Norplant, subdermally implanted slow-release levonorgestrel, is an effective and widely used contraceptive agent but has a high rate of discontinuation due to unacceptable abnormal uterine bleeding. Matrix metalloproteinases (MMPs) are expressed in normal cycling endometrium and are postulated to be responsible for the tissue breakdown at menstruation. We have compared the immunolocalization of MMP-9 and migratory cells in endometrium from Indonesian women using Norplant with normal controls. Positive MMP-9 immunostaining was observed intracellularly within stromal and intravascular leukocytes and extracellularly in areas of tissue lysis adjacent to these migratory cells. The MMP-9 positive cells were identified as neutrophils, eosinophils, CD3+ T-cells and macrophages. Quantitative assessment revealed that the number of MMP-9 positive cells, neutrophils and eosinophils were significantly increased in those endometrial biopsies from Norplant users displaying a shedding morphology and in normal controls at menstruation. There was no correlation between the number of MMP-9 positive cells and the number of bleeding days reported. Endometrial immunostaining for tissue inhibitor of metalloproteinases was similar in Norplant users and normal controls. These results suggest that MMP-9, an enzyme capable of degrading basement membrane components, may be involved in endometrial breakdown in women using Norplant.

Growth, development and health of infants whose mothers used progestogen-only contraceptives during lactation were examined in a prospective, non-randomized study carried out in seven centres in five countries (Egypt, Thailand, Kenya, Chile and Hungary). The results on growth are reported here. Breastfeeding women requesting effective contraception were admitted to the study at six weeks postpartum. Infants of acceptors of progestogen-only methods (pill, DMPA, NET-EN or NORPLANT implants) and non-hormonal methods (IUD, barrier methods or sterilization) formed the study groups. The follow-up was at monthly intervals until the end of the first postpartum year. Participating in the study were 2466 mother-infant pairs. The mean duration of exclusive breastfeeding varied from 68 to 159 days, but did not differ significantly between study groups within centres. In anthropometric measures (weight, arm circumference and triceps skinfold), the mean rates of change varied over time as expected, and across the centres. However, there were very few statistically significant differences in these rates of change between groups within centres. Since a large number of statistical comparisons were made, and there was no consistency either across centres, over time, or in the direction of the differences, we conclude that in this study, the progestogen-only contraceptives used during lactation did not adversely affect infant growth.

OBJECTIVE

Our goal was to evaluate both the continuation and pregnancy rates and the side effects experienced during the first year of use by adolescents who selected Norplant implants as compared with those who chose oral contraceptives for contraception. Furthermore, side effects experienced at 6 versus 12 months among Norplant implant users were compared to determine whether they diminished with continued use of this method.

METHODS

We conducted a case-control study of 56 adolescents < or = 18 years old who selected implants as compared with 56 age-matched controls who chose oral contraceptive pills during the same time period.

RESULTS

Only 34% of patients prescribed oral contraceptives as compared with 91% of Norplant implant patients were still using their chosen method 1 year later. As a result 25% of oral contraceptive users became pregnant within 12 months as compared with none who selected Norplant implants. Side effects were reported by>> 80% of patients in both groups, with menstrual irregularities reported more often by Norplant implant users than by oral contraceptive users (73% vs 5%, p = 0.01). Furthermore, Norplant implant users gained more weight than oral contraceptive users (8.7 vs 4.2 pounds) and were twice as likely to have an abnormal Papanicolaou smear. Finally, little diminution in side effects was observed during the second 6 months of Norplant implant use.

CONCLUSIONS

These data confirm that Norplant implants provide better protection against unintended pregnancy in an adolescent population but may be associated with more side effects. Clinicians should be aware of these findings so they can adequately counsel young patients about these two methods of contraception.

BACKGROUND

Inadequate contraception is common among sexually active female adolescents, resulting in a high incidence of unwanted pregnancy. The authors were interested in comparing continuation rates for the different forms of hormonal contraception in this age group.

