Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia.

PURPOSE: To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms. MATERIALS AND METHODS: We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain. RESULTS: Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect). CONCLUSION: E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.

A phase 3 study in Europe and Russia showed that Estetrol/Drospirenone, a new combined oral contraceptive, significantly improved the MDQ scores for domains Pain, Water Retention and Negative Affect in women starting COC use, while switchers showed minimal changes.

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials.

OBJECTIVE: In the 24-week, phase 3 LIBERTY 1 (L1) and LIBERTY 2 (L2) trials, relugolix combination therapy (relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg)) reduced uterine fibroid (UF)-associated symptoms. This post hoc analysis assessed safety and efficacy of relugolix-CT in European women from L1/L2. METHODS: Premenopausal women (aged 18-50 years) with UF-associated heavy menstrual bleeding (HMB) were randomized 1:1:1 in L1 (N = 388) and L2 (N = 382) to relugolix-CT or placebo for 24 weeks, or delayed relugolix-CT (relugolix 40 mg then relugolix-CT; 12 weeks each). Primary endpoint: proportion of responders (menstrual blood loss (MBL) <80 mL and reduction of ≥50% from baseline MBL volume) over the last 35 days of treatment. Secondary endpoints: MBL volume, amenorrhea, UF-associated pain, symptom severity, distress related to bleeding and pelvic discomfort, health-related quality of life (HRQoL). Safety endpoints included adverse event (AE) reporting and bone mineral density (BMD) assessment. RESULTS: In European women from L1/L2 (N = 124, 16%), a significantly greater proportion of treatment responders was observed with relugolix-CT vs. placebo (85.4% vs. 19.1%, respectively; nominal p < .0001). There were statistically significant improvements with relugolix-CT vs. placebo for several secondary endpoints: reduction in MBL volume, amenorrhea rate, proportion achieving mild-to-no pain, reduction in symptom severity and distress from bleeding and pelvic discomfort, and improvement in HRQoL. Incidence of AEs and percentage changes in BMD from baseline to week 24 were similar for relugolix-CT and placebo. CONCLUSIONS: In European women with UF and HMB, once-daily relugolix-CT vs. placebo improved UF-associated symptoms and preserved BMD.

The impact of serum homocysteine on intima-media thickness in normotensive, white-coat and sustained hypertensive adolescents.

BACKGROUND AND PURPOSE: In recent decades, elevated levels of homocysteine (Hcy) have been found to be associated with an increased risk of vascular events. Additionally, in some case-control studies, hyperhomocysteinaemia has been found to be related to higher intima-media thickness (IMT), but the results are inconclusive. Therefore, in the present study we intended to assess the relationship between serum levels of Hcy and IMT in normotensive and hypertensive adolescents. PATIENTS AND METHODS: 59 normotensive 47 white coat hypertensive and 73 sustained hypertensive adolescents were included in our study. IMT of the common carotid arteries was measured by B-mode ultrasonography. Plasma NOx as well as homocysteine levels were measured in all cases. The relationship between IMT and Hcy and NOx were assessed by a pooled analysis. Additionally, serum levels of Hcy and NOx were compared between normotensives and hypertensive subgroups. RESULTS: IMT was elevated in hypertensive adolescents (means ± SD: 0.055 ± 0.01 cm) compared with normotensives (0.048 ± 0.008 cm, p < 0.01). Higher serum concentrations of homocysteine were measured in hypertensive teenagers (11.9 ± 7.25 µmol/l for hypertensive and 9.85 ± 3.12 µmol/l for normotensives respectively, p < 0.01). In contrast to this, serum NOx was lower in patients (28.8 ± 14.9 µmol/l) compared with controls (38.8 ± 7.6 µmol/l, p < 0.01). The pooling of homocysteine and IMT data of hypertensive and normotensive adolescents revealed a significant positive relationship between the two parameters (r = 0.43, p < 0.001). CONCLUSIONS: We conclude that elevated serum levels of homocysteine may play a role in increased IMT in adolescent hypertension.

Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials.

OBJECTIVE: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen. STUDY DESIGN: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors. RESULTS: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2 of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception. CONCLUSION: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. IMPLICATIONS STATEMENT: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.

Pooled analysis of two phase 3 trials evaluating the effects of a novel combined oral contraceptive containing estetrol/drospirenone on bleeding patterns in healthy women.

