This essay examines the history of Norplant from its development in the 1960s, to its approval by the FDA in 1990, through its tumultuous reception in American society, to its removal from the market in 2000. The rejection of Norplant by women was influenced by the social and political climate of the 1990s, in which a feminist health agenda, a consumerist ideology in health care, a growing tendency toward class action litigation, and increasing distrust of the pharmaceutical industry worked together to empower women to take charge of their reproductive decision making. The rhetoric of population control in the 1960s, when the pill and IUD were introduced, was very different from the language of individual choice that dominated in the 1990s, the era of Norplant. This investigation of Norplant extends the historical analysis of reproductive politics to the very end of the twentieth century.

Twenty-four parous women were included in this study. Sixteen cases were using the Norplant implant contraceptive system for more than 6 months (Group A) while eight cases served as matched controls in the secretory phase (Group B). Norplant implant users belonged to one of two equal subgroups according to whether they experienced regular menstrual bleeding (Subgroup A1) or prolonged episodes of amenorrhoea (Subgroup A2). Endometrial samples were processed for nuclear oestrogen receptor assay and for evaluation of the receptor's binding affinity to oestrogen. The results showed marked reduction in endometrial nuclear oestrogen receptors in Norplant users compared with controls as the majority of users had undetectable receptor levels. This down-regulation effect was significantly more pronounced among women with prolonged episodes of amenorrhoea. The affinity section of the study revealed no significant differences between groups or subgroups probably due to the small number of subjects with detectable receptor concentrations for comparison. These data may help in the understanding of contraceptive mechanisms and menstrual associated problems, and in the development of therapeutic measures.

Sixty-eight patients had Norplant inserted between May 1992 and November 1993 as part of a pre-introductory study. The main side effect was weight change which occurred in 85.3% (58 patients); weight loss occurred in 25.0% (17 patients, one patient voiced a complaint) and weight gain occurred in 60.3% (41 patients, 10 of whom voiced a complaint). Menstrual problems were the next most frequent side effect occurring in 70.4% (48 patients); spotting occurring in 22% (15 patients, none of whom complained) and heavy bleeding in 7.3% (five patients, all of whom complained). Amenorrhoea occurred in 41.1% (28 patients). Other complaints were minor. No pregnancies have been recorded to date. There were no procedural complications and all patients were satisfied with the cosmetic appearance. To date there have been 36 removals, the majority for menstrual complications. Norplant is a safe, effective means of 'reversible sterilisation' which should be utilised in family planning programmes throughout the country.

BACKGROUND

Despite their high effectiveness, progestin-only contraceptives are considered less than ideal by the many women who experience irregular vaginal bleeding when using them. Current treatments to control these bleeding problems are not sufficiently effective.

OBJECTIVE

We evaluated preventive and therapeutic approaches to normalise bleeding irregularities associated with the use of progestin-only contraceptives.

METHODS

Literature was identified through database searches, reference lists, organisations and individuals, covering the period until May-June 2012.

METHODS

Trials with random or systematic allocation, testing interventions for the prevention or treatment of bleeding irregularities associated with the use of progestin-only contraceptives were eligible.

METHODS

Results are expressed as relative risks (RR) with 95% confidence interval (CI) for categorical data and as weighted mean difference (WMD) with 95% CI for continuous data. When we encountered heterogeneity (visual or statistical) we used the random-effects model (quantitative) or did not produce a summary estimate (qualitative).

RESULTS

Thirty-three randomised controlled trials enrolling 3677 participants were included. Two thirds of the trials were determined to reflect low to moderate risk of bias.Estrogen treatments reduced the number of days of an ongoing bleeding episode in DMPA and Norplant users. However, treatment frequently led to more discontinuation due to gastrointestinal upset.Combinations of oral ethinyl estradiol and levonorgestrel improved bleeding patterns in Norplant users, but method discontinuation rates were unchanged. One trial reported successful use of combined oral contraceptives in treating amenorrhea among DMPA users.Norplant users, but not Implanon users, administered the anti-progestin mifepristone reported fewer days of bleeding during treatment than those given placebo. Mifepristone used monthly by new Norplant acceptors reduced bleeding, when compared to placebo.A variety of NSAIDS have been evaluated for their ability to treat abnormal bleeding, with mixed results.Norplant users receiving SERM (tamoxifen) had less unacceptable bleeding after treatment and were more likely to continue using Norplant than those receiving placebo.Tranexamic acid, mifepristone combined with an estrogen and doxycycline were more effective than placebo in terminating an episode of bleeding in women using progestin-only contraceptives, according to three small studies.

