Norplant contraceptive implants: rods versus capsules

Norplant contraceptive implants are silastic implants containing levonorgestrel. When placed subcutaneously in the medial aspect of the upper arm, they release low levels of levonorgestrel in a constant manner over an extended period of time. Comparative studies of two silastic rods versus six capsules containing levonorgestrel were studied in 250 subjects for 4,464 months of use. Only one pregnancy occurred during the study. Side effect patterns were similar in both groups; the major side effect being irregular uterine bleeding. The bleeding, however, was well tolerated by subjects in both groups and discontinuation rate was very low. The two-rod system offers the advantages of easier insertion technique and shorter insertion time as well as ease of removal as compared to the six-capsule system. Norplant contraceptive implants offer a highly effective means of contraception which is particularly suited for women who are concerned about failure and compliance with oral contraceptives. This type of contraception should become well accepted, not only in underdeveloped countries, but in developed countries as well.     

Pregnancy after removal of Norplant implants contraceptive

Many concerns have been expressed regarding the introduction of a new contraceptive method into family planning programmes. One of the concerns is the return of fertility after discontinuing the method. To evaluate the subsequent fertility status of the Indonesian women after removal of Norplant, a prospective longitudinal study was undertaken in Klinik Radeb Saleh, Jakarta. Fifty-one women whose Norplant were removed because of their wish to become pregnant were followed-up for a period of two years or until pregnancy occurred, whichever was earlier. Two groups of women who had Lippes C IUD removed or discontinued the use of DMPA for planning pregnancy served as control and were followed-up for equal length of time. The cumulative conception rate for ex-Norplant users, ex-IUD users and ex-DMPA users at one year was 76.5, 74.7 and 70.2 per 100 women, respectively. There was no significant difference between the groups (p greater than 0.05). The present study, along with other studies, indicate that the prolonged use of Norplant do not impair the return of fertility.     

Long-term experience with Norplant contraceptive implants in Finland

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 124 women. During five years of use no accidental pregnancy occurred. The first year continuation rate was 90% and the five-year continuation rate was 54%, including terminations for wish to become pregnant. The medically relevant continuation rate was 68% after five years. Menstrual irregularities were the most frequent reason for termination, but only in the first two years. 70% of the terminations for that reason occurred during the first two years. Terminations for other steroid-related reasons were infrequent. The follow-up will continue up to the end of the seventh year. Seven of seventeen women who requested removal of the implants because they wanted to become pregnant conceived during the first two cycles and only three were not pregnant one year after removal.     

Androgen levels in women using Norplant implants

Plasma concentrations of sex hormone binding globulin (SHBG), testosterone, free testosterone, androstenedione (A4) and levonorgestrel were studied in 17 women before and during use of two levonorgestrel covered rods resulting in identical plasma concentrations of levonorgestrel as Norplant implants. There was a highly significant decrease in SHBG during treatment. Total testosterone and A4 also decreased significantly. Free testosterone remained unchanged. Diurnal variations were found to occur for A4, total and free testosterone, but not for SHBG or levonorgestrel. Moreover, plasma concentrations of testosterone, free testosterone, levonorgestrel and SHBG were measured in a second group of 88 women participating in a clinical study on Norplant implants, who at the one year follow-up visit either denied or claimed to have developed increased facial acne during treatment. There was no difference regarding SHBG, total testosterone, free testosterone or levonorgestrel between the groups of women with and without facial acne. However, the women in the group noticing increased acne during treatment, reported significantly more often to have had acne before treatment compared to the women who did not notice increased acne during treatment. It is concluded that treatment with Norplant implants does not result in increasing plasma levels of androgens.     

