Enhanced metabolism of levonorgestrel during phenytoin treatment in a woman with Norplant implants

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.     

Plasma levels of levonorgestrel in women during longterm use of Norplant

Levonorgestrel plasma levels were determined by a specific radioimmunoassay in a group of 110 women at various intervals between 1 and 60 months fallowing 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.     

Anovulation, inadequate luteal phase and poor sperm penetration in cervical mucus during prolonged use of Norplant implants

Blood samples for progesterone assay were collected for a total of 49 cycles, from 27 volunteers using the NORPLANT system. Levonorgestrel determinations were carried out in the same samples. A group of 12 women with normal cycles were studied in the same manner to serve as controls. Of the 49 cycles studied, 20 (41%) were ovulatory. The mean levonorgestrel level in ovulatory patients was 0.34 +/- 0.11 ng/ml (S.D.) compared to 0.42 +/- 0.14 ng/ml (S.D.) in anovulatory cycles. Compared to the control group, progesterone levels were significantly lower for users of NORPLANT implants during days -12 to -10 (p less than 0.025), -9 to -7 (p less than 0.05), -6 to -4 (p less than 0.0005) and days -3 to -1 (p less than 0.01). Cervical mucus evaluations and post-coital tests were done around mid-cycle in 29 of the cycles studied. All samples of cervical mucus were of poor quality, viscous and scarce, with a mean SPK of 4.1 +/- 2.3 cm. Most had absent or atypical ferning. Twenty-one subjects (73%) had a post-coital score of 1, and 4 (14%) of zero. Thus, anovulation, inadequate luteal phase and the direct effect of the continuous administration of levonorgestrel over cervical function, all seem to contribute to the effectiveness of NORPLANT implants.     

Effect of long-term use of Norplant implants on haemostatic function.

This study describes the effects of Norplant on haemostatic function after 5 years of use in 97 women. There was a decrease in vitamin-K dependent Factors II, V, VII and reduction in fibrinolytic activity at 2 and 4 years of use. Increased platelet numbers and accelerated platelet aggregation were found throughout the 5 years of Norplant use, whilst raised alpha 2-Macroglobulin (a2-M) and antithrombin III (ATIII) antigen level were observed for up to 4 years of use. Prolonged Norplant use does not appear to activate the coagulation system and does not enhance a state of hypercoagulation.     

Levonorgestrel concentrations in maternal and infant serum during use of subdermal levonorgestrel contraceptive implants, Norplant, by nursing mothers

The transfer of levonorgestrel to infants was studied in 42 lactating women in whom the contraceptive subdermal implants, Norplant, were inserted 30 to 40 days postpartum. The women breastfed their infants for one year. Simultaneous mother and infant blood samples were taken once during the year. The levonorgestrel serum concentrations were measured by radioimmunoassay. During the first postinsertion month, the levonorgestrel concentration in the infants serum amounted, on the average, to 5% of the maternal concentration. Thereafter, the ratio ranged from 8 to 13%. The implications of this finding are discussed.     

Effect of levonorgestrel contraceptive implants, Norplant, on blood coagulation

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

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

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

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

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

Clinical chemistry in women treated with levonorgestrel implants (Norplant) or a TCu 200 IUD

Two groups of implant users and two groups of IUD users participated in the study at different times. In the first groups, fractionation of lipoproteins was performed on serum samples from 28 subjects who had used the implants for 37 months and from 26 subjects who had used the Copper TCu 200 for 30 months. Users of the implants had significantly lower levels of total cholesterol, triglycerides and LDL-cholesterol than users of the IUDs. HDL-cholesterol levels were not different between the groups. In the other groups of women, general chemistries and selected hormone assays were carried out on samples from 30 subjects who had used implants for 51 months and from 24 subjects who had used the TCu 200 IUDs for 43 months. The parameters studied were the SM-12 chemistry group profile, estradiol, cortisol, testosterone, triiodothyronine, thyroxine and thyroid stimulating hormone. In the implant group, mean serum glucose levels were statistically significantly elevated and inorganic phosphorus levels were significantly reduced as compared to the IUD group. In both cases all individual measurements were within the normal range for the population. Testosterone and triiodothyronine levels in the implant group were significantly lower than in the IUD group, but no individual values were outside the normal range for the population. Mean values for all other parameters were not significantly different between the groups.     