CONCLUSIONS

Some women may benefit from the interventions described, particularly with cessation of current bleeding. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger trials. The results of this review do not support routine clinical use of any of the regimens included in the trials, particularly for long-term effect.

The time to resumption of ovulation following the discontinuation of levonorgestrel subdermal implants (Norplant) was assessed in 10 women. A blood sample (2 ml) was taken at the time of Norplant removal and then twice weekly until the first evidence of ovulation (serum progesterone concentration greater than or equal to 5 ng/ml) was documented. Ovulation was resumed in 80% of the cases by 3 weeks and in all the cases by 7 weeks. Prompt return of ovulation following Norplant removal is an additional advantage of this mode of long-acting contraception.

The mechanisms responsible for Norplant implants-induced menstrual irregularities remain poorly understood. It is unclear whether local changes in endometrial haemostasis are involved. The aim of the present study was to examine the immunohistochemical staining for von Willebrand factor (vWF) in endometrial biopsies taken from 37 women exposed to Norplant implants for 3-12 months and to compare it with 73 controls at various phases of the normal menstrual cycle. The vWF staining intensity was quantified by subjective scoring and by objective computerised colour image analysis. Results from the Norplant implants group were additionally correlated with their bleeding patterns, endometrial histology, and plasma oestradiol (E2) and progesterone (P4) levels. No differences were found between control and Norplant implants subjects in the localization of vWF staining, which was specifically confined to the endothelium of endometrial blood vessels. vWF staining intensity in Norplant implants endometrium was significantly lower than in controls during mid cycle, and reached a mean (+/- SE) level (subjective staining score 2.05 +/- 0.13, n = 37) in the range of the early proliferative and mid secretory phase normal endometrium; nevertheless, it remained significantly higher than that of menstrual and late secretory phase normal endometrium. No significant variations in vWF staining could be related to either the histology of the endometrium or the bleeding pattern of the users. Correlation of vWF staining with either serum E2 or serum P4 prior to biopsy, or to the number of days of Norplant implants exposure revealed no significant relationships. However, vWF staining was positively correlated (r = 0.419, P < 0.01) to the number of bleeding/spotting days within a 90-day reference period prior to biopsies being taken. These results demonstrate that there are major differences in the mechanism responsible for normal menstruation and Norplant implants-induced intermenstrual bleeding and spotting, and show that menstrual disturbances associated with the use of Norplant implants are unlikely to be due to changes in vWF levels in endometrial endothelial cells.

The Government of Sri Lanka has established a new scheme to pay cash incentives to women who use the loop method of contraception. The payment for the first year will be Rs. 125, for the second year Rs. 250, and for the third year Rs. 375. This scheme is part of a larger strategy by government officials to reduce emphasis on sterilization and promote birth spacing and family planning methods. In 1988, the Government also approved for contraceptive use the subdermal implant, Norplant. See IPPF, People, Vol. 15, No. 3 1988, p. 27 and IPPF Open File, 20 January 1988, pp. 33-34.

The acceptability and efficacy of norplant (levonorgestrel sub- dermal implants) was assessed over a period of two years among 445 married women aged 19 to 45 years. Twenty women were lost to follow-up while the remaining 425 were regularly followed-up. At the end of two years, 388 women were still continuing with norplant (91.2%). During this period, there was only one pregnancy (0.26%). There was no significant change in mean systolic or diastolic blood pressure. However, there was a significant increase (P < 0.001) in mean weight and decrease (P < 0.001) in the mean duration of menstrual cycle. Thirty-seven women (8.7%) got the implant removed. The major reason for removal (67.6%) was menstrual disturbances. Nine acceptors (18.59%) developed side effects, which were related to the type of symptoms often associated with steroid contraception. These findings are similar to those reported from other countries. The high efficacy (99.74%) and acceptability (continuation rate of 91.29%) as well as long acting (5 years) nature of norplant suggest that this method of contraception can safely be promoted in Pakistan.

