Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α₂- and β₂-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α₂/β₂-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β₂-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β₂-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

The aim of the present investigation was to determine which subtypes of the α₂-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [³H]rauwolscine to human myometrial membranes was specific and of high affinity with K_d of 2.8 ± 0.6 nM and B_max of 95 ± 5 fmol/mg protein. Results from competition for the binding of [³H]rauwolscine using subtype-selective ligands, oxymetazoline (α₂A-subptype), chlorpromazine (α₂B-subtype) and prazosin (α₂B-α₂C-subtype), suggested that the α₂A- and α₂B-subtypes are being co-expressed. In order to examine if also the α₂C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α₂A- and α₂B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α₂C-subtype also is being expressed. The expression of α₂C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

In conclusion, our results suggest that all three subtypes of α₂-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α₂-expression is dominated by the α₂A-subtype.

ICSI is a highly efficient treatment of male factor infertility and therefore increasingly used to treat infertile men successfully. However, when used to treat patients with a genetic cause for their infertility, there may be an increased risk for the offspring. Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia. These genetic defects could be identified before treatment, in which case informed decisions could be made by the couple to be treated concerning the treatment, prenatal testing or preimplantation genetic diagnosis. Therefore, we propose that men with very low sperm counts (<5 × 106/ml) considering ICSI should always be informed of the possibility of genetic testing. The information should include a precise statement of the implications of the results for the patient, his family and his offspring, and reassurance that a decision to test or not to test, or the subsequent test results will not be used as a reason for withholding treatment. Testing should always remain voluntary, and the couples themselves should decide whether or not they choose to be tested. If an abnormality is identified, patients should be referred to specialist genetic counselling.

The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.

The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.

Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.

The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.

The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.

In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.

One way to study the stressfulness of childbirth is to examine the output of stress hormones. In this study, urinary catecholamines and salivary cortisol from 50 primiparous women were collected for 1 day during gestational weeks 37 to 39, hourly during labor and delivery, and 2 hr and 2 days postpartum. All three stress hormones increased statistically significantly from pregnancy to labor. The increase in adrenaline and cortisol was more than 500%, and the increase in noradrenaline was about 50%. After labor, the output decreased but not statistically significantly below the levels during late pregnancy. Hormone levels during late pregnancy, during labor and delivery, and during the period postpartum mostly did not correlate systematically. However, noradrenaline and adrenaline, as well as adrenaline and cortisol, were positively correlated during labor. After administration of epidural analgesia, there was a moderate but significant decrease in noradrenaline and adrenaline, whereas cortisol did not change. In conclusion, the results of this study support the assumption that childbirth is a very stressful event and that the stress responses vary considerably among women. The substantial increase of adrenaline and cortisol compared with noradrenaline indicates that mental stress is more dominant than physical stress during labor.

The aims of the present study were: (a) to examine whether it was possible to measure women’s cognitive appraisals hourly during the whole process of labor and delivery, and (b) to explore how the appraisals varied during labor. Measurements from 12 nulliparous women are presented. The findings indicate that it is possible to study psychological appraisals directly, in detail and continuously during the process of labor and delivery. The women’s cognitive appraisals varied throughout labor both per individual woman and between the participating women.

Background. The aims of the present study were to compare primiparous and multiparous women’s experiences of fear of delivery during an early stage of active labor (cervix dilatation 3–5 centimeters) and to study whether fear of delivery, measured during the early stage of active labor, was a predictor of the amount of pain relief received during the remaining part of labor (cervix dilatation 5 cm – partus), of the duration of the remaining part of labor, and of the occurrence of instrumental vaginal delivery and emergency cesarean section.

Method. Thirty-five primiparous and 39 multiparous women answered the Delivery Fear Scale (DFS) once during the early stage of labor and before they had received any pain relief.

Results. Primiparous women reported higher levels of fear than multiparous women did. Fear during the first phase of labor predicted only the total amount of pain relief received during labor.

Conclusion. The clinical implications of the study are that the delivery staff should consider women’s fear during labor and pay attention especially to primiparous women’s increased risk of higher levels of fear during an early stage of active labor, as compared with multiparous women’s. The challenge for staff of a delivery ward is to support the woman in labor in a way that decreases fear, which in turn might reduce the woman’s need of pain relief.

Aims: The aims of the present study were 1) to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during labor (phase 1: cervix dilatation 3-5 cm), and 2) to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia (EDA) during labor.

Method. During gestation weeks 37-39, in 47 nulliparous women fear of childbirth was measured by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A. Early during labor (labor phase I = cervix dilatation 3-5cm) the women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale) were measured hourly. Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

Results. Fear of childbirth during pregnancy and in the three postpartum measures was positively related to fear during labor, phase I. Pain during phase 1 of labor was neither associated with fear of childbirth measured during late pregnancy, nor with postpartum fear. There were no differences in fear of childbirth during late pregnancy between those women who received EDA and those who did not. Postpartum fear was higher in those women who had received EDA.

Conclusion. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartum.

