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Background Available research suggests that menstrual inequity has an impact on (menstrual) health outcomes and emotional wellbeing. It is also a significant barrier to achieve social and gender equity and compromises human rights and social justice. The aim of this study was to describe menstrual inequities and their associations with sociodemographic factors, among women and people who menstruate (PWM) aged 18–55 in Spain. Methods A cross-sectional survey-based study was conducted in Spain between March and July 2021. Descriptive statistical analyses and multivariate logistic regression models were performed. Results A total of 22,823 women and PWM were included in the analyses (Mean age = 33.2, SD = 8.7). Over half of the participants had accessed healthcare services for menstruation (61.9%). The odds for accessing menstrual-related services were significantly higher among participants with university education (aOR: 1.48, 95% CI, 1.13–1.95). Also, 57.8% reported having had partial or no menstrual education pre-menarche, with odds being higher among participants born in non-European or Latin American countries (aOR: 0.58, 95% CI, 0.36–0.93). Lifetime self-reported menstrual poverty was between 22.2–39.9%. Main risk factors for menstrual poverty were identifying as non-binary (aOR: 1.67, 95% CI, 1.32–2.11), being born in non-European or Latin American countries (aOR: 2.74, 95% CI, 1.77–4.24), and not having a permit to reside in Spain (aOR: 4.27, 95% CI, 1.94–9.38). Completed university education (aOR: 0.61, 95% CI, 0.44–0.84) and no financial hardship Conclusions Our study suggests that menstrual inequities affect a high number of women and PWM in Spain, especially those more socioeconomically deprived, vulnerabilised migrant populations and non-binary and trans menstruators. Findings from this study can be valuable to inform future research and menstrual inequity policies.

Puntos para una lectura rapida • Cualquier acto asistencial es un momento adecuado para repasar y actualizar el calendario vacunal. • La administracion simultanea de varias vacunas reduce el numero de visitas y aumenta la cobertura. • Para mejorar registros vacunales deberia haber un sistema centralizado a nivel nacional y un calendario vacunal unico. • Argumentar la importancia de la vacunacion por parte del personal sanitario es una buena estrategia para aumentar coberturas.