Helping patients choose the proper contraceptive requires familiarity with the specific advantages and disadvantages, as well as failure rates, of available methods. Spermicides, condoms and contraceptive sponges are inexpensive and do not require physician prescription. Diaphragms and cervical caps help protect against sexually transmitted diseases but are more difficult to use effectively. Oral contraceptives are highly effective but have estrogen- and progesterone-related side effects. Norplant is ideally suited for less motivated users but requires an office surgical procedure. Depo-Provera provides another long-term option but may result in amenorrhea. Intrauterine devices provide long-term contraception without hormonal side effects but increase the risk of pelvic infection and may cause heavy menstrual bleeding. Tubal ligation and vasectomy are options for permanent contraception when childbearing is no longer desired.

Five hundred and eighteen Norplant acceptors (260 ever-users and 258 current users) were interviewed to assess their perceptions about Norplant. The mean age of the acceptors was 32.6+/-5.7 years (mean +/- SD). The mean parity was 4.3 and many of the users (40.2%) were illiterate. The most common reason to choose Norplant was its long duration of action (70.1%) followed by doctor's advice (10.4%) and use by other women (10.1%). Norplant was recommended by family planning workers in 35.3% cases, doctors in 29.2% cases and friends in 17.4% cases. Advertisement did not play any role in the women's choice of Norplant. In 77.3% cases, the decision to use Norplant was a joint decision. Only 15% of the users had fears/anxieties before insertion. Most of these women (44%) were concerned about possible ill-effects of Norplant on their health rather than efficacy. The social acceptance of Norplant was very high (76%) and more than half of the users (52.5%) were satisfied with the method. Among current users, 83.9% wanted to continue Norplant for 5 years. Only 39 users (15.1%) intended to discontinue. The main reason for discontinuation was menstrual disturbance (69.2%), followed by weight gain (12.7%). The study suggests that long duration of effective action and high social acceptance are likely to make Norplant a popular method among Pakistani women.

OBJECTIVE

Removal of contraceptive implants (e.g. Norplant) is an issue affecting its worldwide acceptability. Reports of difficult, painful removals have resulted in lawsuits and reduced demand. To improve quality of care, we developed a scoring system to anticipate difficult removals. We report on the usefulness of such a system and present client perspectives about the removal experience.

METHODS

A 9-point scoring system based on the visibility, arrangement, and position (VAP) of Norplant capsules was used to assess the anticipated difficulty of removal in 53 consecutive patients. The VAP score was then correlated with removal time and related parameters.

RESULTS

Mean removal time was 14.74 min (range 4.75-47). In 20% of patients, the VAP score indicated a potentially difficult removal and the VAP score correlated significantly with removal time (r = 0.3, p = 0.05). Patients expected removal to be moderately difficult (mean visual analog score 4.7 out of a possible 10), but after removal they rated the actual removal experience as relatively easy (mean score 2.6/10). Before the removal, only 48% of patients said they would recommend Norplant to a friend but after removal, 70% said they would do so.

CONCLUSIONS

A scoring system such as the VAP score can help identify potentially difficult removals so that an experienced remover can be present at the time of removal or an appropriate referral made. However, the VAP score cannot predict variables such as the density of the subcutaneous fibrous tissue "envelope". Although patient anxiety concerning removal may be high, the presence of a competent remover and an easy removal experience reduces this anxiety and encourages patients to be more positive about this method. The value of having properly trained, competent personnel available to perform removals cannot be over-emphasized.

OBJECTIVE

To determine the vaginal flora of first time urban Family Planning clients at Korle-Bu Teaching Hospital and to assess its implications for the contraceptive choices made.

METHODS

A cross sectional study.