Problem: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. Method of study: We studied the in vivo effects of transdermal estrogens (50 ╡g 17 ▀-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-?, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. Results: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-?, IL-4 or IL-10 in relation to estrogen or placebo treatment. Conclusions: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

Pre-eclampsia is a serious multi-system disorder with general endothelial disease, often with a component of hepatic dysfunction. The pathogenesis of pre-eclampsia is not fully understood, and no specific diagnostic tests are available for early and reliable diagnosis, or for monitoring of the disease process. Hyaluronan is an extracellular matrix polysaccharide present at low concentrations in plasma. Normally, it is rapidly eliminated from the blood by the liver. Increased concentrations of circulating hyaluronan are seen in conditions with impaired hepatic function such as liver cirrhosis, and hyaluronan concentrations have previously been used to evaluate hepatic function in other diseases. In the present study, 11 pregnant women admitted to the intensive care unit with severe pre-eclampsia or eclampsia were studied. As control 31 healthy pregnant women, 18 undergoing vaginal delivery and 13 caesarean section, were included. Plasma hyaluronan was measured before and after delivery. Increased concentrations of plasma hyaluronan were found in the pre-eclampsia group both before (171 (75-586) ╡g/L (p < 0.01) and after delivery (215 (124-768) ╡g/L (p < 0.001) (median and inter-quartile range), as compared to both caesarean section (13 (7-28) ╡g/L before and 28 (18-48) ╡g/L after delivery) and vaginal delivery healthy controls (12 (8-24) ╡g/L before and 30 (13-63) ╡g/L after delivery). In the control groups, a small increase in plasma hyaluronan was seen after delivery, after both caesarean section (p < 0.05) and vaginal delivery (p < 0.01). In conclusion, plasma hyaluronan is increased in severe pre-eclampsia and eclampsia. The cause of the increase is unknown.

A study was made of the occurrence of congenital malformations in the southeast region of Sweden, utilizing all available relevant health registries. Östergötland county had been pinpointed in a routine surveillance as having an increased malformation risk. Various validations of the register data were undertaken and different types of errors were detected. An increased risk was seen, in Östergötland county compared to the reference counties, for specific types of malformations: preauricular appendices, pylorostenosis, uterine/vaginal malformations, foot deformities, limb reduction defects and cardiovascular malformations. Variable classification or registration artefacts explained the excess among the first four conditions. Limb reduction defects were also mis-coded, but the increased risk in Östergötland county may persist.

Conclusion: There is an increased risk of major cardiovascular malformations in Östergötland county compared to the reference counties that also shows an uneven distribution within the county.

Objective: To investigate the effects of increased exposition to female sex hormones and physical strain on the prevalence of low back pain (LBP) in women. To study the etJect of increased exposition to female sex hormones on spinal sagiual mobility.

Background: Scientific data and clinical observations suggest an increased prevalence of LBP in women as compared with men, especially in athletes. Estrogen receptors arc present in the musculo-skeletal apparatus and in the central nervous system and female sex hormones have been suggested to affect the stability of the pelvic joints and the perception of pain. The impaired stability together with a hypermobile spine may cause increased isometric muscular work, and as a consequence, pain. Also the perception of pain may be altered by female sex hormones. Because LBP is more common in female athletes than in male athletes, increased exposition to both female sex hormones and physical strain may affect the occurrence of LBP in women. Such an exposition occurs during pregnancy, with a well-known increase in prevalence of LBP.

Methods: 28 women with an increased exposition to physical strain (female soccer players) and a history of LBP underwent a clinical examination and were then observed prospectively during 6 months to study variations in the occurence and severity of LBP during the different phases of the menstrual cycle. 716 female elite athletes and 113 controls answered a questionnaire with regard to their use of oral contraceptives (OCs) and the occurrence of LBP. 1103 women, 55 or 56 years old, answered a questionnaire concerning the occurrence and severity ofLBP and use of hormone replacement therapy (HRT). 52 women with and 67 women without a history of disabling LBP during a pregnancy in 1983-84 answered a questionnaire concerning LBP during subsequent pregnancies. 24 young, healthy women were followed prospectively over a period of 12 months to measure spinal sagittal mobility before use of OCs and after 3 and 12 months of OC-use.

Results: No differences were observed with regard to occurrence or severity of LBP between the different phases of the menstrual cycle or between OC-users and non-users. LBP was more common in the athletes as compared with the controls. The prevalence ofLBP was slightly increased among the HRT-users (OR 1.30; 95% CI 1.02-1.41) compared with non-users. 94% of the women with previous disabling LBP during pregnancy reported LBP in a subsequent pregnancy compared with 44% of the controls. Also concequenccs of LBP, as sick-leave, were more common in the group of women with disabling LBP during a previous pregnancy. No change in spinal sagittal mobility was observed in the group of women before and after the women began to use OCs.

Conclusions: Use of oral contraceptives does not seem to increase the prevalence of LBP. There is nothing in our results to suggest that women with LBP with an unspecific origin should discontinue their use of oral contraceptives. Postmenopausal women who use HRT had a slightly increased prevalence of LBP, but this increase is probably of no clinical significance. Women who had suffered from LBP during a previous pregnancy run a high risk for LBP in the future, both during a subsequent pregnancy and during the non-pregnant state. Increased exposition to exogenously administered female sex hormones does not increase spinal sagittal mobility in young, healthy, nullipareous women.