Cholesterol and HDL-cholesterol values in women during use of subdermal implants releasing levonorgestrel

Plasma concentrations of cholesterol, HDL-cholesterol, and levonorgestrel were determined in two groups of women using levonorgestrel-releasing subdermal implants. One group used six capsules (NORPLANT)*; the other six covered rods. Plasma concentrations of levonorgestrel among NORPLANT users averaged 700 pg/ml in the first two weeks of use, decreased to 300 pg/ml at 8 weeks, and to about 230 pg/ml by 50 weeks. Concentrations among covered rod users were 1.4 to 1.7 times higher at comparable time periods. Total serum cholesterol and HDL-cholesterol were decreased as compared with controls at all sampling intervals during the 114 weeks of the trial, although the differences did not meet tests of significance at all time periods. Decreases during the test period were of the order of 10 percent, except for total cholesterol among covered rod users where the decrease was less. Cholesterol to HDL-cholesterol ratios did not differ significantly from control values at any sampling period.     

Abnormal endocrine profile among women with confirmed or presumed ovulation during long-term Norplant use

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

Hormonal changes during the first year of use of subdermal levonoregestrel implants, Norplant

Sixty-three women had NORPLANT implants inserted during the first eight days of the menstrual cycle. Blood specimens were withdrawn at the time of insertion and every three days during one of the following months of observation; the first, third, sixth, ninth and twelfth month after insertion. Ten subjects were sampled at multiple times during implant use. A total of 83 months of observation was available. The serum concentrations of levonorgestrel (LNG), FSH, LH, prolactin (PRL), estradiol (E2) and progesterone (prog) were measured in each specimen. LNG concentration rapidly declined during the first 15 days of use, the decline became more gradual during the subsequent two weeks, and an almost steady level was reached during the remainder of the year. There were no significant trends of change in the levels of FSH, LH, E2 and prog during the year. Frequent peaks in E2 concentration were observed and were generally associated with or followed by LH surges. PRL concentration showed a slight but significant rise during the second half of the year. Rises in prog concentration suggestive of ovulation occurred in 36 percent of the months of observation. However, in all these instances, there were evidences suggestive of deficient luteal phase. The bleeding episodes were usually, but not always, related to decline in E2 and prog concentrations.     

Bleeding pattern, outcome of accidental pregnancies and levonorgestrel plasma levels associated with method failure in Norplant implants users

The aim of this study was to characterize the bleeding pattern, the outcome of pregnancies and the levonorgestrel plasma levels associated with method failures in Norplant implants users. Nineteen pregnancies are reported in 458 woman and 21,589 woman-months observed during the first eight years of Norplant use. Pregnancy rates increased slightly during the first six years of use, attaining a Pearl Index above three thereafter. All women who became pregnant had experienced a regular bleeding pattern in the six months preceding conception. Levonorgestrel plasma levels observed at different intervals before conception and during the conceptional cycle were similar to those observed in non-pregnant women at comparable intervals after Norplant insertion. The nineteen pregnancies ended in thirteen term deliveries, one premature delivery, three abortions and two ectopic pregnancies. No abnormalities were found in the infants. The two ectopic pregnancies are the only ones reported for Norplant users in The Population Council studies. The overall incidence is less than 0.8 per 1000 woman-years.     

Plasma levels of levonorgestrel and free levonorgestrel index in women using NORPLANT implants or two covered rods (NORPLANT-2)

Plasma levels of levonorgestrel, sex hormone binding globulin (SHBG) and estradiol were studied during four years in 283 healthy women using either NORPLANT implants or two covered rods (NORPLANT-2). The women were randomized to use either type of implant. Both implant systems have previously been shown to have similar release rates of levonorgestrel. In both groups plasma levels of levonorgestrel decreased throughout the study, and there were no statistically significant differences between the two groups in mean plasma levels of levonorgestrel. During the study 8 women became pregnant. All pregnancies but one occurred after 35 months of implant use and only in women using the covered rods. No significant differences were seen between the women who became pregnant and the rest of the group using two covered rods with respect to plasma levels of levonorgestrel. SHBG capacity tended to be somewhat higher in women using the two covered rods. As levonorgestrel is to a great extent bound to SHBG, and in that form not biologically active, a "free levonorgestrel index" was calculated as a ratio between levonorgestrel and SHBG. This index was significantly lower in users of two covered rods than in users of NORPLANT implants at 1, 12 and 48 months of use. Women who became pregnant had significantly lower "free levonorgestrel index" than had the rest of the group. It is postulated that the difference in "free levonorgestrel index" between users of the two implant systems reflect differences in release rate, the covered rods having a lower release rate of levonorgestrel than NORPLANT throughout the observation period. It is concluded that "free levonorgestrel index" is a better parameter than levonorgestrel plasma levels to describe implant function, and to discriminate women who are at risk of pregnancy.     

Immediate postabortal contraception with the levonorgestrel intrauterine device, Norplant, and traditional methods

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.     