METHODS

A retrospective chart review. The setting was an urban clinic in a large Midwestern city. Participants were 64% black, 34% white, and the average age was 15.5 years (+/- 1.6 SD), with implant users significantly older than oral contraceptive pill (OCP) users (P < .05). Interventions were self-selection to depo-medroxyprogesterone acetate (Depo-Provera; DMPA), levonorgestrel implants (Norplant), or oral contraceptive pills (OCPs). Previous pregnancy was significantly more prevalent in implant and DMPA users than in OCP users (P < .001). Over 4 years of follow-up, continuation rates were significantly higher for implant users than for the other hormonal groups (P < .001). At 1 year, continuation rates were as follows: 82% implants, 45% DMPA, and 12% OCPs. Combining these rates with those of the subsample who switched without interruption to another hormonal method, "continued protection" rates were much higher after 1 year: 96% implants, 83% DMPA, and 49% OCPs. Calculations of contraceptive "restarts," i.e., hormonal method use in those who discontinued and then restarted after a gap of time, also increased to the prevalence of contraceptive protection.

CONCLUSIONS

Continuation rates for levonorgestrel implants were significantly higher than those for DMPA and OCPs, the latter group having the lowest continuation rates. Factoring in switches and restarts to other hormonal methods further boosted the prevalence rates of contraceptive use in the adolescent population.

Women seeking legal first trimester abortion were counseled concerning contraception methods available for use immediately postabortion. Fifty women each accepted hormonal methods that were available only in the clinic and were novel to the country, the levonorgestrel IUD and Norplant implants, whereas another 50 chose either coitus interruptus or abstinence. All were experienced contraceptors, but larger percentages of women selecting the levonorgestrel IUD or implants had used the pill or IUDs previously, were under age 30, and weighed less than 60 kg compared to the other study participants. In the initial 2-6 weeks postabortion, women using the long-acting hormonal methods resumed sexual activity earlier and experienced more bleeding and spotting days than did other study participants, but their hematocrits were not adversely affected. No clinically significant side effects were noted in any group in the 6 weeks following the abortion. At the end of 1 year of follow-up, women using the hormonal methods had experienced no pregnancies and had high rates of continuation. IUD and implant participants had greater weight gain than did the other participants, but their mean weight remained below that of participants using traditional methods. No significant between-group differences in levels or changes in levels from admission were noted in hematocrit and blood pressure. The women found the levonorgestrel implants and IUDs easy and safe to use and highly effective. Bleeding disturbances, including amenorrhea, were the principal features the women disliked.

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 101 women. During five full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for termination of use but only during the first year. More than half of the terminations for this reason were in the first year. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years. From the second through the sixth year of use, the implants delivered a constant 30 micrograms per day of levonorgestrel to the subjects, and even after six years 57% of the original steroid content remained in the capsules. Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.

A 26-year-old woman, treated with phenytoin for 10 years because of epilepsy, had Norplant subdermal implants inserted after a legal abortion. She became pregnant again after nine months of Norplant use. Her plasma levonorgestrel (LNG) levels were followed during one month during phenytoin treatment and then later during one month after discontinuation of phenytoin. During phenytoin treatment, plasma LNG levels were markedly below the levels found in healthy women with Norplant. There was a pronounced, statistically significant increase in plasma LNG levels after discontinuation of phenytoin. The plasma levels of sex hormone binding globulin were markedly above those found in normal healthy women during treatment with phenytoin and decreased significantly after cessation of phenytoin. The effects on the pharmacokinetics of LNG were reflected by effects on the menstrual cycle. During phenytoin treatment, the woman had regular ovulatory menstrual cycles. After cessation of phenytoin, her cycles became irregular and during the study period of one month, no signs of ovulation were found. It is concluded that treatment with phenytoin during use of Norplant subdermal implants enhances the metabolism of LNG to an extent where the contraceptive efficacy is endangered.

