OBJECTIVE

Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication.

METHODS

One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed.

RESULTS

Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001).

CONCLUSIONS

The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites.

Irregularity in vaginal bleeding patterns is the most common clinical side effect causing discontinuation of the method reported by the-users of the newer contraceptive methods, especially hormonal ones. An objective assessment of vaginal bleeding pattern is, therefore, critical in evaluation of a new contraceptive method for its acceptance and continued use. The menstrual diary records of women participating in clinical trials of several contraceptive methods undertaken by the Indian Council of Medical Research were analysed. It was observed that the long-acting progestogen-only hormonal contraceptives like levonorgestrel (LNG)-releasing subdermal implants Norplant or intrauterine devices (LNG-IUD) as well as injectable contraceptive NET-EN 200mg given 2 or 3 monthly produced disturbances in bleeding pattern in the majority of their users. Very heavy or prolonged bleeding, a potential health hazard was uncommon and a shift more towards infrequent bleeding was observed. In Norplant-II implants users, 75 to 80% of women had irregularities in bleeding pattern during the first year of use which improved with prolonged use. However, even at 4 years of use, about half of the users of Norplant-II implants continued to have irregular bleeding patterns. The bleeding disturbances occurred in 80% users of 200mg NET-EN injectable contraceptives also during first year of use, however unlike Norplant-II implants users, there was no improvement with prolonged use. Combined monthly injectable contraceptives containing 50mg NET-EN and 5mg estradiol valerate caused less bleeding problems with half of the users experiencing normal pattern during one year of its use. Combined low-dose oral pills, both triphasic and monophasic, produced much better cycle control as compared to any of the other hormonal contraceptive-treated groups; about 90% of combined oral pill users had normal bleeding patterns during one year of method use. The use of copper IUDs was associated with increased bleeding in 18 to 20% of women during the initial period of three months which improved with prolonged use. It was observed that the women having frequent or prolonged bleeding had discontinued the contraceptive method more often as compared to those having delayed bleeding episodes or oligomenorrhoea. However, discontinuation rates due to bleeding irregularities at one year were lower in Norplant-II implants users as compared to other long acting hormonal contraceptive methods such as injectables or IUDs in spite of similar or better bleeding patterns in women using these methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Recent studies have provided substantial evidence to highlight abnormalities in the structure of endometrial microvessels in users of progestogen-only contraception. Structural changes alone are unlikely to lead to breakthrough bleeding, but appear to be associated with a reduction in vessel integrity, and may reflect alterations in the control and growth of endometrial microvessels in those exposed to exogenous progestogens. In users of low-dose progestogens, immunohistochemical studies have demonstrated changes in superficial endometrial vascular morphology, density and in endometrial migratory cell populations. In Norplant users the endometrial endothelial basal lamina is deficient in the initial months of exposure, when bleeding problems are most common. The basal lamina refers to the very thin structure consisting mostly of collagen IV and laminin seen underlying endothelial and epithelial cells at the electron microscope level. In addition, hysteroscopic studies have demonstrated increased fragility of superficial vessels. Changes in endometrial microvascular anatomy associated with normal menstruation have been reviewed, and are compared with those seen following contraceptive steroid exposure. Likely mechanisms of breakthrough bleeding such as increased superficial vascular fragility and the possible alterations in endometrial vascular structure leading to this are discussed.

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 December 2006.

METHODS

Trials with random or alternate 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

Twenty three randomised controlled trials enrolling 2674 participants were included. Seventy per cent 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 study 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 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 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.

