Norplant Users Research Articles

Endothelin and menstruation.

Endothelin (ET) and its mRNA are present in human endometrium. Its expression varies across the menstrual cycle, reaching maximal levels in the pre-menstrual phase. Human endometrial epithelial cells are the major in-vitro source of ET, and its release is affected by the stage of the menstrual cycle from which the endometrium is taken and by the cytokines transforming growth factor-beta 1 and interleukin-1 alpha. The cyclical variation in both ET mRNA and protein expression across the normal menstrual cycle, and the differences observed in abnormal uterine bleeding (specifically reduced immuno-reactivity in luminal and glandular epithelium in the endometrium of Norplant users), are consistent with a role for ET in the control of menstrual bleeding. The role of epithelial cell ET is not yet understood. Whether this source of ET is important in endometrial regeneration and repair following menstruation or in vaso-constriction to cease menstrual bleeding remains to be determined.

Endometrial lymphomyeloid cells in abnormal uterine bleeding due to levonorgestrel (Norplant).

Endometrial lymphomyeloid cell subsets were evaluated in samples from normal women and from women with abnormal uterine bleeding due to subcutaneous levonorgestrel implants (Norplant) or an intrauterine device (IUD). The frequency of CD3(+), CD68(+), CD43(+) and endometrial granulated lymphoid cells was evaluated by immunohistochemical or phloxine-tartrazine staining of formalin-fixed paraffin-embedded samples. In normal women, cyclic variation in lymphomyeloid subsets was seen. In women using Norplant for contraception, the frequency of CD3(+), CD68(+) and CD43(+) cells was dramatically decreased, compatible with endometrial atrophy. When Norplant users with abnormal bleeding were compared to women without bleeding, however, the number of CD68(+) cells was significantly increased and the number of CD3(+) and CD43(+) cells was preserved, contrary to the hypothesis that this group would show a greater degree of atrophy and hence, tissue fragility. A similar pattern was seen in a preliminary study of women with bleeding associated with use of copper-only IUD contraception, and in samples taken from late secretory and menstrual biopsies from normal cycling women. Whether these changes in endometrial lymphomyeloid cells represent a result of bleeding arising from a common mechanism or rather cause the uterine bleeding is discussed.

Immunohistochemical detection of cathepsin D in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle.

A previous report has shown that progesterone up-regulates cathepsin D expression in human endometrial cell culture. In women using the levonorgestrel-releasing Implant Norplant, the plasma levonorgestrel and immunoreactive endometrial progesterone receptor concentrations are elevated. However, the functional status of these receptors is not known. This study used endometrial cathepsin D expression both as an indirect marker for the functional status of endometrial progesterone receptors, and to identify the cell types that express cathepsin D. The results show that cathepsin D is primarily found in glandular epithelia and luminal epithelia in control and Norplant endometria. There is no significant difference in cathepsin D expression between the control and Norplant endometria, between the various stages of the menstrual cycle, or between Norplant users with varying degrees of breakthrough bleeding. Cathepsin D is also detected in cells scattered in the stroma in both control and Norplant endometria. The majority of these cells are macrophages. These data indicate that there is no evidence for progesterone regulation of cathepsin D in the human endometrium. Cathepsin D thus cannot be used as a marker for the functional status of progesterone receptors found in the Norplant-exposed endometrium.

Using OCs to Treat Irregular Bleeding in Norplant Users

Irregular and frequent bleeding is the most common reason women request removal of Norplant contraceptive implants. Such bleeding occurs in 60% to 70% of new users but typically decreases after the first year. This study randomized 150 Norplant users with prolonged or frequent bleeding …

Immunolocalization of endothelin and neutral endopeptidase in the endometrium of users of subdermally implanted levonorgestrel (Norplant).

