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A survey intended to ascertain the rate of use and type of contraceptive methods applied by Spanish women aged 40 to 50 years, and to determine the proportion of women in this group at risk of an unwanted pregnancy, was designed and validated. To achieve representative national results for the study population, it was estimated that a sample size of 2000 women was required. Women were selected using probabilistic, stratified random sampling. The survey questionnaire was prepared by the research group with the collaboration of experts in the conduct of population studies of this type. Participants were interviewed face to face by qualified and trained staff from a specialised company external to the research group. Overall, 1039 women (52%) resorted to some contraceptive method, of which (male or female) sterilisation was the most common. We estimate that in Spain there are 840,000 women (31.8%) aged 40 to 50 years at risk of unwanted pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Our hypothesis was that during pregnancy nitric oxide acts as mediator in the hemodynamic response to volume expansion.Study Design: The study was performed on 12 rats on days 19 to 20 of pregnancy. Six rats were injected intravenously with hexamethonium bromide plus the inhibitor of nitric oxide synthase L-nitro-arginine methyl ester. For a control group, six rats were injected with hexamethonium bromide plus the L-nitro-arginine methyl ester vehicle. A volume expansion (1.2% body weight) was performed in both groups by intravenous infusion of bovine albumin (6%) solution.Results: In the control group volume expansion induced a hyperdynamic circulation characterized by increased cardiac output, decreased total vascular resistance, and no change in arterial pressure; however, in the study group volume expansion induced a pressor response without hyperdynamic circulation.Conclusion: During pregnancy volume expansion induces a hyperdynamic circulatory state possibly mediated by nitric oxide release. A defect in the release of nitric oxide may be responsible for an inadequate hemodynamic response to volume expansion. [ABSTRACT FROM AUTHOR]

Objective: Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies., Design: Randomised controlled double-blind multicentre trial (1:1:1)., Setting: The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain)., Population: Women with dichorionic diamniotic twin pregnancies., Methods: The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis., Main Outcome Measure: Preterm birth rate., Results: The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200- versus 400-mg progesterone groups. No serious adverse effects were encountered., Conclusions: Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

The concentration of long chain polyunsaturated fatty acid (LCPUFA) in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA) during gestation and development of cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is the maternal circulation. Both in vitro and human in vivo studies using labeled fatty acids have shown preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA) and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts, and even re-esterified and stored in lipid droplets. Although trophoblast cells are not specialized for lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ) and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA-synthetases and adipophilin or other enzymes involved in lipolysis, modifying the rate of placental transfer, and metabolism. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge of the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F(0)) with reproductive parameters, and in the somatic cells of the resulting foetuses (F(1)) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

Objective: To know the contraceptive use and trends in the Spanish female population., Study Design: Since 1997, we have conducted a survey every 2 years on the use of contraceptive methods among a representative sample of Spanish women of childbearing potential (15-49 years)., Results: In the period 1997-2003, the percentage of use of contraceptive methods in Spain rose from 55.6% to 71.2%. The most commonly used method was the condom (21% in 1997, 21.9% in 1999, 29.5% in 2001 and 35.7% in 2003), followed by the contraceptive pill (14.2%, 16.5%, 19.2% and 18.3%, respectively). Male or female sterilization remained stable with percentages of use of 5-7%. IUDs are used by about 5% of women., Conclusions: The use of contraceptive methods among Spanish women of childbearing potential generally fits quite well the patterns found in other developed countries, and we observed a trend towards increased use of effective methods.

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic activity in the breast and oestrogenic effects in various tissues such as the endometrium, bone and cardiovascular territory. As adjuvant hormone therapy, it has a clear beneficial effect in patients with breast cancer, reducing relapses, contralateral breast cancer and mortality. Its most important secondary effect is a greater rate of occurrence of endometrial cancer. Although the risk/benefit ratio is clearly positive, the follow-up on these patients is still an issue. In women with metrorrhagia, it is clear that an endometrial sample must be obtained for histological examination and the best procedure today is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic patients is not universally accepted. The vaginal ultrasound scan gives a great number of false positives. This entails more aggressive and more expensive procedures such as hysteroscopic-directed biopsy, meaning greater expense and more complications. As a result, the cost/benefit ratio is not very favourable. The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases were diagnosed in asymptomatic patients. In this article, we analyse the literature on the need to screen patients on tamoxifen and about the most appropriate diagnostic protocol.

Cocaine use during pregnancy results in an increase in different maternal and perinatal complications. The fetal effects of cocaine could be mainly related to the disturbances in the brain development, microcephaly being the most common brain abnormality. The aim of this study was to analyze maternal outcome and fetal somatic effects of cocaine and to evaluate the hypothesis that maternal cocaine exposure would specifically impair fetal global brain development. Fifty-four timed-pregnant female Sprague-Dawley rats were daily injected with 15 or 40 mg/kg per day from gestational day (GD) 1 or 8 and sacrificed at gestational day 20. By analyzing different maternal and fetal outcomes, it could be suggested that the cocaine exposure in pregnant rats decreased maternal weight gain without significant maternal mortality, did not affect the mean number of fetuses by litter, although notably increased stillbirths, reduced fetal birth weight, and reduced the fetal central nervous system weight. Present results are globally in agreement with the literature and underline a possible selective effect of cocaine on the fetal CNS resulting in symmetrical intrauterine fetal growth retardation in contrast to the asymmetrical retardation of undernutrition.