Menstrual health and menstrual inequity have been neglected in social, economic, healthcare and political spheres. Although available evidence is scarce, it already suggests a link between experiencing menstrual inequity (which refers to the systematic disparities in accessing menstrual health and education, menstrual products and spaces for menstrual management, among other aspects) and menstrual health outcomes. The aim of this study was to explore experiences of menstrual health and menstrual inequity among women and people who menstruate aged 18-55 in Barcelona and surrounding areas (Spain).A qualitative study, using a critical feminist perspective, was conducted. Sampling was purposeful and selective. Recruitment was through sexual and reproductive health centres, social media and snowball sampling techniques. Thirty-four semi-structured photo-elicitation interviews were conducted between December 2020 and February 2021. Interviews took place in sexual and reproductive health centres, public spaces, and by telephone. Data were analysed using Reflexive Thematic Analysis.Three themes were identified: "Systemic neglect of menstruation and the menstrual cycle", "When "the private" becomes public: menstrual management" and "Navigating menstrual health: between medicalization and agency". Experiences of menstrual inequity appeared to be widespread among participants. They referred to the impact of having to conceal menstruation and the barriers to managing menstruation in public spaces. Choosing menstrual products was often influenced by price and availability; several participants reported menstrual poverty. A general lack of menstrual education was described. Menstrual education was usually gained through personal experience and self-learnings, or through families and friends. Menstruation and the menstrual cycle had a significant impact on participants' day-to-day. Accessing and navigating the healthcare system was challenging, as participants mostly reported feeling dismissed and almost exclusively offered hormonal contraception as a panacea to address menstrual health.The impact of menstrual inequity appears to be far-reaching. Multidimensional structural policies should promote agency in individuals and communities to enable opportunities for menstrual education, access to menstrual products, healthcare services and adequate menstrual-management facilities. Health professionals' training is also necessary to improve access to and quality of menstrual healthcare. Policies need to be inclusive of non-binary and trans people, and vulnerable populations.INTRODUCCIóN: La salud y la inequidad menstrual no han sido bien atendidas en las esferas social, económica, sanitaria y política. Aunque la evidencia disponible es escasa, ya sugiere un vínculo entre experiencias de inequidad menstrual (relativa a las dificultades sistemáticas para el acceso a la salud y educación menstrual, productos menstruales y espacios de manejo menstrual, entre otros aspectos) y la salud menstrual. El objetivo de este estudio fue explorar las experiencias de salud e inequidad menstrual en mujeres y personas que menstrúan (18–55 años) en Barcelona y alrededores (España). MéTODOS: Estudio cualitativo desde una perspectiva feminista crítica. El muestreo fue intencionado y selectivo. El reclutamiento se realizó en centros de salud sexual y reproductiva, redes sociales y a través de técnicas de bola de nieve. Se realizaron 34 entrevistas semi-estructuradas utilizando foto-elicitación, entre diciembre de 2020 y febrero de 2021. Las entrevistas se llevaron a cabo en centros de salud sexual y reproductiva, espacios públicos y por teléfono. Los datos se analizaron mediante Análisis Temático Reflexivo.Se identificaron tres categorías: “Descuido sistemático de la menstruation y el cycle menstrual”, “Candy “lo privacy” se vuelve public: manejo menstrual” y “Navegando la salad menstrual: entree la medicalización y la agencia”. Las participantes compartieron diversas experiencias de inequidad menstrual. Diversas participantes compartieron experiencias de pobreza menstrual, al no poder acceder o escoger productos menstruales debido a su precio y disponibilidad. Según las participantes, los aprendizajes menstruales son escasos. Estos suelen darse a través de la experiencia propia y el autoaprendizaje, o de familiares y amigas. La menstruación y el ciclo menstrual parecen tener un impacto significativo en el día a día, incluyendo el impacto de tener que ocultar la menstruación y las barreras para manejar la menstruación en los espacios públicos. Se identificaron barreras para acceder y utilizar el sistema sanitario. Las participantes también reportaron la prescripción sistemática de anticonceptivos hormonales como panacea para abordar la salud menstrual.Es necesario desarrollar e implementar políticas estructurales y multidimensionales para promover la agencia de las mujeres y personas que menstrúan, así como de las comunidades, para generar oportunidades para aprender sobre la menstruación, acceder a productos menstruales y servicios de atención sanitaria, así como a espacios adecuados para el manejo menstrual. Fomentar la formación de profesionales de la salud es también crucial para mejorar el acceso y la calidad de la servicios para la salud menstrual. Estas políticas deben incluir a las personas trans y no binarias, así como a poblaciones más vulnerables.There is a lack of research on menstrual health and menstrual inequity. However, we already know that menstrual inequities may have a negative effect on menstrual health. Yet, politicians, policymakers and healthcare professionals rarely pay attention to menstrual inequity and menstrual health. This study had the objective to collect experiences of menstrual inequity and menstrual health among women and people who menstruate (trans and non-binary people) between 18 and 55 in the Barcelona area (Spain). Thirty-four participants took part in interviews between December 2020 and February 2021. We used photographs during the interviews to deepen discussions with participants. We did the interviews in sexual and reproductive health centres, in public spaces and over the phone. Participants shared a variety of experiences of menstrual inequity and health. For instance, some participants explained that they had experienced financial issues to buy menstrual products. Others, that it was often difficult to find adequate spaces to change menstrual products at schools, workplaces and public spaces. Participants told us that they mostly learned about menstruation through their own experiences and talking to family and friends. They had little information on menstruation. Also, when participants sought medical help they usually found that health professionals usually only offered hormonal contraception to treat menstrual issues. They felt frustrated and dismissed. In general, they thought that menstruation affected their daily lives. Therefore, it is very important to train professionals, continue research and put policies for menstrual inequity and health in place.

Background Menstrual products are necessary goods for women and people who menstruate to manage menstruation. Understanding the use and perceptions of menstrual products is key to promote menstrual equity and menstrual health. This study aimed at assessing the use and perceptions on menstrual products among women and people who menstruate aged 18–55 in Spain. Methods A mixed-methods study was conducted, including a cross-sectional study (N = 22,823), and a qualitative study (N = 34). Results Participants used a combination of products. Non-reusable products were the most used, while over half used reusable products. Usage changed when data were stratified by age, gender identification, completed education, country of birth and experiencing financial issues. It also varied between trans and cis participants. Menstrual products’ use also shifted based on experiences of menstrual poverty and access to information and products. Overall, reusable products were perceived to be more acceptable than non-reusable. Barriers to use the menstrual cup were also identified, including experiences of menstrual inequity (e.g., menstrual poverty, lack of access to information or menstrual management facilities). Conclusion Perceptions and choices of menstrual products need to be acknowledged, especially when designing and implementing menstrual policies to address menstrual inequity and menstrual health.