Subdermally implanted slow-release levonorgestrel (Norplant), a widely used effective contraceptive, has a high rate of discontinuation due to unacceptable menstrual bleeding disturbances. Endothelin (ET), a potent vasoconstrictor, varies across the menstrual cycle in normal endometrium. It has been proposed that ET has a potential paracrine role in the regulation of uterine blood flow. Neutral endopeptidase (NEP), a membrane-bound ecto-enzyme, can inactivate ET and is localized principally in endometrial stroma. We have compared the immuno-localization of ET and NEP in endometrial biopsies from Indonesian women using Norplant with normal controls. Differences were observed in the glandular and luminal epithelium of Norplant-treated subjects, where ET immunostaining was low while NEP immunoreactivity was increased. The latter may represent a local increase in enzyme activity, potentially explaining the reduced ET immunoreactivity. There was no correlation of ET immuno-reactivity with the duration of implant use or total number of bleeding days. The marked differences in the ET immunostaining pattern in Norplant users, with their increased risk of abnormal uterine bleeding, suggest that ET may be important in controlling menstrual bleeding. Whether endometrial epithelial cell ET has a role as a mitogen in endometrial repair and regeneration, or as a vasoconstrictor important in the cessation of bleeding following menstruation, remains to be determined.

Reduced endothelial cell migratory signal production by endometrial explants from women using Norplant contraception

Bleeding problems can be one of the major reasons for women to discontinue the use of hormonal contraceptives. Causes of endometrial bleeding can include disturbances in endometrial regeneration and angiogenesis. Endothelial cells migrate and proliferate rapidly as part of the angiogenic process under the influence of appropriate stimuli. The aim of this study is to investigate the production of endothelial cell migratory signals by endometrial explants from women receiving Norplant and to compare it to that of those with a normal menstrual cycle. The subjects were selected from Norplant users with an exposure of 3-9 months. The endothelial cell migratory signal production was assayed using the Folkman method (1989), modified by Rogers (1992). Blood serum concentrations of oestradiol, progesterone and sex hormone binding globulin were monitored for 2 weeks prior to endometrial biopsy. Endothelial cell migration toward endometrial explants of 30 women as control and 46 Norplant acceptors was assayed. The results showed that endothelial cell migratory activity toward endometrial explants from the control group was significantly higher than toward those from Norplant acceptors (z = 3.89, P < 0.001). There were no differences between endometrial endothelial cell migratory activities in Norplant acceptors with bleeding or without bleeding problems.

Birth control counseling for HIV seropositive pregnant women

Testing for HIV antibody at the antenatal clinic in Siriraj Hospital started on 1 July 1991. It was found that the percentage of HIV seropositive pregnant women rapidly increased from 1.2% in 1992 to 1.9% in 1993. During those 2 years, 487 seropositive women were admitted for delivery or abortion; 23.8% were adolescents and 47.0%, young adults. Prevention of HIV transmission from mother-to-baby was birth control; 95 women (19.5%) chose to abort their pregnancy. After termination of all pregnancies by abortion or delivery, 83% requested sterilization, 12.9% accepted Norplant, 1.8% the pill and only 2.3% refused anything at all. Condoms were used regularly for prevention of HIV infection by 29.4% of men although Thai men generally do not accept them for birth control. Seropositive Norplant users had more bleeding than general Norplant users but treatments were the same.

Exploring the aetiology of increased endometrial bleeding in norplant users: The role of local factor?

Exploring the aetiology of increased endometrial bleeding in norplant users: The role of local factor?

Which teen mothers choose Norplant?