Important elements in the curriculum at the Faculty of Health Sciences in Link÷ping are vertical integration, i.e. integration between the clinical and basic science sections of the curriculum, and horizontal integration between different subject areas. Integration throughout the whole curriculum is time-consuming for both teachers and students and hard work is required for planning, organization and execution. The aim was to assess the importance of vertical and horizontal integration in an undergraduate medical curriculum, according to opinions among students and teachers. In a questionnaire 102 faculty teachers and 106 students were asked about the importance of 14 different components of the undergraduate medical curriculum including vertical and horizontal integration. They were asked to assign between one and six points to each component (6 points = extremely important for the quality of the curriculum, 1 point = unimportant). Students as well as teachers appreciated highly both forms of integration. Students scored horizontal integration slightly but significantly higher than the teachers (median 6 vs 5 points, p=0.009, Mann-Whitney U-test), whereas teachers scored vertical integration higher than students (6 vs 5, p=0.019, Mann-Whitney U-test). Both students and teachers considered horizontal and vertical integration to be highly important components of the undergraduate medical programme. We believe both kinds of integration support problem-based learning and stimulate deep and lifelong learning and suggest that integration should always be considered deeply when a new curriculum is planned for undergraduate medical education.

Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis. Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks. Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholestrol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year. Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.

Objective: We investigated the effects of 2-year transdermal continuous combined estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) (Estragest TTS) on bleeding and on the endometrium. Design: This double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years past menopause with intact uteri. Patients received a transdermal patch delivering either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo. Of the 266 women initially included, 135 (96 Estragest TTS, 39 placebo) completed a second year open follow-up, where all women had the estradiol/norethisterone patch. Endometrial biopsies were performed at weeks 0, 48 (n = 171), and 96 (n =109). Effects on endometrial morphology and uterine bleeding were studied. Results: The overall incidence of endometrial hyperplasia after treatment with the estradiol/norethisterone acetate patch for one year was 0.8% with only one case of atypical hyperplasia. There were no clinically significant changes in endometrial thickness in either treatment group. The proportion of bleed-free patients with the estradiol/norethisterone acetate transdermal system increased from 55% in cycles 1-3 to 83% in cycles 10-12. By the 12th cycle, 92% of patients receiving estradiol/norethisterone acetate patches were bleed-free. No additional hyperplasia was seen during the second year follow-up. Conclusions: A continuous combined transdermal patch delivering 0.025 mg estradiol/day and 0.125 mg norethisterone acetate/day provided good endometrial protection. The dose maintained a consistently high rate of amenorrhea in postmenopausal women.

Objective: The objective of this study was to estimate the effects of low and high gestational weight gain, in different maternal Body Mass Index (BMI) classes, on obstetric and neonatal outcomes. Method: A prospective population-based cohort study of 245,526 singleton term pregnancies. Women were grouped in five categories of BMI and in three gestational weight gain categories, < 8 kg (low weight gain), 8-16 kg and > 16 kg (high weight gain). Obstetric and neonatal outcomes were evaluated after adjustments for maternal age, parity, smoking, year of birth. Result: Obese women with low gestational weight gain had a decreased risk for the following outcomes (adjusted odds ratio, 95% confidence interval): preeclampsia (0.52, 0.42-0.62), cesarean section (0.81, 0.73-0.90), instrumental delivery (0.75, 0.63-0.88), and LGA births (0.66, 0.59-0.75). There was a 2-fold increased risk for preeclampsia and LGA infants among average and overweight women with excessive weight gain. High gestational weight gain increased the risk for cesarean delivery in all maternal BMI classes. Conclusion: The effects of high or low gestational weight gain differ depending on maternal BMI and the outcome variable studied. Obese women may benefit from a low weight gain during pregnancy.

In the most recent analysis of Swedish data on congenital malformations, it appeared that in the county of Östergötland, the prevalence of infants with a diagnosed congenital malformation was higher than in the rest of the country. This observation initiated an effort to make a more complete identification of all infants born with a congenital malformation in that county and to compare it with the other two counties in the Southeast region of Sweden (Jönköping and Kalmar), utilising all the relevant Swedish medical health registers available. A total of 10,171 infants with a congenital malformation of any type were identified in the region: 4,698 infants in Östergötland county (6.2%), and 5,473 in the reference counties (5.4%). A 15% excess malformation risk in Östergötland compared with the two reference counties. Various validations of the register data were undertaken and different types of error were detected. Limb reduction defects seemed to occur more often in Östergötland county and there was an increased risk of cardiovascular malformations in Östergötland county (22%).

The next step comprised an exploration of putative risk factors for cardiac defects in the area. Maternal body mass index (BMI) >29 was found to be a significant risk factor for cardiac defects. Maternal diabetes mellitus and maternal use of antiepileptics were associated with an increased risk of cardiac defects in the offspring.

To explore if the pregnant women in Östergötland county differed from the women in the reference counties, a comparative analysis of potential risk factors was performed. The only single putative risk factor that could contribute to the excess risk of cardiac defects in Östergötland county was matemal residency in a rural district. Notably, nearly all the potential risk factors studied i.e. spontaneous abortions, involuntary childlessness, maternal disease, high maternal body mass index, matemal medical during use and alcohol use in early pregnancy, parental employment and paternal age were stronger in Östergötland county compared to the reference area. A conceivable explantation is that one or more unidentified factors could activate prevalent and weak teratogenic risk factors for cardiac defects.

