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The aim of this study was to evaluate the association of postmenopausal estradiol-progestagen therapy (EPT) with the risk for precancerous lesions, squamous cell carcinoma and adenocarcinoma of the uterine cervix. All Finnish women who had used EPT in 1994-2008 for at least 6 months ( n = 243,857) at the age of 50 years or more were identified from the national Medical Reimbursement Registry and linked to the Finnish Cancer Registry. The incidence of cervical precancerous or cancerous lesions among EPT users was compared to that in the background population. There were 210 EPT users with squamous lesions (178 with precancerous and 32 with cancer) and 79 EPT users with glandular lesions (14 precancerous and 65 adenocarcinomas). The ever use of EPT did not associate with the incidence of precancerous lesions, but the risk for squamous cell carcinoma decreased (standardized incidence ratio 0.41; 95% confidence interval 0.28-0.58) and that for adenocarcinoma increased (1.31; 1.01-1.67). After the use of EPT for 5 years, the risk for squamous cell carcinoma decreased (0.34; 0.16-0.65), and the risk for adenocarcinomas increased (1.83; 1.24-2.59). The prolonged use of EPT is associated with the occurrence of cervical malignancies. If the association would be a causal one, the use for 5+ years among 10,000 women followed for 10 years would mean about two to three fewer cases of cervical squamous cell carcinoma but about two extra cases with adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective. To compare cervical fluid nitric oxide release in women with and without Chlamydia trachomatis and high-risk human papillomavirus infection (hrHPV). Design. An open clinical study. Setting. University Hospital of Helsinki. Population. Thirty-nine women with ( n=21) and without C. trachomatis ( n=18). Methods. Chlamydia trachomatis and/or hrHPV were studied by using specific RNA- and DNA-based tests. Levels of cervical fluid nitric oxide metabolite (NOx) were assessed by the Griess reaction. Main Outcome Measures. The difference in cervical fluid NOx between women with and without C. trachomatis and hrHPV. Results. Fourteen (67%) C. trachomatis-infected women and three (17%) noninfected women had concomitant hrHPV. The level of cervical fluid NOx in women with C. trachomatis (median 37.5μmol/l, 95% confidence interval 26.1-50.9) was higher ( p=0.02) than that in C. trachomatis-noninfected women (median 19.7μmol/L, 95% confidence interval 5.6-30.0). The presence of hrHPV did not associate with any difference in NOx levels between C. trachomatis-infected or -noninfected women. Conclusions. Chlamydia trachomatis was associated with increased release of nitric oxide metabolites in the uterine cervix. This stimulus was stronger than that of hrHPV, because no additional rise in NOx was seen in women with concomitant C. trachomatis and hrHPV infection. [ABSTRACT FROM AUTHOR]

The article discusses a study on the levels of cervical fluid nitric oxide metabolite (NOx) in women with or without high-risk (hr) human papillomavirus (HPV) and the value of which in the prediction of HPV persistence. The study involved women aged 18 to 64 years old in Finland. The study found that hr HPV persisted in 64% of the women and disappeared in 36%. Women with persistent hr HPV had higher median basal levels of NOx than those with eradicated hr HPV.

The article reports on a study evaluating the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk among the 50 to 80 years women in Finland. A tendency toward an elevated risk both for exposure of <5 years was shown after the use of long-cycle EPT. The use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk while the use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer.

Objective. Smoking is an important risk factor for placental abruption with strong dose-dependency. Pregnant smokers often underreport tobacco use which can be objectively assessed by measuring serum cotinine levels. We examined the accuracy between self-reported smoking habits and early pregnancy serum cotinine levels in women with or without placental abruption. Design. Retrospective case-control study. Setting. University Hospital. Population. A total of 175 women with placental abruption and 370 control women. Methods. Serum samples collected during the first trimester were analyzed for serum cotinine levels. Cotinine concentration over 15 ng/ml was considered as the cutoff indicating active smoking. Smoking habits of the women and their partners were recorded at the same visit. Main outcome measure. Placental abruption. Results. Of the cases of women with placental abruption, 27.4% reported smoking compared with 14.3% of the controls ( p < 0.001). Based on serum cotinine levels, 30.3% of the case women and 17.6% of the control women were considered smokers ( p = 0.003). Serum cotinine levels among smokers were higher in the abruption group than in the control group (median 229.5 ng/ml (interquartile range 169.8-418.1) vs. 153.5 ng/ml (56.6-241.4), p = 0.002). Self-reported number of cigarettes smoked daily correlated well with the cotinine levels ( r = 0.68, p < 0.001). Of the women reporting as nonsmokers, approximately 7% were considered smokers based on cotinine testing. Conclusion. Pregnant women with subsequent placental abruption are heavier smokers than pregnant control women. Self-reported smoking habits correlate well with serum cotinine levels in Finland. Therefore, self-reported smoking can be considered as a risk marker for placental abruption. [ABSTRACT FROM AUTHOR]