METHODS

A standardized questionnaire surveying the sociodemographic characteristics and the choice of Family Planning method was administered to 100 clients at the Korle Bu Teaching Hospital between March and September 2001. High vaginal and endocervical swabs were also taken during the inspection of the vagina and cervix using a sterile bivalve speculum. The specimens were transported in Amies transport medium to the Microbiology laboratory for processing.

RESULTS

The age range of the clients was 19-48 years with a modal age of 28 years. Ninety-six percent of them were married while 86% lived in urban slums. Sixty-three percent were sure of their last menstrual period. Potential pathogens were isolated from culture in 56% of the clients. Organisms causing bacterial vaginosis were the most prevalent in their genital tract. The intrauterine contraceptive device (IUCD) was the most common Family Planning method chosen, followed by the Norplant and the Depo-Provera injections. Potential pathogens were isolated from culture in 50% of those who chose the IUCD.

CONCLUSIONS

Potential pathogens were isolated from culture in 56% of these first-time clients and organisms causing bacterial vaginosis were the most prevalent in the genital tract. It is suggested that Family Planning clients who screened positive for potential pathogens and opt for the IUCD should be considered for prophylactic antibiotics at insertion.

Research into contraception is producing new techniques that involve everything from vaccinations to nasal sprays. Steroids are the basis of the conventional contraceptive pill and much current research is on alternative ways of introducing the same drugs into the woman's reproductive system. Norplant is 1 approach. It involves implanting 6 tiny silicone-rubber tubes just beneath the skin of a woman's underarm. The tubes contain a drug, widely used as an ingredient of the contraceptive pill, which is slowly released from the tubes over a period of 5 years. It is understandable that much contraceptive research is focused on the womb. The brain, however, seems a strange place to be concerned with when trying to prevent conception. But it is the brain that controls a woman's ovulation by sending signals to the reproductive system via the pituitary gland. And now it is possible to synthesize chemicals which, when given in the form of a nasal spray, will inhibit ovulation by mimicking the brain's signals to the pituitary gland. It may even be possible to develop drugs which act directly on parts of the brain itself--a prospect we should be aware of, whether we would approve of it or not. There has been such an explosion of knowledge of the neural transmission systems that this may not be so far-fetched as it sounds. Research in China tends to concentrate more on naturally occurring substances--like a new form of female sterilization which involves not anesthetics or surgery but a substance called "mucilage"--1 of the ingredients of birds-nest soup. If mucilage is passed through the cervix into the fallopian tubes it causes them to block up and so prevents the passage of the ovum. There is a Western "high-tech" alternative to this, called methylcyanoacrylate--you might be more familiar with it as "superglue" or "crazy glue." Used carelessly it can stick your fingers together, but this tendency to join human tissues can be more productively used to block up the fallopian tubes. The Chinese are also looking at another natural substance as the basis of the possible "male pill." This is gossypol which occurs in cottonseed. A major reason why most research has been focused on contraception for women is that men present problems of quite a different order of magnitude. While a woman only ovulates once every 28 days or so, male sperm are produced continuously, with 200-400 million of them in each ejaculation. But drugs based on gossypol, which seems to have the effect of reducing the sperm count, may be the answer. Under the auspices of the World Health Organization, research on gossypol and other plants with contraceptive potential is now going on over all the world. Some 350 have been put under the microscope so far and about 30 look worth pursuing.

In this longitudinal study involving 100 Singaporean acceptors, the effects of Norplant-2 rods on metabolic function was evaluated. The mean serum bilirubin during the second year remained significantly raised from its preinsertion value (p less than 0.001). Furthermore the total proteins and globulin were still significantly decreased (p less than 0.001). Thus with respect to liver function, the results still indicate possible dysfunction at the end of two years. As regards lipid metabolism, the serum triglycerides, total cholesterol and LDL-cholesterol still remained significantly decreased at the end of two years when compared to preinsertion values. The HDL-cholesterol levels which showed no significant change during the first year of use decreased significantly during the second year of use. As a result the HDL-cholesterol/Total cholesterol - HDL-cholesterol decreased significantly and was 12.0% lower than the pre-insertion ratio (p less than 0.01). Similarly the LDL-cholesterol/HDL-cholesterol increased during the second year of use and was 2.6% higher than its preinsertion ratio. However, this increase was still not statistically significant. As we have not incorporated a simultaneous non-steroid treated control group, the observed changes in lipid metabolism could be attributed to extraneous factors such as diet, exercise or other environmental changes. Nevertheless, the findings at the end of two years, though speculative, still indicate Norplant-2 use to be non-contributory to cardiovascular risk in this population. The use of Norplant-2 was not associated with any significant effect on glucose tolerance after two years of use.

