Seventy-five women with a mean age of 27.5 years who requested Norplant implants for contraception were studied over a five-year period. The patients kept daily diaries of their vaginal bleeding and coital frequency, and were seen at least every six months at which time their weight was measured. This study examines the impact of Norplant implants use on menstrual regularity, body mass index and coital frequency. Irregular bleeding was most prevalent during the first two years of Norplant implants use and accounted for the primary reason for discontinuation of this method. No increase in Body Mass Index (BMI) was noted in Norplant implants users over the five-year study period. Women with irregular bleeding did not have a higher or lower BMI compared to women with regular bleeding and irregular bleeding patterns did not impact on coital frequency. Over five years, four pregnancies occurred during Norplant implant use. Norplant implants are a highly effective contraceptive method and women using this method should not expect an increase in body weight. Irregular bleeding is most frequent during the first two years of use and menstrual cyclicity resumes in the majority of women by the third year of use and continues to the fifth year of use.

OBJECTIVE

To evaluate endometrial and ovarian effects, and bleeding patterns, among users of Depo-Provera(®), Norplant(®), and Implanon(®).

METHODS

One-hundred and fifty women, who had been using one of these long-acting progestin-only contraceptives (LAPCs) for at least the previous six months, with fifty in each of the groups, were assessed.

RESULTS

All results are mentioned in the following sequence: (1) Depo-Provera(®), (2) Norplant(®), and (3) Implanon(®). Normal bleeding was reported by 0%, 52%, and 8%; amenorrhoea or infrequent bleeding by 68%, 24%, and 72%; and abnormal bleeding by 32%, 24%, and 20%, respectively (p < 0.001). Histological evaluation revealed an atrophic endometrium in 84%, 32%, and 28%, respectively (p < 0.0001); a progestin effect in 16%, 28%, and 62%, respectively (p < 0.0001), and a proliferative pattern in 0%, 40%, and 10%, respectively (p < 0.0001). Endometrial thickness was 3 ± 0.41 mm, 3.62 ± 0.65 mm, and 5.2 ± 0.84 mm, respectively (p < 0.0001). Follicular growth in the ovaries was observed at ultrasound in 12%, 40%, and 72%, respectively (p < 0.001).

CONCLUSIONS

Bleeding patterns, endometrial thickness, ovarian activity, and endometrial histology among Egyptian users of LAPCs differed significantly depending on the nature of the contraceptive.

This paper reports on a study that compared the clinical performance of NORPLANT implants in two separate but similar cohorts: 200 NORPLANT users from 1975 through 1978, when the method was first introduced in the clinic, and 212 users in the same population from March 1982 through December 1983. Two different cohorts of Copper T IUD users were included as controls. Continuation rates, at one and two years of use, were significantly higher in the second group of NORPLANT users (88.1 vs. 60.5 and 76.5 vs. 40.8, respectively). Statistically significant differences between the NORPLANT cohorts were observed in discontinuation due to bleeding, amenorrhea, other medical causes, total medical causes, and personal reasons. No differences in clinical performance of the IUD were observed between the two control groups. The higher continuation rate in the second group of implant users is attributed to greater confidence and experience among the clinic staff between 1982 and 1983, and greater knowledge of and familiarity with the method among those in the target population. The study also shows that the first clinical trials of a new contraceptive method may not provide an accurate picture of that method's ultimate performance.

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.

This study documents the counseling experiences and beliefs about Norplant implants that are held by an ethnically diverse sample of low income clinic patients in the United States. Virtually all implant acceptors, but only about half of those choosing other contraceptives, receive information about the Norplant system during clinic-based counseling. Exposure to group counseling and to a film regarding Norplant implants are associated with high levels of knowledge among acceptors. Several important patterns emerge in comparing the beliefs of patients choosing the Norplant system with those of patients choosing other methods of birth control. Substantial proportions of the latter group adhere to several inaccurate beliefs about the method, associating its use with: long-term health problems, problems for future babies, future fertility problems, infection, and high cost. These outcomes in particular, as well as several others described, should be systematically addressed and reviewed in contraceptive counseling.

In 1991, shortly after Norplant became available in the United States, 678 women who had received the implant from 17 providers in Texas were surveyed. Forty-five percent of these women were under 21 years old. The majority (56%) had tried the implant because they were dissatisfied with their previous contraceptive method. Forty-four percent of the sample indicated that the implant was one of the first contraceptive methods they had used and that they had only recently decided to prevent unplanned pregnancy. The average number of children per woman was 1.2, and one-third of the sample had had at least one abortion. While 37% of the women said they wanted no more children, 63% said they were using the implant as a spacing method. The reasons for choosing the implant and concerns about it varied according to the user's age, educational level and race or ethnic group.