Endometriosis-associated infertility is poorly treatable with various forms of surgery. Therefore, assisted reproduction techniques (ARTs), such as controlled ovarian hyperstimulation, intrauterine insemination, or in vitro fertilization, are commonly used for endometriosis-associated infertility. Endometriosis impairs the efficacy of in vitro fertilization. There is no evidence that ovulation suppression before ART would enhance the efficacy of ART. Resection of minimal/mild endometriosis and/or restoration of the normality of pelvic anatomy may enhance the efficacy of ART, but aggressive ovarian surgery should be avoided, because it reduces the ovarian reserves and the likelihood of pregnancy after ART. The outcome of ART pregnancy is not affected by the history of endometriosis, but the presence of endometrioma may predispose to preterm birth or fetal growth retardation in ART-induced pregnancies. As a whole, infertility due to endometriosis is best treated with various forms of ART, and the earlier clinicians apply these techniques, the more likely pregnancy may ensue. [ABSTRACT FROM AUTHOR]

Objective. Placental abruption is an important cause of preterm birth, and perinatal morbidity and mortality. Although more common with male fetuses, outcomes have not been evaluated by sex. Our aim was to find out whether short-term morbidity differs by infant sex in cases with placental abruption and in controls. Design. Register-based case-control study. Setting. National Hospital Discharge Register and Medical Birth Register data 1987–2005. Population. The study population consisted of 4,081 women with placental abruption and singleton infant. Three control women without placental abruption were selected for each case matched by maternal age, parity, year of birth, and hospital district. A total of 3,688 cases and 12,695 controls had liveborn infants. Methods. Data on pregnancy, delivery, and perinatal outcomes were collected. Main outcome measure. Placental abruption. Results. The sex ratio (proportion of male) of cases was 0.548 and of controls 0.516 ( p = 0.001). Compared with females, male fetuses in the placental abruption group were born earlier ( p = 0.018). Compared with controls, cases with placental abruption were born earlier ( p < 0.001), had lower birthweight ( p < 0.001), were more often growth restricted ( p < 0.001), had lower Apgar scores ( p < 0.001) and pH ( p < 0.001). Newborn cases needed special care, respirator treatment, antimicrobial and phototherapy more often ( p < 0.001) than controls. There was no difference in perinatal outcomes between female and male infants in the placental abruption group. Conclusions. Placental abruption occurred earlier in pregnancy with male fetal sex but otherwise the outcomes were similar. Compared with controls newborns in the placental abruption group had a worse outcome. [ABSTRACT FROM AUTHOR]

Objective. To study placental abruption-associated maternal deaths out of all maternal deaths in Finland. Design. Register-based study. Setting. The Finnish Medical Birth Register (MBR), the Hospital Discharge Register (HDR), and the Cause-of-Death Register data during 1972-2005. Methods. The maternal deaths were identified by linking data from the MBR, the HDR, and the Cause-of-Death Register. The clinical data were collected from the case records and death certificates. Main outcome measures. Cause-specific maternal death with special reference to placental abruption. Results. During the study period, a total of 2,104,436 live births and 117 direct maternal deaths (caused by a disease or its management unique to the pregnancy) occurred in Finland. The direct maternal mortality ratio (MMR) was 5.6 per 100,000 live births. The two leading causes were thromboembolism (24.0%) and hemorrhage (22.3%) representing almost half of all maternal deaths. Altogether 7,735 placental abruptions were identified with three maternal deaths giving a case fatality rate of 0.4 per 1,000 cases. The MMR (38.8 per 100,000) was nearly seven times higher than the overall MMR (5.7 per 100,000) (p=0.010). Conclusion. The direct MMR in Finland is at the level generally seen in Western Europe. The main causes to maternal death are thromboembolism and obstetric hemorrhage. Deaths to placental abruption are rare, but still seven times higher than the overall MMR. [ABSTRACT FROM AUTHOR]

