Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening condition associated with increased vascular permeability. The vascular endothelial growth factor (VEGF) system and its receptors have been identified as the main angiogenic factors responsible for increased capillary permeability and are therefore discussed as crucial for the occurrence of OHSS. Recently, a number of soluble receptors for the VEGFs have been detected (sVEGF-Rs) and it has been shown that these sVEGF-Rs compete with the membrane-standing VEGF-R to bind VEGFs. METHODS: We analyzed the serum levels of soluble VEGF-R1, -R2 and -R3 in 34 patients suffering from OHSS and in 34 controls without this disease. In a subgroup analysis, we correlated the severity of the OHSS with the detected amounts of VEGF-R1, -R2 and -R3. In addition, we determined the amount of total VEGF-A in the samples. RESULTS: All the three soluble VEGF receptors tended to be higher in the control group compared with that in the OHSS group but this difference only reached significance for sVEGF-R2 (mean ± SEM: 15.5 ± 0.6 versus 13.8 ± 0.5 ng/ml, respectively, P< 0.05). In the subgroup analysis, sVEGF-R2 levels decreased as the severity of OHSS increased (OHSS-I: 16.8 ± 1.9 ng/ml and OHSS-III: 12.7 ± 1.0 ng/ml, P< 0.05) Moreover, the serum levels of total VEGF-A were higher in the OHSS group than those in the controls (537.7 ± 38.9 versus 351 ± 53.4 pg/ml, respectively P< 0.05). CONCLUSIONS: We propose that VEGF-A plays a role in the occurrence of OHSS, that the amount of biologically available VEGF-A is modulated by sVEGF-Rs and that different combinations of VEGF-A and sVEGF-R levels might contribute to the severity of OHSS.

The effect of different vitrification protocols on cell survival in human ovarian tissue: a pilot study.

BACKGROUND: Vitrification has superseded the slow freezing method for cryopreservation of oocytes, embryos, and sperm, but there are as yet no standard protocols for its use in ovarian tissue cryopreservation (OTC). Published protocols diverge mainly with regard to the extent of supplementation of dimethyl sulfoxide (DMSO) to the vitrification medium, and to the use of an open or closed vitrification system. We investigated the viability of cells after vitrification/warming, using ovarian tissue of transgender patients, by means of Fluorescence Activated Cells Sorting (FACS), and histomorphological analyses using a DMSO-containing (P1) and a DMSO-free protocol (P2) in an open or closed vitrification setting. RESULTS: Twelve ovarian samples were donated from female-to-male transgender patients: 6 were vitrified according to protocol 1, the other 6 according to protocol 2. The amount of viable cells was 90.1% (P1) and 88.4% (P2) before vitrification. After vitrification and subsequent warming, viable cells were reduced to 82.9% (P1, p = 0.093) and 72.4% (P2, p = 0.019). When comparing the closed and the open systems, the decline in cell viability from pre- to post-vitrification was significant only for the latter (p = 0.037). Histological examination reveals no significant differences with respect to degenerated follicles before or after vitrification. CONCLUSION: These results led us to conclude that a protocol containing DMSO results in a higher viability of ovarian cells than a protocol that uses ethylene glycol as cryoprotective agent in vitrification. The use of an open vitrification system led to significant decline in the rate of viable cells. TRIAL REGISTRATION: NCT03649087 , retrospectively registered 28.08.2018.

Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart.

The basic helix-loop-helix (bHLH) factor Hand1 plays a role in the developing chicken heart and is required for trophoblast giant cell differentiation and cardiac looping of mouse embryonic development. Here, we report the cloning of the human Hand1 cDNA and gene from a heart-specific cDNA library and a genomic lambda-DNA library, respectively. We present the nucleotide sequence of a 1.75kb cDNA clone, encoding the presumptive 215 amino acid human Hand1 protein, and show homology comparison of the conserved bHLH region between different species. In vitro transcription-translation of Hand1 mRNA and analysis of protein size suggest that the Hand1 polypeptide is (post)translationally modified. By Southern blot analysis we demonstrate that the isolated genomic DNA clone harbours the entire Hand1 gene and describe molecular structure and sequences of the two 799 and 938bp exons and the single 1.56kb intron. The expression pattern of the mRNA in different human tissues revealed that Hand1 transcripts are restricted to the heart, suggesting that the protein could be required for cardiac-specific gene transcription and function in adults. Hand1 transcripts were undetectable in a non-tumorigenic villous trophoblast cell line, immunopurified cytotrophoblasts undergoing in vitro differentiation, and first trimester placental tissue, suggesting that the transcription factor is not involved in the development of villous and extravillous trophoblast cell lineages. Hand1 mRNA, however, was abundantly expressed in cytotrophoblastic Jeg-3 and BeWo cells, suggesting that Hand1 could be required for early trophoblast differentiation.