Recent advances in OCPs include less androgenic progestins and lower doses of ethinyl estradiol. All low-dose OCPs are safe in terms of venous thrombosis risk in appropriately chosen patients. DMPA is a safe and effective long-acting contraceptive agent; clinical attention should be directed to its most common side effect, irregular bleeding. DMPA does not seem to affect mood, and it is uncertain what impact it has on weight changes. More research needs to be conducted on its impact on adolescent bone metabolism. Norplant continues to be the only subdermal contraceptive implant marketed in the United States. It provides safe and effective contraception and has the best continuation rate of all types of hormonal contraception. Its most common side effect is irregular bleeding. Norplant may be especially well suited for adolescents who have recently been pregnant or who are not tolerating other types of contraception. Emergency postcoital contraception continues to be underused in the United States, with a lack of awareness among patients and clinicians. Mechanisms of action include a delay in ovulation and interference with implantation. Research and public health groups are striving to increase patient and provider awareness and use of emergency contraception.

Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle. This disturbance in the angiogenic process may be caused by an imbalance of pro- and antioxidant processes in the endometrium of Norplant users. The aim of this study is to investigate the effect of vitamin E on the endometrial angiogenic activity and to assess the efficacy of vitamin E supplementation in treating endometrial bleeding in Norplant users. Subjects for this study were selected from Norplant users with an exposure of at least 3 months, with endometrial bleeding and recruited on the basis of fully informed consent. TBA reaction was used to measure degradation products of lipid peroxidation. The endometrial angiogenic response was assayed according to Folkman et al. (Folkman et al., 1989. Nature 239, 58-61). Samples from endometrial biopsies were incubated in vitro with vitamin E or placebo before angiogenic measurement. For in vivo supplementation, vitamin E 200 mg/day, or placebo for 10 days/month were given to the subjects with double blind randomisation. The results showed that the blood levels of TBA-reactive substances were significantly higher in Norplant users than in controls. In the endometrium from Norplant users with bleeding problems, in vitro supplementation of vitamin E resulted in a significantly higher angiogenic score than placebo. Although a highly significant reduction of bleeding days in both groups, vitamin E and placebo, was seen during the 2 months of the study, the number of bleeding days was significantly lower in women treated with vitamin E than with placebo.

The U.S. Food and Drug Administration has recently approved two new contraceptive methods, and others are nearing approval. In addition, several innovative approaches to contraception are under investigation. This paper details the latest information on the following methods: Paragard Copper T 380A intrauterine device, cervical cap, NORPLANT, vaginal pouch, long-acting injectables, hormonal vaginal ring, transdermal patch, experimental male methods, inhibin, and contraceptive vaccines.

Norplant subdermal implants containing levonorgestrel were used for contraception and compared with the Copper T, Model T Cu 200, during 42 months of use in an open study in Chile, the Dominican Republic, and Finland. Among 324 women enrolled for the implant regimen, there were no pregnancies in the 1st 2.5 years, and 2 by the end of 42 months. 1st segment net and gross cumulative pregnancy rates were 0.7 and 1.2/100 respectively, at 3.5 years. Cumulative pregnancy rates for the T Cu 200 group were 2.9, net and 3.5/100, gross at 42 months. More than 1/2 of the implant acceptors, 51.6/100 were continuing use at 3.5 years, somewhat above the continuation rate of the T Cu acceptors, 43.5/100, but not significantly so.