Objective. Endostatin, an important anti-angiogenic factor produced by endothelial cells, is elevated in established pre-eclampsia. We measured maternal serum endostatin concentrations in early pregnancy associated with later pre-eclampsia and intrauterine growth retardation (IUGR). Design. Retrospective case-control study. Setting. University Central Hospital. Sample. Serum samples were collected at 12-15 and 16-20 gestational weeks from a total of 124 pregnant women of whom 49 developed pre-eclampsia, 16 gave birth to infants with IUGR without pre-eclampsia, and 59 remained normotensive giving birth to healthy, normal-weight infants. Methods. Enzyme-linked immunosorbent assay. Main outcome measures. Endostatin concentrations in serum. Results. At 12-15 gestational weeks, there was no difference in median endostatin concentrations between the groups. At 16-20 gestational weeks, the median endostatin concentration was higher in the women with subsequent pre-eclampsia (p=0.026), especially preceding a later severe form of the disease (p=0.041), than in the controls. The results were further confirmed by receiver operating characteristic (ROC) analysis showing an area under the curve (AUC) of 0.64 (95% confidence interval: 0.50-0.81) for endostatin to identify subsequent pre-eclampsia, and 0.71 (0.53-0.89) in cases of severe pre-eclampsia. Optimal cut-off values were determined and used for calculations of sensitivity and specificity, which were 80 and 52% (cut-off value = 58.0 µg/L) in pre-eclampsia, and 80 and 65% (cut-off value = 65.5 µg/L) in the severe form of the disease. Conclusions. The concentrations of endostatin in maternal serum at 16-20 weeks' of gestation are associated with an increased risk of pre-eclampsia but not IUGR. [ABSTRACT FROM AUTHOR]

Objective. The human uterine cervix is capable of producing nitric oxide (NO). We studied the impact of cytological changes on the release of cervical NO. Design. Population-based case-control study. Setting. City of Helsinki, Finland. Population. Cervical cytology tests and cervical fluid samples were collected in 297 women. Methods. Cervical cytology tests, classified according to Bethesda criteria, were specifically analyzed for changes typically seen in human papillomavirus (HPV) infection, and the level of NO metabolites (NOx) in cervical fluid was assessed by Griess reaction. Main outcome measures. The difference in cervical fluid NOx between normal and abnormal cytology. Results. Cervical cytology was normal in 219 women and abnormal in 78 women. Among women with abnormal cytology there was both a higher detection rate (89% vs. 71%) and a higher concentration of NOx (median 22.5 µmol/l, 95% CI 14.6-31.9 vs. 11.0 µmol/l, 95% CI 8.0-16.7) compared to women with normal cytology. Age, parity, use of oral contraceptives, phase of the menstrual cycle, or history of miscarriage or termination of early pregnancy were not linked to an increased cervical NOx level. Conclusions. Cervical cell changes (suggestive of HPV infection) are accompanied by an increased release of NO in the human cervix. The significance of this finding remains uncertain, but in theory, increased release of NO could modify the outcome of cervical infection. [ABSTRACT FROM AUTHOR]

Objective: High level of soluble endoglin (sEng), a potent antiangiogenic factor, predicts pre-eclampsia. We compared the serum levels of sEng in early second trimester in women with and without subsequent placental abruption. Proangiogenic placental growth factor (PlGF) and antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) were also studied. Methods: Serum samples of 42 women with placental abruption and 50 control women, collected at 15 to 16 gestational weeks were analyzed for sEng, sFlt-1 and PlGF by immunoassays. Results: The levels of sEng showed no difference between the cases and controls, but parous or smoking women with abruption had lower levels of sEng. Similarly, sFlt-1, PlGF, or sFlt-1/PlGF ratio showed no difference between the cases and the controls. Conclusion: Our data suggest that sEng, PlGF and sFlt-1 levels in early second trimester fail to predict placental abruption. [ABSTRACT FROM AUTHOR]

