Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study.

Combined oral contraceptives (OC) are known to increase the risk of venous thromboembolism. The aim of this randomized, cycle-controlled, cross-over study in 28 healthy volunteers was to assess potential differences between the effects of an OC containing 150 microg levonorgestrel (as representative of the so-called second generation OC) and an OC containing 150 microg desogestrel (as representative of the third generation OC) in combination with 30 microg ethinylestradiol on several coagulation factors and markers of thrombin formation. All participants used each OC for two cycles, and were switched to the other OC after a washout period of two menstrual cycles. The plasma concentrations of factors II, VII, X, and fibrinogen significantly increased during use of both the levonorgestrel- and desogestrel-containing OC's. The plasma concentrations of factor VIII increased, and of factor V decreased, changes which only reached statistical significance during the use of the desogestrel-containing OC. During exposure to the desogestrel-containing OC, as compared with the levonorgestrel-containing OC, both factor VII and factor II showed a greater increase (FVII: 32% and 12% respectively; p <0.0001; FII: 16% and 12% respectively; p = 0.048), whereas factor V showed a greater decrease (-11% and -3% respectively; p = 0.010). Only one of the markers for ongoing coagulation (prothrombin fragment 1+2) showed a significant increase during OC use, whereas concentrations of thrombin-antithrombin complexes and soluble fibrin remained unchanged. For these markers, there was no difference between the tested OC's. We conclude that there are differences between the effects of levonorgestrel and desogestrel-containing OC's on some coagulation factors. Whether these changes provide a biological explanation for the reported differences in venous thromboembolic risk is as yet unclear. The real challenge now becomes to define a pattern of changes in the various systems which, if affected simultaneously, may tip the hemostatic balance towards a prethrombotic state and may lead to overt clinical venous thromboembolism.

Teenage pregnancy and ethnicity in The Netherlands: frequency and obstetric outcome.

OBJECTIVES: To study differences in frequency and obstetric outcome of teenage pregnancy (not ending in induced abortion) between the main ethnic groups in The Netherlands. DESIGN: A retrospective cohort study based on the 1990-93 birth cohort in the National Obstetric Registry. SUBJECTS: A total of 10,583 teenagers and 54,501 20-24-year-old women who had a singleton pregnancy and were primiparous. MAIN OBSTETRIC OUTCOME MEASURES: These were perinatal death occurring between the 16th week of pregnancy and 24 h after birth, preterm birth and operative delivery (vaginal extraction and Cesarean section). METHOD: Comparison of the frequency of teenage pregnancy between ethnic groups and by bivariate and multivariate analysis of the three outcome measures between the teenage groups, the teenage groups and ethnically related 20-24-year-old women, and the teenage groups and Dutch 22-24-year-old women. RESULTS: A total of 55.2% of pregnant teenagers had non-Dutch ethnicity compared to 13.8% of all pregnant women. Islamic-Mediterranean teenagers constituted the largest group, one in four of all primiparous Mediterranean women being younger than 20 years of age, followed by black teenagers. Except for Hindustani teenagers, perinatal death occurred in all non-Dutch teenage groups more frequently than in Dutch teenagers, but the differences were only significant for black teenagers (odds ratios of black compared to Dutch teenagers were 2.89 (95% confidence interval (CI) 1.89-4.4) and 1.53 (95% CI 1.19-1.98), respectively). Rates for preterm birth were higher in black and Asian than in Dutch teenagers, but the difference was only significant for black teenagers (odds ratio 1.53, 95% CI 1.19-1.98). Compared to ethnically related 20-24-year-old women, rates of perinatal death and preterm birth were significantly higher in Dutch, black and Asian teenagers and, for preterm birth only, in Mediterranean teenagers. Correction for preterm birth showed that only part of these differences in perinatal death could be explained by preterm birth. Vaginal extraction and Cesarean section occurred less frequently in teenagers than in ethnically related (and in Dutch) 20-24-year-old women. Mediterranean teenagers had the lowest Cesarean section rate and Blacks the lowest vaginal extraction rate. CONCLUSION: Teenage pregnancy in The Netherlands is much more common in minority ethnic groups than in the indigenous population, particularly among Islamic-Mediterraneans and Blacks. Obstetric outcomes vary considerably, these being best in Hindustani and poorest in black teenagers, and being worse in teenagers than in 20-24-year-old women. However, teenagers less often had assisted delivery.

[Teenage pregnancy distribution by ethnicity in the Netherlands, 1990-1993]. / Tienerzwangerschappen naar etniciteit in Nederland, 1990-1993.