Hormonal changes associated with bleeding during low dose progestogen contraception delivered by Norplant subdermal implants

The main side effect associated with the use of Norplant contraceptive implants is a disruption of the menstrual bleeding pattern. To explore the relationship between bleeding and hormonal changes, we analyzed the estradiol (E₂) and progesterone (P) patterns that preceded bleeding episodes or that corresponded to periods of amenorrhea in 103 cycles observed among 82 women using Norplant subdermal implants.Five different bleeding patterns were defined: normal (24–25 day cycles), oligomenorrhea (46–90 day cycles), amenorrhea (over 90 day cycles), irregular/frequent bleeding (less than 25 day cycles), and prolonged bleeding (continuous bleeding/spotting for more than 10 days). All normal cycles were associated with a rise followed by a fall in E₂ levels preceding bleeding. In half of the normal cycles (28/54), a rise and fall of P was also observed. The same pattern was found in oligomenorrheic cycles, but only two of 12 cycles had a rise and fall of both E₂ and P.None of the subjects with amenorrhea had luteal activity. Six of the nine amenorrheic cycles displayed persistently low E₂ levels (below 75 pg/ml). The remaining three had a moderate elevation in E₂ levels during the sampling period. Sixty percent of the subjects who showed irregular/frequent bleeding (15/25) had low E₂ levels (<75 pg/ml), without luteal activity, and bleeding occurred without clear evidence of a further drop in E₂ levels. In the remaining 40%, bleeding was preceded by a rise and drop of E₂ without luteal activity, with the exception of one woman, who exhibited a rise and fall of both E₂ and P.Samples were obtained in only three subjects during continuous bleeding. One had low E₂ levels, and the remaining two bled continuously, in spite of having E₂ levels in the normal range.We conclude that ovarian hormones continue to influence endometrial shedding during the use of Norplant contraceptive implants.Resumé L'effet secondaire principal lié à l'utilisation de l'implant contraceptif Norplant est la perturbation du cours normal des pertes sanguines menstruelles. Pour explorer la relation entre le saignement et les changements homonaux, nous avons analysé, sur 103 cycles observés chez 82 femmes utilisant les implants sous-cutanés Norplant, les caractéristiques de l'estradiol (E₂) et de la progestérone (P) au cours des épisodes qui précèdent les pertes menstruelles ou qui correspondent aux périodes d'aménorrhée.Nous avons défini cinq types de saignement différents: normal (cycles de 24 à 45 jours), oligoménorrhée (cycles de 46 à 90 jours), aménorrhée (cycles de plus de 90 jours), saignements irréguliers/fréquents (cycles de moins de 25 jours), saignements prolongés (continus/microrragies pendant plus de 10 jours).Tous les cycles normaux ont été associés à une élévation, suivie d'une baisse, des niveaux de E₂ avant le saignement. On a également observé une élévation puis une baisse de P dans la moitié des cycles normaux (28/54).Les mêmes caractéristiques ont été retrouvées dans le groupe des oligoménorrhées, mais une élévation et une baisse à la fois de E₂ et de P n'ont été constatées que pour deux sur 12 cycles.Aucune activité lutéale n'a été constatée dans les cas d'aménorrhée. Six parmi les neuf cycles d'aménorrhée ont révélé de façon persistante des niveaux faibles de E₂ (inférieurs à 75 pg/ml). Pour les trois autres, les niveaux de E₂ étaient modérément élevés pendant toute la période d'investigation.Chez 60% des patientes ayant des saignements irréguliers/fréquents (15/25), les niveaux de E₂ étaient bas (<75 pg/ml), l'activité lutéale était inexistante et le saignement s'était produit sans preuve concluante d'une baisse supplémentaire du niveau de E₂. Dans les 40% de cas restants, les saignements étaient précédés d'une élévation puis d'une baisse de E₂, sans activité lutéale, à l'exception d'une femme qui présentait à la fois une élévation et une baisse de E₂ et de P.Des échantillons ont été obtenus dans trois cas seulement de pertes sanguines continues. Chez une de cas femmes, les niveaux de E₂ étaient bas et les deux autres présentaient des pertes continues malgré des niveaux de E₂ restant dans la gamme normale.Nous en concluons que les hormones ovariennes continuent d'influer sur les pertes de tissu endométrial pendant l'utilisation des implants contraceptifs Norplant.