Objective To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSβ-hCG) levels to placental abruption. Methods Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSβ-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. Results The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) ( p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity ≥ 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP ≥ 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSβ-hCG MoM did not differ between the cases and the controls. Conclusion Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2-4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene. [ABSTRACT FROM AUTHOR]

Background. To study the risk factors of placental abruption during the index pregnancy. Methods. One hundred and ninety-eight women with placental abruption and 396 control women were identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. The clinical manifestations of placental abruption were also studied. Results. The overall incidence of placental abruption was 0.42%. The independent risk factors were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), pre-eclampsia (2.7; 1.3, 5.6), and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%), and fetal heart rate abnormalities (69%) were the most common manifestations. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% had preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). Retroplacental blood clot was seen by ultrasound in 15% of the cases. Conclusions. Maternal alcohol consumption and smoking, and smoking by the partner turned out to be independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption. [ABSTRACT FROM AUTHOR]

Background: To define the prepregnancy risk factors for placental abruption.Methods: One hundred and ninety-eight women with placental abruption and 396 control women without placental abruption were retrospectively identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Relevant historical and clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors.Results: The overall incidence of placental abruption was 0.42%. Placental abruption recurred in 8.8% of the cases. The independent risk factors were smoking (OR 1.7; 95% CI 1.1, 2.7), uterine malformation (OR 8.1; 1.7, 40), previous cesarean section (OR 1.7; 1.1, 2.8), and history of placental abruption (OR 4.5; 1.1, 18).Conclusions: Although univariate analysis identified many risk factors, only smoking, uterine malformation, previous cesarean section, and history of placental abruption remained significant after multivariate analysis, increasing the risk of placental abruption in subsequent pregnancy. It may be possible to approximate the risk for placental abruption based on these simple prepregnancy risk factors. [ABSTRACT FROM AUTHOR]

Objective: The cells of the human uterine cervix synthesize nitric oxide, which may be a factor in cervical ripening. We studied the effect of misoprostol on cervical nitric oxide release in nonpregnant and pregnant women. Study design: Seventy-two nonpregnant (n = 15) and pregnant (n = 57; 26 in early pregnancy, 31 in late pregnancy) women were treated with either vaginal misoprostol (n = 54) or vaginal placebo (n = 18). The dose of misoprostol was 400 µg in nonpregnant and early pregnancy group, and 25 µg in late pregnancy group. Serial cervical fluid samples, collected before and up to 3 hours after misoprostol/placebo, were assessed for the concentration of nitric oxide metabolites by means of the Griess reaction. Results: Placebo had no effect on cervical fluid nitric oxide metabolite level. In 1 to 3 hours, misoprostol induced 4.3- to 5.2-fold elevations in cervical fluid Nox concentrations in early pregnancy (P < .01), and 4.4- to 18.2-fold elevations in late pregnancy (P < .01), but these responses did not differ significantly from each other. Misoprostol had no effect on cervical fluid nitric oxide metabolites in nonpregnant women. There was a trend towards a relationship between cervical nitric oxide stimulation after misoprostol and cervical ripening. Conclusion: Vaginal misoprostol stimulates cervical nitric oxide release in pregnancy. This suggests a joint action of nitric oxide and prostaglandins in cervical ripening. [ABSTRACT FROM AUTHOR]