Background: Available evidence suggests that menstrual health and management have been impaired during the COVID-19 syndemic. However, research in this area is scarce, and it is failing to voice the experiences of women and people who menstruate regarding their menstrual experiences. Objectives: This study aimed to explore the experiences of menstrual health and menstrual management among women and people who menstruate in the Barcelona area (Spain) during the COVID-19 syndemic. Design: This is a qualitative study, conducted taking a critical feminist approach, is embedded in the ‘Equity and Menstrual Health in Spain’ project. Methods: It includes photo-elicitation individual interviews with 34 women and people who menstruate in the area of Barcelona (Spain). Data were collected in person and through telephone calls between December 2020 and February 2021. Analyses were performed using Thematic Analysis. Results: Main findings navigated through the menstrual changes experienced by some participants, especially women living with long COVID-19, and the barriers to access healthcare and menstrual products during COVID-19. While some participants experienced menstrual poverty, this did not appear to be exacerbated during COVID-19. Instead, access to menstrual products was compromised based on products’ availability and mobility restrictions. Menstrual management and self-care were generally easier, given that menstrual experiences were almost exclusively relegated to private spaces during lockdown periods. Conclusions: Our findings highlight the need to further research and policy efforts towards promoting menstrual health and equity, considering social determinants of health, and taking intersectional and gender-based approaches. These strategies should be further encouraged in social and health crises such as the COVID-19 syndemic.

Gestational diabetes (GD) occurs in 5.8% to 25.1% of pregnant women. This disorder has been linked with intrauterine growth delays, congenital anomalies, and neurobehavioral disorders following birth. As to ophthalmological effects, changes in macular thickness and hypoplasia of the upper quadrant of the papilla have been described. To investigate whether GD has an effect on ophthalmological development in the children born of mothers with this condition. Observational study carried out in children seen in the ophthalmological outpatient clinic of a pediatric hospital in Barcelona (Spain) between January 2011 and December 2015. Participants were ultimately divided into two groups, a study group whose mothers had GD managed either by insulin or diet (GD group) and a control group of children with non-diabetic mothers. Pregestational diabetes cases, were excluded. Complete information was collected on the children’s refraction status, ophthalmological disease, and congenital malformations. Data were compiled on 350 children (229 children born of mothers with GD-186 managed with diet vs 43, with insulin- and 121 controls). The prevalence of amblyopia and strabismus was similar between the groups, but children of mothers with GD had a three-fold greater probability of having refractive errors than children born to mothers without GD. Hyperopia (14.8% vs. 7.4%) and myopia (3.5% vs 0%) were found to be significantly more prevalent in children born of mothers with GD than in the controls (p = 0.027 in both groups).The prevalence of astigmatism was similar in both groups (1.7% vs 0.8%). Refractive errors are more common in children born of mothers with GD. These conditions are easily managed, but if they are not detected, they can lead to amblyopia or accommodative strabismus, interfere with acquisition of fine motor skills, and lead to learning problems. Regular ocular examinations would be recommended in these patients.

A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, β-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L−1 range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L−1, respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed This study was financed by the SpanishMinistry of Science and Innovation through projects CTM2011-28765-C02-02 and CGL2013-48802-C3-2-R, and an FPI grant (Ref. BES-2009-024892) awarded to C. Valls-Cantenys

Aims: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. Methods: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. Results: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. Conclusions: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.