Effect of levonorgestrel contraceptive implants, Norplant, on blood coagulation

A longitudinal study of coagulation parameters was carried out on 47 women using the levonorgestrel subdermal implants, NORPLANT. The study comprised measurement of platelet count, prothrombin time, thrombin time, partial thromboplastin time with kaolin, clotting factors I, II, V and VI through XIII, plasminogen, antithrombin III (AT III), alpha 1 antitrypsin, alpha 2 macroglobulin and fibrinogen degradation products. The tests were done at admission and after one, three and six months of NORPLANT use. Parallel and similar studies were done on two groups of oral contraceptive users; the first group used a pill containing 1 mg norethisterone and 50 micrograms mestranol, and the second a pill consisting of 150 micrograms levonorgestrel and 30 micrograms ethinylestradiol. Results from this ongoing study have indicated that women using NORPLANT implants evidenced lack of effects on most of the parameters tested except for factor VII activity which was increased and AT III concentration which was decreased after six months of use. The combined pill users evidenced marked changes in the platelet count, the screening tests and in most of the coagulation-promoting factors; the changes were apparent after three months of use and became more pronounced after six months. The results demonstrate, with marked contrast, that the implants had less pronounced effects on the blood coagulation system than did the combined pills used in this study.     

Health and growth of infants breastfed by Norplant contraceptive implants users: a six-year follow-up study

The objective of the study was to evaluate safety to infants whose mothers used Norplant levonorgestrel implants during breastfeeding. A nonrandomized clinical trial design was used. Participants were 220 and 222 healthy breastfed infants of mothers initiating use of Norplant or T-Cu IUD, respectively, at 55 days to 60 days postpartum. Infants were followed from birth through age 6 years. Breastfeeding pattern, infant growth, and disease events were recorded monthly in the first year, three-monthly in the second, and annually thereafter. Most mothers continued use of Norplant (96.4%) and T-Cu (94.1%) during lactation, and 2140 months of infant exposure to levonorgestrel were accumulated. Breastfeeding pattern and infants growth, from admission through age 6 years, were similar in both groups. In the first year, breastfed infants in the Norplant group had higher incidence rates (p < 0.05) of mild episodes of respiratory infections (adjusted RR 1.17, CI 1.08-1.27), skin conditions (adjusted RR 1.46, CI 1.20-1.79), and eye infections (unadjusted RR 1.49, CI 1.03-2.18) than the control group. Later on, a higher proportion of infants in the T-Cu group showed neurological conditions. Although breastfeeding patterns and infant growth is not affected by Norplant use during lactation, the effect on infants' health of steroidal contraception should be further evaluated.     

Transition from Norplant to Jadelle in a clinic with extensive experience providing contraceptive implants

OBJECTIVE: The purpose of this study was to understand the transition process from providing Norplant, the six-capsule first contraceptive implant system, to providing Jadelle, the two-rod second-generation system, in a clinical setting with extensive experience providing Norplant implants. MATERIALS AND METHODS: Two hundred forty-nine women requesting contraceptive implants from the PROFAMILIA clinic (Santo Domingo, Dominican Republic) were provided with information regarding the differences and similarities between the two implant systems being studied, including the easier insertion and removal procedures and the possible shorter use life associated with Jadelle. A questionnaire evaluating their preference and the reason why they chose either system was provided. The health care providers' opinions about the two systems were also studied. RESULTS: Fifty-three percent of the women preferred Jadelle over Norplant. The main reason behind their preference for Jadelle was its reduced number of implants with easier insertion and removal and less visibility in the arm, whereas that for Norplant was greater familiarity. Providers overwhelmingly preferred Jadelle. A 1-h presentation was sufficient training for providers experienced with Norplant. None had any problem with the management of Jadelle. CONCLUSION: The inclusion of Jadelle in a clinic with extensive experience with Norplant was easy and uneventful, but both methods should be available during a transition period of several months while confidence in the new method is being acquired by the community.     