OBJECTIVE

This study was designed to assess users' perceptions of and satisfaction with the Norplant contraceptive implant.

METHODS

A questionnaire was mailed to all women having had Norplant inserted one or two years before the study initiation in seven public out-patient family-planning clinics in the capital area of Finland, of whom 82% responded (n = 207).

RESULTS

Practically all women (97%) had experienced some side-effects and 72% considered at least one of them to be disruptive. Of these side-effects, bleeding irregularities proved most often bothersome during the first 6 months of use, but depression and nervousness were relatively more important reasons for early removal. Regardless of the ubiquity of side-effects, 78% were satisfied with Norplant. High satisfaction was common especially among older users with their second set of capsules. Dissatisfaction with the method was best explained by the experience of unexpected and disruptive side-effects.

CONCLUSIONS

Our results suggest that mental problems related to Norplant use have received too little attention and that satisfaction is highest in carefully selected users among older women.

NORPLANTTM (Laboratorios Gutfol, S.A., Mexico City, Mexico) subdermal implants containing levonorgestrel were accepted by 816 women in a two-phase study initiated in 1975 and augmented in 1978. Through 3 years of first-segment use, acceptors experienced five pregnancies, a cumulative net rate of 0.7 per 100, and a gross pregnancy rate of 1.1 per 100. First-segment continuation at 3 years was at the rate of 44.6 per 100, an annual average of 76 per 100. NORPLANT users experienced irregular menstruation, with high interindividual variation, but with normal average numbers of bleeding days and of bleeding episodes. Hemoglobin levels increased moderately during implant use. The incidence of systolic blood pressure readings above 145 mm Hg or diastolic readings above 95 mm Hg was similar to that observed among users of the TCu 200 intrauterine device enrolled under the same selection criteria in the same clinics between the two phases of the NORPLANT study. Comparative data on pregnancy and other rates are also given for these intrauterine device acceptors.

Premature removal of contraceptive implants (Norplant [levonorgestrel implants], Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a cause of a sizable national medical expenditure in the United States. Understanding the factors that influence the decision to remove the implants and being able to predict which users are likely to elect discontinuation prematurely could provide useful information for counseling patients as they are considering contraceptive implants so that potentially enormous long-term savings could be achieved. This study surveyed 98 women who had Norplant inserted and removed between January 1991 and December 1994. Data were collected from chart review, and when necessary, a questionnaire was used to extract information not found in the chart. The chi-squared statistic and t-test were used to compare demographic variables. All but one subject received comprehensive pre-implant counseling. The main reason given for electively removing the Norplant prematurely was irregular menstrual bleeding (60%). Pre-implant counseling did not influence the decision for removal. These results indicate the importance of clarifying patients' doubts regarding menstrual bleeding irregularities during follow-up visits rather than relying on the information patients received during preimplant counseling.

OBJECTIVE

The purpose of this study was to investigate side effects such as menstrual irregularities, weight gain, and blood pressure changes among adolescent females who had been implanted with Norplant eight or more months.

METHODS

A retrospective chart review was completed on adolescents who received care through an outpatient adolescent gynecology service. Subjects (n = 110) with an average age of 17.2 years were implanted with Norplant between March 1991 and February 1992. The mean length of time since implantation was 12.7 months and 64% were African-American. Data collected included: dates of all medical visits; presence of acne, mood changes, and menstrual patterns following implantation. Measurements of blood pressure and weight were taken at implantation and at all subsequent visits.

RESULTS

Weights for Caucasian females at the last visit were significantly higher than at baseline (P < .02). With regard to the African-American females' weight, significant differences were found between baseline weight and each follow-up visit. Although we could not determine the bleeding patterns in 22% of our study sample, almost 40% of the adolescent females followed reported their bleeding to be light as well as regular and cyclic.

CONCLUSIONS

Weight gain was the most frequently observed side-effect of Norplant in adolescents in this study.

A clinical follow-up study conducted in Shanghai, China confirmed earlier reports that the Norplant implants, Norplant-1 and Norplant-2, are both highly effective with high continuation rates. The implants, however, tend to cause menstrual disturbance, spotting and bleeding. The mean hemoglobin value, however, did not change and the blood pressure remained stable. The report of 8 cases of thrombocytopenia among 301 Norplant-2 users is a source of concern.

