven physicians known to have experience with Norplant and chosen by a snow-ball method, and (3) a random sample of 22 physicians in charge of public family planning services stratified by municipality and degree of urbanization. The articles reflected a positive attitude towards Norplant, but the authors did not believe that Norplant should replace any previous method of contraception. In the random sample the amount of experience with Norplant was low. In both groups the general attitude towards Norplant was reserved. It was not used as a method of first choice, but was considered a good method for carefully selected women. Norplant was considered troublesome for the physician, requiring surgical procedures, producing side-effects and demanding time for counselling. Adequate use of Norplant calls for a good health care infrastructure, hygienic facilities and trained personnel. These are often lacking in Third World settings.

In the 1980s and 1990s, the litigious climate in the US had a catastrophic effect on sales of many major contraceptives. Although oral contraceptives escaped controversy, the intrauterine device (IUD) and Norplant(R) were two targets of damaging litigation. The IUD was withdrawn from the market in 1985. Since 1994 when the attacks began against Norplant, its US sales have dramatically declined, even though no fault has been found in the method or its development. In general, pharmaceutical companies were extremely hesitant to develop new contraceptives during this period. The bleak outlook, however, began to shift in the late 1990s, as fertility rates began to decrease worldwide and contraceptive users increased. By 2025, 2500 million women will comprise the customer base for contraception. Global pharmaceutical companies are now participating in expanding markets overseas and have launched and continue to develop a range of new long-term reversible, and highly effective, contraceptive products outside the traditional oral contraceptive field. Two new contraceptives on the way to the US market are: Mirena, a levonorgestrel-releasing intrauterine system manufactured by Schering-Leiras; and Implanon, a single implant system manufactured by Organon of the Netherlands. Other birth control methods soon to be launched include: emergency contraceptives, the contraceptive patch, monthly contraceptive injections, mifepristone for medical abortion, and modified oral contraceptives.

Having presented an overview of the available methods of contraception, the authors present one approach to prescribing contraceptives based on their experience. First, adolescent patients in our practice are discouraged from engaging in sexual intercourse. Abstinence is the only fail-safe method of contraception and provides benefits both emotionally and physically (i.e., prevention from sexually transmitted diseases and unwanted pregnancies). If the adolescent plans to be sexually active, however, she is encouraged to select some form of hormonal contraception, namely Norplant, Depo-Provera, or oral contraceptives, in conjunction with condoms. The authors have had little success recommending barrier methods alone. Condoms are used sporadically and the diaphragm is very awkward for adolescents who are still uncomfortable with their bodies and with touching themselves. Of the three hormonal methods, Depo-Provera seems to be well-accepted by our patients. It offers several advantages that we believe make it attractive. First, it does not require any forethought by the patient other than coming in for the injection every 3 months. There is an effective grace period, so the patient is afforded good contraception even if she is up to a month late for her injection. The frequent visits for injections actually can be looked upon as positive, frequent contacts with the patient and can provide opportunities for counseling. In addition, some patients become amenorrheic, which teens view as an advantage, increasing compliance. If it is not likely that a patient will be compliant with every-3-month injections, Norplant is recommended. Studies have shown good acceptance of Norplant by adolescents and that has been the experience of the authors. With appropriate counseling prior to insertion and a counseling session with patients who request removal, the number of actual Norplant removals has been limited. If Depo-Provera and Norplant are not acceptable to the patient, then oral contraceptives are recommended. Of the three methods, more opportunities for failure exist with oral contraceptives. Pills are missed for a variety of reasons, including going away for the weekend; not having a regular schedule, which can interrupt pill-taking; and even ambivalence about becoming pregnant. One recent study demonstrated certain patient characteristics that were associated with good compliance with oral contraceptives, including white race, higher education level, suburban residence, and older age of both the patient and her mate. Keeping these characteristics in mind may be helpful when prescribing oral contraceptives. Of course, it is the patient's prerogative to choose the type of contraception she feels will be best suited for her.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE

The purpose of this study was to prospectively evaluate the continuation rate of subdermal contraceptive implants (Norplant) among adolescent (< 20 years) and adult >> or = 20 years) women in the clinic population of a tertiary care medical center.

METHODS

Adolescents and adults desiring contraception for greater than a 6-month period were eligible for Norplant insertion. Prior to insertion, personal counseling and extensive education were provided. Following insertion, rapid access, personal counseling, and prompt treatment were provided for complications that occurred. Device removal was available to all individuals at any time upon patient request or if side effects could not be ameliorated. Patient demographic, historical, physical, and follow-up data were entered into a computer data base.