Simple, precise, and low-cost methods for the simultaneous determination of phenolic endocrine disrupting compounds such as bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water samples were developed. The Direct, in situ derivatization methods are based on polydimethylsiloxane rod extraction followed by liquid desorption and chromatographic analysis by liquid chromatography and diode array detection. Several parameters affecting the extraction and desorption of the phenolic compounds and their acetylated derivates were studied, as well as the chromatographic and detection conditions. For the direct method, determination coefficients (r2) > 0.990 and LODs in the 0.6–2 μg/L range were obtained for all compounds except bisphenol A (9.5 μg/L). With the derivatization-based method, based on in situ acetylation, lower limits of detection (0.3–0.9 μg/L) were obtained for all the compounds with r2 > 0.988 and RSDs in the 2–9% range. The developed methods were applied to the analysis of spiked water samples obtaining recoveries of between 60.2 and 131.7% for the direct method, and of between 76.6 and 108.2% for the derivatization-based method. The results demonstrate the feasibility of using these two methods for determining bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water.

This study presents the development and validation of a new analytical method for the simultaneous determination of fifteen analytes classified as halogenated flame retardants (HFRs) – nine brominated diphenyl ethers (BDEs) and six novel HFRs – in different kinds of mollusks using matrix solid-phase dispersion (MSPD) followed by gas chromatography coupled to negative chemical ionization-mass spectrometry (GC–NCI-MS). The proposed method is the first one developed for such a broad range of HFRs in aquatic biota, featuring several advantages, including low solvent and sample intake, simplicity of operation, reduced cost and integration of extraction and clean-up into a single step. Under optimal conditions, 0.5 g of freeze-dried sample, 0.5 g of a primary-secondary amine (PSA) as solid support, a sorbent combination of 1.75 g of florisil (deactivated with 5% Milli-Q water), 1.75 g of acidified silica (10% (w/w) H2SO4) and 0.5 g of silica, and 10 mL dichloromethane as elution solvent were used. Standard addition over the extract was required however for the correct quantification due to matrix effects in the GC system, particularly for novel HFRs, that could not be compensated with the internal standards. The method afforded LODs in the range of 0.003–0.07 ng g−1 dry weight (0.0006–0.014 ng g−1 on a wet weight basis, assuming an 80% sample water content), except for decabromodiphenyl ethane (DBDPE) (0.6 ng g−1 dry weight, 0.12 ng g−1 wet weight). The accuracy of the method was evaluated with three different types of spiked mollusk species using surrogate standards and standard addition over the extract for quantification and the recoveries were in the 70–120% range, except for bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (DEHTBP) in clam (Ruditapes philippinarum) samples (46% recovery). Moreover, the method was successfully validated with standard reference materials (SRMs) of salmon and mussel tissues for BDEs. Finally, the method was applied to the determination of HFRs in different kind of freeze-dried mollusks: mussel (Mytilus galloprovincialis), cockle (Cerastoderma edule) and clam (R. philippinarum). Raft cultured mussels showed the highest concentrations of HFRs (up to 0.8 ng g−1 wet weight of BDE-209).

Women remained invisible in health sciences until the late twentieth century because they were not included in the cohorts used in researched studies. Thanks to the work done by different groups of feminist researchers, we were able to visualise the need to change those paradigms. But while gender perspectives have allowed us to research new aspects of science, gender has sometimes contributed to rendering female-specific health issues as invisible. For women to be treated equally, their differences have to be recognised, precisely so that the equal right of both sexes to quality of life can be defended. Therefore, the science of difference should be included in research and taught in all health science specialisations.

La ciencia medica no ha tenido en cuenta hasta finales del siglo XX que existen diferencias en el modo de enfermar y en el tipo de enfermedades mas frecuentes entre mujeres y hombres. Existen sesgos de genero en la escasa valoracion de las diferencias tanto biologicas, como psicologicas y sociales. Nuestro grupo ha definido el termino “morbilidad femenina diferencial” para describir y visibilizar estas diferencias. Los factores de riesgo diferenciales destacables para la mortalidad prematura diferencial son los problemas cardiovasculares, el cancer de mama y el de colon. En cuanto a la morbilidad, la menstruacion y sus trastornos es el primer factor diferencial por edad, y las enfermedades endocrinas y el dolor osteomuscular los que causan los problemas mas prevalentes. Tambien son importantes la deficiencia de hierro y las carencias de vitamina D.