Drinking water could be such a factor. By using a geographical infmmation system (GIS) it was possible to obtain individual data on drinking water characteristics. An increased tisk of a congenital cardiac defect seemed to be associated with the chlorination procedure, in particular the use of chlorine dioxide, and with increasing total trihalomethane concentration.

OBJECTIVE: To establish optimal gestational weight gain for each maternal body mass index (BMI) category based on significant risk estimates of adverse maternal and fetal outcome. METHODS: The study population consisted of 298,648 singleton pregnancies delivered in Sweden between January 1, 1994, and December 31, 2004. The number of individuals in each weight gain class was compared with the number of individuals in all other weight gain classes in the same BMI group with regard to adverse maternal and fetal outcome. Odds ratios were calculated after suitable adjustments. RESULTS: The optimal gestational weight gain in women by prepregnancy BMI was 9-22 lb (4-10 kg) for BMI less than 20, 5-22 lb (2-10 kg) for BMI 20-24.9, less than 20 lb (less than 9 kg) for BMI 25-29.9, and less than 13 lb (less than 6 kg) for BMI of 30 or more. CONCLUSION: The gestational weight gain limits for BMI categories determined in this large population-based cohort study from Swedish Medical Registers showed that a decreased risk of adverse obstetric and neonatal outcomes was associated with lower gestational weight gain limits than was earlier recommended, especially among obese women. © 2007 The American College of Obstetricians and Gynecologists.

Objective: To estimate whether obese women have an increased risk of orofacial clefts in their offspring, compared with average-weight women. Design and Participants: The study was based on information on maternal body mass index (BMI) collected in early pregnancy and on the existence of orofacial clefts in the offspring, ascertained from multiple sources. The study included 1686 women who had infants with an orofacial cleft and as controls all delivered women (n = 988,171) during the study period, 1992 through 2001. Infants with chromosome anomalies were excluded. The women were divided into underweight (BMI <19.8), average weight (reference group, BMI 19.8 to 26), overweight (BMI 26.1 to 29), and obese (BMI >29). Adjustments were made for year of birth, maternal age, parity, and maternal smoking. Results: Obese (BMI >29) mothers had an overall increased risk for having an infant with orofacial clefts: odds ratio 1.30 (95% confidence interval 1.11 to 1.53). This increased risk was higher when the cleft was associated with other major malformations than when it was isolated. There was no statistically significant difference between the risk estimates for cleft lip and cleft palate. Conclusions: In this large sample, a positive association appears between maternal obesity in early pregnancy and orofacial clefts in the offspring. The explanation for this association is not known, but a relationship with undetected type 2 diabetes is one possibility.

Objective: This study determined whether obese women have an increased risk of cardiovascular defects in their offspring compared with average weight women. Research Methods and Procedures: In a case-control study, prospectively collected information was obtained from Swedish medical health registers. The study included 6801 women who had infants with a cardiovascular defect and, as controls, all delivered women (N = 812,457) during the study period (1992 to 2001). Infants with chromosomal anomalies or whose mothers had pre-existing diabetes were excluded. Obesity was defined as BMI >29 kg/m2, and morbid obesity was defined as BMI >35 kg/m2. Comparisons were made with average weight women (BMI = 19.8 to 26 kg/m2). Results: In the group of obese mothers, there was an increased risk for cardiovascular defects compared with the average weight mothers [adjusted odds ratio (OR) = 1.18, 95% CI, 1.09 to 1.27], which was slightly more pronounced for the severe types of cardiovascular defects (adjusted OR = 1.23, 95% CI, 1.05 to 1.44). With morbid obesity, the OR for cardiovascular defects was 1.40 (95% CI, 1.22 to 1.64), and for severe cardiovascular defects, the OR was 1.69 (95% CI, 1.27 to 2.26). There was an increased risk for all specific defects studied among the obese women, but only ventricular septal defects and atrial septal defects reached statistical significance. Discussion: In this sample, a positive association was found between maternal obesity in early pregnancy and congenital heart defects in the offspring. A suggested explanation is undetected type 2 diabetes in early pregnancy, but other explanations may exist.

Objective: To evaluate whether pregnancies with infants affected by congenital heart defects are associated with adverse obstetric and perinatal outcome. Study design: In a prospective population-based cohort study from Sweden (1992-2001), 6346 singleton pregnancies with infants affected by congenital heart defects were, after suitable adjustments, compared to all delivered women. Results: The prevalence of cardiovascular defects was 9.1 per 1000 births. Among them, mothers of 6346 infants (71%) had information on maternal smoking habits and maternal height and weight in early pregnancy that enabled the calculation of BMI. All cases with known chromosomal abnormalities and/or maternal pre-existing diabetes were excluded. Eighty-four percent (n = 5338) had an isolated cardiovascular defect. Severe types occurred in 21.7% (n = 1378). In the group of pregnancies with infants affected by congenital heart defects as compared to all delivered women, there was an increased risk of the following outcomes (adjusted OR (95%CI)): pre-eclampsia (1.21 (1.06-1.37)), cesarean section (1.91 (1.79-2.03)), instrumental delivery (1.21 (1.10-1.34)), pre-term delivery (2.58 (2.39-2.79)), small-for gestational age (1.96 (1.77-2.16)), meconium aspiration (1.51 (1.28-1.77)), and fetal distress (1.38 (1.17-1.63)). Conclusions: Pregnancies with infants affected by congenital heart defects are associated with several obstetric and neonatal complications. © 2005 Elsevier Ireland Ltd. All rights reserved.

