Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microvascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in vascular fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of vascular fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.

Prior evaluations of carbohydrate metabolism in Norplant implant users, using the oral glucose tolerance test, have shown mild but clinically insignificant deterioration of insulin sensitivity. Using the more sensitive insulin tolerance test, the effects of the Norplant implant system on insulin sensitivity was studied in normal women. Insulin tolerance tests were performed before Norplant implant insertion in ten ovulatory female volunteers and repeated after 12 weeks of use. Both fasting glucose and fasting insulin values were similar before and after the use of Norplant implants. There was no significant difference in either the Kitt glucose value or the Kitt insulin value at baseline and at 3 months of use. Furthermore, the insulin-to-glucose ratio did not differ before and after the use of Norplant implants. There was a significant correlation with BMI and Kitt glucose value (r = -0.45, p < .05), as well as between fasting insulin and BMI (r = 0.6, p = 0.006). In the first three months of use, the levonorgestrel-containing implant system, Norplant, does not affect sensitivity to insulin or glucose in normal, nondiabetic women.

During the five year review period (January 1993-December 1997), 19,470 clients visited the family planning clinic of the University of Nigeria Teaching Hospital, Enugu. Of these, 2402 clients (12%) were new patients and 17,068 (88%) were old patients. Among the new clients, 2262 (94%) eventually accepted a contraceptive method. The majority of the women (60%) chose the intrauterine contraceptive device (IUCD), 20% chose the injectables, while bilateral tubal ligation and norplant were chosen by 8% and 7%, respectively, of the clients. The oral contraceptive pill was the least popular (1%). Variations in the pattern of contraceptive use among clients at the family planning clinic were discussed. Measures to increase the contraceptive prevalence, and particularly strategies to meet the specific contraceptive needs of clients at the clinic, were also examined.

Norplant, a systemic contraceptive, has been used extensively throughout the world. A major problem for consumers utilizing Norplant has been irregular, unpredictable uterine bleeding or spotting. This study seeks to determine whether or not an appropriate treatment could be found that will reduce the incidence of spotting and bleeding. Both a pilot study and an interim report of a multi-center trial utilizing ethinyl estradiol 20 micrograms for 10 days, versus Ibuprofen 800 mg three times a day for 5 days, versus placebo is reported. Based on the interim analysis of the multi-center trial, there is a reduction in the mean number of spotting days with one of the three treatments compared to the other two treatments (p = 0.044). There was no difference in the number of bleeding days between treatment regimen. It appears from a review of the literature that both oestrogen, progesterone, and non-steriodal anti-inflammatory agents may reduce the number of bleeding days or inhibit acutely the bleeding in women utilizing Norplant. The completion of this randomized multi-center trial will hopefully give us further insight into an effective treatment for controlling the irregular bleeding and/or spotting that occurs in Norplant users.

Seventy to 80% of women using subdermal contraceptive implants (Norplant) have reported side effects, such as uterine bleeding, headache, mastalgia, and local pain at the site of insertion. This is a report of two patients who presented with peripheral neuropathy associated with the implants. One patient responded to removal of the device. The second patient, whose symptoms were thought to be related to trauma, was successfully treated with nonsteroidal anti-inflammatory agents.

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed>>/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age>>/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged>>/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.

Endometrial bleeding problems can be the major reason for discontinuing progestin-only contraception. In this study the endometrial angiogenic response in Norplant users was found to be lower than in women with normal menstrual cycles. These disturbances in angiogenic response may be caused by oxidant-antioxidant imbalance in the endometrium. The aims of this study were to investigate the effect of progestin only contraceptives on blood concentrations of lipid peroxide and vitamin E, and the effect of vitamin E supplementation on endometrial angiogenic response in vitro. The subjects for this study were Norplant users, depo-medroxyprogesterone acetate (DMPA) users, and controls. Circulating lipid peroxide and vitamin E concentration was measured by routine methodology. Endometrial angiogenic response was assayed using an endothelial cell migration assay. The results showed that the blood concentrations of lipid peroxide from Norplant users with bleeding problems were significantly higher than normal menstrual controls (P < 0.05) and supplementation of vitamin E (in vitro) increased the endometrial angiogenic score. Blood concentrations of lipid peroxide were significantly increased (P < 0.05), and the blood concentrations of vitamin E were significantly decreased (P < 0.05) after 3 months exposure to Norplant or DMPA. The endometrial angiogenic scores in Norplant and DMPA users were significantly lower than in controls (P < 0.02). It is concluded that in progestin-only contraceptive users, higher lipid peroxide and lower vitamin E concentration may cause endometrial cell damage and decrease the endometrial angiogenic response. It is suggested that vitamin E supplementation may counteract these unwanted side-effects.