Suppression and subsequent rebound of ovarian activity using a progestin (levonorgestrel; Norplant) versus a GnRH antagonist (antide) was assessed in the domestic cat via fecal estradiol and progesterone metabolite analyses. Following an initial dose-response trial, queens were assigned to one of four treatments: (1) antide, two 6 mg/kg injections 15 days apart (n = 8 cats); (2) levonorgestrel, six silastic rods (36 mg levonorgestrel/rod) implanted for 30 days (n = 8); (3) control injections (n = 5); and (4) control implants (n = 5). Steroid metabolites were quantified from daily fecal samples for 90 days before, 30 days during, and 90 days after treatment. Antide and levonorgestrel inhibited estrous cyclicity in contrast to continued cyclicity in controls. Cats already at estradiol baseline in antide (n = 7) and levonorgestrel (n = 4) groups remained inhibited during treatment. In females with elevated estradiol levels at treatment onset (Day 0), a normal estradiol surge was completed before concentrations declined to baseline (approximately Days 5-7) and remained suppressed throughout the remaining treatment period. Additionally, 56% of treatment animals exhibited at least one spontaneous ovulation during the pre-treatment period, but no female ovulated during treatment with levonorgestrel or antide. Antide-treated cats exhibited lower (P < 0.05) baseline estradiol concentrations during treatment compared to pre- and post-treatment. In contrast, levonorgestrel induced elevations in baseline estradiol following treatment compared to pre- and during treatment intervals. Control females showed no change (P>> 0.05) in baseline estradiol throughout the study period. All levonorgestrel and antide cats returned to estrus after treatment withdrawal. Results demonstrate that: (1) both antide and levonorgestrel are effective for inducing short-term suppression of follicular recruitment and ovulation in the cat; (2) inhibition is reversible; and (3) GnRH antagonists and progestins differentially regulate basal estradiol secretion. This study also confirmed a relatively high incidence of spontaneous ovulation in the cat, a species generally considered to be an induced ovulator.

Disrupted, prolonged and irregular endometrial bleeding are major unwanted side-effects of progestin-only contraceptives. The aim of this paper is to review current information on steroid control of the microvasculature, microvascular heterogeneity and microvascular fragility, with emphasis on the relevance of these issues to the endometrial microvasculature in women receiving Norplant implant contraception. Subjects were either Indonesian women with between 3 and 12 months exposure to Norplant (n = 191) or Caucasian controls recruited in Melbourne, Australia. Norplant endometrium was always thinner than control endometrium, with a varied histology that usually included a basalis-type appearance, signs of haemorrhage and some dilated and congested subepithelial vessels. Thin-walled vessels were seen which could have been either blood vascular or lymphatics. Steroid control of the vasculature can operate through numerous direct and indirect mechanisms, with up to 30 genes relevant to vascular function having consensus oestrogen response elements in their promoter regions. The vasoactive effects of progesterone are less well documented. However, experimental data for direct effects on the endometrial vasculature are mounting. Progestin-induced endometrial breakthrough bleeding is often focal, suggesting that microvascular heterogeneity may be an important factor in understanding this phenomenon. Increased susceptibility to bleeding may result from increased microvascular fragility, possibly as a consequence of progestins altering the balance of angiogenic promoters and inhibitors in the endometrium, thus leaving the vessels in a permanently weakened state.

Abnormal uterine bleeding accounts for the unacceptably high discontinuation rate of progestin-only contraceptives. Previously, we found that in-vivo and in-vitro decidualization of human endometrial stromal cells was associated with elevated concentrations of tissue factor (TF), the primary initiator of haemostasis. Moreover, enhanced TF expression required progesterone receptor (PR) and epidermal growth factor receptor (EGFR) mediation. In the current study, endometrial biopsies were sampled from bleeding (BL) and non-bleeding (NBL) sites under camera-directed hysteroscopic guidance after Depo-provera injections. When compared with control biopsies, immunohistochemical examination revealed that 3 months of Depo-provera contraception reduced TF concentrations at the BL sites. However, there were ample EGFR and PR concentrations at BL and NBL sites. Moreover, there was a trend towards the appearance of pathologically enlarged blood vessels at the BL sites. The use of Western blotting revealed that after 3 months of Depo-provera, concentrations of both PRB and PRA isoforms were lower at BL versus NBL sites with decreased PRA concentrations attaining statistical significance. Separate sampling of endometrial BL and NBL sites as shown here for Depo-provera contraception could prove particularly useful in identifying local factors that determine the onset of bleeding during the more protracted time-course of Norplant contraception.

OBJECTIVE

To review new evidence regarding ten controversial issues in the use of contraceptive methods among women with special conditions and to present World Health Organization recommendations derived in part from this evidence.