Background. To determine the detection rate of fetal structural abnormalities by a routine 11-14-week ultrasound scan for dating in an unselected pregnant population. Methods. A prospective observational cohort study of 2,708 unselected pregnant women attending an abdominal ultrasound examination at 11-14 weeks gestation. The number of major fetal structural abnormalities diagnosed after birth was obtained from a computerized database at the same unit. Results. Out of 2,708 pregnant women, 89 (3.3%) were found to have a missed abortion at the time of the ultrasound scan and 33 (1.2%) were diagnosed as twins. Thirteen major structural abnormalities were detected, three cases of anencephaly (one case also had a spina bifida), one case with hydranencephaly, one fetus with Dandy-Walker syndrome, two cases with gastroschisis, one case with a bilateral hydronephrosis, one case with a generalized hydrops, one fetus with multiple malformations, and three cystic hygromas. An additional 19 major structural defects were detected at birth. Four cases of neural tube defects and nine fetuses with congenital heart defects were diagnosed. The antenatal ultrasound detection rate was 40.6% (13/32). Nine patients had a nuchal translucency greater than 3.0 mm (excluding cystic hygromas), two of them had chromosomal abnormalities (trisomy 21 and trisomy 18). Conclusions. Fetal structural abnormalities were detected in 41% (95%CI = 24-59) of the cases in an unselected pregnant population at a routine 11-14-week ultrasound scan for dating purpose. Two out of nine fetuses with a nuchal translucency greater than 3.0 mm had a chromosomal abnormality. © 2006 Taylor & Francis.

The aim of this study was to investigate various putative risk factors in a county in Sweden, described as having a 28% increased prevalence of cardiovascular malformations, and to compare them with the risk factors in two reference counties. Women giving birth in the studied counties differed in age and parity distribution, smoking, and educational level but these differences could not explain the increased risk of cardiovascular malformations in the county, since after stratification for these variables, the risk estimate did not change substantially. A number of potential risk factors were studied in a case/control design: spontaneous abortions, involuntary childlessness, maternal disease, body mass index, medical drug use, alcohol use, parental employment, paternal age, and urban/rural residency. No single factor could be attributed to the increased rate, with the exception of living in a rural district. Nearly all risk factors, however, were stronger in the county studied than those in the reference counties (0.02 > p > 0.01).

Conclusion: The only single putative risk factor that could have contributed to the increased risk for cardiac defects described in the county studied was maternal residency in a rural district. Notably, nearly all potential risk factors studied were stronger in the county studied compared with those in the reference area. A conceivable explanation is that one or more unidentified factors related to rural residency could potentiate prevalent and weak teratogenic risk factors for cardiac defects.

Objectives The aim of this study was to identify risk factors for cardiovascular malformation.

Methods In a case-referent study prospectively collected data were obtained from original medical records. The study included 277 woman who had infants with a severe cardiac defect, and for each case two referents (medical records study) were included. Data on parental age, maternal reproductive history, disease in early pregnancy, reported maternal use of drugs and alcohol, smoking habits, parental occupation, and maternal body mass index (BMI) were extracted. When data were available from Swedish medical health registers, a comparison was made (register study) between all infants with cardiovascular defects (2208) and all infants born (175 768).

Results Maternal diabetes mellitus was associated with an increased risk for cardiovascular malformation [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.36-4.15], as was a high BMI (>29) (OR 1.46, 95%CI 1.12-1.90). A tendency towards an increased risk was found for involuntary childlessness, spontaneous abortion, thyroid drugs, and nonsteroid anti-inflammatory drugs.

Conclusions Some known risk factors for cardiac defects (eg, maternal diabetes mellitus and the use of antiepileptics) could be identified. Other postulated risk factors could not be verified, for example, paternal age and parental occupation. The use of medicinal drugs seems not to be a major factor in the etiology of cardiac defects. It is possible, however, that there is an association with the use of nonsteroid anti-inflammatory drugs or drugs for thyroid disease. The relationship between a high BMI and cardiovascular malformation observed in this study may be explained by impaired maternal glucose tolerance.

Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00–2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

Prolonged exposure to sex steroids may constitute a risk factor for the development of breast cancer. The biological mechanisms involved in breast carcinogenesis are not well understood.

Basic knowledge of sex steroid effects on the normal human breast is still limited, one reason being the lack of an available in vivo technique for investigations of breast tissue metabolism.