Levonorgestrel has an inhibitory effect on sex hormone binding globulin (SHBG). This decrease in SHBG leads to an increase in the free levonorgestrel index (FLI), which has a stronger biological effect. The interaction between serum levels of levonorgestrel and SHBG in long-term users of Norplant implants has been described. This study was designed to understand the same interaction immediately after the insertion of the implants, in a group of 16 women, sampled at 0 and 6 h and at 1, 3, and 7 days after Norplant implant insertion. Peak serum levonorgestrel levels were achieved at 24 h after insertion, remaining stable on day 3 and decreasing by>> 10% by day 7. SHBG did not change during the first 24 h, but decreased by 19% and 60% on days 3 and 7, respectively. FLI more than doubled from day 1 to day 7 after insertion. The large decrease in SHBG and doubling of FLI is not followed by a similar reduction in levonorgestrel, which is hard to explain without an increase in the release rate of the steroid from the capsule.

Levonorgestrel serum levels and sex hormone binding globulin (SHBG) were measured in 82 women during different years of use of Norplant implants. The ratio between levonorgestrel and SHBG was calculated as an indicator of the free biologically active fraction of levonorgestrel (free levonorgestrel index, FLI). These parameters were then correlated with the presence of luteal activity, as determined by progesterone levels above 9.6 nmol/L, in a sampling run of 10 samples taken twice a week for five consecutive weeks. Levonorgestrel serum levels remained constant around 1.0 nmol/L during the five-year period. SHBG levels were below normal for the first 18 months of use, returning to normal levels during the last three years of use. The FLI in the first two years was significantly higher than that observed in the later years. The frequency of cycles with luteal activity was 12% during the first 2 years, increasing to 44% in the latter years, when FLI levels were lower. Our results suggest that the changes in SHBG and consequently in the free biologically active fraction of levonorgestrel may largely account for the differences in degree of ovarian suppression observed between the first two years of use of Norplant implants and the latter three, even in the absence of a significant variation in total levonorgestrel concentrations.

Estradiol-(E2) plasma levels were assessed in forty-seven women treated for one through seven years with the same set of Norplant implants. Each woman was subjected to one (n = 34), two (n = 11) or three (n = 2) sampling runs. At each sampling run, blood samples were drawn every third or fourth day during 5 or 6 consecutive weeks. Sampling runs were classified as ovulatory (n = 11), anovulatory (n = 49) or uncertain (n = 1) according to progesterone levels. Controls were Copper T users (n = 8), all classified as ovulatory. No significant differences were found for the mean E2 levels between Norplant users and Copper T users and between ovulatory and anovulatory cases. The mean of the peak E2 value found in each sampling run was significantly higher in anovulatory Norplant subjects than in the control group. The mean of the minimum E2 level observed was significantly lower in Norplant cases than in Copper T users. A single woman from the Norplant group and none from the Copper T group had all E2 values below 370 pmol/l. The inhibition of the reproductive function induced by Norplant implants is associated with a wider range of E2 circulating levels. None of the values observed at the extremes should cause serious concerns. High peaks are transitory and opposed by the antiestrogenic effect of levonorgestrel. Persistent low levels which could be associated with a hypoestrogenic state were observed in a single case.

OBJECTIVE

To review the implications of pregnancy in women in their forties and the contraceptive options open to them.