OBJECTIVE: To determine and compare the obstetrical results of teenage pregnancies among the main ethnic groups in the Netherlands. DESIGN: Retrospective cohort study. METHODS: From the cohorts 1990-1993 of the Landelijke Verloskundige Registratie (LVR, National Obstetrical Registration) the data were analysed concerning primiparae aged 14-19 years with a single pregnancy. RESULTS: During the period 1990-1993, 14.9% of the women whose parturitions were recorded in the LVR were allochtonous, of the teenage pregnancies recorded 55.2% occurred in an allochtonous population group. The numbers (percentages) of teenage pregnancies (primiparae, singles) in the various ethnic groups were 4742 (2.2%) in the autochtonous group, 3974 (25.9%) in the (Muslim) mediterraneous, 340 (7.8%) in the non-Dutch European, 588 (14.9%) in the Afro-allochtonous, 316 (9.7%) in the Hindustani, 263 (5.5%) in the Asian (excluding Hindustani and Asian Turkish) and 360 (10.4%) in the remaining ethnic groups. Hindustani and orthodox Muslims regard teenage pregnancy positively. The perinatal mortality was higher among Afro-allochtonous than among autochtonous teenagers (odds ratio: 2.89 (95% confidence interval: 1.89-4.40)), and the same was true of premature and immature parturition. Both findings occurred significantly more often in the autochtonous, Afro-allochtonous and Asian population parts than among women of the same ethnic groups aged 20-24 years. In relation to autochtonous women aged 20-24, the odds ratios for perinatal mortality and premature and immature parturition among Afro-allochtonous women were 3.64 (2.50-5.30) and 2.02 (1.59-2.55), respectively; after correction for pre- and immature parturition the odds ratio for perinatal mortality decreased to 2.35 (1.51-3.66). Low birth weight was less frequent among the Mediterraneans and more frequent among the Afro-allochtonous and Hindustani than among the autochtonous. Induced vaginal deliveries were less frequent among allochtonous teenagers, the risk of caesarean section was lower among Mediterranean teenagers but higher among Afro-allochtonous, Hindustani and other ethnic teenagers than among autochtonous teenagers. All groups of teenagers had lower frequencies of induced delivery than women of the same ethnic groups aged 20-24 years. CONCLUSIONS: Teenage pregnancy in the Netherlands occurs much more often among allochtonous than among autochtonous women and is encountered most often among (Muslim) mediterranean and Afro-allochtonous groups. Obstetrical results vary greatly from one ethnic teenage group to another; they are poorest among the Afro-allochtonous, best among the Hindustani group. Among the mediterranean teenagers, they are similar to those among the autochtonous group.

Perinatal death in ethnic minorities in The Netherlands.

OBJECTIVES: To investigate differences in perinatal death rate and associated obstetric risk factors between ethnic groups in the Netherlands. DESIGN: Retrospective cohort study based on the 1990-1993 birth cohorts in the National Obstetric Registry. SUBJECTS: 569,743 births of which 85,527 were for women belonging to ethnic minorities. MAIN OUTCOME MEASURES: Perinatal death occurring between 16th week of pregnancy and 24 hours after birth. METHOD: Bivariate and multivariate analysis of perinatal death rate per ethnic group. A total of 42,282 women living in the three main cities of the Netherlands were classified on the basis of postal code districts into four socioeconomic (SES) classes for analysis of the relation between SES, perinatal death, and preterm birth. RESULTS: Black mothers had the highest perinatal death rate compared with indigenous Dutch (odds ratio 2.2, 95% CI 1.9, 2.4) followed by a group "others", consisting of women of mixed or unknown ethnicity (odds ratio 1.8, 95% CI 1.5, 2.0), Hindustani (odds ratio 1.4, 95% CI 1.2, 1.6), and Mediterraneans (odds ratio 1.3, 95% CI 1.2, 1.4). Asians (excluding West Indian Asians) and non-Dutch Europeans did not have higher rates than Dutch women. The increased rates of black and Hindustani women could be explained fully and that of the group "others" partially by higher rates of preterm birth. Controlling for age and parity lowered the odds ratio of the Mediterraneans slightly. The risk of ethnicity was independent of SES. CONCLUSION: Ethnic minorities in the Netherlands except immigrants from Asia and other European countries have higher rates of perinatal death than indigenous Dutch women. With a twofold increase, black women had the highest rate, which was related to an equally large increased rate of preterm birth.

[International conference on population and development in Cairo]. / De internationale conferentie over bevolking en ontwikkeling in Cairo.