Safe, effective and affordable contraceptives have been available for a few decades, yet, in many countries, the struggle for reproductive rights continues. Children, still, are forced to give birth to children in many nations. In most industrialized countries, where contraceptive counselling and abortions have been options, fertility rates have reached all time lows. Effective contraception improves health and well-being as well and may be used for conditions other than birth control. Young girls often initially take oral contraceptives primarily to reduce menstrual pain and blood loss; they also welcome a contraceptive that eliminates menstrual bleeding. Women using oral contraceptives and Norplant experience about 50% reduction in menstrual blood; 90% reduction in blood loss is achieved with the levonorgestrel intrauterine system (Mirena). Teenagers and their parents are often misinformed about the side-effects of oral contraceptives and birth control in general, which may adversely affect compliance. Adequate, user-friendly and supportive information about contraception is necessary to ensure proper use of the pill and other birth control methods. In addition, emergency contraceptives should be easily accessible. The mortality and morbidity of young women would be dramatically reduced by the global use of medical abortion as well. Only a combined effort by policy makers, educators, parents and health-care providers can enhance the reproductive (and future!) health of both young females and males.

This report describes the five-year experience of the first 250 acceptors of NORPLANT implants in Assiut, Egypt. The five-year net continuation rate was 58.6 per 100 women. The five-year net cumulative pregnancy rate was 1.6 per 100 women. About three-fourths of those who continued use of this contraceptive through the fifth year reported having regular cycles. There was definite improvement in the bleeding pattern with time. The five-year net termination rate because of bleeding problems was 17.7 per 100 women. After 5 years of NORPLANT use there was a slight, statistically insignificant increase in weight, systolic and diastolic blood pressures. Of those who used contraceptives after the end of the five-year term of NORPLANT, about one-third opted to have reinsertion of the implants for a second term. About 96% of those who used NORPLANT through the fifth year reported that their experience with the contraceptive had been satisfactory.

BACKGROUND

Women's satisfaction with their chosen method of contraception has seldom been evaluated, especially in the primary care setting. This study compared women who use Norplant with those who use oral contraceptives with regard to patient satisfaction with, and the perceived advantages and disadvantages of, their birth control method.

METHODS

We sent questionnaires to 115 Norplant users and 148 oral contraceptive users. The questionnaire asked for demographic data; a rating of level of satisfaction with their contraceptive; whether they would choose their method again; whether they would recommend their contraceptive to a friend; and what they perceived as its advantages and disadvantages.

RESULTS

Sixty percent of responding Norplant users were satisfied with their method as compared with 72% of oral contraceptive users (P>> .05). Sixty-three percent of Norplant users indicated that they would use their method again, compared with 88% of oral contraceptive users (P < .05). Seventy-four percent of Norplant users said they would recommend their method to a friend as compared with 97% of oral contraceptive users (P < .05). Oral contraceptive users reported significantly less menstrual bleeding and cramping than did Norplant users (P < .05), and Norplant users reported significantly more acne and bleeding irregularities (P < .05).

CONCLUSIONS

In our study, the majority of responding Norplant and oral contraceptive users were satisfied with their current method of contraception. However, Norplant users reported being less willing to use their method again or to recommend it to a friend, as compared with women using oral contraceptives. Norplant users noted more bleeding irregularities, more cramping, and increased acne.

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.

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.

Acceptability and social characteristics of a cohort of Norplant, IUD, pill and depo-med-roxyprogesterone acetate (DMPA) acceptors who were seen at the University of Ilorin Family Planning Clinic over a 10-week period of the pre-introductory clinical trial of Norplant, are compared. Findings indicate that Norplant and DMPA are adopted as an alternative to sterilization by women advanced in reproductive age and of high parity. The pill and IUD are adopted mainly as birth-spacing methods. Women's education, but not previous use of a contraceptive method, influenced the adoption of Norplant. The continuation rate at 12 months, a measure of acceptability, was highest, 93.7 per 100 women, for Norplant and 77.9, 46.7 and 27.7 per 100 women for the IUD, DMPA and the pill, respectively. The need to address the high family size norms in the African subregion is discussed.

Endometrial progesterone receptor plays an important role in determining the biological activity of progestogens in fertility regulation. Studies during the normal menstrual cycle have shown that the concentrations of endometrial progesterone receptor and its mRNA vary in glandular epithelia but remain steady in stromal cells. There is general agreement between progesterone receptor mRNA and protein levels during the normal menstrual cycle. Norplant endometrium had an increase in immunoreactive progesterone receptor concentration but a reduction in progesterone receptor mRNA levels compared with controls. An immunohistochemical study, using the expression of the lysosomal protease cathepsin D as a marker for the functional status of progesterone receptors, failed to confirm the functionality of the receptors in Norplant endometrium. Together, these results suggest that (i) there is a differential sensitivity of glandular and stromal progesterone receptors to steroid regulation during the normal menstrual cycle; (ii) there appears to be a dissociation between the concentrations of progesterone receptor and its mRNA in Norplant endometrium; and (iii) there was significantly more progesterone receptor mRNA and lower plasma oestrogen concentrations in Norplant subjects with amenorrhoea than with endometrial bleeding. The clinical significance of the differences in progesterone receptor mRNA levels and plasma oestrogen concentrations between the amenorrhoea group and the bleeding group requires further investigation.