METHODS

Medline and popline reviews of the literature.

RESULTS

Women in their forties are still potentially fertile, and pregnancy in this age group is attended with increased maternal mortality, spontaneous abortion, fetal anomalies and perinatal mortality. In developing countries, these risks are compounded by high parity and poor medical care. Contraception for women in this age group has special risks and benefits, both should be balanced to choose between the different options available. Recent epidemiological and clinical pharmacology studies have indicated the safety of extending the use of combined oral contraceptives (COCs) beyond the age of 35 years and up to menopause. The improved picture of COCs has largely resulted from the use of low-dose-formulations, and avoidance of their use in women with risk factors for developing cardiovascular diseases. Besides their high reliability, which is desirable at this age, COCs will prevent the occurrence of climacteric symptoms and menstrual irregularities which are frequently complained of in the premenopausal years. Moreover, the use of COCs has a substantial protective effect against ovarian and endometrial cancers. Women who have reasons for avoiding COCs can use progestogen-only contraceptives like pills, depot injectables and implants. Norplant combines high efficacy and the long-term effect. Both copper-releasing and levonorgestrel-releasing IUDs (LNG-IUD) combine the advantages of high efficacy and long term effect. The reduced fecundity above the age of forty can allow extending the use beyond the accepted term, and up to one or two years beyond the menopause without the need for replacement. The levonorgestrel IUD has the advantage of reducing the amount of menstrual bleeding. The extent of use of barrier methods will depend upon the availability of a back-up by abortion service in case of failure. The condom has the added benefit of protection against STDs. Male or female sterilization is an excellent contraceptive option, provided that this approach is culturally acceptable and available at reasonable cost and low risk.

CONCLUSIONS

Increasing the number of contraceptive options available to premenopausal women will improve proper counseling and enhance compliance.

In this study involving 100 women, the metabolic changes seen with Norplant use were evaluated. Besides a significant increase in serum bilirubin, there were no other changes in liver function to suggest possible hepatocellular dysfunction at the end of five years. Even the raised mean levels of bilirubin remained within the normal clinical range for the local population. As regards lipid metabolism, total triglycerides, cholesterol and LDL-cholesterol were decreased through the five years of Norplant use. The HDL-cholesterol showed a significant increase in the first year; it then decreased over the years to its preinsertion level at the end of five years. As a result, the HDL-cholesterol/Total cholesterol - HDL-cholesterol showed a significant increase in the first year and then decreased to almost its preinsertion value at the end of five years. The findings appear to indicate Norplant use not to be contributory to cardiovascular risk. The use of Norplant was not associated with any significant effect on carbohydrate metabolism.

Changes in lipid metabolism in 25 healthy female volunteers during a 24-month application of Norplant-2 were evaluated in an open clinical trial. Total serum cholesterol decreased significantly (p less than 0.05/p less than 0.05) by 10%/9% after 12 months and by 3%/7% (n.s./n.s.) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). Serum triglycerides decreased by 34%/28% (n.s./p less than 0.05) after 12 months and by 29%/25% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). HDL-cholesterol decreased significantly by 18%/12% (p less than 0.01/p less than 0.05) after 12 months and by 12%/12% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). No statistically significant difference between serum levels of LDL-cholesterol prior to and after 12 and 24 months of Norplant-2 use could be found. VLDL-cholesterol levels decreased significantly by 38%/38% (p less than 0.05) after 12 and by 25%/25% after 24 months of Norplant-2 application (p less than 0.01) (all subjects/subjects completing 24 cycles). Apolipoprotein Al decreased significantly by 23%/23% (p less than 0.001/p less than 0.01) after 12 and by 21%/22% after 24 months of Norplant-2 application (p less than 0.01/p less than 0.01) (all subjects/subjects completing 24 cycles). No statistically significant difference between apolipoprotein All levels prior to and after 12 and 24 months of Norplant-2 implantation could be found. Apolipoprotein B decreased significantly by 27%/17% (p less than 0.05/p less than 0.05) after 12 months of Norplant-2 application (all subjects/subjects completing 24 cycles). The decline after 24 months of Norplant-2 use was not significant. Changes in lipid metabolism caused by oral hormonal contraceptives differ in the various clinical trials; however, most investigators found that serum levels of total cholesterol and triglycerides increase under the application of OCs. Contrary to this, a decrease of total cholesterol and triglycerides under Norplant-2 use was noted. Furthermore, we found a significant decrease of lipoproteins and apolipoproteins--with the exception of LDL-cholesterol and apolipoprotein All, which did not show any significant modifications. Thus, Norplant-2 seems to be non-contributory to cardiovascular risk and might even provide protection against such risks.