In this study, the microdialysis technique was developed and evaluated as a method for measurements of tissue-specific concentrations of amino acids, lactate, pyruvate and glutathione in normal human breast tissue during the menstrual cycle. The technique was successfully applied to breast tissue and it was observed that the concentrations of several amino acids as well as glutathione changed during the menstrual cycle. Oxidative damage to cells is one of the mechanisms which may be involved in the development of breast cancer. Normal aerobic metabolism generates potentially dangerous oxidants which are controlled by a variety of antioxidant systems. The exact regulatory mechanisms of these systems are not yet fully understood. We studied the effects of estradiol and progesterone on antioxidative activity in normal human breast tissue, in vivo with the microdialysis technique, and in vitro using normal human breast epithelial cells in culture. The in vivo levels of the antioxidant glutathione were measured early and late in the menstrual cycle in breast tissue and subcutaneous fat. The glutathione levels were higher late in the menstrual cycle in both tissues, when the serum levels of estradiol and progesterone were high. In vitro, breast epithelium exposed to estradiol and progesterone exhibited decreased activity of the antioxidative enzymes catalase and glutathione reductase, whereas the activity of glutathione peroxidase tended to increase compared with cells grown in medium without added sex hormones. The vulnerability to oxidative stress, induced by hydrogen peroxide, increased in cells grown with estradiol and progesterone present in the media. α-Tocopherol, and α-tocopherol in combination with ascorbic acid, but not ascorbic acid alone, protected from cell death induced by hydrogen peroxide. This effect was not dependent on estradiol and progesterone exposure.

In conclusion, the data suggest an effect of estradiol and progesterone on antioxidative activity in normal human breast tissue both in vivo and in vitro.

Microdialysis will be a useful tool in future research of these and other aspects concerning human breast tissue.

In this study a technique for insertion of microdialysis catheters and the influence of the position of the catheters within normal human breast tissue were evaluated by measuring amino acids. Moreover, to assess variability over time, the levels of amino acids were measured during a period of 3 h. In nine healthy women two parallel microdialysis catheters were implanted, guided by a catheter for intravenous use, into the breast tissue. All insertions were successful and there were no complications. The levels of amino acids were equal in the two parallel catheters and varied less than 10% over a period of 3 h. Insertion of the microdialysis catheter via an intravenous catheter is suitable for the dense breast tissue. The position of the microdialysis catheter within the same breast seems to be of minor importance for measurements of amino acids. Thus, the described technique is a safe and reproducible way of investigating the human breast in vivo.

Objective. To determine if maternal age (35 years of age or older) in primiparous women is a risk factor for the development of obstetric anal sphincter rupture (OASR) and to identify obstetric factors associated with it. Material and methods. This is a retrospective case-control study. The study population was made up of the 5,345 primiparous women aged 24-45 years who delivered vaginally with singleton live-born neonates during 1990-99 at the Department of Obstetrics and Gynecology, Linköping University Hospital, Sweden. As cases the 327 primiparous women aged 35-45 years at delivery were selected. For each case two primiparous controls ten years younger were selected, matched for gestational age and year of delivery, in all 654 controls. Maternal, obstetrical, and neonatal data were obtained from the delivery records. Obstetric factors for the development of OASR were assessed with multivariate logistic regression analysis. Results. No significant association was found between the primiparous age category and OASR. Vacuum extraction, forceps delivery, and the head circumference of the neonate were found to be independent risk factors for OASR, while the use of mediolateral episiotomy or epidural analgesia were independent protective factors for developing OASR. Conclusions. Primiparous women, 35 years of age or older, do not seem to have a greater risk of OASR than younger primiparous women. Risk factors for OASR are instrumental vaginal delivery and the size of the neonate. Mediolateral episiotomy and epidural analgesia seem to reduce the risk for OASR. © 2006 Taylor & Francis.

Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evi-dence as to whether our present evaluation is correct.

Problem-based learning (PBL), combined with early patient contact, multiprofessional education and emphasis on development of communications skills, has become the basis for the medical curriculum at the Faculty of Health Sciences in Link÷ping (FHS), Sweden, which was started in 1986. Important elements in the curriculum are vertical integration, i.e. integration between the clinical and basic science parts of the curriculum and horizontal integration between different subject areas. This article discusses the importance of vertical integration in an undergraduate medical curriculum, according to experiences from the Faculty of Health Sciences in Link÷ping, and also give examples on how it has been implemented during the latest 15 years. Results and views put forward in published articles concerning vertical integration within undergraduate medical education are discussed in relation to the experiences in Link÷ping. Vertical integration between basic sciences and clinical medicine in a PBL setting has been found to stimulate profound rather than superficial learning, and thereby stimulates better understanding of important biomedical principles. Integration probably leads to better retention of knowledge and the ability to apply basic science principles in the appropriate clinical context. Integration throughout the whole curriculum entails a lot of time and work in respect of planning, organization and execution. The teachers have to be deeply involved and enthusiastic and have to cooperate over departmental borders, which may produce positive spin-off effects in teaching and research but also conflicts that have to be resolved. The authors believe vertical integration supports PBL and stimulates deep and lifelong learning.

Objectives: To establish the prevalence of unsteadiness and rotatory vertigo in peri- and postmenopausal women, and whether balance disturbances are more common in women with vasomotor symptoms and without hormone replacement therapy (HRT). Method: A validated questionnaire was sent to all 1523 women aged 54 or 55 years in Linkoping, Sweden. Results: Daily or weekly unsteadiness was reported by 5%, and daily or weekly rotatory vertigo by 4% of all women. The frequency of vasomotor symptoms correlated with reported unsteadiness (rs = 0.23, p < 0.001). Fourteen per cent of women with daily vasomotor symptoms reported weekly or daily unsteadiness, compared with 3% of those without vasomotor symptoms (odds ratio (OR) 7.58, 95% confidence interval (CI) 3.72-15.45). The frequency of vasomotor symptoms correlated with rotatory vertigo (rs = 0.19, p < 0.001). Ten per cent of women with daily vasomotor symptoms reported weekly or daily rotatory vertigo, compared with 2% of women without vasomotor symptoms (OR 5.21, 95% CI 1.07-25.52). No correlation was seen between vasomotor symptoms and falls. Users of HRT had the same prevalence of balance disturbances as non-users. Conclusions: Women with frequent vasomotor symptoms seem to run a greater risk of unsteadiness and rotatory vertigo than do women without symptoms. This association may not be explained by means of a cross-sectional study, but there might exist a causal connection between vasomotor symptoms and balance disturbances.