The objective of this study was to determine if there are sociodemographic differences between adolescent mothers who choose to use Norplant after delivery and those who do not. We hypothesized that those adolescent mothers who are at highest risk for repeat adolescent pregnancy are least likely to select Norplant as a postpartum contraceptive. We prospectively compared the prevalence of epidemiologic risk factors for repeat adolescent pregnancy in a group of 187 consecutively delivered 13-18-year-olds who were enrolled in a comprehensive, multidisciplinary, adolescent-oriented maternity program. The study subjects were interviewed at delivery; 100 subsequently had a Norplant inserted (Norplant users). Student's t-tests and chi-square analyses were used to compare Norplant users and refusers. We found no statistically significant differences between Norplant users and refusers with regard to: age, race, Medicaid, or marital or school status. Compared to Norplant refusers, Norplant users were less likely to be primiparous (79% compared to 90%; p = .04) and more likely to have poor school grades (20% compared to 7%; p = .001). Norplant users were more likely to state that they had had trouble remembering to use contraceptives in the past (32% compared to 14%; p = .005). These data do not support the study hypothesis and are encouraging because they suggest that Norplant may reduce repeat pregnancy among adolescent parents.

Compliance with return appointments for reproductive health care among adolescent Norplant users

Norplant's long duration of action may result in users being less motivated than non-users to return for reproductive health care appointments. This study determined compliance with scheduled return appointments among adolescents using Norplant and those using other methods of contraception. We retrospectively reviewed the records of all teenagers (age < or = 18 years) who received Norplant between June 1991 and August 1993, as well as those of a comparison group of adolescents, matched for age and race, using other methods of contraception. Subjects receiving Norplant were given appointments for a two-week and an annual examination. Comparison subjects were given only an appointment for an annual examination. Norplant users not returning within 5 weeks or any subject not presenting within 12 months for an annual examination, were considered non-compliant. Eighty-eight adolescents received Norplant during the study period and the records of 85 were available for review. Only 48 of the 85 Norplant users returned for scheduled two-week check-up, while 18 of 43 subjects who had Norplant at least 12 months were compliant with annual examinations. The compliance rate with annual examinations among the 89 subjects not using Norplant was 38%, not dissimilar from that of the Norplant group. These data demonstrate that compliance with return appointments for reproductive health care among adolescent Norplant users is poor but not significantly worse than that of non-users of Norplant. Strategies promoting the benefits of return visits need to be improved for adolescents receiving contraception.

Serious adverse events in norplant users reported to the food and drug administration's medwatch spontaneous reporting system

To describe serious adverse events in Norplant users from reports submitted to the Food and Drug Administration's (FDA) MedWatch Spontaneous Reporting System. Reports of certain serious adverse events in Norplant users in the United States from February 1991 to December 1993 were reviewed and analyzed. From the introduction of Norplant in the United States in February 1991 to December 1993, the FDA received reports of 24 women hospitalized for infections at the insertion site, 14 hospitalized or disabled because of difficulties removing the capsules, 14 hospitalized for stroke, three for thrombotic thrombocytopenia purpura, six for thrombocytopenia, and 39 for pseudotumor cerebri. The comparison of reported rates with expected rates and the relationship of some of these disorders with oral contraceptives raises the suspicion of a causal association with Norplant. The FDA has received reports of hospitalization or disability for infections, capsule removal difficulties, stroke, thrombotic thrombocytopenia purpura, thrombocytopenia, and pseudotumor cerebri in Norplant users. Health care professionals need to be trained in Norplant insertion and removal to ensure the proper technique. Studies are needed to determine if stroke, thrombocytopenia, and pseudotumor cerebri are causally related to Norplant use.

Use of levonorgestrel implants versus oral contraceptives in adolescence: A case-control study

