Ilkka Rauramo

Advance information improves user satisfaction with the levonorgestrel intrauterine system.

OBJECTIVE To evaluate parameters associated with and the impact of advance information given in a regular outpatient setting on user satisfaction with the levonorgestrel‐releasing intrauterine system. METHODS A questionnaire was sent to 23,885 women in Finland who had had a levonorgestrel intrauterine system inserted between 1990 and 1993. The number of returned questionnaires was 17,914 (response rate 75%). Cumulative logistic regression analysis was based on the five‐grade scale of satisfaction as a dependent variable. RESULTS Most users of the levonorgestrel‐releasing intra‐uterine system (74%) were very or fairly satisfied with it, although over 70% of them had chosen it because of dissatisfaction with their previous method of contraception. User satisfaction increased with age and was associated with the amount of information about different symptoms (menstrual, greasiness of hair/skin, pregnancy, pelvic inflammatory disease, and missed periods) regardless of whether the symptom in question was actually experienced. The women who received information about the possibility of absence of menstruation were more satisfied than the less informed women (odds ratio 5.0, 95% confidence interval 4.1, 5.9). CONCLUSION Information received at the insertion visit is strongly associated with increased user satisfaction among the users of the levonorgestrel intrauterine system. The association between high user satisfaction and advance information was strongest regarding the possibility of missing periods.

Use of the levonorgestrel-releasing intrauterine system and breast cancer.

OBJECTIVE: The effect of exogenous hormones on the incidence of breast cancer has been extensively studied. Most studies regarding hormonal contraception have focused on combined oral contraceptives, and there is paucity of literature regarding nonoral and progestin-only contraceptives. The present study analyzed the relationship between breast cancer and use of the levonorgestrel-releasing intrauterine system. METHODS: This study was based on data gathered from a large postmarketing study on levonorgestrel-releasing intrauterine system users (n = 17,360) carried out in Finland. The results present an incidence comparison between levonorgestrel system user data and the data on average Finnish female population (derived from the Finnish Cancer Registry), between 30 and 54 years of age. RESULTS: Based on the 95% confidence intervals for the incidences of breast cancer, and the Fisher exact test, there is no indication of a difference between the levonorgestrel system users and average Finnish female population in any of the 5-year age groups. The incidence rate per 100,000 woman-years was for the age groups 30–34 years 27.2 and 25.5, for 35–39 years 74.0 and 49.2, for 40–44 years 120.3 and 122.4, for 45–49 years 203.6 and 232.5, and for 50–54 years 258.5 and 272.6, in the levonorgestrel system group and in Finnish female population, respectively. CONCLUSION: The results suggest that the use of the levonorgestrel-releasing intrauterine system is not associated with an increased risk of breast cancer. LEVEL OF EVIDENCE: II-2

Long-term treatment of menorrhagia with levonorgestrel intrauterine system versus endometrial resection.

OBJECTIVE: The purpose of this study was to compare the long-term efficacy of the levonorgestrel intrauterine system and transcervical resection of the endometrium in the treatment of menorrhagia. METHODS: This study was an open, randomized 3-year trial. Patients with menorrhagia were assigned randomly to either the levonorgestrel intrauterine system (n = 30) or endometrial resection (n = 29). Pictorial blood loss assessment charts were used to measure menstrual blood loss. A pictorial blood-loss assessment chart score exceeding 75 (representing menstrual blood loss ≥60 mL) was used to diagnosis the patient as having menorrhagia. Discontinuations and cases requiring repeat operations were evaluated. RESULTS: Pictorial blood loss scores decreased from a baseline median of 261.5 (range, 60–1503) to 7 (range, 0–101; P < .001) for the levonorgestrel intrauterine system and from 311 (range, 81–2506) to 4 (range, 0–182; P < .001) for transcervical resection of the endometrium. Nineteen women of 30 using the levonorgestrel intrauterine system completed the 3-year follow-up compared with 22 of 29 for transcervical resection of the endometrium. CONCLUSION: Both treatments efficiently reduced menstrual bleeding. The high continuation rate suggests that the levonorgestrel intrauterine system is comparable with transcervical resection of the endometrium. LEVEL OF EVIDENCE: I

Pancreatic secretory trypsin inhibitor from human amniotic fluid and fetal and neonatal urine: concentrations and physicochemical characterization

The levels and physicochemical properties of the pancreatic secretory trypsin inhibitor, also known as Kazal type trypsin inhibitor, were studied in human amniotic fluid. In the second trimester, the median concentration was 160 ng/ml, which exceeds the maternal serum levels 20-fold. Towards term, the amniotic fluid levels declined about 5-fold, whereas the maternal serum values remained constant. In fetal urine, the concentration of the trypsin inhibitor was similar to that in amniotic fluid in early gestation, whereas in newborn urine, the median level was 4-to 5-fold higher than in term amniotic fluid. The physiochemical characteristics of the trypsin inhibitor in amniotic fluid, neonatal urine and cancer urine from an ovarian cancer patient were similar, as studied by gel filtration, high performance reverse phase liquid chromatography, and complete immunological identity in immunodiffusion. The physicochemical similarity and levels in various compartments suggest fetal contribution to amniotic fluid levels of the trypsin inhibitor.