Objective:Adiponectin is an adipocyte-derived protein with profound insulin-sensizing, anti-inflammatory, and antiatherogenic effect. Surprisingly, recent evidence suggests that adiponectin concentrations are increased during preeclampsia, which is characterized by insulin resistance. We studied whether serum adiponectin is related to insulin sensitivity in preeclamptic and normotensive pregnant women.Methods:We measured serum adiponectin concentrations and insulin sensitivity (intravenous glucose tolerance test/minimal model) in 22 women with preeclampsia and 15 normotensive controls with similar pre-pregnancy body mass index (BMI) (range 18-29 kg/m2) between 29 and 39 weeks of gestation. Fourteen cases and 10 controls were also studied 6-22 weeks after delivery. No subject had gestational diabetes.Results:During pregnancy, the mean adiponectin concentration in preeclamptic women was 10.3 (SD 4.2) μg/mL as compared to 7.9 (SD 2.9) μg/mL in normotensive controls (95% confidence interval [CI] for difference 0.1-5.3 μg/mL; P = .04). Adiponectin concentrations were unrelated to insulin sensitivity both in preeclamptic and normotensive subjects; insulin sensitivity was decreased in preeclampsia (P = .01). After delivery, mean adiponectin concentration was lower than during pregnancy: 7.4 (SD 3.0) μg/mL in preeclamptic subjects (P = .001) and 7.1 (SD 1.6) μg/mL in normotensive controls (P = .06) and similar in cases and controls (95% CI for difference - 1.7-2.3 μg/mL, P = .7).Conclusions:Despite their reduced insulin sensitivity, preeclamptic women have higher adiponectin concentrations than normotensive pregnant women. These concentrations are unrelated to insulin sensitivity. After pregnancy, the difference in adiponectin concentrations is no longer present between the two groups. These findings are consistent with a role of adiponectin in the pathophysiology of preeclampsia. [ABSTRACT FROM PUBLISHER]

To study the role of progesterone (P4) in the regulation of circulating leptin in early human pregnancy, we measured the levels of leptin before and after administration of the antiprogestin mifepristone, followed by misoprostol in early pregnancy.Thirty-four women requesting termination of pregnancy, with≤63 days of amenorrhea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Five serial serum samples were assayed for leptin, human chorionic gonadotrophin (hCG), P4, estradiol (E2), cortisol, and mifepristone.Circulating leptin concentrations decreased by 8.7 ± 29.7% (mean ± standard deviation) (p < 0.05) following the ingestion of mifepristone. After misoprostol administration on day 2, a decrease of 12.6 ± 17.0% (p < 0.05) was followed by a rebound on day 3 to 87.6 ± 25.7% of the pretreatment values. Two weeks after mifepristone, leptin levels had declined by 25.4 ± 30.4%. In contrast, E2, P4, and hCG concentrations continued to increase following mifepristone, followed by rapid declines from day 2 to day 3. Serum cortisol concentrations increased by 89.7% ± 82.7% in response to mifepristone, but this increase did not correlate with the decrease in leptin. The decrease in leptin levels on day 2 correlated with the decreases in P4 (r = 0.37,p < 0.05) and in E2 (r = 0.44,p < 0.05) levels.The fall in leptin levels following mifepristone implies a role for P4 in the regulation of leptin in early pregnancy. Moreover, the significant correlation between the changes in leptin and those of P4 and E2 at the time of luteolysis suggests that corpus luteum may also play a role in the regulation of circulating leptin in early pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND. Fatty acid esters of 17β-estradiol (E2) are estrogen metaboiites associated with lipoproteins in blood. AIM. To study the effects of estrogen therapy on concentrations of serum E2 fatty acid esters in postmenopausal women with a history of an estrogen-related liver disorder, intrahepatic cholestasis of pregnancy (ICP), and in healthy women in a double-blind, crossover fashion. METHOD. ICP (n = 10) and control women (n = 10) received increasing doses of E2 valerate orally 2–4 mg/day, or transdermal E2 50–100 μg/day for 6 weeks. After a 4-week wash-out period, the subjects crossed over to the alternate E2 treatment. Concentrations of serum E2 fatty acid esters were quantified after saponification by fluoroimmunoassay. RESULTS. Oral E2 administration increased median serum E2 fatty acid ester concentrations from 57 to 73 pmol/L in the 1CP and from 56 to 74 pmol/L in the control group, in association with elevations in serum E2, estrone and sex hormone-binding globulin levels. Transdermal E2 treatment did not increase serum E2 ester levels. CONCLUSIONS. The increase in serum E2 fatty acid esters during oral E2 administration may be attributed, at least partly, to the higher estrogen dose during oral compared with transdermal therapy. A history of ICP did not affect esterification of E2 during estrogen therapy. [ABSTRACT FROM AUTHOR]