RESULTS

Since February 1991, 1800 subdermal contraceptive implants were inserted. Of these 1688 patients were prospectively followed, providing 45,576 women-months of data for analysis. Adolescents comprised 40% of the study population. Over a 50-month period, the cumulative continuation rate for adolescents was 93.6%, and for adults it was 91.1%. The mean duration of use among adolescents was 26.5 months and for adults was 27.6 months.

CONCLUSIONS

There was no significant difference between adolescent and adult subdermal contraceptive implant continuation rates for up to 50 months of use. In this patient population, high continuation rates may result from a combination of extensive patient education and intensive surveillance by a well-trained and dedicated multidisciplinary staff. When all patients are enrolled in a program that provides aggressive education and supportive follow-up, age is not a significant factor in continuation rates.

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.

Long-acting contraceptive methods are appropriate choices for women who prefer the convenience and high contraceptive efficacy of methods not requiring frequent compliance, and women for whom contraceptive doses of estrogen are either medically contraindicated or associated with persistent intolerable side effects. Annual pregnancy rates for the three methods described below are less than 1 per 100 woman-years. As currently formulated, levonorgestrel implants (Norplant) consist of six 34 x 2.4 mm soft plastic implants, each filled with 36 mg of crystalline levonorgestrel. Irregular and often persistent menstrual bleeding and spotting constitute the most important side effects experienced by and leading to method discontinuation in implant users. Implant removal is technically more difficult and time-consuming than insertion. Depot-medroxyprogesterone acetate (DMPA or Depo-Provera) is injected as an aqueous suspension of microcrystals. Intramuscular injection of 150 mg of DMPA results in more than 3 months of contraception. Irregular bleeding and spotting followed by amenorrhea, constitute the most importance side effects experienced by DMPA users. Because DMPA use can result in prolonged (but not permanent) infertility, DMPA is not an optimum contraceptive choice for women who may want to conceive in the next one or two years. The Copper T380A intrauterine device (IUD) provides reversible contraception for up to 10 years. IUDs act as contraceptives, not early abortafacients. Recent epidemiologic data indicate that long-term IUD use does not increase the occurrence of pelvic inflammatory disease. Heavier menstrual flow and cramps constitute the main side effects experienced by women using the copper IUD. Intrauterine device insertion and removal are accomplished during brief office-based procedures.

The study of Norplant implants use in HIV-1 infected women was conducted at the Family Planning Clinic, Department of Obstetrics and Gynaecology. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, from January 1993 to June 1996. The purpose of the study was to evaluate efficacy, clinical effects, side effects, and menstrual patterns of the Norplant system in HIV-1 infected acceptors. Forty one cases of asymptomatic HIV-1 positive women voluntarily participated in using Norplant implants after delivery or abortion. The mean age was 25.4 years. The most common menstrual pattern was irregular bleeding (63.4%). Mean blood pressure, body weight, and hemoglobin level were not different at insertion and at 12 months (p>> 0.05). No pregnancy occurred during a 12-month period. It was concluded that the Norplant system was safe, efficacious, and well tolerated in HIV-1 positive women and is an appropriate contraception in these women.

This paper presents a secondary analysis of 3419 Norplant users from 11 countries throughout Asia, Africa and Latin America. The main objective was to identify the menstrual problems associated with a high risk of early discontinuation of Norplant use. Eligible participants were divided into two groups: those who continued use (n = 2667) for the first 3 years and those who discontinued use because of bleeding or pain (n = 752) during the first 3 years of use. Menstrual characteristics of the women were compared between groups using a logistic regression model with generalized estimating equations. Flow duration of more than 7 days, excessive amount of flow, dysmenorrhea and intermenstrual bleeding for more than 7 days were associated with a significant risk of discontinuation. The highest risk was observed in association with flow duration of more than 7 days (adjusted odds ratios of 1.85, 2.01 and 2.20 at 1, 2 and 3 years, respectively). The appropriate management of prolonged or excessive bleeding, namely by continuous counseling, is essential for successful Norplant use.