METHODS

We searched MEDLINE and PREMEDLINE databases for English-language articles, published between January 1995 and December 2001, for evidence relevant to ten key contraceptive method and condition combinations: combined oral contraceptive (OC) use among women with hypertension or headaches, combined OC use for emergency contraception and adverse events, progestogen-only contraception use among young women and among breast-feeding women, tubal sterilization among young women, hormonal contraception and intrauterine device use among women who are human immunodeficiency virus (HIV) positive, have AIDS, or are at high risk of HIV infection. Search terms included: "contraception," "contraceptives, oral," "progestational hormones," "medroxyprogesterone-17 acetate," "norethindrone," "levonorgestrel," "Norplant," "contraceptives, postcoital," "sterilization, tubal," "intrauterine devices," "hypertension," "stroke," "myocardial infarction," "thrombosis," "headache," "migraine," "adverse effects," "bone mineral density," "breast-feeding," "lactation," "age factors," "regret," and "HIV."

METHODS

From 205 articles, we identified 33 studies published in peer-reviewed journals that specifically examined risks of contraceptive use among women with pre-existing conditions.

RESULTS

Combined OC users with hypertension appear to be at increased risk of myocardial infarction and stroke relative to users without hypertension. Combined OC users with migraine appear to be at increased risk of stroke relative to nonusers with migraine. The evidence for the other eight method and condition combinations was either insufficient to draw conclusions or identified no excess risk.

CONCLUSIONS

Of ten contraceptive method and condition combinations assessed, the evidence supported an increased risk of cardiovascular complications with combined OC use by women with hypertension or migraine. As new evidence becomes available, assessment of risk and recommendations for use of contraceptive methods can be revised accordingly.

OBJECTIVE

The objectives of this study were to examine the reasons for discontinuation of the long-acting contraceptives Depo-Provera and Norplant in adolescents, and to assess the adolescents' experience after discontinuation of the methods.

METHODS

A total of 35 adolescents [gynecologic age 4.7 +/- 0.3 years, and body mass index (BMI) 24.2 +/- 0.6] who discontinued Depo-Provera, and 31 adolescents (gynecologic age 3.4 +/- 0.3 years, BMI 24.1 +/- 0.9) who discontinued Norplant were periodically assessed during use of the methods and up to 12 months after discontinuation.

RESULTS

The most common reasons for discontinuation of both Norplant (after 21.8 +/- 1.6 months of use) and Depo-Provera (9.2 + 0.9 months of use) were irregular menstrual bleeding (64%), weight gain (41%), and increased headaches (30%). Resumption of menstrual regularity and dysmenorrhea was noted sooner after discontinuation of Norplant, compared with Depo-Provera. The increase in BMI noted at discontinuation of Depo-Provera (1.1, P = .0005) and Norplant (1.3, P = .03) persisted up to 6 months after discontinuation of either method (0.6, P = .01 post-Depo-Provera discontinuation; and 0.9, P = 0.02 post-Norplant discontinuation). Only 62% of the adolescents reported no break in contraceptive practice. The condom was the most popular method (37%) after discontinuation of Depo-Provera, and oral contraceptive (39%) after discontinuation of Norplant. The cumulative conception proportion reached 0.93 at 12 months after discontinuation of Norplant, and was significantly higher (P = .01) compared with the cumulative proportion of conception after discontinuation of Depo-Provera (P = .50).

CONCLUSIONS

Health care providers should aggressively manage physical problems associated with Depo-Provera and Norplant use, and expedite the transition to a new contraceptive method to minimize the high pregnancy rate observed after discontinuation of these methods in adolescents.

Although review articles have provided much information on the NORPLANT system, information on insertion site complications based on multi-country trials has been limited to infection rates. This paper examines 2,674 NORPLANT acceptors from seven countries who were enrolled and followed for one year. The one-year incidence rates of infection (0.8%), expulsion (0.4%) and local reaction (4.7%) varied widely among countries and clinics within a country. In contrast to previous reports that insertion site complications occur during the first few weeks of use, these data show that a substantial proportion of insertion site infections (34.6%) and implant expulsions (64.3%) were reported after the first two months of use, while 35.7% of local reactions were reported after 4.5 months of use. Of the 16 women with infections who did not have the implants immediately removed, 8 eventually required or requested removal, indicating that the ICCR recommendation for immediate removal in case of infection appears appropriate. An awareness of the frequency of insertion site complications, distribution of the time of onset post-insertion and potential sequelae of complications will aid clinicians in better client counseling and complication management.