Interleukin-1 stimulates tumor necrosis factor-alpha (TNF-alpha) release from cytotrophoblastic BeWo cells independently of induction of the TNF-alpha mRNA.

Constitutive tumor necrosis factor-alpha expression (TNF-alpha) has been detected in first trimester trophoblast cells and differentiated syncytiotrophoblasts. However, molecules which induce TNF-alpha release from these cells and their mechanism of action have not been defined. We show for the first time that interleukin-1 (IL-1), a regulator of trophoblast development, induces TNF-alpha expression in proliferating cytotrophoblastic cells and purified term trophoblasts. Both IL-1alpha and beta stimulate TNF-alpha release from BeWo cells and TNF-alpha mRNA was transiently expressed. In growth-arrested/differentiated BeWo cells TNF-alpha mRNA was detectable without inducer, however, in the presence of IL-1beta TNF-alpha secretion was weakly stimulated compared to proliferating cells. Cycloheximide strongly increased IL-1beta-induced TNF-alpha mRNA concentration indicating that de novo protein synthesis is not required for TNF-alpha gene expression. However, treatment with cycloheximide did not prevent IL-1beta-stimulated release of TNF-alpha, indicating that the cytokine can regulate TNF-alpha secretion at a posttranslational level, independently of TNF-alpha mRNA induction. Besides demonstration of this novel mechanism of IL-1-stimulated TNF-alpha expression, our data indicate an important role of IL-1 in TNF-alpha production of cytotrophoblastic cells.

Hypoxia downregulates continuous and interleukin-1-induced expression of human chorionic gonadotropin in choriocarcinoma cells.

The effects of hypoxia on JEG-3, BeWo, and JAr cells were investigated and it was demonstrated that choriocarcinoma cells can be used as a model to study the molecular mechanism of hypoxia-mediated repression of human chorionic gonadotropin (hCG). Cells were maintained under hypoxia (3.5 per cent O2) for 72 h without loss of variability, as demonstrated by the fact that 93-98 per cent of the cells excluded trypan blue. Up to 48 h, cell growth was not significantly influenced by hypoxia, and analysis by flow cytometry did not reveal major changes in cell cycle distribution. JEG-3, BeWo, and JAr cells which were grown for 48 h under hypoxia secreted 81, 67, and 71 per cent less hCG than cells cultivated under normoxic conditions. The extent of hCG reduction was dependent on the oxygen concentration. Moreover, release of the hormone from hypoxic JAr cells was not stimulated upon addition of interleukin-1 (IL-1). Treatment of JEG-3 cells with methotrexate (MTX) led to a 4.3-fold augmentation in hCG secretion and to an increase in the amount of G0/G1 cells. However, when cells were cultured in the presence of MTX and hypoxia, hCG secretion decreased 10-fold and beta hCG mRNA declined to almost undetectable levels suggesting that downregulation of beta hCG mRNA is the major cause of diminished hCG release under hypoxic conditions.

Adjunctive antibiotic treatment in preterm labor and neonatal morbidity: a meta-analysis.