OBJECTIVE: To evaluate the bleeding patterns of a new combined oral contraceptive containing estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in a 24/4-day regimen. STUDY DESIGN: We pooled bleeding data from two parallel, open-label, 13-cycle phase 3 trials that enrolled participants 16 to 50 years old with body mass index (BMI) ≤35 kg/m2. Participants reported vaginal bleeding/spotting in daily diaries. For this bleeding analysis, we included participants with at least one evaluable cycle. We calculated mean frequencies of scheduled and unscheduled bleeding/spotting episodes and median duration of bleeding/spotting episodes, and assessed associations between treatment compliance, BMI and recent hormonal contraceptive use on bleeding/spotting outcomes. RESULTS: We included 3409 participants with 33,815 cycles. Scheduled bleeding/spotting occurred in 87.2% to 90.4% of participants/cycle, with a median duration of 4 to 5 days. Unscheduled bleeding/spotting decreased from 27.1% in Cycle 1 to 20.6% in Cycle 2 to ≤17.5% from Cycle 5 onwards. Most (66.5%) unscheduled bleeding/spotting episodes were spotting-only. Between 5.8% and 7.8% of users/cycle experienced absence of any scheduled or unscheduled bleeding/spotting. Missing one or more active pills resulted in a higher occurrence of unscheduled bleeding/spotting (adjusted odds ratio [aOR] 2.13 [95% confidence interval 1.68-2.70]) and absence of scheduled bleeding/spotting (aOR 2.36 [1.82-3.07]). Participants with a BMI ≥30 kg/m2 reported more absence of scheduled bleeding/spotting (aOR 1.68 [1.37-2.05]). Switchers and starters reported similar frequencies of unscheduled bleeding/spotting (aOR 0.94 [0.83-1.07]) and absence of scheduled bleeding/spotting (aOR 1.00 [0.85-1.19]). Three percent of participants discontinued for a bleeding-related adverse event. CONCLUSION: E4/DRSP use results in a predictable bleeding pattern with limited unscheduled bleeding/spotting. Noncompliance and BMI affect bleeding patterns. IMPLICATIONS STATEMENT: Most estetrol/drospirenone users experience a predictable and regular bleeding pattern. Providers can educate patients about the expected bleeding patterns and should advise users that they may infrequently experience no scheduled bleeding/spotting. This information may improve user acceptability and continuation of this new oral contraceptive.

Tolerability and safety of the estetrol/drospirenone combined oral contraceptive: Pooled analysis of two multicenter, open-label phase 3 trials.

OBJECTIVES: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials. STUDY DESIGN: The two trials enrolled participants aged 16-50 years with a body mass index ≤35.0 kg/m2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings. RESULTS: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment. CONCLUSIONS: E4/DRSP is associated with a favorable tolerability and safety profile. IMPLICATIONS STATEMENT: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks.

Factors influencing adolescent blood pressure: the Debrecen Hypertension Study.

AIM: To obtain epidemiological data on the blood pressure (BP) status of high school students and factors influencing BP. METHODS: Subjects filled out a questionnaire and three repeated BP measurements were taken. All high school attending students in Debrecen (final sample n = 10,194, mean age 16.6 ± 1.0 years) participated in the study. RESULTS: Boys had significantly higher systolic BP (+11.3 mm Hg) and diastolic BP (+2.2 mm Hg) than girls (p < 0.001). There was a positive correlation between weight and BP (r(syst) = 0.42, r(diast) = 0.29), height and BP (r(syst) = 0.33, r(diast) = 0.15), body mass index (BMI) and BP (r(syst) = 0.31, r(diast) = 0.27). Multiple regression was used for statistical analysis. Gender (ß = 0.36), BMI (ß = 0.25), hypertension of parents (father ß = 0.04 and mother ß = 0.02), smoking, alcohol consumption and age determined systolic outcomes in descending order. For the diastolic model, BMI remained a strong determining factor (ß = 0.25) and gender was also significant (ß = -0.09). Entering independents together accounted for 28.2% of the total variance in systolic and for 18.1% in diastolic BP. CONCLUSION: Body weight is central to determining BP. Because that is an alterable cardiovascular risk factor, we presume that lifestyle modification will not only result in reduced weight, but also in decreased BP.

The prevalence of adolescent hypertension in Hungary - the Debrecen hypertension study.