Women enrolled in a multicenter prospective study were evaluated to identify any possible relationship between depressive symptoms and the use of contraceptive implants. Women choosing Norplant implants (n = 910) were evaluated before starting this contraceptive and were reinterviewed at 6 months and 2 years. Women who continued the method had lower depressive symptom scores before initiating Norplant implants than did the women who discontinued the method or who were lost to follow up. Among the continuing Norplant implant users, the mean scores were similar before starting Norplant and at 6 months (7.9 vs 7.7). The strongest overall predictor of the depressive symptom score was relationship satisfaction. At 24 months, the subgroup of continuing users with decreased relationship satisfaction had an increase in depressive symptom score, but those with stable or improved relationships had stable depressive symptom scores. The subjects with the highest (i.e., worst) scores at enrollment demonstrated improved scores during follow-up. These results are reassuring for women who are concerned that Norplant use may adversely affect their mood.

BACKGROUND

The contraceptive implant Norplant (levonorgestrel) had a fairly short life in the UK. This made it a convenient subject for a case study of how media coverage alters over time. We set out to produce a critical description of national newspaper coverage of Norplant over the course of its use in the UK.

METHODS

We searched newspaper databases and press-clippings files for articles about Norplant printed between 1992 and 1996. For those that met our inclusion criteria, we extracted bibliographical data, made a standardised judgment about the "slant" of the article towards Norplant, and used qualitative techniques to analyse the content of the articles.

RESULTS

101 national newspaper articles were included in the study. Norplant attracted media coverage over the course of its career, but the slant of articles shifted dramatically over time from a favourable to a negative presentation. This reflected the use of different story types over the course of time. Early reports presented Norplant very positively as either a clear improvement on existing contraceptive methods or a valuable addition to the range. Any disadvantages were down-played. The positive image of Norplant was reinforced immediately after its official launch by reports that it was in great demand but women might be denied access to it. Less than a year later, however, newspaper reports about Norplant were dominated by the stories of individual women who had had bad experiences with the product.

CONCLUSIONS

Three main reporting themes were seen. At first, Norplant was presented as a positive new development, and one that might be denied to people. In later coverage it became a flawed and damaging product. These themes recur in media reporting of health technologies, and the fact that they occur at different stages in a product's career means that a balanced assessment of the technology is not usually feasible from media reporting at any one time. An appreciation of the forms and implications of these reporting frameworks could help health-care providers and users to appraise media reports more critically.

OBJECTIVE

To document the practices and attitudes of the US physician members of the Society for Adolescent Medicine (SAM) regarding adolescent abortion and contraception, as well as physician willingness to prescribe medical abortion if approved by the Food and Drug Administration (FDA).

METHODS

Cross-sectional questionnaire survey. Participants. The entire physician membership of SAM (N = 1001) was surveyed. A total of 713 physicians responded, with 668 usable surveys yielding an adjusted response rate of 70%.

RESULTS

Of the respondents, 81% were trained as pediatricians; 58% had additional adolescent medicine training. Ninety-six percent prescribed contraception for their patients. Sixty-one percent of respondents identified abortion as an option for pregnant adolescents in all circumstances, whereas 4% believed abortion should never be an option. Eighty-nine percent referred their patients for abortions; 90% were aware of medications to induce abortions medically. If these medications (methotrexate and misoprostol, RU-486) were FDA-approved, 42% would prescribe them for their patients; 34% were unsure. Fifty-four percent believed if medical abortions were routinely available, they should be available from primary care physicians. Physicians were significantly more likely to consider prescribing medical abortions if the physician were female, offered postcoital contraception, performed Norplant insertions, referred adolescents for abortions, or performed postabortion medical checkups. Physicians were no more likely to consider prescribing medical abortions according to physician age, specialty training, or date of residency training. Religious affiliation per se was not associated with likelihood of prescribing medical abortions, but Catholic physicians were significantly less likely to consider prescribing medical abortions.