OBJECTIVE: To estimate the effect of prophylactic antibiotics on neonatal mortality and morbidity in patients with preterm labor, based on a meta-analysis of seven published randomized clinical trials. DATA SOURCES: We searched 18 medical data bases, including MEDLINE from 1964 and EMBASE from 1974, to identify all literature included under preterm or premature labor and antibiotics. We scanned all abstracts from the computer printouts, the retrieved full-text reports, the references from each retrieved report, and review articles to determine whether studies met our inclusion criteria. METHODS OF STUDY SELECTION: The following criteria were used to select studies for inclusion: article-original published report written in English; study design-randomized controlled trial; population-patients with preterm labor, defined as labor before 37 weeks' gestation; intervention-antibiotic treatment; and one or more of the following outcomes-neonatal mortality, sepsis, pneumonia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. TABULATION, INTEGRATION AND RESULTS: We analyzed study patients and methods, and abstracted quantitative outcome data. For each outcome, both odds ratio (OR) and 95% confidence interval (CI) were calculated. Seven trials, published between 1989 and 1995 included a total of 795 patients. Adjunctive antibiotic therapy appeared to reduce the risk of pneumonia (OR 0.45, 95% CI 0.12-1.72) and necrotizing enterocolitis (OR 0.38, 95% CI 0.14-1.08) and to increase the risk of neonatal mortality (OR 3.25, 95% CI 0.93-11.38), but it had no effect on neonatal sepsis (OR 0.98, 95% CI 0.34-2.83), respiratory distress syndrome (OR 0.93, 95% CI 0.54-1.87), and intraventricular hemorrhage (OR 1.01, 95% CI 0.20-5.10). None of the effects observed reached a significance level of P < .05. CONCLUSION: The results of this meta-analysis do not support the routine use of adjunctive antibiotic treatment in patients with preterm labor diagnosed on the basis of subjective uterine contractions and the resulting cervical changes.

Transfer of erythropoietin across the placenta perfused in vitro.

OBJECTIVE: The purpose of this study was to investigate the placental passage of erythropoietin in a placental perfusion model ex vivo. METHODS: In an open system 18 placentas were perfused on both the maternal and the fetal side. Erythropoietin and a reference substance were added to either the maternal or fetal perfusion medium. In the first series of experiments, radiolabeled erythropoietin was added to the perfusion medium in four different concentrations to help determine the transfer rate of erythropoietin. Based on the results of these experiments unlabeled erythropoietin was added to the perfusate in three different concentrations. Radiolabeled erythropoietin was used in addition to erythropoietin because measuring radioactivity in a gamma counter is less expensive than measuring by immunoassay. RESULTS: Accumulation of radioactivity in the venous portion of the fetal circuit was only 3.21% of the activity added to the maternal circuit. No evidence of transfer of erythropoietin to the contralateral compartment was noted, regardless of whether the test substance was added maternally or fetally. These results were independent of the concentration used. The reference compound antipyrine showed a mean transfer rate of 27.9%, which is in keeping with previous results. CONCLUSION: There is no transport of erythropoietin across fetal membranes. This finding is particularly remarkable in view of results published recently indicating the placenta as a site of erythropoietin production. The lack of its transport across the human placenta is most likely due to its high molecular weight.

The transfer of interleukin-8 across the human placenta perfused in vitro.

OBJECTIVE: To assess the placental transfer of interleukin (IL)-8 in vitro. METHODS: Eighteen placentas obtained immediately after delivery were perfused with a mixture of 125I-labeled IL-8 (IL-8*) and unlabeled IL-8 in two different concentrations. Antipyrine was coinfused in all experiments as a reference compound. Fetal-to-maternal and maternal-to-fetal perfusions were performed. Radioactivity was measured in a gamma counter at the end of each perfusion experiment. In four experiments, unlabeled IL-8 was analyzed in addition to labeled IL-8 to exclude a change in the IL-8/IL-8* ratio resulting from membrane transfer. RESULTS: Two of the 18 experiments had to be discarded because of poor transfer of antipyrine. There was only faint accumulation of radioactivity in the transplacental compartment, regardless of whether the test substance was added maternally or fetally. Because measurement of unlabeled IL-8 yielded negative results, the radioactivity is clearly attributable to free iodine 125, which is generated during IL radiolabeling or which disassociates from IL-8 in small amounts after radiolabeling. CONCLUSION: Interleukin-8 does not appear to cross the placenta by simple diffusion, regardless of the concentration or the perfusion rate. The impermeability of the placenta to the diffusion of IL-8 might explain why there is insufficient correlation between serum and amniotic fluid cytokine concentrations of pregnant women and the presence of the amnion infection syndrome.

Treatment of ectopic pregnancy by means of prostaglandins.

A new conservative method of terminating ectopic pregnancies is described. A high degree of success was achieved by administering PG F2alpha by laparoscopy and PG E2 analogue systemically.