Post-marketing surveillance of Norplant contraceptive implants: I. Contraceptive efficacy and reproductive health

The subject of this study to examine the safety and contraceptive efficacy of Norplant, we undertook a 5-year study of follow-up of women initiating use of Norplant, intrauterine device (IUD) or sterilization in eight developing countries. Women attending family clinics were enrolled if they consented and were medically eligible to use Norplant, IUD, or female sterilization. Women who chose to initiate use of IUDs or surgical sterilization served as controls and were frequency matched in 5-year age-bands with women who chose to use Norplant. At admission women had a physical examination, and their medical histories, demographic, and socio-economic characteristics were recorded. Follow-up visits were scheduled in the first 6 weeks after admission and semi-annually thereafter for 5 years irrespective of change of contraceptive method. Incidence rate ratios of health events were estimated for initial and current contraceptive method use. This paper reports reproductive health events and contraceptive efficacy. Altogether, 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of surgical sterilization were admitted. Their mean ages at initiation were 28.5, 28.5, and 29.6 years, respectively. More than 99% were married or cohabiting, and parous. Five-year follow-up was completed by 94.6% of the women. By the end of 5 years, the mean duration of first segment use per initiator was 4.16 years for Norplant, 4.10 years for IUDs, and 4.96 years for sterilization accounting for 39,337 woman-years for Norplant, 31,915 for IUDs, and 7,071 for sterilization. The study accumulated 78,323 woman-years of observation. Pearl pregnancy rates for Norplant, copper IUDs and female sterilization were 0.27, 0.88, and 0.17 per 100 woman-years, respectively. Users of Norplant, copper IUDs, and sterilization had rates of ectopic pregnancy of 0.30, 0.68, and 0.13 per 1,000 woman-years, respectively. Major health events related to the reproductive system were rare. Rates of acute PID were significantly lower among Norplant users than IUD users (p = 0.004). The rate of ovarian enlargement was significantly higher in Norplant users than controls (p <0.001), but not rates of hospitalization for this condition. Vaginitis and vaginal discharge, and low abdominal pain were significantly less frequent in Norplant users than in the other groups. Bleeding disturbances were more frequent among Norplant users than controls but not anemia. The study confirms the high contraceptive efficacy of Norplant, copper IUDs, and female sterilization. The incidence rates of major reproductive health problems were low. There was no significant excess of serious reproductive morbidity among users of Norplant compared to users of IUDs and sterilization.     

Effect of subdermal levonorgestrel contraceptive implants, Norplant, on liver functions

Forty-seven normal health women were studied longitudinally for changes in liver functions during the use of the levonorgestrel contraceptive implant system, NORPLANT. Samples were collected before insertion of the implants and after one, three and six months of use. The enzymes studied were the transaminases (SGOT and SGPT), alkaline phosphatase and gamma-glutamyl transferase. Serum bilirubin and bile acid levels were also measured. The protein synthetic function of the liver was tested by estimation of total proteins, albumin, transferrin, hemopexin, ceruloplasmin and haptoglobin. The three main immunoglobulins, G, M and A, were also measured. There were no significant changes in the liver enzymes after NORPLANT use. Serum bilirubin and bile acid concentrations showed rises in the first month of use which ameliorated in subsequent months. Serum albumin was transiently increased during the first and third months. Ceruloplasmin decreased significantly at the sixth month. The concentrations of total serum proteins and the other individual proteins showed no significant change. The results point to safety of NORPLANT implant use, as regards hepatic functions.     

Effect of subdermal levonorgestrel contraceptive implants, Norplant, on serum lipids

Forty-seven normal non-smoking parous women were enrolled in a longitudinal study of the effect of use of the subdermal levonorgestrel implants, NORPLANT, on serum lipids. Blood samples were collected after an overnight fast before insertion and after three, six, nine and twelve months of use. The high-density lipoprotein cholesterol showed no change until the twelfth month when it was increased (P less than .05). Total cholesterol, low-density lipoprotein cholesterol and triglyceride levels decreased significantly during NORPLANT use.     

A detailed analysis of menstrual blood loss in women using Norplant and Nestorone progestogen-only contraceptive implants or vaginal rings