FSH, LH, estradiol and progesterone were serially assayed during 8 cycles of six subjects using six subdermal implants releasing levonorgestrel (NORPLANT) for a period of 2 to 6 years. All 8 cycles studied had a very low LH peak and a low or nonexistent FSH peak as compared to 8 control cycles. The mean LH peak for NORPLANT users was 33.9 mIU/ml as compared to 142 mIU/ml in the control group; and FSH was 13.0 mIU/ml as compared to 31.3 mIU/ml in controls. A subsequent rise in progesterone was observed in the 8 cycles studied, but the mean mid-luteal levels were significantly lower than in controls (9.0 ng/ml vs. 15.6 ng/ml). No differences were observed in the estradiol curve. Two of the subjects using NORPLANT had a laparotomy performed on days 17 and 20 of the cycle, for surgical sterilization purposes. A distinctive corpus luteum with a stigma was observed. Our results indicate that women under prolonged use of NORPLANT do not have normal endocrine cycles, even though they may ovulate. It is doubtful however, that these ovulatory cycles can be fertile under the abnormal endocrine conditions found in our subjects. In addition to the possible effect of luteal insufficiency, the normal maturation of the oocyte may be impaired.

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.

The main side effect associated with the use of Norplant contraceptive implants is a disruption of the menstrual bleeding pattern. To explore the relationship between bleeding and hormonal changes, we analyzed the estradiol (E2) and progesterone (P) patterns that preceded bleeding episodes or that corresponded to periods of amenorrhea in 103 cycles observed among 82 women using Norplant subdermal implants. Five different bleeding patterns were defined: 'normal' (24-45 day cycles), oligomenorrhea (46-90 day cycles), amenorrhea (over 90 day cycles), irregular/frequent bleeding (less than 25 day cycles), and prolonged bleeding (continuous bleeding/spotting for more than 10 days). All 'normal' cycles were associated with a rise followed by a fall in E2 levels preceding bleeding. In half of the 'normal' cycles (28/54), a rise and fall of P was also observed. The same pattern was found in oligomenorrheic cycles, but only two of 12 cycles had a rise and fall of both E2 and P. None of the subjects with amenorrhea had luteal activity. Six of the nine amenorrheic cycles displayed persistently low E2 levels (below 75 pg/ml). The remaining three had a moderate elevation in E2 levels during the sampling period. Sixty percent of the subjects who showed irregular/frequent bleeding (15/25) had low E2 levels (less than 75 pg/ml), without luteal activity, and bleeding occurred without clear evidence of a further drop in E2 levels. In the remaining 40%, bleeding was preceded by a rise and drop of E2 without luteal activity, with the exception of one women, who exhibited a rise and fall of both E2 and P. Samples were obtained in only three subjects during continuous bleeding. One had low E2 levels, and the remaining two bled continuously, in spite of having E2 levels in the normal range. We conclude that ovarian hormones continue to influence endometrial shedding during the use of Norplant contraceptive implants.

A microtiter plate enzyme immunoassay (EIA) is reported for the measurement of levonorgestrel (LNG) in serum and urine samples of human and non-human primates, and the results are compared to data obtained by radioimmunoassay (RIA). Rabbit polyclonal antibodies were raised against the bovine serum albumin conjugate of the 3-O-carboxymethyl oxime (CMO) derivative of LNG. The enzyme label was produced by the conjugation of horseradish peroxidase to LNG at the 3-position by the same CMO bridge used for the immunogen. The assay requires 2.5 hours to perform using 2.2-azino-di-(3-ethylbenzthiazoline sulfonic acid) diammonium salt as the chromogenic substrate. Serum (100 microliters) is extracted with petroleum ether prior to assay, whereas urine samples (25 microliters) are diluted and measured directly. The sensitivity of the assay is 0.25 pg/well with a 50% displacement of label at 7.5-9.5 pg and a linear response through 250 pg/well. Minimum levels of 8.7 and 10.0 pg/ml can be detected in serum and urine samples, respectively. Changes in serum LNG concentrations were measured in women and non-human primates following LNG implantation or injection. In the non-human primate study, serum LNG concentrations began to rise rapidly following i.m. injection of LNG, with peak levels occurring on days 3 to 5, then decreasing to approximately 25-35% of peak levels for the duration of the study. Circulating concentrations of 1.86 +/- 0.18 ng/ml LNG were reached in women the first week post-insertion of Norplant implants and decreased by 50% at 7-10 days, 75% after 14-21 days, followed by a steady decrease during the next 60-70 days to constant low levels that exhibited a high individual variation. Correlation coefficients of EIA and RIA results were 0.988 for human serum, 0.926 for human urine, and 0.972 for non-human primate serum.