PIP: The UN Conference on Population and Development was held in Cairo in September 1994, and dealt with a range of sensitive issues that were eventually recorded in an action program. In addition, a sort of shadow conference was also held by various organizations. The precedents of this conference were the conferences held in Bucharest in 1974, which stressed the world crisis and population explosion, and in Mexico in 1984, where the first signs of the slackening of population growth induced less emphasis on family planning programs and more on the status of women. At Cairo again a crisis atmosphere reigned because rapid population growth has not been followed by rapid development. Birth control discussions also focused on ethical and religious norms, human rights, and emancipation problems. Most of all, the sustainability of development programs was stressed. Global decline of mortality combined with a continuing high birth rate has resulted in a population growth of 3% or more. In the course of 40 years the growth was 46% in industrialized countries as compared to 161% in the poorest lands. The total world population has reached 5 billion, of which only 20% live industrial countries. The influence of the AIDS epidemic on the demographic figures is not likely to be as much as anticipated a few years ago. Other problems are demographic aging, population decline (a below replacement fertility rate in Japan, Spain, and Italy), and uncontrolled internal and international migration (refugees in developing countries and flight to major cities). In the next 30 years almost two-thirds of the population of developing countries will be living in shabby, sprawling megacities. In 1989, in preparation for the Cairo conference, an international forum was held in Amsterdam on population. It dealt with the reproductive rights of women, the negative impact of structural readjustment programs on family planning, and the priority of women's education.^ieng

Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene.

A cross-over study of two oral contraceptive formulations, containing 30 micrograms ethinylestradiol in combination with 150 micrograms desogestrel (Marvelon) or 75 micrograms gestodene (Femovan), has been performed to compare the serum distribution and pharmacokinetics of gestodene and the active metabolite of desogestrel, namely 3-ketodesogestrel. Serum concentrations of both sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) were also measured and were increased more than 3-fold and 2-fold, respectively, on day 21 of the treatment cycle, with no statistically significant difference between treatment groups. In addition, 35 days after ingestion of either oral contraceptive had ceased, the serum SHBG and CBG concentrations were similar to the pretreatment values. During treatment cycles, increased serum SHBG levels were associated with a redistribution of 3-ketodesogestrel and gestodene such that the non-protein-bound (NPB) and albumin-bound fractions were reduced in concert with an increase in the relative proportions bound to SHBG. The proportion of gestodene bound to SHBG was consistently higher than that observed for 3-ketodesogestrel, and this undoubtedly reflects the higher affinity of SHBG for gestodene (Kd = 1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel (Kd = 4.7 nM at 37 degrees C). It also probably accounts, in part, for the much higher total serum levels of gestodene (8.58 nmol/L) when compared to 3-ketodesogestrel (2.37 nmol/L) during the treatment cycles. Consequently, the absolute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are significantly higher than those measured for 3-ketodesogestrel. It is concluded that ethinylestradiol-induced increases in serum SHBG levels during treatment with Marvelon or Femovan, influenced the distribution and total amount of 3-ketodesogestrel and gestodene in serum, respectively, and that this, combined with the higher affinity of SHBG for gestodene, results in a greater amount of bioavailable gestodene compared to 3-ketodesogestrel, despite the smaller dose of gestodene administered.

The effect of two regimens of hormone replacement therapy on the haemostatic profile in postmenopausal women.

The effect of two different regimens of hormone replacement therapy on coagulation and fibrinolysis was measured in 30 women taking Tibolone (Livial) and 30 taking oestradiol valerate, sequentially combined with cyproterone acetate (Climen). Blood samples were taken before the beginning of the medication, then six and twelve months afterwards. The Livial group showed a rise of fibrinolytic activity as measured by the alpha 2-antiplasmin-plasmin complexes. Tissue plasminogen activator antigen and plasminogen activator inhibitor-1 decreased simultaneously. No effect was seen in the coagulation variables. In the Climen group no significant alterations were noticed, either in the coagulation or in the fibrinolysis variables. In the direct comparison of both substances only factor VII appeared to be significantly higher in the Climen group after six months and one year of treatment.

Uterine rupture. A seat belt hazard.

A case is described of a uterine rupture resulting from a car accident occurring in a woman who was wearing a seat belt as generally recommended. The rupture was initially not recognised and only became apparent after attempts to induce labor which led to expulsion of the fetus into the abdominal cavity.

[Obstetrical outcome in teenage pregnancies in The Netherlands]. / Verloskundige uitkomsten tienerzwangerschappen in Nederland.

OBJECTIVE: To compare the course of teenage pregnancies and deliveries with that in women between the ages of 20 and 29. DESIGN: Observational. SETTING: The Netherlands. METHOD: Using data from the 1989 National Obstetric Database (LVR), 4500 teenage pregnancies were studied, to compare the risk of preterm birth, low birth weight and delivering a small for gestational age (SGA) baby between teenagers and older women. RESULTS: Women between the ages of 13 and 19 ran one and a half times as high a risk of having a preterm baby as women between the ages of 20 and 29 years (p < 0.0001). The risk of intrauterine death was 4 times as high for age 13-17 and 2 times as high for age 18-19 compared with older women (p < 0.0001). These results were found for teenage mothers of Dutch origin as well as for young mothers of foreign descent. Deliveries by teenagers were more often spontaneous, were of shorter duration and less often needed assistance than deliveries in older mothers (p < 0.001). CONCLUSION: Even in the Netherlands, with the lowest teenage pregnancy rate in the Western world and a prenatal care system generally considered of high quality, teenage pregnancies have less favourable outcomes than those in older women. Since we had no information on cultural background, socioeconomic status or life style, further research into determinants of outcomes of Dutch teenage pregnancies is indicated.