This study evaluated the performance of progesterone vaginal rings (n = 187), progestin-only pills (n = 117), Norplant implants (n = 120), and Copper T 380-A intrauterine devices (n = 122) in lactating women. Contraceptive efficacy, bleeding pattern, and influence of the method upon breastfeeding duration and infant growth were compared with those of untreated women (n = 236) who relied on lactational infertility. Participants were healthy, 18 to 38 years, had had a normal delivery, and were intending to breastfeed for as long as possible. Contraceptives were initiated at day 57 +/- 3 postpartum. Results are reported for the first year of use. All methods were highly effective, with pregnancy rates below 1%. None affected breastfeeding performance or the rate of infant growth. Users of the progestin-only methods experienced a period of lactational amenorrhea 4 to 5 months longer than did users of Copper T or untreated women. More than half of the women in each contraceptive group reported a bleeding in the first month after treatment initiation, which was not considered in the calculation of the duration of amenorrhea. Prolonged or frequent bleedings were infrequent. The proportion of bleedings lasting more than 10 days ranged from 0 in the progestin-only pills group to 7% in the Norplant implants group. The four methods, initiated around the eighth postpartum week, provided effective contraception with no negative effects upon lactation or infant growth and without the bleeding problems associated with their use in nonlactating women.

Growth, development and health of infants whose mothers used progestogen-only contraceptives during lactation were examined in a prospective, non-randomized study that was carried out in seven centres in five countries (Egypt, Thailand, Kenya, Chile and Hungary). The results on development are reported here. Breastfeeding women requesting effective contraception were admitted to the study at six weeks postpartum. Infants of acceptors of progestogen-only methods (pill, DMPA, NET-EN or NORPLANT implants) and non-hormonal methods (IUD, barrier methods or sterilization) formed the study groups. The follow-up was at monthly intervals until the end of the first postpartum year. At each visit, the infant examination included, among other things, a set of developmental tests covering the following areas: gross motor, vision and fine motor, hearing, language and concept development, and self help and social skills. Participating in the study were 2466 mother-infant pairs. The comparisons between the study groups were carried out within centres using life table methods and Cox-model analysis having the time to first passing the test as the criterion. There were altogether 247 comparisons between the study groups. Thirty-two (13%) of these comparisons showed statistically significant differences: 20 differences showed that the infants in the progestogen-only groups passed the tests at an earlier age and 12 at a later age than infants in the non-hormonal groups. Since no consistent trends were observed across the centres, we conclude that in this study the progestogen-only contraceptives used during lactation did not adversely affect infant development.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

A high incidence of irregular uterine bleeding is the primary patient complaint limiting the utility of long term, progestin-only contraceptive agents such as Norplant. The onset of hemorrhage requires both inadequate hemostasis and impaired vascular integrity. Thus, we first tested whether Norplant-associated endometrial bleeding was accompanied by altered expression of perivascular stromal cell tissue factor (TF), the primary initiator of hemostasis. Norplant effects on TF messenger ribonucleic acid (mRNA) and protein expression by endometrial stromal cells were assessed by in situ hybridization and immunohistochemical examination of endometrial biopsies obtained from normally cycling control women (n = 14) and from patients experiencing Norplant-induced abnormal uterine bleeding (n = 24). TF mRNA and protein expression was increased 150% in secretory vs. proliferative phase endometrial specimens. By contrast, endometrial TF mRNA and protein levels were reduced during 1-6 months of Norplant treatment by about 2-fold (P < 0.05 for protein) compared to the values for control secretory phase specimens. These changes were consistent with observations that patients on Norplant begin to bleed during this interval. Further reductions of TF mRNA and protein levels to 2- and 3-fold of those in secretory phase control specimens were observed in endometria obtained after 6-12 months of Norplant therapy (P < 0.05 and P < 0.01, respectively). A modest rebound in TF mRNA and protein expression was observed after 12 months of Norplant therapy, which occurred commensurate with reduced patient complaints of abnormal uterine bleeding. Pathologically enlarged venous sinusoids were ubiquitous in endometrial specimens obtained after Norplant therapy. The combination of fragile blood vessels and reduced TF expression may account for bleeding in patients receiving Norplant therapy.