CONCLUSIONS

Virtually all SAM physician respondents (96%) reported that abortion for pregnant adolescents should be available under some circumstances. Forty-two percent would prescribe medical abortion if the medications were FDA-approved, suggesting that medical abortion would potentially be available to adolescents from a larger group of physicians than is currently available.

In 1986-87, a qualitative research project was conducted in the Dominican Republic, Egypt, Indonesia, and Thailand to expand understanding of the acceptability of NORPLANT contraceptive implants beyond inferences made on the basis of continuation rates. In each of the four study sites, focus group discussions or in-depth interviews were held with potential acceptors, current NORPLANT users, discontinuers, husbands of women in these three groups, and service providers. Nonclinical participants generally had little formal education and lived primarily in urban or semi-urban areas where NORPLANT has been available for at least five years. The study focused on attitudes, perceptions, and experiences of each group regarding NORPLANT implants. Results suggest that factors having an impact on the acceptability of NORPLANT implants fall into three general categories: medical/technical, cultural/religious, and informational/educational. This article discusses each of these categories, including programmatic implications of the findings, and puts forward recommendations for enhancing NORPLANT introduction efforts on the basis of these findings.

In a randomized three-year clinical trial at seven clinics, the performance of levonorgestrel rod (LNG ROD) implants used by 600 women was compared with that of soft tubing NORPLANT implants used by 598 women. No pregnancies occurred in either group of women and, accordingly, body weight did not affect the efficacy of either type of implant. There were neither statistically significant nor important differences in termination rates for any reason over the three years. Complaint and illness rates during use of either of the two implant types were statistically indistinguishable and were attributable to the same set of conditions. Seventy-one per 100 of the women using each implant regimen continued to the three-year point, for an average annual continuation rate of 89 per 100. Removals of LNG ROD implants were accomplished in about half the time required for removal of Norplant capsule implants (p < 0.001).

OBJECTIVE

To review selected data on the effectiveness, safety, cost and technical ease of intrauterine device (IUD) use compared with Norplant and surgical sterilization.

METHODS

Literature review.

RESULTS

IUDs are highly effective, safe and relatively inexpensive methods of contraception that may offer advantages for some women over other long-term methods, such as sterilization and Norplant. IUDs provide protection against pregnancy comparable to that provided by female sterilization, and they may be more effective than Norplant. IUDs have a long duration of effectiveness: the copper T 380A (TCu380A) is effective for at least 10 years, and the levonorgestrel (LNg) IUD appears to be effective for at least 7. Norplant is effective for only five years. Both types of IUD can disrupt menstrual bleeding patterns, although the patterns of bleeding are different. Copper IUDs often increase blood loss, whereas the LNg IUD, like Norplant, substantially reduces menstrual bleeding. The most important adverse outcome associated with IUD use is higher rates of pelvic inflammatory disease; careful attention to proper insertion techniques can reduce this risk substantially, and LNg IUDs may cause no increase in risk. IUDs, like both sterilization and Norplant, provide no protection against sexually transmitted disease. The TCu380A IUD is extremely cost-effective. There is as yet no public sector price for the LNg IUD, which has not been approved by the U.S. Food and Drug Administration and is not provided by family planning donor organizations. If it can be made available to the public sector at a price substantially less than its present market price, the LNg IUD would be a useful addition to the contraceptive armamentarium for developing countries.

CONCLUSIONS

Providers, consumers and family planning program managers should begin to see IUDs as potential substitutes for both surgical sterilization and Norplant.

BACKGROUND

The objective of this systematic review is to determine whether obese women who use progestogen-only contraceptives are more likely to experience weight gain or serious adverse events as compared to nonobese users.

METHODS

We searched PubMed for all articles (in all languages) published in peer-reviewed journals from database inception through October 2008, for evidence relevant to obesity and progestogen-only contraceptives. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence.