A longitudinal, short-term study of women using NORPLANT (levonorgestrel implants) was conducted. Cholesterol content of the major lipoproteins along with total cholesterol and triglycerides were measured in fasting blood samples from 32 women volunteers. Results for lipids and lipoproteins determined 6 and 12 months post-NORPLANT insertion were compared with values obtained for samples taken just before implantation. Total serum triglycerides was significantly reduced (p < 0.01) from 1.14 +/- 0.44mmol/l (mean +/- SD) to 0.89 +/- 0.25mmol/l at six and to 0.89 +/- 0.34mmol/l at twelve months post-insertion. Serum total cholesterol was 3.97 +/- 0.53mmol/l at the time of insertion while at six and twelve months post-insertion, they were 3.65 +/- 0.49mmol/l and 3.56 +/- 0.71mmol/l, respectively. These changes in values from the time of insertion to twelve months, were statistically significant (P < 0.02). As regards lipoprotein fractions, high density lipoprotein-cholesterol (HDL-chol) exhibited statistically significant reduction (P < 0.001) from 1.38 +/- 0.34 mmol/l to 0.71 +/- 0.30 mmol/l (mean +/- SD) six months post-insertion. Although the value had improved to 1.14 +/- 0.38mmol/l by twelve months, the value was still significantly different from the pre-insertion value. The low density lipoprotein-cholesterol (LDL-chol) had a mean value (+/- SD) of 2.08 +/- 0.45 mmol/l at the time of insertion. This was significantly elevated (P < 0.001) at six months to 2.54 +/- 0.48mmol/l (mean +/- SD). The twelve-month post-insertion value of LDL-chol (2.02 +/- 0.79) was similar to the pre-insertion value. The shift in HDL-cholesterol and LDL-cholesterol within six months followed by a virtual return to the pre-insertion values may represent only a transient change in metabolism of lipids and lipoproteins consequent upon NORPLANT contraception.

Depo-medroxyprogesterone acetate (DMPA) is an effective injectable contraceptive with worldwide availability. However, it is associated with a high incidence of breakthrough bleeding (BTB) during the first 6 months of use which often leads to discontinuation. Mifepristone is a progesterone receptor antagonist that has been demonstrated to decrease BTB caused by the levonorgestrel subdermal implant (Norplant). The purpose of this study was to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks. Percent days of BTB and number of cycles with bleeding intervals>> or =8 and>> or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors.

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.

The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 micrograms/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant. There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch.

The expression of endometrial progesterone receptor mRNA during the human menstrual cycle and in Norplant users was studied using digoxigenin-labelled ribonucleic probes for in-situ hybridization on 6 microns paraffin embedded endometrial sections. The staining intensity was scored blind semi-quantitatively. Blood ovarian steroid concentrations were measured in Norplant users. All data were analysed by analysis of variance. Glandular progesterone receptor mRNA concentrations were low during the menstrual-to-early proliferative stage but increased during the early-to-mid to late-proliferative stage then declined non-significantly over the secretory stage. No such variation was observed in stromal cells. Progesterone receptor mRNA concentrations were lower in Norplant than controls during early-to-mid to late-proliferative stages (in glandular epithelium and stroma) and during secretory stage (in stroma only). Norplant subjects with amenorrhoea had higher concentrations of stromal progesterone receptor mRNA but lower plasma oestrogen concentrations than subjects with breakthrough bleeding. The pattern of variation in progesterone receptor mRNA concentrations during the normal menstrual cycle resembles the published pattern for the receptor protein. The results demonstrate: (i) a differential sensitivity of glandular and stromal progesterone receptors to steroid regulation; (ii) in contrast to previous findings of an increase in immunoreactive progesterone receptor protein in Norplant endometrium, progesterone receptor mRNA concentrations in these tissues were reduced; and (iii) there was significantly more progesterone receptor mRNA in subjects with amenorrhoea than in those with breakthrough bleeding.