The amniotic fluid (AF) when incubated with the patient's own plasma diminishes the lytic activity of the plasma. It is suggested that this inhibition is due to the presence of fibrinolytic inhibitors in the AF. The inhibitors rate increases as pregnancy advances. Evaluating these inhibitors in a group of 65 women before and after the 38th week of pregnancy, a higher rate of fibrinolytic inhibitors is found after the 38th week. The said differences are statistically significant. For the moment it does not seem that the increasing of the inhibitors in the last part of pregnancy might be used as a fetal maturity test.

A population of 40 mother-newborn pairs with a wide range of birth weight has been studied. Seventeen of the mothers were diabetic, while the other 23 were normal pregnant women. The chronic blood glucose levels were assessed in the mothers through the percentage of glycosylated hemoglobin (HbA1) at delivery. The functional activity of the pancreatic beta-cells in the newborns was estimated through the concentration of insulin and C-peptide in the cord blood. Maternal HbA1 was not quantitatively related to the birth weight ratio. In contrast, both insulin and C-peptide correlated significantly with it. Is is concluded that in populations with a good metabolic control, blood glucose levels, as measured by HbA1, are not the major determinant of fetal growth.

The role played by insulin and the adrenergic system in the development of hypokalemia due to intravenous ritodrine has been evaluated. Fifteen women presenting with premature labor (group 1) were treated with ritodrine infusion, whereas seven pregnant women not in labor (group 2) were given 100 g glucose per os to induce hyperinsulinemia without participation of ritodrine. Serum glucose, insulin, potassium, sodium, chloride, and calcium were measured hourly. Whereas insulin levels were higher in group 2, potassium decreased markedly and significantly only in group 1. It is concluded that ritodrine-induced hypokalemia, that results partially from hyperinsulinemia, is mostly determined by other factors and is possibly a consequence of direct beta-adrenoceptor stimulation. Significant hypocalcemia of unexplained origin was observed with ritodrine.

Lactate concentrations were measured during labor and at delivery in blood samples from the fetal presenting part and from the umbilical cord with the use of a rapid electrochemical technique. The value of these measurements to discriminate between normal and distressed fetuses was compared to that of pH, base excess, PCO2 and PO2 measurements in the same blood samples. The fetuses were divided into three groups, normal, prepathologic, and pathologic, according to the presence and severity of fetal distress as evaluated by Apgar score, intrapartum cardiotocography, meconium staining of the amniotic fluid, and cord arterial pH at birth. Lactate and pH provided the best parameters to distinguish between groups, with lactate having the most discriminating power at least in early labor and midlabor. The prospective value of discriminant functions derived from lactate and pH data was good when the fetuses were allocated into the normal group but poor when an attempt was made to allocate the fetuses into prepathologic and pathologic groups, with a high false negative rate. However, the discriminating ability was improved when prepathologic and pathologic fetuses were included into one single abnormal group. These results confirm the potential use of rapid fetal blood lactate measurements for the early diagnosis of intrapartum fetal distress.

Danazol, testosterone and dihydrotestosterone (DHT) were tested as competitors for estrogen receptors on immature rat uterus cytosol. No competitive binding could be demonstrated for any of these steroids. After that, prepubertal Wistar rats were exposed to danazol, testosterone or propylene glycol (control) for 3 days or 17 days. After the appropriate exposure to medication, the animals were killed. Both danazol and testosterone appeared to be uterotropic after 3 days of treatment, although the increase in the uterine weight was significant only in the danazol-treated group (p less than 0.05). This effect was lost after 17 days of treatment. Estradiol receptor binding assays were done on the cytosolic and nuclear fractions of the homogenized uterine tissue of each group. The estrogen binding capacity of cytosols was increased in both the danazol (p less than 0.05) and the testosterone (p less than 0.01) groups after 3 days of treatment. A parallel increase was found in the nuclear fraction of both groups. After 17 days of treatment, the comparison between the 3 groups showed no differences in the cytosolic or nuclear estrogen binding capacity. The information provided by this study suggests that some effects of danazol may be due to an androgenic action and that may be associated to increases in the free fraction of testosterone.

A case of male pseudohermaphroditism with 17 alpha-hydroxylase deficiency is reported in a 23-year-old woman presenting with primary amenorrhoea and a history of bilateral inguinal hernia repair. She was tall, had hypoplastic external genitalia with a blood pressure of 220/140 mm Hg. Her karyotype was XY. Acute adrenal failure occurred following exploratory laparotomy. After treatment with glucocorticoids and oestrogens, the hormone and electrolyte profiles returned to normal and the blood pressure fell. The biochemical implications of this enzyme deficiency are discussed.

The functionality of the hypothalamic-pituitary-ovarian axis was explored in 27 women with perimenopausal dysfunctional uterine bleeding. The positive feedback effect of estradiol on LH and FSH was studied by the estrogen challenge test, which was performed by a single i.m. injection of estradiol benzoate. An early decline of both LH and FSH was followed by an increase of LH, mainly due to the cases in which the estrogen test was positive. FSH remained low through the whole period tested. The results were compared with those found in 5 normal menstruating women. The frequency of positive estrogen tests, defined by an acute estradiol-induced discharge of LH, was lower in the perimenopausal patients (P less than 0.025). The results of the tests used in our study showed an impairment of the positive feedback system in the perimenopausal-dysfunctional-bleeding group.

A case report of a male with persistent Müllerian structures is presented. The patient was 34 yr old and had a left inguinal hernia, bilateral cryptorchidism and azoospermia. His karyotype was 46 XY. At operation a uterus with vestigial Fallopian tubes and a hypoplastic testis were found inside the hernial sac. Histological studies confirmed the persistence of Müllerian structures. The clinical implications of anti-Müllerian hormone dysfunction are discussed.