PIP: In vitro studies have demonstrated a marked increase in tubal muscle cell activity and pronounced constriction of tubal arteries as a result of incubation with prostaglandins, particularly prostaglandin (PG) F2 alpha and PG E2. This finding has potential implications for the termination of ectopic pregnancies. To test this approach, 22 women with laparoscopically confirmed ectopic pregnancies received local application of PG F2 alpha by means of laparoscopy as well as systemic treatment with a PG E2 analog. The pregnancy site was ampullary in 15 cases and isthmic in the remaining 7 cases. Analysis of post-treatment beta-human chorionic gonadotropin (hCG) values indicated that this regimen was successful in 18 cases; the 4 failures occurred in women with pre-treatment beta-hCG values that were above the mean. Of the 1st 9 women treated in this series, all of whom received 2-3 mg of PG F2 alpha, 3 exhibited transient tachycardia and blood pressure elevation immediately after intraluteal application and 1 of these women developed pulmonary congestion postoperatively. Thus, the PG F2 alpha dose was replaced with 25 mg of estrogen, and this change produced no side effects or reduction in effectiveness. In 8 of the 9 women on whom hysterosalpingography was performed in 1 of the ensuing menstrual cycles, there was complete tubal patency. More widespread use of this conservative yet highly effective method is recommended.

Prostaglandin versus expectant management in early tubal pregnancy.

Since ectopic pregnancy may terminate in spontaneous recovery we compared treatment by means of prostaglandin (PG) application with expectant management in laparoscopically verified tubal gestations. Twelve patients received local and systemic PG, 4 patients were treated with sodium chloride and in 7 patients laparoscopy was discontinued without medical therapy. The comparison between the PG group and the placebo groups revealed a highly significant difference with regard to a subsequent necessary surgical intervention and hospitalisation. Expectant management may only be recommended in very selected cases, whereas PG treatment seems to produce favourable results in cases of early tubal pregnancy.

Successful treatment of a heterotopic pregnancy by sonographically guided instillation of hyperosmolar glucose.

OBJECTIVE: To describe a new conservative approach in the treatment of heterotopic pregnancy. DESIGN: Case report. SETTING: A university hospital and an outpatient IVF center. INTERVENTION(S): Transvaginal ultrasonography-guided puncture of the ectopic gestational sac and instillation of hyperosmolar glucose. RESULT(S): The ectopic pregnancy resolved without further intervention. The intrauterine pregnancy resulted in a full-term live birth. CONCLUSION(S): Transvaginal injection of hyperosmolar glucose may be an effective conservative treatment for unruptured ectopic pregnancies in cases of heterotopic pregnancy.

Effects of tibolone on auditory brainstem responses in postmenopausal women--a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the influence of tibolone, a synthetic steroid, in modifying auditory brainstem response (ABR) in postmenopausal women. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient menopausal clinic in a university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Administration of either tibolone or placebo for 12 weeks; evaluation of ABR and hormone levels before and after treatment. MAIN OUTCOME MEASURE(S): Changes in auditory brainstem response latencies. RESULT(S): Comparison of the ABR latency data from the two treatment groups showed a significant decrease in wave II, III, and V peak latencies in women receiving tibolone. No significant differences in pretreatment and posttreatment circulating hormone concentrations were observed between the tibolone and placebo group. Furthermore, there was no significant increase in hormone levels in either of the groups at 12 weeks. CONCLUSION(S): Our findings show an improvement in auditory function via brainstem auditory neural pathways sensitive to tibolone in postmenopausal women. Tibolone may offer new therapeutic strategies in otologic disorders.

The passage of granulocyte-macrophage colony-stimulating factor across the human placenta perfused in vitro.

OBJECTIVE: The purpose of this study was to investigate the placental passage of granulocyte-macrophage colony-stimulating factor in a placental perfusion model ex vivo. METHODS: In an open system, 11 placentas were perfused on both the maternal and the fetal side immediately after delivery. Granulocyte-macrophage colony-stimulating factor was added to the maternal perfusion medium in concentrations from 10-55 micrograms/mL. Maternal and fetal samples were taken, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by enzyme-linked immunosorbent assay. RESULTS: Accumulation of granulocyte-macrophage colony-stimulating factor in the fetal circuit averaged 2.42% of the concentration added initially to the arterial portion of the maternal circuit. CONCLUSION: There is only low transfer of GM-CSF across the fetal membranes. This finding is particularly remarkable in view of recently published results suggesting that administration of recombinant granulocyte growth factors to pregnant women with imminent preterm delivery helps prevent neonatal sepsis.