In December 1990, the Food and Drug Administration approved Norplant (Wyeth-Ayerst, Radnor, PA) for general US use. This approval comes during a time period when the number of contraceptors relying on sterilization has risen, echoing known dissatisfaction with other reversible methods. During the past year, data have been presented that refute concern that Norplant may be an abortifacient. Continued estradiol production with development of follicles and ovulation in regularly menstruating women was documented. Ovulatory dysfunction among Norplant users, despite follicular development, was also detailed. Changes in carbohydrate metabolism were confirmed to be clinically insignificant. International development of biodegradable and non-biodegradable implants and 1, 3, or 6 months injectables continues. These injectable and implantable contraceptives promise diversity in contraceptive options to match diversity in contraceptive need and life style.

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.

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament protein family. They are expressed in all simple epithelial tissues, including endometrium, and are recognised as dynamic structures that can be affected by numerous external factors. The Norplant system is a subdermal slow release levonorgestrel implant commonly used as a long-acting progestogen contraceptive. Norplant implants have been shown to have atrophic effects on endometrial epithelial and stromal cells, and cause a range of endometrial bleeding problems among users. The aim of this study is to describe changes in the immunohistochemical expression and distribution of cytokeratins 8, 18 and 19 in endometrial epithelial cells of Norplant implants users and normal menstrual cycle controls. Endometrial biopsies were collected from 65 control normal cycle women and 37 Norplant implants acceptors. The normal menstrual cycle was classified histologically into 9 stages; one menstrual, five proliferative and three secretory. Norplant implants bleeding patterns were categorised into 6 groups according to current World Health Organisation (WHO) definitions; amenorrhoea, frequent bleeding, infrequent bleeding, irregular bleeding, "normal" bleeding, and prolonged bleeding. The tissues were fixed in formalin, embedded in paraffin, and stained immunohistochemically. Semi-quantitative scoring of the staining intensity was performed. Apical versus basal intracellular cytokeratin distribution was also evaluated. The staining intensity was significantly stronger in control endometrial tissue compared to Norplant implants tissue. In control tissues, cytokeratins were predominantly located in the apical region of epithelial cells (52% of biopsies) and in Norplant implants tissues they were predominantly distributed equally between the apical and basal portions of epithelial cells (43% of biopsies). There was no particular cytokeratin distribution pattern associated with the different stages of normal cycle or the different Norplant implants bleeding patterns. It was concluded that long-term exposure to levonorgestrel significantly reduced the cytokeratin expression in endometrial epithelial cells (P < 0.001).

A causal relationship between sex steroids and meningioma proliferation has long been suspected. We report a case of the clinical progression of a sphenoid wing meningioma after the placement of Norplant, a subcutaneous contraceptive implant containing levonorgestrel, a progesterone agonist. Although not proof of causation, this observation lends further credence to the importance of progesterone receptors in the growth and possible treatment of meningiomas.

Ten breastfeeding women had the contraceptive implants NORPLANT inserted between days 30 and 39 postpartum. The immunoglobulins IgG, IgM and IgA were measured in the serum of the mothers and the infants before insertion and five months later. A control group of breastfeeding mothers who did not use any contraception or used local barrier methods were similarly studied. Although there were changes in the immunoglobulin levels with time in both mothers and infants, there were no group differences; this indicates that the use of NORPLANT does not influence these factors of humoral immunity.