Changes to the pattern of menstrual bleeding are almost universal in women using progestogen-only methods of contraception, and are an important cause of discontinuation of these methods. The present study was designed to explore the changes in menstrual bleeding patterns and objectively measure menstrual blood loss (MBL) in 110 women before and during one year of use of 4 different progestogen-only contraceptives: Norplant subdermal levonorgestrel implants; Nestorone progestogen 4-cm or 6-cm implants nominally delivering 100 microg or 150 microg daily; or a vaginal ring (CVR) delivering 100 microg of Nestorone (NES) daily (CVR users were limited to only 6 months of use). Groups could not be directly compared because of the differences in numbers of subjects and durations of treatment. The total MBL during each of the three 8-week collection periods during treatment decreased significantly in each group compared to the total blood loss in the two control cycles (greater than 50% decrease in all groups during the first 6 months), although the differences between individual women at the extremes remained considerable. The highest blood loss measured on any single day during the treatment collection periods was significantly reduced (p <0.001) in users of all four devices in all three collection periods compared to the control period (CVR users did not have a 3rd collection period). The Nestorone-releasing CVR was associated with an 88% reduction in mean MBL and a high incidence of amenorrhea at 6 months. There was considerable variation in percentage reduction in total blood loss at 6 and 12 months between individual women ranging from 100% (women with amenorrhea) to a small minority experiencing an increase compared with control cycles. The increases in measured blood loss during treatment were almost entirely in women with light bleeding in the control period and were related to prolonged episodes of light bleeding rather than heavy bleeding. Women contemplating use of a progestogen-only contraceptive method need to be counseled about alterations to the menstrual cycle but can be reassured that total blood loss will usually be much less than with normal cycles.     

Effect of Implanon and Norplant subdermal contraceptive implants on serum lipids--a randomized comparative study

The objective of this study was to assess the possible differences in effects of Implanon (etonogestrel 68 mg, single-rod) and Norplant (levonorgestrel 36 mg, six capsules) implants on serum lipids over 2 years of use. In this 2-year open randomized study of 80 implant acceptors, selected serum lipids were tested before implant insertion and at 6, 12 and 24 months after implant insertion. The lipid parameters evaluated were: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, apolipoprotein A-I and apolipoprotein B. During the 2 years, the serum lipid pattern in the Implanon users was not significantly different from that of the Norplant users. There was slight decrease in HDL-C levels in both the groups but there were no significant changes in the HDL/TC ratio and the HDL/LDL ratio. Although it was statistically significant, the magnitude of decrease in HDL-C from preinsertion levels in Implanon users was only 5.8% at the end of 2 years.     

Post-marketing surveillance of Norplant((R)) contraceptive implants: II. Non-reproductive health(1)

This controlled cohort study aimed to evaluate the safety and efficacy of Norplant contraceptive implants in developing countries. Women initiating Norplant implants were index subjects and women initiating intrauterine devices (IUDs) or surgical sterilization were controls. Consenting participants at 32 clinics in eight developing countries were admitted and followed-up every 6 months for 5 years. Major and less serious health events during follow-up were recorded. Incidence rate ratios of health events adjusted for clinic were estimated for initial and current method use. This paper reports non-reproductive health events. The study involved 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of sterilization. Five years follow-up was completed for 94.6% of the women. The study accumulated 78,323 woman-years of observation. The initial method chosen accounted for 84.4% or more of observed woman-years in users of Norplant, IUD, or sterilization. Twenty-two of the recorded 34 deaths were due to accidents, suicide or homicide. Few deaths or major health events were due to cancer or acute cardiovascular diseases and were not associated with the contraceptive method used. The incidence rates of major health events were low and with two exceptions, there was no significant excess risk of serious morbidity for Norplant users compared with controls; among Norplant initiators gallbladder disease occurred at an incidence rate of 1.5 per 1,000 woman-years and was weakly associated with use of Norplant (rate ratio 1.52 [95% C.I. 1.02, 2.27]). For current Norplant users compared to controls, the rate ratio of a combined variable of hypertension and borderline hypertension was significantly elevated (1.81, [1.12, 2.92]). The occurrence of less serious health events was also low and several of them were significantly more often reported among Norplant users. Headache-migraine, weight gain, mood disturbances, pruritus, eczema, and acne had incidence rates among Norplant users of 11.5, 4.5, 2.8, 1.5, 1.4, and 0.9 per 1,000 woman-years, respectively, and were significantly higher than in controls. Respiratory health problems, nonspecific symptoms, and several ill-defined conditions were also significantly more often reported for Norplant users, but some of the excess incidence may be attributable to reporting and detection bias. The study confirms the safety with respect to serious disease of Norplant, IUDs, and sterilization.     