Objective: To assess whether estrogen treatment given to postmenopausal women without vasomotor symptoms improves balance more than placebo. Methods: Forty healthy postmenopausal women without vasomotor symptoms were randomized to transdermal 17▀-estradiol (E2) 50 ╡g/day for 14 weeks or identical transdermal placebo patches. Postural balance was measured with dynamic posturography before and after 4, 12, and 14 weeks of therapy. In this test, the visual, vestibular, and somatosensory systems were provoked with increasing difficulty and body sway was measured with a dual forceplate. A low score showed large sway and a score of 100 showed no sway at all. Results: Thirty-eight women completed the study. Both groups had normal balance for their ages and near maximum scores in the three easier balance tests at baseline. In the most difficult test, both groups improved their postural balance significantly (from 13 to 32 and from 22 to 39, respectively) after 4 weeks. Thereafter, no change was seen. One problem was low statistical power, but the relative change in balance did not differ between groups. The comparison did not show even a minute advantage of E2 over placebo, so a study with higher power would probably not have shown a more pronounced effect of estrogen than placebo. The change over time did not differ between groups, which indicates a significant learning effect.Conclusion: In women without vasomotor symptoms, estrogen therapy did not seem to increase postural balance significantly more than placebo. However, we could not rule out that estrogens affect postural balance in women with vasomotor symptoms. Copyright (C) 2000 The American College of Obstetricians and Gynecologists.

  Licentiate thesis in Teenage Obstetrics and Gynecology to be publicly defended at a licentiate seminar in B-husets aula Örebro University Hospital, Örebro. Friday October 6, 2006.   

Introduction: One of the targets of national health programs is to prevent unintended pregnancies, especially among teenagers. It is well established that these often lead to abortion. Preventive programs aimed at decreasing abortion rates should identify target groups at risk for unintended pregnancies. Purpose: This study was conducted to determine whether young mothers under 20 years of age constitute a group at risk for new unintended pregnancies. Methods: A retrospective cohort study comprising teenagers giving birth to their first child from 1996 to 2000 was performed at Örebro University Hospital, Sweden. Data were collected from antenatal and medical records with particular regard to compliance with the postpartum visit and to whether a contraceptive method was prescribed. Information concerning repeat pregnancies during the 12 months after delivery was obtained. Results: A total of 250 deliveries were recorded, 70% of the mothers attended the postpartum visit, and 71% received contraceptive prescriptions. At the 12-month follow-up, 56 (25%) had a new pregnancy, and of those, 20 (36%) had a legal abortion, making the abortion rate fivefold higher than expected in this age group. Conclusion: This study shows that teenagers giving birth constitute a high-risk group for future unintended pregnancies and legal abortion. © 2006 Elsevier Inc. All rights reserved.

Background. Quality of perinatal care was evaluated in relation to size of delivery unit and size of catchment area for deliveries. Methods. Neonatal outcome, measured as neonatal mortality, low Apgar scores at 5 min, and the occurrence of respiratory disorders and cerebral palsy was analyzed during a 15-year period from 1985 to 1999 inclusive. Figures were derived from the Swedish Medical Birth Registry and the Hospital Discharge Registry. Odds ratios were estimated for the different outcomes in relation to size of delivery unit (actual and estimated number of births) and the provision of a pediatric department at the hospital. Seven possible confounders were considered: year of birth, maternal age, parity, smoking during pregnancy, gestational age, parental cohabitation, and maternal body mass index. Results. Neonatal mortality was significantly higher for infants in families living within the catchment area of the smallest units without a pediatric department. Small differences in the occurrence of respiratory disturbances and Apgar scores are probably due to diagnostic differences. There were no differences in the incidence of cerebral palsy. Neonatal mortality continued to decrease during the observation period. Conclusions. Differences were minor, pointing to a fairly homogeneous quality of perinatal care and an efficient referral system for risk pregnancies. Mortality continues to decrease in spite of a reduction in the number of units caring for deliveries. © 2006 Taylor & Francis.

Background. Untreated bacterial vaginosis (BV) is a risk factor for postabortion pelvic inflammatory disease (PID). Methods. Eight hundred and eight women who requested therapeutic abortion were consecutively examined for the presence of BV, using either pH/whiff test or QuickVue Advanced® pH and Amines test. All patients who tested positive to BV were treated with clindamycin or metronidazole prior to abortion. Results. Based on the wet smear examination, the incidence of BV was 21.6%. Positive pH and whiff test had a sensitivity of 53%, specificity of 98% and Kappa index 0.59 ( n =239). Values for QuickVue Advanced® pH and Amines test were 53%, 97%, and 0.58 respectively ( n =508). The incidence of PID among all patients was 2.4% after pharmacological abortion and 4.9% after surgical abortion. Among the patients with microscopic presence of BV diagnosed positive by the pH/whiff test or QuickVue Advanced® pH and Amines test and treated with antibiotics, no PID occurred. Patients with negative pH/whiff test or QuickVue pH and amines test who consequently did not receive preoperative antibiotics, but who later demonstrated microscopic presence of BV, had an incidence of 14.3% (5/35) postoperative PID compared to women with normal lactobacilli flora 4.3% (10/234) (OR 3.73, 95% CI 1.21-9.21). Conclusions. Although the pH/whiff test and QuickVue pH and Amines test failed to ascertain BV in almost half of the participants later found to have BV, we found that preabortal screening and subsequent treatment of those who test clinically positive does lower the incidence of postabortion PID.