Forty-two healthy women volunteered to have blood samples drawn at 2, 4, 8, 24, 48, and 168 h (7 days) following placement of levonorgestrel-releasing rod (LNG rod) or of Norplant capsule implants to permit measurement of drug concentrations. Three clinics recruited 10 women each, half of whom used each type of implant. Twelve additional subjects were later enrolled at one site to provide greater detail for the capsule implants. Throughout the week, women with Norplant implants had apparently higher mean drug concentrations than did women with LNG rod implants, but the differences were significant only in the first 48 h after placement (p < 0.05). Maximum levels for capsule implants were found at the 24-h sample (mean, 1358 to 1474 pg/mL) and for the LNG rod implants at 48 h (772 pg/mL). Body weight was negatively correlated with levonorgestrel concentrations at all times (p < 0.05). For several sampling times, differences between clinics in mean concentrations were statistically significant after weight adjustment. Despite differences by implant type, weight, or clinic location, drug concentrations compatible with contraceptive effect were attained within 24 h in users of LNG rod or of Norplant implants, insofar as all women had levonorgestrel concentrations above 250 pg/mL at the 24-h sample.

Between January 1992 and January 1993, there were 280 teens (ages 13-18) who either delivered a baby or terminated a pregnancy at Johns Hopkins Bayview Medical Center. Of these, 92 chose to contracept with Norplant implants, and 188 chose another method including "no" method. In July 1993, telephone interviews were conducted with 37 of those who chose Norplant implants and 41 of the non-Norplant implants users. After 1 year, 47% of oral contraceptive (COC) users had discontinued the method compared to only 16% of Norplant implants users (P < 0.03). Reasons for discontinuation centered on side effects for both groups but with some COC and condom users, discontinuing use due to "forgetfulness" or failure (pregnancy). Among the COC group (which was the most common choice after Norplant implant), 25% of the adolescents had experienced a subsequent unplanned pregnancy compared to 0% of the Norplant implant group (P < 0.01). Norplant implants were clearly an acceptable and effective contraceptive for these post-partum and post-abortal teens, who articulated a high motivation to avoid a subsequent unplanned pregnancy. However, it is clearly not the only method teens will choose to use, and more attention must be paid to adequate counseling of those choosing another method.

As men play a prominent role in reproduction, it is therefore extremely useful to assess and encourage them to be involved in contraception, particularly in developing countries, where contraceptive goals have not been reached. This study was carried out in Kayseri, Turkey, in order to determine the attitudes and behavior of married men concerning family planning. A questionnaire was presented to 123 married men. In our study, 91.9% of men approved of family planning, but only 54.4% actually used any contraceptive methods; 66.7% of the men said that the decision should be a joint one, 66.4% wanted to limit their family size. Approximately one fourth of the men had never heard of voluntary sterilization. No one in the study group was aware of the mini-pill, diaphragm or Norplant. In the study group, 26.8% of the men did not want their wives to use intrauterine devices and 31.7% of them did not agree with women using the contraceptive pills. Among those unwilling to use a condom (46.3%), 70.1% stated that it might interrupt intercourse. If a contraceptive pill for males could be used, 25.2% of members of the group would be prepared to use it. Only 17.5% men in the study group had contacted a doctor or a health foundation to obtain information. The main sources of family planning information were TV/radio, followed by friends and newspapers/magazines. In order to encourage men's involvement in family planning, the use of mass media and continual training programs, to try to reach both men and women, could be very useful.

The introduction of the contraceptive implant Norplant has focused attention on how social factors may affect contraceptive use. In the United States, race is a central category of social organization which may impact Norplant use. I use data from the 1995 National Survey of Family Growth to answer three main questions. (1) Are women of color more likely to use Norplant? (2) To what extent can racial differences in Norplant use be explained by a structural bias in the provision of medical care? (3) To what extent can racial differences in Norplant use be explained by life circumstances which may affect individual women's contraceptive decisions? I find that African American and Native American women are more likely than white or Asian American women to be recent Norplant users. There are no differences in recent use by Hispanic origin. Both a structural bias in the provision of care and differences in life circumstances account for the disparity in Norplant use between African Americans and whites. However, none of the factors examined here explain Native American women's high rate of use. Concerns about health risks for Norplant use are also discussed. These findings point out the importance of examining structural, individual and health status factors in studies of the use of health services.