Serum lipids in Norplant implants users: a cross-sectional study

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).     

Insertion and removal of Norplant contraceptive implants by physicians and nonphysicians in an Indonesian clinic

This paper reports on a study in which the performances of physicians were compared to those of nonphysician health personnel in inserting and removing NORPLANT subdermal contraceptive implants. The study was conducted in Raden Saleh Clinic at the University of Indonesia, Jakarta, from September 1982 to August 1984. In a group of 828 women who accepted NORPLANT 285 insertions were performed by physicians and 543 by nonphysician health personnel. During the study period, 122 removals were performed (43 by physicians and 79 by nonphysicians). This small proportion of removals reflects the high continuation rate for NORPLANT. There was no significant difference between the two groups of acceptors regarding age, parity, education, or side effects. The average insertion times were 7.6 minutes for the physician group and 7.4 minutes for the nonphysician group (p greater than 0.1). The average removal times were 21.7 minutes for physicians and 21.8 minutes for nonphysicians (p greater than 0.9). Complications during and following insertion and removal were minimal for both groups, and no significant differences were found. It was concluded that nonphysician health personnel are qualified to administer the NORPLANT contraceptive implants.     

Focal brachial cutaneous neuropathy associated with Norplant use: suggests careful consideration of the recommended site for inserting contraceptive implants

A case of neuropathy in the medial antebrachial cutaneous nerve of the forearm following a Norplant(R) removal is described. The incidence of this problem is uncertain. The suggested sitting of the contraceptive implants directly over the bicipital groove is questioned.     

Mechanisms that explain the contraceptive action of progestin implants for women

Four different contraceptive implants for women, in the form of capsules or covered rods, that release either one of the synthetic progestins levonorgestrel, etonogestrel, Nestorone, or Elcometrine and nomegestrol acetate were considered. These progestins act by binding to their receptors located in diverse target cells, which are distributed along the hypothalamic-pituitary-gonadal-genital tract axis. These implants differ in the extent to which each one interferes with various steps of the reproductive process and in the intensity with which each one affects the same process along its effective life, but they have in common the ability to interfere with several key processes required for gamete encounter and fertilization. The steps they interfere with most are the ovulatory process, through partial or complete inhibition of the gonadotropin surge, and by changing the quality of cervical mucus; they restrict or suppress the access of fertile spermatozoa to the site of fertilization. Changes in endometrial development also occur, but this contribution to the contraceptive action is difficult to determine at the present time.     

Statement on Norplant subdermal contraceptive implant system

At its September 1985 meeting, the International Medical Advisory Panel of the International Planned Parenthood Federation drafted a statement concerning Norplant, the subdermal contraceptive implant system developed by the Population Council. The statement, intended for use by physicians, administrators, and other health personnel in the field of family planning, summarizes current knowledge of this means of fertility control. Norplant is particularly recommended for women who seek longterm protection from pregnancy, but either may desire another child in the future or do not wish to undergo sterilization. Insertion during the 1st 7 days after menstruation onset, or immediately postabortion or postpartum (in nonbreastfeeding women), is advised. Capsules should be removed after 5 years of use. Annual pregnancy rates range from 0.2-1.3/100 women/year, with a cumulative pregnncy rate of 5 years of 2.6. The most frequently reported side effect is irregular menstrual bleeding, especially during the 1st year of use. Continuation rates are 60-90% at the end of the 1st year, and about 50% after 5 years. Counseling, especially regarding bleeding irregularities, is critical to continued acceptability. 40% of women who request Norplant removal in order to conceive become pregnant within 3 months of removal, and 76% achieve pregnancy within 1 year. Epidemiologic studies of the longterm safety of Norplant implants are under way. It is noted that program use of Norplant poses several managerial challenges. Formal training in insertion and removal techniques, as well as the risks and benefits of the method, must be planned and back-up and referral facilities identified. Since Norplant is a new delivery system, a carefully designed public information system is also important.