BACKGROUND: The aim of this study was to obtain epidemiological data and to determine the prevalence of adolescent hypertension implementing a blood pressure (BP) screening. METHODS: We performed a cross-sectional, population-based survey in a major Hungarian city (Debrecen, population 230,000). After a 10-min resting period, three consecutive BP measurements were taken. RESULTS: Complete records were obtained for 10,194 subjects (5163 boys and 5031 girls). The mean age was 16.6±1.0 years. BP for boys was higher than for girls (ΔBP(syst)=11 mmHg; ΔBP(diast)=2 mmHg, p<0.001). A significant decrease was observed in BP during the three consecutive measurements (time 1-3: ΔBP(syst)=4 mmHg; ΔBP(diast)=2.5 mmHg; p<0.001). Systolic and/or diastolic BP exceeded the age-, gender- and height-adjusted 90th percentile in 1614 (15.84%) adolescents. Following two lots of three extra measurements on 1461 subjects of this sub-sample, hypertension (systolic and/or diastolic BP exceeded the 95th percentile) was confirmed in 2.12% of the subjects (male: 2.27%, female: 1.97%). Considering there were individuals either already diagnosed with hypertension (n=19) or refusing further participation, the prevalence of hypertension was 2.53% in adolescents in the age range 15-18 years. CONCLUSION: Our population-based study was the first to determine the point-prevalence of adolescent hypertension in Central-Eastern Europe. Identifying and following-up cases of confirmed hypertension is inevitable to prevent or delay the manifestations of target organ damage and reduce hypertension-related mortality.

Efficacy and safety of vilaprisan in women with uterine fibroids: Data from the phase 2b randomized controlled trial ASTEROID 2.

OBJECTIVE: To assess the efficacy of vilaprisan compared with placebo in the management of the symptoms of uterine fibroids (UF), with a secondary objective to provide a descriptive comparison with ulipristal acetate. STUDY DESIGN: The randomized, parallel-group, double-blind, placebo- and active-controlled, multicenter ASTEROID 2 trial assessed the efficacy and safety of vilaprisan versus placebo and ulipristal acetate for two 12-week treatment periods in women with ≥1 UF experiencing heavy menstrual bleeding (HMB). The primary endpoint compared the efficacy of vilaprisan with placebo at 12 weeks, assessed as the absence of bleeding/spotting by bleeding diary. Secondary endpoints compared the efficacy of vilaprisan with ulipristal acetate. Results of the first 12-week treatment period are reported here. RESULTS: Women (mean age 42.5 years) were enrolled from 1 June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL. In total, 155 women completed the initial 12-week treatment period. Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9 % of women receiving vilaprisan versus 0.0 % with placebo (p < .001); 55.4 % of women treated with ulipristal acetate reported absence of bleeding/spotting. The predefined HMB response (<80 mL and >50 % reduction from baseline during the last 28 days of treatment) was observed in 95.7 % of subjects treated with vilaprisan and 86.5 % of subjects treated with ulipristal acetate. Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF by 29.9 % and 23.8 %, respectively, whereas an increase of 6.3 % was observed in the placebo group. No safety concerns, including multiple laboratory parameters, were identified. CONCLUSION: Daily administration of vilaprisan 2 mg induced amenorrhea, controlled bleeding, decreased UF size, and was well tolerated in women with HMB associated with UF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02465814 https://clinicaltrials.gov/ct2/show/NCT02465814.

Rationale and design of ASTEROID 2, a randomized, placebo- and active comparator-controlled study to assess the efficacy and safety of vilaprisan in patients with uterine fibroids.

BACKGROUND: Uterine fibroids (UFs) may be treated with progesterone receptor modulators (PRMs), which have been shown to reduce heavy menstrual bleeding and the size of UFs. To date, one PRM (ulipristal acetate) has received regulatory approval for the treatment of UFs; therapy comprises intermittent treatment courses of up to 3months each, followed by a break to allow two menstruations to occur. We report the design of ASTEROID (Assess Safety and efficacy of vilaprisan in patients with uTERine fibrOIDs) 2, a phase 2 study examining the efficacy and safety of a novel PRM, vilaprisan, in women with UFs. METHODS/DESIGN: In this randomized multi-arm study, vilaprisan (2mg daily) will be administered in different regimens: continuous treatment for 12 or 24weeks, or two 12-week treatment periods separated by a break to allow one menstruation to occur. Efficacy and safety will be compared with that of ulipristal acetate (5mg daily) and placebo. Patients randomized to receive placebo for 12weeks will also be given active treatment for 12weeks. The primary measure of efficacy will be amenorrhoea rate; secondary measures include time to normalized menstrual bleeding and percentage change in UF volume. Endometrial changes will be monitored throughout the study. DISCUSSION: The placebo- and active comparator-controlled trial ASTEROID 2 is the first study to evaluate systematically the efficacy and safety of different treatment regimens of PRMs in women with UFs. The findings of this study will direct the planning of future clinical trials of vilaprisan.