OBJECTIVE

To identify reasons for inconsistent contraceptive use that antedate conception and continue to predispose participants in adolescent-oriented maternity programs to unsafe sexual practices after delivery. We hypothesized that teens who attributed their failure to use contraceptives before their first conception exclusively to concerns about their side effects and/or their own lack of motivation to prevent conception would report less consistent contraceptive use and more repeat conceptions than would teens who attributed their previous failure to use contraceptives to their lack of capacity to do so.

METHODS

We conducted a 2-year, prospective, longitudinal study of contraceptive use and repeat conceptions in a racially/ethnically diverse population of poor 13- to 18-year-olds. The 198 study participants were enrolled consecutively during their first pregnancies from an adolescent-oriented maternity program.

RESULTS

The majority (84%) of the teens attributed their failure to use contraceptives before their first pregnancy partially to a lack of capacity to do so. As hypothesized, these teen mothers were significantly more likely to use hormonal contraceptives (85% vs 62%), (particularly Norplant, 47% vs 19%) and less likely to conceive again (13% vs 41%). Most teens attributed their inconsistent contraceptive use during the postpartum study period to three factors: side effects, plans to abstain from sexual intercourse, and their lack of motivation to postpone additional childbearing.

CONCLUSIONS

The reasons teen mothers give for not using contraceptives consistently before their first pregnancies predict the occurrence of subsequent conceptions during adolescence. Those who attribute their previous failure to use contraceptives consistently to side-effect concerns and their own lack of motivation to postpone childbearing are least likely to use hormonal contraceptives after delivery and most likely to conceive again. Our findings suggest that future research should focus on the development of more effective interventions for preventing repeat conceptions among adolescent mothers who had the capacity to prevent their first pregnancies.

The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use.

BACKGROUND

Norplant is a relatively new long-acting subdermal implant system that is used widely for contraception. In a recent report, Wagner and Berenson described two cases of Norplant-associated major depression and panic disorder. These were the first reports of severe psychiatric disorders linked to the use of Norplant.

METHODS

Five cases are described of women who developed major depression, two of whom also developed obsessive-compulsive disorder and one of whom also developed agoraphobia, while using the Norplant system.

RESULTS

These women who had no prior psychiatric history developed major depression within 1 to 3 months after Norplant insertion. The depression worsened over time and in all cases resolved within 1 to 2 months after Norplant removal. There was no recurrence of depression after 7 to 8 months in four cases available for follow-up. In addition to major depression, obsessive-compulsive disorder developed in two women and symptoms of agoraphobia developed in one woman during Norplant treatment, which resolved after Norplant removal.

CONCLUSIONS

These cases provide further support for the association between Norplant and major depression, as well as a broad spectrum of anxiety disorders. It is important to design prospective studies to carefully examine the incidence of major depression and anxiety disorders in women who use Norplant. Risk factors for these disorders require further clarification.

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of such abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMP)s and mast cells (MC)s are postulated to be involved in endometrial breakdown observed in normal menstruation. In this study comparisons were made of the immunolocalization of MMP-1 and -3 and MC in endometrium from women using Norplant or depot medroxyprogesterone acetate (DMPA) with normal controls. Positive MMP immunostaining was observed focally in stromal cells and adjacent extracellular matrix. Quantitative assessment revealed significantly higher MMP-1 immunostaining associated with the use of Norplant compared with DMPA or menstrual phase controls. Endometrial MMP-1 immunostaining in DMPA users was similar to that in menstrual controls. Positive MMP-3 immunolocalization was observed in a minority of endometrial samples. Activated MC, shown by the presence of extracellular MC tryptase, predominated in the endometrium of Norplant and DMPA users as also observed in menstrual phase controls. There was no correlation between MMP immunostaining, number of MC and number of bleeding days reported. These results indicate that in women using progestin-only contraceptives, endometrial MMP-1, -3 and MC demonstrate similarities to menstrual phase controls but also variation with different progestins.