OBJECTIVE: We compared continuation rates, effectiveness, satisfaction with method, side effects, and condom practices among adolescents using levonorgestrel implants (Norplant, Wyeth-Ayerst Laboratories, Philadelphia) as compared with oral contraceptives. STUDY DESIGN: We conducted a case-control study comparing 94 adolescents ≤ 18 years odl who received Norplant between March 1, 1992, and Nov. 1, 1993 (cases), with 94 age-matched controls who selected oral contraceptives during this same time period. By use of a structured questionnaire, information was obtained on pregnancy status, duration of use, patient satisfaction, side effects, and condom practices 6 months after initiation. Objective measures included weight on Norplant and oral contraceptive users and hematocrit on implant patients. RESULTS: Forty (43%) oral contraceptive patients compared with no Norplant patients discontinued their selected method before the 6-month interview ( p = 0.00). Six patients prescribed oral contraceptives became pregnant. Ninety-three percent of Norplant users expressed overall satisfaction despite experiencing menstrual irregulatiry and cramping, amenorrhea, nervousness, abnormal hair growth or loss, rashes, and an increase in appetite more often than oral contraceptives users. Although Norplant patients also reported an increase in the duration of menstrual flow and number of days of spotting more often than oral contraceptive users, evaluation of hematocrits in these patients demonstrated a significant increase over the 6-month period ( p = 0.00). Assessment of condom practices since initiation demonstrated that Norplant patients used condoms less often than oral contraceptive users ( p - 0.00). CONCLUSION: Use of levonorgestrel implants may cause more side effects than oral contraceptives in the early months after initiation but provide superior protection against unintended pregnancy. We concluded that Norplant is a reasonable alternative for adolescents, especially when compliance is an issue.

Physicians' experience with Norplant implantable contraceptives in Finland.

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.

Problems and prospects of implants as a contraceptive method in Bangladesh

To assess the quality of Norplant service provision in Bangladesh, 1327 acceptors (half the country's total number of acceptors) from seven centers were selected for interviews in late 1991; a total of 1151 were successfully interviewed. The mean age of acceptors was 28.6 years and the mean number of living children was 3.1. Two-thirds did not desire any additional children. Past Norplant users were the most frequently cited (61%) source of information about the method; 86% selected the implants because of their long duration of action. Acceptors received thorough pre-insertion counseling about side effects and two-thirds adhered to the recommended follow-up appointment schedule. The method continuation rate was 99% at one month, 97% at six months, 92% at one year, 75% at two years, and 61% at three years. There was a significant positive correlation between method retention and user satisfaction. A third of acceptors had requested Norplant removal by the time of interview, primarily due to menstrual disorders, and 90% of these women were able to have the implants removed--with no provider opposition--at the center where they were inserted. 88% of acceptors were highly satisfied or satisfied with the services received; 10% were somewhat satisfied and 2% were dissatisfied. Clients who were visited in the home in addition to attending the clinic expressed higher rates of satisfaction. Although these results indicate that Norplant acceptors in Bangladesh are generally receiving good quality care, the findings that some women faced obstacles in accessing method removal and many of those who had the implants removed were not provided with an alternate contraceptive method merit consideration.

The Use of Levonorgestrel Implants (Norplant) for Contraception in Adolescent Mothers

Although levonorgestrel implants (Norplant) would appear to be a good contraceptive option for adolescent mothers, there is little information about the use of Norplant in this population. We studied 100 postpartum adolescents who chose a contraceptive method at an urban teaching hospital between September 1991 and July 1992. Structured interviews were conducted and medical records were reviewed soon after delivery and at a mean (+/- SD) of 15.5 +/- 2.9 months post partum. Forty-eight of the adolescent mothers chose Norplant, 50 chose oral contraceptives, and 2 (not further studied) chose barrier methods of contraception. The factors significantly associated with the choice of Norplant were older age (16.7 years among those who chose Norplant, vs. 16.2 years among those who chose oral contraceptives), multiparity (24 subjects vs. 6 subjects), and previous use of oral contraceptives (34 subjects vs. 21 subjects). During follow-up, there were no differences between the Norplant group and the oral-contraceptive group in the frequency of clinic visits (an average of 2.3 visits per subject in each group), failure to return after the postpartum visit (9 subjects vs. 11 subjects), or the incidence of sexually transmitted diseases (42 percent vs. 36 percent). At follow-up, 95 percent of the subjects in the Norplant group and 33 percent of those in the oral-contraceptive group were still using the method they had chosen (P < 0.001). During the first postpartum year 1 subject in the Norplant group and 19 in the oral-contraceptive group became pregnant (P < 0.001). Norplant users did not differ from all other adolescents studied with regard to sexual activity or condom use. The selection of Norplant by adolescent mothers as a method of contraception is associated with higher rates of continued use and lower rates of new pregnancy than the selection of oral contraceptives and does not affect the use of health care services, sexual activity, condom use, or the rate of sexually transmitted diseases.