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Resumen El principal efecto secundario relacionado con la utilización de implantes anticonceptivos Norplant es la perturbación del curso normal de las pérdidas sanguíneas menstruales. A fin de explorar la relación entre las pérdidas menstruales y los cambios hormonales, analizamos, en 103 ciclos observados en 82 mujeres que utilizaban implantes subcutáneos Norplant, las características del estradiol (E₂) y de la progesterona (P) en el curso de los episodios anteriores a las pérdidas menstruales o que corresponden a períodos de amenorrea.Definimos cinco tipos de pérdidas diferentes: normales (ciclos de 24 a 45 días), oligomenorreas (ciclos de 46 a 90 días), amenorreas (ciclos de más de 90 días), pérdidas irregulares/frecuentas (ciclos de menos de 25 días) y pérdidas prolongadas (continuas/microrragias durante más de 10 días).Todos los ciclos normales estuvieron asociados con una elevación, seguida de una disminución, de los niveles de E₂ antes de las pérdidas. Se observó asimismo una elevación y luego una disminución de P en la mitad de los ciclos normales (28/54).Las mismas características se observaron en el grupo de las oligomenorreas, pero sólo se observó una elevación y una disminución al mismo tiempo de E₂ y de P en dos de 12 ciclos.No se observó ninguna actividad lútea en los casos de amenorrea. Seis de los nueve ciclos de amenorrea señalaron de modo persistente niveles bajos de E₂ (inferiores a 75 pg/ml). En los tres restantes, los niveles de E₂ fueron moderadamente elevados durante todo el período de investigación.En el 60% de las pacientes con pérdidas irregulares/frecuentes (15/25), los niveles de E₂ fueron bajos (<75 pg/ml), sin actividad lútea, y las pérdidas se produjeron sin pruebas concluyentes de una disminución adicional del nivel de E₂. En el 40% restante, las pérdidas fueron precedidas de una elevación y luego una disminución de E₂, sin actividad lútea, con la excepción de una mujer que presentaba al mismo tiempo una elevación y una disminución de E₂ y de P.Se obtuvieron muestras en tres casos solamente de pérdidas continuas. Una de las mujeres señaló niveles bajos de E₂ y las otras dos presentaron pérdidas continuas a pesar de que los niveles de E₂ estaban en la gama normal.Llegamos a la conclusión de que las hormonas ováricas continúan influyendo sobre las pérdidas de tejido endometrial durante la utilización de implantes anticonceptivos Norplant.

     

Acceptability of levonorgestrel subdermal implants versus tubal ligation for long-term contraception in a rural population of Zimbabwe

This prospective cohort study of 257 rural Zimbabwean women was designed to compare patient satisfaction with levonorgestrel subdermal implants (Norplant and reg;) versus tubal ligation (TL) as a method of long-term contraception. Women were equally satisfied with both methods. At 1 year, 96% of Norplant users and 97% of the TL group reported being “satisfied” or “very satisfied,” and 98% of Norplant users, and 99% of the TL cohort would recommend their chosen method to a friend or relative. Rating scores at both 6 months and 1 year were high and equal, with women in each cohort rating their method, on average, as 9 out of 10. Norplant users were significantly more likely to rate birth spacing as a reason for satisfaction with their method, whereas women in the TL cohort were more likely to select multiparity. The 1-year continuation rate with Norplant was 90%, with 4% discontinuing in order to have more children. Selecting the most appropriate method depends primarily on the potential desire of the woman to have more children.     

Tamoxifen treatment of bleeding irregularities associated with Norplant use

ObjectivesTo evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use.Material and MethodsRandomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception.ResultsThere was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group.ConclusionTamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.     

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

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

Immediate postabortal contraception with Norplant: levonorgestrel, gonadotropin, estradiol, and progesterone levels over two postabortal months and return of fertility after removal of Norplant capsules

Six Silastic levonorgestrel-releasing capsules, Norplant, were introduced subcutaneously into the ventral aspect of the left forearm or upper arm of thirteen patients immediately after first trimester pregnancy termination. Blood samples were taken twice a week over two months after abortion and from one subject over one month after removal of Norplant capsules. Plasma concentrations of levonorgestrel were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. If removal of Norplant capsules took place because of planning pregnancy, the subjects were asked to inform us if they had become pregnant. During the first month after abortion the mean levonorgestrel concentration (489 pg/ml) was statistically significantly higher than during the second month (237 pg/ml). The mean estradiol values fell to prefollicular levels within four days, remaining a little suppressed. The mean progesterone concentrations were below 2 ng/ml three days after abortion. Three subjects had a transient increase in plasma progesterone concentrations nine days after abortion. Thereafter no ovulatory progesterone concentrations were seen. The LH concentrations ranged within normal values of the follicular phase and FSH values were just beneath the lower limit of follicular phase FSH values, apart from a few peaks, indicating mild suppression. After removal of Norplant capsules, progesterone concentrations increased to ovulatory levels fifteen days after removal. The Norplant capsules were removed from two subjects because of planning pregnancy and they delivered healthy babies 9.5 and 12.5 months after removal.