RESULTS

From 579 articles, we identified nine studies fitting our selection criteria. Evidence from five studies suggests that among adult women, baseline weight or body mass index is not associated with weight gain among depot medroxyprogesterone acetate (DMPA) users (Level II-2, Fair). Evidence from three studies suggests that among adolescent women, overweight or obese DMPA users may gain more weight than normal weight DMPA users or overweight/obese nonusers (Level II-2, Fair). Evidence from one small study of Norplant users showed no differences in weight gain by baseline weight (Level II-3, Poor). We did not identify studies of other progestogen-only contraceptive methods that examined weight change by baseline weight, nor did we identify studies that reported on any serious adverse events by baseline weight.

CONCLUSIONS

Adolescent DMPA users who are obese may gain more weight than normal weight users. This observation was not seen in adult DMPA users or adolescent Norplant users.

Implanon is a single-rod contraceptive implant containing the progestin etonogestrel. Implants require insertion and removal by medical professionals. Detailed and unbiased counseling before insertion is essential, and should include contraceptive efficacy, insertion and removal procedures, and possible adverse events. Insertion and removal times have been measured in six open studies and in seven comparative studies in which Norplant (the six-capsule levonorgestrel implant) was used as the reference product. In comparative studies, the mean time needed for insertion of Implanon was 1.1 min and removal took 2.6 min. Insertion as well as removal of Implanon was four times faster than with Norplant. Complications with insertion and removal are rare in the hands of medical professionals familiar with the techniques.

The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to vascular fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.

A randomized comparative study of levonorgestrel-releasing intrauterine device (LNG-IUD) and Norplant-2 implants was carried out in 200 women for 36 months. Three thousand one hundred woman-months of use were observed with each device. Only one pregnancy occurred in users of LNG-IUD at the 12th month of use. The change in bleeding pattern was the most frequent reason for discontinuation. The discontinuation rate for irregular bleeding with Norplant-2 was 17.3 and 26.8 at 24 and 36 months, respectively, as compared to 3.3 with LNG-IUD at both 24 and 36 months. The differences were statistically significant. Removal for amenorrhea and pain only occurred in acceptors of LNG-IUD. About 20-40% of women using Norplant-2 had prolonged bleeding through 36 months. The percentage of amenorrhea in LNG-IUD was the highest (29.3%) at the end of two years of use. More than 97% of subjects reported satisfaction with the methods used by themselves.

OBJECTIVE

To evaluate safety and efficacy of levonorgestrel-releasing contraceptive implants (Norplant; Leiras Oy, Turku, Finland) in developing countries.

METHODS

We used controlled cohort methodology. Women attending family planning clinics in eight developing countries selecting Norplant were enrolled, together with women of similar age choosing intrauterine devices (IUDs) or surgical sterilization. Participants were interviewed and examined at semi-annual visits and followed-up for 5 years regardless of change of contraceptive methods. Incidence rate ratios of health events were estimated for initial and current method use.

RESULTS

Altogether, 7977 women initiated Norplant, 6625 IUD, and 1419 sterilization. The overall follow-up rate was 94.6% and 78,323 woman-years of observation were accumulated. Pregnancy rates for Norplant, copper IUDs, and sterilization each averaged less than 1 per 100 woman-years. With two exceptions, no significant excess risk of serious morbidity was detected for Norplant users compared with controls. The incidence of gallbladder disease was higher in women who initiated Norplant use than in controls (rate ratio 1.52, 95% confidence interval [CI] 1.02, 2.27), as was the incidence of hypertension and borderline hypertension in current implant users (rate ratio 1.81; CI 1.12, 2.92). Other new findings were increased risks of respiratory diseases and decreased risks of inflammatory disease of the genital tract in Norplant users compared with IUD users and sterilized women.

CONCLUSIONS

The study confirms the safety with respect to serious disease and the high contraceptive efficacy of Norplant, copper IUDs, and sterilization.