A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.

OBJECTIVE: Our purpose was to investigate the effect of tibolone in a prospective randomized, double-blind pilot study in postmenopausal women with clinically palpable mastopathic changes. METHODS: Twenty postmenopausal non-users of hormone replacement therapy undergoing mammography were randomly allocated to receive either 2.5 mg tibolone (Livial, Organon) or placebo (2 mg lactose). Mammographic density according to the Wolfe classification, severity of breast discomfort, parity, smoking habits, body weight and follicle-stimulating hormone (FSH) and estradiol (E(2)) levels were documented at baseline and after 6 months of treatment. RESULTS: There were no statistically significant differences between the two treatment groups in terms of parity, smoking, body weight and FSH and E(2) levels. At 6 months, four patients in the tibolone group showed reduced breast density, compared with one patient in the placebo group. Whereas no significant differences were found between the two treatment groups when the categories 'minimal reduction' and 'reduction' in mammographic density were combined, combination of the categories 'no change' and 'minimal reduction' showed a significant difference (P<0.036). Also, women in the tibolone group showed a statistically significant improvement in breast discomfort (P<0.019). CONCLUSION: This pilot study showed decreases in breast density as well as an attendant significant alleviation of breast discomfort in women with baseline mastopathic changes treated with tibolone for 6 months, which may be due to the inhibitory effect of tibolone on the enzymes involved in the biosynthesis of estradiol demonstrated in previous trials and should be further evaluated in long-term studies.

Beta-endorphin levels during the climacteric period.

Hot flushes are not caused by hypergonadotrophinaemia. This is apparent because peaks of gonadotrophin in the serum do not coincide with cutaneously measured hot flushes while such flushes still occur in hypophysectomized women. Gonadotrophin-releasing hormone and other neurotransmitters (possibly beta-endorphin) affect thermoregulation. The following hypothesis is advanced. During the climacteric period neurotransmitter changes, a decrease in catechol oestrogens, a decrease in alpha-2-adrenoceptor activity and cessation of ovarian steroid production may lead to alterations in endogenous opiate activity and thus to disturbances of thermoregulation, resulting in the occurrence of hot flushes. Low beta-endorphin levels in the peripheral plasma, which rise again following oestrogen treatment, are observed during the climacteric. On the other hand, women with severe hot flushes caused by a stress event show enormously increased beta-endorphin values, which are normalized by hormone substitution therapy acting via still unknown neuroendocrinological feedback mechanisms.

Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints.

OBJECTIVE: Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron, 2 x 5 mg daily for 12 days each month). METHODS: One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months. RESULTS: With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group. CONCLUSION: Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.

Low dose oral contraceptives and quality of life.

This study investigated the effects of a low dose oral contraceptive (OC) (Mercilon) on women's satisfaction and quality of life based on a detailed questionnaire. A total of 614 first-time users of oral contraceptives were enrolled by 102 gynecologists for a treatment period of > or = 4 months. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) was filled in both before and during pill intake. The total quality of life score was significantly increased under OC intake. In contrast to older preparations, modern low dose OCs appear to act favorably on a number of psychological parameters, thus increasing satisfaction with various aspects of daily life and, consequently, improving quality of life.

PIP: A study was conducted to determine the tolerability of a low-dose oral contraceptive (OC) containing 20 mcg ethinyl estradiol and 150 mcg desogestrel (Mercilon) among first-time users and to evaluate its effects on women's satisfaction and quality of life. The study was conducted between January 1997 and May 1998 using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) submitted to 614 first-time users of OCs. Results showed that modern low-dose OCs act favorably on a number of psychological parameters by comparison with older preparations. The total quality of life rating increased significantly with use of OC. The improvement in patient satisfaction and quality of life observed in this study is a significant finding with respect to the matter of OC acceptability and patient compliance.

Ovarian function during low-dose oral contraceptive use.