Objective: To review the evidence of the efficacy of postmenopausal hormone replacement therapy (HRT) in secondary prevention of coronary artery disease or stroke. Results: Although a number of rather large and prolonged non-randomized observational studies have produced convincing and consistent evidence of the efficacy of HRT in the prevention of recurrence of cardiac events, the first randomized, placebo controlled trial (RCT) on heart disease and estrogen replacement study (HERS) reported no benefit of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in secondary prevention of cardiac events in women with established coronary artery disease. This was supported by RCT reporting no effect of CEE or CEE+MPA on the progress of coronary sclerosis. Similarly, some nonrandomized observational studies have evaluated the risk of recurrent stroke in regard to the use of HRT, and the data are conflicting reporting a reduced or increased risk of recurrence for HRT users. One RCT has shown that low-dose estrogen treatment can only slow down the progression of carotid arteriosclerosis in high-risk postmenopausal women, whereas two other RCTs have shown no benefit (or risk) of using HRT for secondary prevention of ischemic stroke or progression of carotid atherosclerosis. Conclusion: The evidence accumutaed so far shows that HRT has no place in secondary prevention of coronary or carotic artery disease. Its use in these patients must be based on solid nonvascular indications and expected benefits from these causes. [Copyright &y& Elsevier]

Background: The aim of this study was to compare the effect of fetal presentation and mode of delivery on infant outcome in a nation-wide study.Methods: In a retrospective observational cohort study, we compared, with the help of Finnish Medical Birth Register and other nation-wide registers, the short-term and long-term outcome of infants born by breech vaginal (n = 1270) or by vertex vaginal delivery (n = 128,683) or through planned cesarean section (CS) in breech (n = 1640) or vertex (n = 4997); the pregnancies were otherwise entirely normal.Results: One perinatal death occurred in the breech vaginal group and 23 deaths in the vertex vaginal group (p = 0.112), but none in either CS group. Breech vaginal delivery was associated with increased risk of Apgar scores 6 or less at age 1 min (OR 7.65, CI 6.41-9.12) and at age 5 min (OR 6.42, CI 4.36-9.45) as compared with vertex vaginal delivery. These odd ratios were also elevated (OR 4.59, CI 3.48-7.08 and OR 7.58, CI 3.09-18.66, respectively) when compared with breech planned CS. Yet the risk for birth trauma of infants in the breech vaginal group was smaller (OR 0.70, CI 0.51-0.96) than that in the vertex vaginal group but this risk was smallest in the planned CS groups. A number of other neonatal complications occurred equally commonly in each group. Breech infants born vaginally needed fewer admissions (OR 0.58, 0.47-0.72) to out-patient departments and the cumulative incidence of long-term morbidity in the breech vaginal group was smaller (OR 0.47, CI 0.28-0.80) to the age of 7 years than that in the breech planned CS. The maturity for starting school and school performance during the first two school years showed no dependence on mode of delivery.Conclusion: Apart from Apgar suppression, elective vaginal delivery of a full-term breech fetus in highly selected pregnancies does not cause additional neonatal hazards as compared with full-term vertex deliveries. The immediate outcome was best for breech or vertex infants born through elective CSs. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effect of fetal presentation and mode of delivery on infant outcome in a nation-wide study. In a retrospective observational cohort study, we compared, with the help of Finnish Medical Birth Register and other nation-wide registers, the short-term and long-term outcome of infants born by breech vaginal ( n = 1270) or by vertex vaginal delivery ( n = 128 683) or through planned cesarean section (CS) in breech ( n = 1640) or vertex ( n = 4997); the pregnancies were otherwise entirely normal. One perinatal death occurred in the breech vaginal group and 23 deaths in the vertex vaginal group ( p = 0.112), but none in either CS group. Breech vaginal delivery was associated with increased risk of Apgar scores 6 or less at age 1 min (OR 7.65, CI 6.41–9.12) and at age 5 min (OR 6.42, CI 4.36–9.45) as compared with vertex vaginal delivery. These odd ratios were also elevated (OR 4.59, CI 3.48–7.08 and OR 7.58, CI 3.09–18.66, respectively) when compared with breech planned CS. Yet the risk for birth trauma of infants in the breech vaginal group was smaller (OR 0.70, CI 0.51–0.96) than that in the vertex vaginal group but this risk was smallest in the planned CS groups. A number of other neonatal complications occurred equally commonly in each group. Breech infants born vaginally needed fewer admissions (OR 0.58, 0.47–0.72) to out-patient departments and the cumulative incidence of long-term morbidity in the breech vaginal group was smaller (OR 0.47, CI 0.28–0.80) to the age of 7 years than that in the breech planned CS. The maturity for starting school and school performance during the first two school years showed no dependence on mode of delivery. Apart from Apgar suppression, elective vaginal delivery of a full-term breech fetus in highly selected pregnancies does not cause additional neonatal hazards as compared with full-term vertex deliveries. The immediate outcome was best for breech or vertex infants born through elective CSs. [ABSTRACT FROM AUTHOR]