Objectives: With age there is an average decline in the concentration of biologically active testosterone. It is still controversial if this leads to a clinically relevant deficit, "partial androgen deficiency of the ageing man" (PADAM). Our objective was to investigate the prevalence of a series of symptoms possibly associated with PADAM in an assumed normal-population of older men. Methods: We developed a questionnaire including items about symptoms possibly associated with PADAM as well as background data covering demography, medical history, mood status, medication, castration therapy, as well as smoking, exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to predict low bio-available T, were also included. The questionnaire was sent to all 1885 men 55, 65 or 75-years-old, living in Linköping, Sweden. Results: We identified a number of symptoms that differed significantly (P<0.01) between age groups, e.g., "increased abdominal circumference", "decrease in muscle strength and/or endurance", "decreased libido", "less strong erection" and "lack of energy". From factorial analysis we found that the symptoms co-varied in four different groups. Conclusion: The prevalence of a number of symptoms differed significantly between age groups, but we cannot infer that there is a causal connection between an average age-dependent decline in testosterone function and these symptoms. There are several other ways to interpret these results like the existence of concurrent somatic and/or mood disorders or ageing as such. For this purpose further studies including measurements of testosterone concentrations relating to the findings of this study have to be performed. © 2004 Elsevier Ireland Ltd. All rights reserved.

We have evaluated a new screening program to detect red cell alloimmunization during pregnancy that was introduced in the south-east region of Sweden in 1981. The screening program is based on two antibody tests at 25 and 35 gestational weeks for all pregnant  women regardless of maternal Rh(D) status. During the period 1983-89, all pregnant women in the region were tested (78,300) and 0.37% were found to exhibit red cell alloimmunization. Antibodies with anti-D specificity were the most common (34%), followed hy anti-E (24%), anti-Kell (17%) and anti-c (11%). These immunizations also caused the most severe cases of hemolytic disease of the newborns. The screening program was efficient since no newborn subjected to exchange transfusion was overlooked. Most of the new immunizations occurred among the Rh(D) positive women (63%). However, the cost of detecting a few severely affected fetuses among the Rh(D) positive women is high. In this group of pregnancies, it seems sufficient with only one antibody screening test, if done at 25 gestational weeks.

The standard variables commonly used to predict fetal hemolytic disease (FHD) were studied. A low antibody titer level in maternal sernm (≤32) accurately predicted unaffected fetuses. When moderately elevated antibody titer levels (≥64) were present, complementary test variables were needed for a relaihle prediction of FHD. In Rh(D) alloimmunizations, the anti-D concentration in maternal serum, with a cut-off level of 0.7 µg/mL, was the best complementary variable. We could accurately distinguish a low-risk group from a high-risk group of pregnancies. Measurement of the bilirubin content in aruniotic fluid (ΔOD₄₅₀) did not give any further information of relevance in predicting PHD.

High-dose intravenous immunoglobulin (IVIG) treatment appeared to prevent a further deterioration of PHD when a moderate to severe FHD was present (B-hemoglobin concentration between 70-100 g/L). This was observed as a stabilized fetal hemoglobin concentration and an increased fetal anti-D concentration, both interpreted as an effect of a decreased erythrophagocytosis in the fetal reticuloendothelial system.

We propose a flowchart with guidelines for the management of pregnancies complicated by red cell alloimmunization.

Objectives: To study the long-term effects of oral estriol tablets on the endometrium of postmenopausal women by TVS and histology. Method: This was a cross sectional, parallel-group, multicenter trial of 241 postmenopausal women, out of whom 125 were treated with oral estriol and 116 were untreated controls. Endometrial histology using Pipelle biopsies and/or dilatation and curettage (D&C) was taken, endometrial thickness was assessed by use of transvaginal ultrasound (TVS), and the relation between endometrial thickness and histology was calculated. Results: No statistically significant differences between the two groups were found in endometrial histology. There were found more polyps in the oral estriol group (14.0%) as compared with the control group (2.9%). The mean endometrial thickness in the oral estriol group was 3.0 mm compared with a mean value of 2.4 mm in the control group: P=0.01. Conclusions: No clinically relevant difference was found between the endometrium status (assessed by histology and TVS) of postmenopausal women on long-term oral estriol therapy and untreated controls. This trial supports the endometrial safety of maintenance treatment with oral estriol tablets. However, there are signs, not statistically significant, that may be associated with more endometrial polyps in postmenopausal women than if therapy is not given and that TVS is a useful instrument for the diagnosis. ⌐ 2002 Elsevier Science Ireland Ltd. All rights reserved.