Long-term medical management of uterine fibroids with ulipristal acetate.

OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of four 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. INTERVENTION(S): Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. MAIN OUTCOME MEASURE(S): Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. RESULT(S): Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. CONCLUSION(S): The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. CLINICAL TRIAL REGISTRATION NUMBER: NCT01629563.

[Epidemiological data of 15-18 year adolescents and the prevalence of hypertension in Debrecen. The Debrecen Hypertension Study]. / A 15-18 éves fiatalok epidemiológiai jellemzoi, és a serdülokori hypertonia elofordulási gyakorisága.

AIM: To perform a blood pressure screening program in Debrecen secondary school students according to international guidelines. To obtain epidemiological data about factors influencing adolescent blood pressure using a questionnaire. To repeat the blood pressure measurements in case of elevated systolic and/or diastolic readings, and to determinate the prevalence of adolescent hypertension in Debrecen. PATIENTS AND METHODS: All high school attending students in Debrecen (n = 10359) participated in the study. Measurements were obtained by a validated, automated, digital OMRON M4 device. RESULTS: Gender distribution was nearly equal in our sample: 50.64% male, 49.36% female. The mean age was 16.55 +/- 0.99 years. Boys were 10 cm taller and 10 kg heavier on average than girls. Hypertension in family history was prevalent in 10.8% of mothers and in 11.7% of fathers. Every fifth adolescent (19.7%) was a regularly smoker, while 12.2% of the studied population drank alcohol in a weekly basis. Leisure time sporting activity was characteristic only for 31.9%, while 11.2% of the young people usually felt stress and 15.1% regularly salted their food. Low birth weight (< 2500 gram) was recorded in 6.7% of the adolescents. Systolic and/or diastolic blood pressure exceeded the 90th percentile for the age, gender and height specific subgroups in 1614 cases. Repeated measurements were performed in 1461 cases on two different occasions. Averaging the 3 x 3 measurements, hypertension was confirmed in 216 cases. The prevalence of the disease in this population was 2.53%. CONCLUSION: The recognition, treatment and follow-up of hypertension among adolescent population, is of immense importance.

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of two 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. INTERVENTION(S): Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. MAIN OUTCOME MEASURE(S): Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. RESULT(S): In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. CONCLUSION(S): Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. CLINICAL TRIAL REGISTRATION NUMBER: NCT01629563 (PEARL IV).

Blood pressure distribution in a Hungarian adolescent population: comparison with normal values in the USA.

OBJECTIVES: To describe the blood pressure characteristics and distribution of all adolescent high school students (aged 15-18 years) in Debrecen (total population 230 000), Hungary. To define threshold values for normal blood pressure by age-, sex- and height-specific groups. To compare our data with results from a USA meta-analysis, which forms the basis of current guidelines. PARTICIPANTS AND METHODS: All young people attending high school in Debrecen (final sample = 10 359) participated in the study. After they had rested for 10 min, three blood pressure measurements were taken from the right upper arm, separated by 5 min intervals. All measurements were obtained by a validated, automated, digital Omron M4 device. RESULTS: The 50th, 90th and 95th percentile values of blood pressure were defined by dividing the adolescent population into age-, sex- and height-specific subgroups. In comparison with USA guidelines, in our sample the systolic blood pressure of boys in the different subgroups was 6-11 mmHg greater, whereas this difference was less marked for girls (1-5 mmHg). There were no marked differences in diastolic blood pressure, but our values were slightly lower. CONCLUSIONS: Our findings demonstrate the influence of geographical and ethnic variations on blood pressure. Acceptance and use of non-population-specific blood pressure distributions may lead to under- or overdiagnosis of adolescent hypertension. The use of geographically more relevant data should be encouraged.

Variable response of Hermansky-Pudlak syndrome to prophylactic administration of 1-desamino 8D-arginine in subsequent pregnancies.

Hermansky-Pudlak syndrome is characterised by oculocutaneous albinism and haemorrhagic diathesis. The bleeding tendency that is associated with this autosomal recessive disease is caused by storage-pool deficiency and has been reported to be controllable by prophylactic administration of 1-desamino 8D-arginine (desmopressin, DDAVP). The DDAVP prophylaxis at the first delivery of our patient did not prevent the severe haemorrhagic sequeal requiring transfusion of packed red cells and platelets, but the same preventive measure was successful at her second childbirth. Response to prophylactic DDAVP administration varies between as well as within patients with Hermansky-Pudlak syndrome.

Fetal arterial redistribution indicating true umbilical cord knot.