The mechanisms responsible for progestogen-induced breakthrough bleeding remain unexplained. The aim of the present study was to examine the expression of three basement membrane components, collagen IV (CIV), laminin and heparan sulphate proteoglycan (HSPG), by immunohistochemistry in sections of endometrium from women receiving the subdermal levonorgestrel implant (Norplant) and normally cycling women. Control biopsies were obtained from 20 normal subjects from Melbourne, Australia, and pre- and post-Norplant-insertion biopsies were obtained from 11 women from Sydney, Australia, with between 3 and 6 months Norplant exposure. It was postulated that in Norplant users a decrease in the amount of basement membrane material present around endometrial vessels may be responsible for increased capillary fragility. The results, however, showed that for all three components, Norplant biopsies exhibited vascular basement membrane immunostaining at least as intense as that found in the mid-late secretory phase of the normal cycle. During the normal cycle, HSPG was only detected in approximately 40% of vessels with CIV and laminin immunoreactivity, and menstrual biopsies demonstrated reduced staining for all three components. Several biopsies exhibited a degree of regional variability in staining intensity, and Norplant biopsies exhibited areas of discrete, decidual-like stromal immunostaining for CIV and laminin. Although no differences were found in microvascular basement membranes in Norplant users that might explain capillary fragility, it is possible that other techniques could yield information on changes in the integrity of basement membrane components that might influence basement membrane strength.

BACKGROUND

Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle.

METHODS

Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1.

RESULTS

The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining.

CONCLUSIONS

The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants.

OBJECTIVE

To understand vaginal bleeding patterns and the regularity in use of Norplant, and find out the main cause of termination that Norplant users can not bear.

METHODS

A total of 306 menstrual diaries of Norplant users for 5 years were analyzed. The analysis of bleeding patterns was carried out by using the reference period approach and followed the guidelings published by WHO.

RESULTS

The total number of vaginal bleeding days and the number of spotting days in the first reference periods were 36.6 days and 21.5 days, respectively. They were decreased obviously in the third reference period. The number of bleeding days was not obviously changed. The percentage of irregular bleeding was predominent in all of the bleeding patterns, 43.1%-57.6% usually. The percentage of prolonged bleeding was 13.4%-31.0%, secondly. The percentage of "normal" was only 33%. The number of bleeding days and the percentage of prolonged bleeding were more in bleeding termination group than in continuation group. The percentage of irregular bleeding was lower.

CONCLUSIONS

During the initial stage of use of Norplant the total number of vaginal bleeding days was increased, but decreased obviously after 6 months. This change was influenced by the number of spotting days. Irregular bleeding and prolonged bleeding were main types of the disturbance of menstrual cycles after use of Norplant, The main cause of termination was prolonged bleeding.

A prospective cohort study of Norplant use in the immediate postpartum period among asymptomatic HIV-1-positive women was conducted in Bangkok, Thailand. The objectives of this study were to evaluate side effects and menstrual patterns of the Norplant system in this group. A total of 88 asymptomatic HIV-1-positive mothers were recruited for this study. All of them voluntarily accepted the use of the Norplant implant as a contraceptive method immediately postpartum. Their mean age was 24.9 years. Most of them had completed primary school. The follow-up period was 24 weeks. There were eight participants lost from the study because of loss of contact. Irregular bleeding was the most common menstrual pattern in these participants. The major side effects were headache, followed by hair loss. No subject terminated Norplant use during the study period. The Norplant implant appears to be safe and well tolerated in asymptomatic HIV-1-positive parturients when inserted immediately postpartum.

This study attempted to quantify an achievable removal rate of subdermal levonorgestrel implants (SLIs) in an unselected population and develop strategies for increasing continuation. Over 16 months, 1,076 SLIs were inserted in eligible patients from a lower socioeconomic group at high risk for unintended pregnancy. Extensive preinsertion and postinsertion counseling and follow-up care were given. Patients developing problems were counseled and managed conservatively. If a patient requested removal of the Norplant after this process, removal was done. Twenty-two removals occurred due to SLI-related problems, for a rate of 2.04%; no trends based on age or parity were found. The most common reasons for removal were bleeding/irregular menses (31.8%), headaches (18.1%) and hair loss (13.6%). An episode of thrombophlebitis, not thought to be caused by the SLI, led to one removal. Seventy-seven percent of removals occurred in the first six months, with peak rates in the fourth and fifth. Five patients became pregnant inadvertently within six months of removal. An extremely low removal rate and high continuation rate are possible in an inner city clinic population at risk for unintended pregnancy. Acceptance will increase if the SLI can be maintained at least past six months. Extensive counseling, patient support and conservative medical management constitute a successful approach.