Effects of smoking on fetal heart rate variability during gestational weeks 27 to 32

8 healthy mothers in weeks 27-32 of pregnancy gave informed consent for this study of the effects of smoking on fetal heart rate. Analyses of fetal heart rate (FHR) variability were performed at 1-minute intervals from an abdominal fetal electrocardiogram 10 minutes before, during, and 25 minutes after the mother smoked. Maternal heart rate (MHR) was recorded manually. An elevation of MHR and blood pressure occurred during smoking. Blood pressure had returned to initial levels either immediately (systolic) or within 10 minutes (diastolic); however, MHR was still elevated 25 minutes after smoking ceased. Baseline FHR increased 5 minutes after maternal smoking and returned to the normal level in 25 minutes. Correlation analysis shows negative correlations between the differential index and FHR, between differential index and pulse pressure (p.001), between differential index and systolic reading (p.01), and between variability indexes and MHR (p.001). There was also a positive correlation between FHR and MHR as well as between interval and differential indexes (p.001). The main finding of this study is that, at the onset of the 3rd trimester, the human fetus shows the decreasing effects of smoking on both interval and differential indexes, as does the term fetus (the differential index describes the short-term variability and the interval index describes the long-term variability of heart rate).

Antepartum fetal heart rate variability and intervillous placental blood flow in association with smoking

Intervillous placental blood flow and indices of fetal heart rate variability were measured from seven healthy pregnant women in the last trimester of pregnancy, once before and twice after smoking one cigarette. A blood flow reduction was observed in seven, a rise in five, and no change in two measurements. When intervillous placental blood flow decreased both indices of variability decreased (p less than 0.001), and when it increased the short-term component of fetal heart rate variability increased more significantly (p less than 0.001) than did the long-term component (p less than 0.01).

Prostacyclin and thromboxane in pregnant and nonpregnant women in response to exercise.

Objectives To compare the effects of a 30-minute standardized submaximal exercise test on the urinary excretion of the metabolites of prostacyclin and thromboxane A2 in healthy pregnant and nonpregnant women. Methods Time-fixed urine samples were collected before, during, and after the exercise test from nine pregnant and six nonpregnant women, and the samples were assayed for 6-keto-prostaglandin (PG) F1α. and 2,3-dinor-6-keto-PGF1α, (prostacyclin metabolites), as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (thromboxane A2 metabolites) by high-pressure liquid chromatography and radioimmunoassay. Results Pregnancy itself was associated with a 3.6–4.3fold rise in prostacyclin excretion, but with no significant change in thromboxane output. The exercise caused stimulation in both prostacyclin and thromboxane excretion. In response to exercise, the maximal rise in 6-keto-PGF1. output was significantly larger among the pregnant subjects, but when compared with its pre-exercise excretion on a relative percentage scale, the range of rise in 6-keto-PGF1, output (58–73%) was comparable in pregnant and nonpregnant subjects. Furthermore, excretion of 2,3-dinor-6-ketoPGF1, rose similarly in the two study groups (68–166%) in response to exercise. The exercise caused a 2.3-fold rise in the output of thromboxane B2 excretion in both pregnant and nonpregnant women, but it stimulated (by a twofold rise) the excretion of 2,3-dinor-thromboxane B2 only in pregnant women. Conclusion Physical activity may stimulate vasoactive prostacyclin and thromboxane excretion during pregnancy. Such changes may play a role in the regulation of blood flow during exercise.

Significant correlation between maternal hemodynamics and fetal heart rate variability

The differential index, describing the short-term component, and the interval index, describing the long-term component, of fetal heart rate variability were measured by an on-line method from the abdominal electrocardiograms of eight fetuses during the third trimester of normal pregnancies while mothers were smoking a cigarette. Maternal heart rate and maternal blood pressure were measured intermittently before, during, and after smoking. Analyses of fetal heart rate variability were performed continuously with the sample time of 1 minute during the experiments. An increase in maternal heart rate and blood pressure, with concomitant decrease in the interval index and the differential index, was observed. The correlation analysis revealed a negative correlation between maternal heart rate and the interval index (p less than 0.001), between diastolic pressure and the differential index (p less than 0.01), and between systolic pressure and the differential index (p less than 0.01).