Lowering the total steroid dose in modern oral contraceptives (OCs) has been connected with a higher incidence of ovarian follicle and cyst formation. To investigate the presence of ovarian follicles and cysts by means of vaginal ultrasonography and serum hormone determinations during use of two low-dose OCs, 65 volunteers were randomized to receive either 20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel (group A) or 35 micrograms EE + 250 micrograms norgestimate (group B) for a 2-month study period. At baseline, 39% of women in group A and 31% in group B exhibited at least one follicle < 35 mm in diameter. By the end of the second treatment cycle, the frequency of these follicles had decreased to 14% in each group. Only one subject in the higher estrogen group developed an ovarian cyst > 35 mm. One subject in each group demonstrated hormone levels characteristic of ovulation; no pregnancy occurred in either group. The 20 micrograms EE preparation was not found to lead more often to ovarian follicles or cysts when compared with a 35 micrograms EE preparation, possibly because of the type and dose of the progestogen used.

PIP: In Austria, health workers randomly allocated 28 women to the group using the low-dose oral contraceptive (OC) Mercilon (20 mcg ethinyl estradiol [EE] + 150 mcg desogestrel) and 35 women to the group using the low-dose OC Cilest (35 mcg EE + 250 mcg norgestimate). No one had used OCs for at least one month before the study. Clinicians used vaginal ultrasonography and serum hormone levels to learn the degree of ovarian suppression during use of these two low-dose OCs by looking for ovarian follicles and cysts. Before beginning to use the OCs, 39% of women in the Mercilon group and 31% of those in the Cilest group had at least one ovarian follicle. By the second treatment cycle, the frequency of ovarian follicles (35 mm) had fallen significantly to 14% in both groups as compared to baseline (p 0.05). No one in the Mercilon group developed a follicle larger than 35 mm in diameter that remained for more than 4 weeks (i.e., ovarian cyst). One woman in the Cilest group did develop an ovarian cyst (46 mm), however. It appeared during the pill-free week after the first pill cycle and steadily decreased to 40 mm during the second pill cycle. One woman in each group had hormone levels indicative of ovulation. No one in either group became pregnant. These findings suggest that the type and dose of progestogen in the Mercilon OC (desogestrel) were responsible for the lower frequency of ovarian follicles and cysts in the lower-dose OC group than that in the higher-dose OC.

Contraceptive knowledge and attitudes of Austrian adolescents after mass media reports linking third-generation oral contraceptives with an increased risk of venous thromboembolism.

We performed a representative survey to determine the level of knowledge of 1,010 Austrian adolescents aged 14 to 24 years about selected facts relating to the recent massive news coverage of the increase in the risk of venous thromboembolism in users of third-generation oral contraceptives and to assess the contraceptive behavior of this population. The overall use rate of oral contraceptives and condoms had increased significantly between 1991 and 1996. Sixty-six percent of the adolescents surveyed stated not having heard or read any media reports on oral contraceptives. Only 8% of those who had knew that most reports focused on the pill as a possible cause of venous thromboembolism, whereas the majority of respondents indicated that the media conveyed doubts regarding the health safety of oral contraceptives in general. Nearly half of adolescents were unable to define what a thrombosis was. Thus, although the mass media play an important role in transmitting medical information, the dissemination of practical, accurate advice on the risks of a drug and competent patient counseling is reserved for the health care professionals.

Efficacy, tolerability, and rare side effects of tibolone treatment in postmenopausal women.

OBJECTIVE: The purpose of this study was to assess the tolerability and side effects of tibolone (Livial, Organon), a synthetic steroid analogue for the treatment of postmenopausal symptoms, in a large population of patients. METHOD: 1189 postmenopausal patients were included in this study. The patients' blood pressure, body weight, general complaints, and the severity of their climacteric complaints were documented at baseline and after 4 months of tibolone treatment. RESULTS: Tibolone significantly relieved all of the classical menopausal complaints. The proportion of patients with bleeding problems dropped significantly from 15.9% to 6.8%. Other complaints, such as headache, vertigo, nervousness, breast tenderness, and hirsutism were also significantly less frequent than before treatment. Only few women reported other rare side effects, and only 14.4% of women discontinued treatment prematurely. CONCLUSION: Tibolone provides an efficient and safe means of treating the postmenopausal syndrome in every-day practice.