Background: Women suffering from fear of labor have reduced pain tolerance during a cold pressor test (CPT) during and after pregnancy.Methods: We compared levels of norepinephrine, adrenocorticotropin (ACTH), cortisol and beta-endorphin before and during the CPT up to 60 min in 20 normotensive women with and 20 without fear of labor at 37.4 +/- 0.2 (mean +/- SE) gestational weeks and at 41.9 +/- 1.6 weeks after delivery.Results: Baseline levels of norepinephrine in the pregnant fear group (1.63 +/- 0.18 nmol/L) were higher (p = 0.068) than in controls (1.38 +/- 0.14 nmol/L) but after delivery they were lower in the fear group (1.75 +/- 0.31 nmol/L vs. 2.31 +/- 0.26 nmol/L, p = 0.064). ACTH, cortisol and beta-endorphin did not differ between pregnant and nonpregnant groups. The CPT caused a 28.4% smaller response in norepinephrine in the pregnant fearful women than in controls, whereas the responses of ACTH and beta-endorphin were similar between groups during and after pregnancy. The CPT caused no significant response in cortisol. Pregnant fearful women had higher diastolic blood pressure (85.6 +/- 4.5 mmHg, mean +/- SE) than the controls (74.9 +/- 3.4 mmHg, p = 0.065).Conclusions: Women with fear of labor were characterized by changes in norepinephrine but not in ACTH, cortisol or beta-endorphin before and during the CPT, indicating a normal pituitary-adrenal axis function. [ABSTRACT FROM AUTHOR]

Background: Diseases with low-grade inflammation perturb endothelial function. We investigated whether preterm premature rupture of membranes (PPROM) is associated with endothelial dysfunction, as assessed by the levels of endothelium-derived nitric oxide metabolites (NOx) and E-selectin in maternal serum.Methods: The concentrations of NOx and E-selectin were measured in 32 pregnant women with PPROM and in 27 healthy gestational age-matched control women. The grade of inflammation was estimated by measuring serum C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations.Results: NOx and E-selectin concentrations were not different in PPROM patients as compared to controls. In 17 patients with PPROM, CRP rose above 12 mg/L. In this group, IL-6 concentration was significantly higher than among controls, but concentrations of NOx and E-selectin remained unaltered. There was a negative correlation between the levels of NOx, CRP and IL-6 and the interval from PPROM to delivery. The levels of NOx correlated positively with those of IL-6.Conclusions: PPROM, with or without CRP and IL-6 surges, does not affect endothelial function markedly, as judged from the unaltered concentrations of NOx and E-selectin in maternal serum. [ABSTRACT FROM AUTHOR]