PIP: The objective was to compare the course of teenage pregnancies and deliveries with those of women between the ages of 20 and 29, using data from the 1989 National Obstetric Database (LVR) when approximately 76% of cases conducted by obstetricians were registered. 4500 teenage pregnancies were studied to compare the risk of preterm birth, low birth weight and delivering a small for gestational age (SGA) baby between teenagers and older women. In the 13-17 year age group, 61.5% were of foreign origin. The 13-17 age group had the lowest percentage of delivery at home, with 10%. Women 13-19 years old ran 1.5 times as high a risk of having a preterm baby as women age 20-29 (p 0.0001). The likelihood of SGA delivery was increased only in the 18-19 age group (13.2%) compared to 11% in the 20-29 age group. The risk of death within 24 hours after delivery was also increased because of the risk of intrauterine death, which was 4 times as high for age 13-17 (1.6%) and 2 times as high for age 18-19 (0.7%) compared with women age 20-29 (0.4%) (p 0.0001). These results were found for teenage mothers of Dutch origin as well as for young mothers of foreign descent. Deliveries by teenagers were more often spontaneous, were of shorter duration and less often needed assistance than deliveries in older mothers (p 0.001). The incidence of home delivery was low in both age groups (8.5%), and it was the same for both Dutch and foreign origin groups. Even in the Netherlands, with the lowest teenage pregnancy rate in the Western world and a prenatal care system generally considered of high quality, teenage pregnancies have less favorable outcomes than those in older women. Since the study was conducted without information on cultural background, socioeconomic status or life style, further research into determinants of outcomes of Dutch teenage pregnancies is indicated.

Vaginal uterine amputation.

Since sexual dysfunction after hysterectomy might be prevented by leaving the portio in place, a technique was developed to perform vaginal uterine amputation. The method appeared to have been described already 40 years ago but has vanished from textbooks since then.

Maternal death due to acute necrotizing colitis in homozygous sickle cell disease.

The case history is described of a 21-year-old female with homozygous sickle cell disease and fatal postpartum haemorrhage from the colon. At autopsy many sickled cells were found in the arterioles of the mucosa and submucosa in combination with necrotic lesions and ulcerations of the sigmoid colon. A causal association between occlusion of blood vessels by sickled cells and the occurrence of vascular necrosis of the sigmoid colon is suspected.

Differential birthweights and the clinical relevance of birthweight standards in a multiethnic society.

Using a computer-stored database, birthweights and related variables over 25,000 infants born in Amsterdam (The Netherlands) were analysed retrospectively. Only after allowing for maternal height, did the difference between mean birthweights of Dutch and Asian infants disappear, whereas Negroid and Mediterranean infants continued to show respectively lower and higher means than the others. These results confirm that the birthweight standards presently used are inappropriate for detection of deviant weight in non-Dutch groups.

Some characteristics of labor in ethnic minorities in Amsterdam.

A retrospective study of labor in immigrants, subdivided into Blacks, Asians and Mediterraneans (Turks and Moroccans) and autochthonous Dutch in Amsterdam over a 10-year period showed definite differences. The second stage was shortest in Blacks and Mediterraneans but they sustained perineal tears and episiotomies less frequently. Differences in positions at birth were small except for occipito-posterior position which was very rare in Asians and Mediaterraneans. The rate of cesarean section was highest and that of instrumental vaginal delivery lowest in Blacks, and latter being highest in Asians. Retained placenta occurred less often in immigrants than in Dutch.

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer.

Lumbar bone mineral density (BMD) determination by dual photon absorptiometry was used to study the influence of adjuvant chemotherapy for premenopausal breast cancer on the risk of premature osteoporosis. Six cycles of combination chemotherapy caused ovarian failure in 31 of 44 (71%) women, amenorrhoea mostly already beginning during treatment. In contrast, only seven of 44 (16%) women, who were pair-matched for age and year of breast cancer surgery and had not been treated with chemotherapy, were post-menopausal at the time of measurement. The mean interval after breast surgery was 3.5 years. The significantly decreased BMD in the treated group (1.17 compared to 1.29 g cm-2) could only be explained by the high incidence of menopause in these women, which on average occurred 10 years prematurely. Extrapolation of these findings suggests that adjuvant chemotherapy may precipitate osteoporotic fractures by some 10 years in a considerable proportion of women cured of premenopausal breast cancer.