A Prospective Study of Adolescents Who Choose Among Levonorgestrel Implant (Norplant), Medroxyprogesterone Acetate (Depo-Provera), or the Combined Oral Contraceptive Pill as Contraception

Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP). Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white. Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP. The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.

Condom use by Norplant users at risk for sexually transmitted diseases.

Norplant is highly effective for long-term pregnancy prevention. Norplant users might not use condoms, and they may acquire human immunodeficiency virus (HIV) and other sexually transmitted diseases as a consequence. The goal of this study was to assess condom use among Norplant users at risk for sexually transmitted diseases. Telephone interviews were conducted with 177 sexually active Norplant users to measure risk for sexually transmitted disease and condom use. According to the measures used in this study, 42% of the study subjects were at risk for sexually transmitted disease and 38% of those at highest risk did not use condoms. Intervention to protect Norplant users from sexually transmitted disease is indicated.

Education and counseling for Norplant users.

Because Norplant provides effective contraception for 5 years, it is an excellent choice for many women. However, it has side effects that have prompted early removal in a significant number of women. Nurses who educate and counsel women about Norplant before insertion and provide support and management of side effects afterward can increase user satisfaction and long-term continuation.

Knowledge and attitudes of norplant among adolescent females

Study Objective: To evaluate adolescent females' knowledge and attitudes of the side effects of the Norplant System.Design: A prospective case control study was employed using multivariate statistical analyses.Setting: An outpatient specialty adolescent gynecology clinic in a rural southern state.Participants: Of the 213 females approached, 206 agreed to participate by providing written informed consent. However, data from only 192 of these 206 adolescents were subjected to statistical tests because data was missing from the other 14 subjects.Main Outcome Measures: Knowledge and attitudes of concern for visibility, general safety, skin discoloration, and irregular menses were used as outcome variables. Demographic and related variables such as sexual activity and race were employed as indicator variables.Results: Logistic regression analyses were conducted on each outcome variable after first completing bivariate analyses. Multivariate analyses found improved knowledge was significantly associated with those adolescents currently using Norplant, sexual activity, and positive history of pregnancy. This same analytic plan found that visibility concerns were most likely associated with higher income and sexually active female Norplant users; similar findings were found for general safety and irregular menses where both were associated with current Norplant use; and skin discoloration was only associated with prior pregnancy history.Conclusions: Our data suggest that knowledge among the general adolescent female population is poor. However, the adolescents who currently employ this contraceptive method possessed better knowledge and were more concerned with possible side effects. Thus, counseling detailing potential side effects and cosmetic changes should be given at each follow-up visit.

Factors influencing attitudes about Norplant contraceptive subdermal implant.

Improving and widening Norplant use requires an understanding of users' complaints. A study was conducted of factors influencing user attitudes, with the goal of improving service delivery. The study used a questionnaire consisting of 26 queries. An interview pertaining to the attitude of 610 users about Norplant implanted 5 years ago or more, was carried out in villages surrounding Semarang City, Central Java, Indonesia. Of the 610 Norplant users, 84.59% expressed positive attitudes; 13.93% were neutral and 1.48% expressed negative attitudes. Factors significantly affecting user acceptance were: low socio-economic status; low education; activities in social groups; young age; more experience and knowledge about Norplant; few or no complaints. Acceptance of Norplant by villagers, depends on the socio-demographic status and the complaints of users. This information can be used as the basis for improving the service delivery system.