True umbilical cord knot often remains undiscovered prenatally due to a lack of characteristic clinical or ultrasound signs. We present a pregnancy with favorable outcome in which a non-stress test (NST) found non-reassuring fetal status. Abnormal Doppler blood flow patterns in the descending aorta and in the middle cerebral artery revealed fetal arterial redistribution with normal circulation in the umbilical artery despite a true cord knot. The benefit of fetal Doppler assessment is discussed. Increased aortic-cerebral ratio may reflect acute hypoxic compromise caused by the transitory constriction of the true umbilical cord knot with unrecognized morphologic and circulatory signs.

[The value of Doppler sonography in the detection of fetal hypoxia]. / A Doppler-ultrahangvizsgálat helye a magzati hypoxia igazolásában.

Doppler ultrasound has become a part of routine antenatal fetal surveillance during the past two decades. It provides insight into the utero-placental and fetal arterial, venous circulation non-invasively. Doppler examination has a key role in the detection of hypoxic risk since abnormal blood flow patterns can be demonstrated before the clinical manifestation of fetal disorder. Doppler velocimetry facilitates judgment in the diagnosis, monitoring fetal well-being during pregnancy and labor, scheduling antenatal tests and timing delivery. Authors review the effects of chronic and acute hypoxia on fetal hemodynamics. On the basis of the present knowledge and experience a brief summary is given about the role of Doppler velocimetry in the early detection of hypoxic fetal jeopardy during pregnancy and labor.

[Management of third-trimester low-risk pregnancies--European survey]. / Terhesgondozás harmadik trimeszterbeli alacsony kockázatú terhességekben--európai felmérés.

AIM: Main objective of pregnancy care is to provide health both for the mother and baby. Two main points of this care are to preselect high and low risk pregnancies and to determine the timing of delivery in case of fetal jeopardy or maternal emergency situations in the third trimester. Although we have evidence based techniques that are effective in reducing perinatal mortality in selected high-risk groups, the content of routine pregnancy care in low-risk third trimester pregnancies is not well defined yet. Management of these patients differs from center to center and from country to country and is mainly determined by obstetrical traditions of different geographical areas. PATIENTS/METHODS: Based on the data of questionnaires about recent practice of 28 European obstetrical departments in 10 countries participating in EuroGRIT trial the authors sketch out current management of third trimester low risk pregnancies. CONCLUSIONS: In spite of current discrepancy in applying functional tests it is absolutely required to introduce new methods in the future only within the framework of evidence based medicine.

[Management of twin births]. / Szülésvezetés ikerszülés esetén.

INTRODUCTION: The rate of multiple births has increased all over the world in the past decade. This is mainly due to the widespread use of infertility treatments and assisted reproductive techniques. Despite of improvements in obstetric and neonatal care, twin pregnancy still mean high risk both for the mothers and their babies. The management of twin delivery remains controversial. PATIENTS AND METHOD: Authors analyzed the data of all twin pregnancies at the Department of Obstetrics and Gynecology, University of Debrecen between January 2002 and December 2003. The data of 113 twin pregnancies were analyzed. Details of gestational age, presentation, birth weight discordance, mode of delivery were reviewed. RESULTS: From the 113 analyzed twin births, 27 pregnancies have been conceived after successful assisted reproductive technique. In 18 cases more than 500 grams of body weight difference was detected between the two babies at the time of delivery. The rate of preterm birth was 69%, and cesarean section was performed in 64% of preterm births compared to 68.6% in the matured delivery group. CONCLUSIONS: On the basis of recent data a large prospective, randomized trial is mandatory to determine the optimal management of twin deliveries.

[Current practice and results of labor induction]. / A szülésindukció gyakorlata és eredményei.

INTRODUCTION: The role of labor induction has been gradually increasing in the last decade all over Europe due to the early detection of fetal jeopardy, improvement of neonatal therapy and availability of cervical ripening agents. Success rate of vaginal delivery depends on maternal, fetal condition and cervical status. PATIENTS: Authors report the outcome of 795 labor inductions during the period from 1996 to 2000 at the Department of Obstetrics and Gynecology at the University of Debrecen, Hungary. Preinduction cervical ripening and induction method was based on Bishop score and clinical situation. RESULTS: The rate of induced labor was 5.97% out of 13312 consecutive deliveries. The outcome of induction is discussed in details. The caesarean section rate after induction of vaginal delivery was 25% in this high risk group, and 33.3% among the total number of inductions. CONCLUSIONS: The clinical application of prostaglandins for cervical ripening among high risk pregnant women facilitates the decision of labor induction and provides a favourable rate of vaginal deliveries.