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMPs) and leukocytes are postulated to be involved in the process of normal menstruation. Immunolocalization of MMPs and leukocytes in (Norplant), and injectable depot medroxyprogesendometrium from women using the progestinterone acetate (DMPA), are widely used, safe and only contraceptives, Norplant or depot medroxyprogesterone acetate (DMPA) compared with normal controls, revealed foci of positive MMP-1 and -3 immunostaining in stromal cells and adjacent extracellular matrix, the presence of MMP-9 in various subtypes of leukocytes and alterations in mast cell phenotype. In women using progestin-only contraceptives, extent of endometrial MMP, neutrophil and eosinophil immunolocalization and the mast cell activation state was similar to or greater than that observed in perimenstrual control women. However, differences in MMP immunostaining were observed in endometrial samples from women using different progestin-only contraceptive agents; in particular, significantly higher MMP-1 immunostaining was observed associated with the use of Norplant compared with DMPA. No correlation was observed with the number of bleeding days recorded. These results suggest that MMP and leukocytes may be involved in endometrial breakdown in women using progestin-only contraceptives.

BACKGROUND

Despite their high effectiveness, progestin-only contraceptives are considered less than ideal by the many women who experience disruption of their normal vaginal bleeding pattern when using these methods. Current treatments to control these bleeding irregularities are not sufficiently effective.

OBJECTIVE

We evaluated preventive and therapeutic interventions of 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 December 2006.

METHODS

Trials with random or alternate 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

19 Randomised controlled trials including 2290 participants were included. Over 60% of these trials had low to moderate risk of bias. Estrogen treatments reduced the number of days of an ongoing bleeding episode in DMPA users and had a positive therapeutic effect in Norplant users. However, treatment frequently led to discontinuation due to gastrointestinal upset. Combinations of oral ethinyl estradiol and levonorgestrel taken by Norplant users experiencing bleeding irregularities, improved bleeding patterns but method discontinuation rates remained the same. Norplant users administered the anti-progestin mifepristone therapeutically reported fewer days of bleeding than those given placebo. Prophylactic oral mifepristone used monthly by new Norplant users reduced bleeding, when compared to placebo.Ibuprofen was reported to decrease the length of bleeding episodes over a year, but the data were not presented in a suitable format for our analysis. Mefenamic acid reduced continued irregular bleeding during treatment in Norplant users, but not among DMPA users. Vitamin E and aspirin had no effect on bleeding patterns in a large trial of women using Norplant. Norplant users receiving tamoxifen had less unacceptable bleeding after treatment and were more likely to continue using Norplant than those receiving placebo.

CONCLUSIONS

Some women may benefit from the interventions described, particularly with cessation of an ongoing bleeding episode. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger scale trials. Intermittent treatment with an agent may help some women to continue the use of a progestin-only contraceptive. 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.

OBJECTIVE

To describe the state of reproductive health services, including access to contraception and health center policies, among school-based health centers (SBHCs) serving adolescents in the United States

METHODS

We examined questionnaire data on provision of reproductive health services from the 1998-99 Census of School-Based Health Centers (response rate 70%). We examined 551 SBHCs in schools with high or middle school grades. We used logistic regression to define factors independently associated with services and policies.

RESULTS

Most SBHCs (76%) were open full-time; over one-half (51%) of centers had opened in the past 4 years. Services provided, either on-site or by referral, included gynecological examinations (95%), pregnancy testing (96%), sexually transmitted disease (STD) diagnosis and treatment (95%), Human Immunodeficiency Virus (HIV) counseling (94%), HIV testing (93%), oral contraceptive pills (89%), condoms (88%), Depo-Provera (88%), Norplant (78%), and emergency contraception (77%). Counseling, screening, pregnancy testing, and STD/HIV services were often provided on-site (range 55%-82%); contraception was often provided only by referral (on-site availability = 3%-28%). SBHCs with more provider staffing were more likely to provide services on-site; rural SBHCs and those serving younger grades were less likely to provide these services on-site. Over three-quarters (76%) of SBHCs reported prohibitions about providing contraceptive services on-site; the sources of these prohibitions included school district policy (74%), school policy (30%), state law (13%), and health center policy (12%). While SBHCs generally required parental permission for general health services, many allowed adolescents to access care independently for certain services including STD care (48%) and family planning (40%). Older SBHCs were more likely to allow independent access.

CONCLUSIONS

SBHCs provide a broad range of reproductive health services directly or via referral; however, they often face institutional and logistical barriers to providing recommended reproductive health care.