Although estrogens have been identified as key endocrine hormones in the control of early mitogenesis and development in the mammary gland, local control of cell proliferation during ductal morphogenesis may be regulated by polypeptides such as TGF-alpha or TGF-beta. Many breast tumors are estrogen dependent, and some breast tumor cell lines are known to produce TGF-alpha, suggesting that the mitogenic pathways controlling early normal mammary growth and the growth of some breast tumors may be similar. While progesterone does not appear to be important in the early program of ductal growth, progesterone and estrogen are necessary for the cyclic proliferation of mammary ductal cells that occurs during the menstrual cycle, and for lobuloalveolar growth during pregnancy. Since increased cell division enhances the chances for the formation of a malignant phenotype in the breast, exogenous hormones containing estrogen alone or estrogen and progesterone may increase breast cancer risk. While DES is no longer prescribed to prevent abortions, it demonstrates that high doses of an estrogen during a period of mammary proliferation can affect breast cancer risk. Whether the addition of progestogens to estrogen replacement therapy enhances breast cancer risk in postmenopausal women remains an unanswered question because of the lack of large, well-controlled prospective studies. There currently is no evidence to indicate that the progestogen-containing subdermal contraceptive Norplant increases breast cancer risk. However, it has not been determined if the elevation of serum estrogens reported in some Norplant users affects breast cancer risk. There is little evidence that combined OCAs enhance breast cancer risk in most women. More research is needed to substantiate the findings that OCA use in young women, especially before a first full-term pregnancy, may enhance breast cancer risk. Animal studies indicate that there are critical periods of susceptibility to chemical carcinogens, since the number and malignancy of tumors are increased when carcinogens are administered to young virgin animals during the proliferative period of ductal morphogenesis. Since the breast appears to be most susceptible to the carcinogenic effects of ionizing radiation during the first decade of life, exposure to other carcinogenic agents during the period of early breast development may be important in determining breast cancer risk. Therefore, more studies are needed to confirm the observation that heavy drinkers and heavy smokers are at higher risk for developing breast cancer when they start smoking or drinking at an early age. The observation that serum and urinary estrogen levels increase with alcohol consumption may provide a basis for the higher risk of developing breast cancer in heavy drinkers. While the restriction of methyxanthine intake may alleviate the symptoms associated with fibrocystic breast disease in some women, there is not enough evidence to suggest that a reduction in caffeine intake will reduce breast cancer risk. Evidence for an association between electromagnetic radiation and breast cancer is limited. Electromagnetic radiation may only pose a risk in certain occupations with exposure to very high levels for extended periods of time. It is not known whether exposure to PCBs transplacentally or though the lipid fraction of human milk can affect breast cancer rates in female offspring. The higher risk of breast cancer in women with elevated DDE levels in their blood underscores the importance of determining the extent to which environmental contaminants affect breast cancer risk.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

OBJECTIVE

To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism.

METHODS

Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement.

METHODS

Yale University Clinical Research Center.

METHODS

Seven previously normally cycling, nonobese, nondiabetic women participated in the study.

METHODS

Norplant insertion.

METHODS

Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion.

RESULTS

Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL.

CONCLUSIONS

Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion.

Levonorgestrel plasma levels were determined by a specific radioimmunoassay in a group of 110 women at various intervals between 1 and 60 months following implantation of six silastic capsules containing levonorgestrel (Norplant). The implants were placed subdermally in the volar aspect of the forearm. Blood samples were taken twice a week for six consecutive weeks in each subject. Blood drawn from the antecubital vein ipsilateral to the implant site contained two to three times more levonorgestrel than contralateral samples. Average systemic plasma levels represented by contralateral samples ranged from 0.35 +/- 0.03 to 0.29 +/- 0.02 ng/ml (Mean +/- S.E.) in the first and fifth year, respectively. The difference between these values is statistically significant at the 5% level. The results of the regression analysis of individual levels suggest that the decline observed throughout the first five years is mainly due to an early decrease taking place in the first two years. When the sampling period was repeated in the same subjects two or three times 10 to 24 months apart, no significant difference was found. A significant negative correlation was found between plasma levonorgestrel levels and body weight and body surface. The data indicate that the contraceptive efficacy of Norplant during the first five years of use is associated with sustained release of levonorgestrel and is in keeping with the estimated life span of Norplant of seven years.