Objective: Cervical tissue expresses all the isoenzymes of nitric oxide synthase. We studied the concentrations of nitric oxide metabolites in the cervical fluid in nonpregnant (n = 11) and pregnant women (n = 106).Study Design: Cervical fluid was collected into a Dacron polyester swab, and nitric oxide metabolites were eluted into physiologic saline solution, which was assayed for nitric oxide metabolites with the Griess reaction. The detection limit of the method is 0.2 micromol/L.Results: Cervical fluid nitric oxide metabolite was detectable in 46% of nonpregnant women (median, <0.2 micromol/L; 95% CI, 0-49), in 63% of women in early pregnancy (median, 11 micromol/L; 95% CI, 0-23) and in 82% of women in late pregnancy (median, 128 micromol/L; 95% CI, 21-276). In late pregnancy, the cervical fluid nitric oxide metabolite level was higher in women with Bishop score of > or =6 (median, 163 micromol/L; 95% CI, 105-276) than in women with Bishop score of <6 (median, 86 micromol/L; 95% CI, 21-99). Cervical fluid nitric oxide metabolite concentration before the onset of labor in parous women (median, 97 micromol/L; 95% CI, 78-283) was higher (P =.008) than that in nulliparous women (median, 28 micromol/L; 95% CI, 0-95). Cervical fluid nitric oxide metabolites before the initiation of labor (median, 33 micromol/L; 95% CI, 0-95) rose to 3.5-fold (median, 115 micromol/L; 95% CI, 78-284) after the commencement of uterine contractions and showed a significant relationship to Bishop score (r = 0.39, P =.01). Cervical fluid nitric oxide metabolite concentrations were not relative to simultaneous plasma nitric oxide metabolite levels (n = 41 women, r = 0.14, P =.41). Rupture of fetal membranes tended to decrease cervical fluid nitric oxide metabolite levels, whereas gentle cervical manipulation elevated it 6.6-fold in 1 minute. The administration of glyceryl trinitrate (0.5 mg, nitric oxide donor) intracervically resulted in a significant rise in the cervical fluid nitric oxide metabolite level in 2 minutes.Conclusion: Cervical fluid nitric oxide metabolite level rises after cervical ripening, nitric oxide donor administration, or cervical manipulation, which supports a role for cervical nitric oxide in cervical ripening. [ABSTRACT FROM AUTHOR]

Background: Misoprostol is widely used in combination with mifepristone for medical termination of pregnancy. We studied the endocrine parameters of trophoblast function during medical termination of early pregnancy using mifepristone in combination with oral or vaginal misoprostol. The effect of prolonged misoprostol administration was also examined.Methods: Thirty-four women, requesting termination of pregnancy and with Results: hCG and progesterone concentrations continued to increase until day 2. Following misoprostol, hCG and progesterone levels declined by 70.5 +/- 8.8% and 61.3 +/- 16.3% (mean +/- SD) respectively, in 24 h. The percentage decline in hCG correlated inversely (P < 0.05) with the time taken to abort. The peak level of mifepristone measured on day 2 did not correlate with the decline in serum hCG or progesterone. The kinetics of hCG, progesterone and mifepristone were similar in the different treatment groups.Conclusions: The route and duration of misoprostol administration have no effect on the kinetics of serum hCG or progesterone during medical termination of early pregnancy. [ABSTRACT FROM AUTHOR]

Background: To decrease exposure to progestin during hormone replacement therapy (HRT), a novel oral regimen consisting of constant 17beta-estradiol (E2) daily plus intermittent norgestimate (NGM) has been developed.Methods: A multicenter study compared the safety and efficacy of E2 1 mg daily plus intermittent NGM 90 micro g (3 days off, 3 days on) (n = 150) vs. a continuous oral dose of E2 2 mg plus norethisterone acetate (NETA) 1 mg (n = 172) daily, for a period of 2 years. Endometrial biopsies were performed at 1 and 2 years. Subjects recorded the occurrence of vasomotor symptoms, uterine bleeding, and adverse events on diary cards.Results: At 2 years' follow-up, no subject had developed endometrial hyperplasia or cancer. Endometrial atrophy was seen in 75% of subjects using the intermittent NGM regimen and in 78% of women using the constant NETA regimen. Both groups maintained a 96% reduction in vasomotor symptoms up to 2 years. The rates of bleeding and/or spotting showed no difference between the groups, and at 2 years' follow-up, 73% of women in the intermittent NGM group and 83% of subjects in the constant NETA group were amenorrheic. There was a lower incidence of progestin-associated side-effects, such as abdominal discomfort, edema, painful bleeding episodes, and breast symptoms, with the intermittent progestin regimen vs. the constant progestin regimen. Intermittent NGM use was associated with an elevation in HDL- and HDL2-cholesterol, whereas constant NETA reduced these lipoproteins.Conclusions: The intermittent administration of a progestin, such as NGM, provides a new, well-tolerated regimen to achieve endometrial safety, an adequate rate of amenorrhea, and effective reduction of vasomotor symptoms in postmenopausal women. [ABSTRACT FROM AUTHOR]

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1α) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (±SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44·0 ± 4·1 versus 19·0 ± 3·6 ng/mmol creatinine, P < 0·001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25·2 ± 3·5 versus 13·6 ± 2·1 ng/mmol creatinine, P < 0·01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins. [ABSTRACT FROM AUTHOR]