Context: The sequence of prenatal growth restraint and infantile catch-up of weight is by the age of 4 yr associated with hyperinsulinemic adiposity. We studied whether the adiposity of post-catch-up children born small for gestational age (SGA) is further amplified between age 4 and 6 yr and whether visceral fat excess has already emerged by the age of 6 yr. Setting: The study took place at a university hospital. Study Population and Design: A longitudinal cohort (age 2–6 yr) of 22 children born appropriate for gestational age (AGA) and 29 born SGA were studied. Auxological, endocrine, metabolic, and body composition (by absorptiometry) assessments were made at 2, 4, and 6 yr, and visceral fat was assessed (by magnetic resonance imaging) at 6 yr. Main Outcomes: Outcome measures included fasting glucose, insulin, IGF-I, neutrophil to lymphocyte ratio, lean mass, and total, abdominal, and visceral fat mass. Results: Between ages 4–6 yr, the relative adiposity of SGA children was further amplified. Between ages 2–6 yr, SGA children gained more total and abdominal fat and raised their insulin, IGF-I, and neutrophil to lymphocyte ratio more than did AGA children (all P < 0.0001). At age 6 yr, the average amount of visceral fat was in SGA children more than 50% higher than in AGA children (P < 0.005). The 0- to 2-yr increment in weight Z-score together with the 2- to 6-yr increment in fasting insulin accounted for 62% of visceral fat variability at age 6 yr. Conclusion: The amount of visceral fat is in post-catch-up SGA children excessive by the age of 6 yr. In populations at risk for type 2 diabetes or metabolic syndrome after fetal growth restraint, the time window for early intervention may have to be advanced into prepubertal childhood.

The design and analysis of research may cause systematic gender dependent errors to be produced in results because of gender insensitivity or androcentrism. Gender bias in research could be defined as a systematically erroneous gender dependent approach related to social construct, which incorrectly regards women and men as similar/different. Most gender bias can be found in the context of discovery (development of hypotheses), but it has also been found in the context of justification (methodological process), which must be improved. In fact, one of the main effects of gender bias in research is partial or incorrect knowledge in the results, which are systematically different from the real values.This paper discusses some forms of conceptual and methodological bias that may affect women’s health. It proposes a framework to analyse gender bias in the design and analysis of research carried out on women’s and men’s health problems, and on specific women’s health issues.Using examples, the framework aims to show the different theoretical perspectives in a social or clinical research context where forms of selection, measurement and confounding bias are produced as a result of gender insensitivity. Finally, this paper underlines the importance of re-examining results so that they may be reinterpreted to produce new gender based knowledge. Spanish Research Network on Health and Gender (RISG)

Summary Background and aim Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin. Design and patients In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23·7 kg/m2], all of whom started on Flu (62·5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7·5 mg/day; n = 19) on the same 21/28 days. Measurements Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year. Results PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P

One of the treatments for hyperinsulinemic hyperandrogenism in nonobese women is combined androgen receptor blockade (with flutamide; Flu), insulin sensitization (with metformin; Met) plus an estroprogestagen contraceptive. We tested whether adding low-dose pioglitazone (Pio; 7.5 mg/d) confers more benefit.The study was conducted at a university hospital.This double-blind study enrolled 38 young women with hyperinsulinemic hyperandrogenism [mean body mass index (BMI) 24 kg/m(2)], all of whom started on Flu (62.5 mg/d) and Met (850 mg/d) plus a transdermal estroprogestagen, each for 21 of 28 d over 6 months. Patients were randomly assigned to receive, in addition, placebo (n=19) or Pio (n=19; 7.5 mg/d) for the same 21 of 28 d over 6 months.BMI, waist to hip ratio, hirsutism score, fasting endocrine-metabolic markers, body composition, abdominal fat (visceral vs. sc), and carotid intima-media thickness were measured at study start and after 6 months.PioFluMet reduced intima-media thickness more than FluMet and lowered glucose, IGF-I, and C-reactive protein more as well as the ratio of low-density lipoprotein to high-density lipoprotein cholesterol and the ratio of neutrophils to lymphocytes. PioFluMet treatment was followed by a leaner body composition and a loss of visceral fat (both P0.001). In the total group, the changes included not only decreases in waist to hip ratio, hirsutism score, and testosterone (all P0.001) but also minor drops in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and lactate dehydrogenase (all P0.005), indicating absence of hepatotoxicity; BMI remained unchanged. Clinical side effects were not detected.In this proof-of-concept study, addition of Pio to FluMet plus an estroprogestagen led to improvements in the endocrine-metabolic condition, in low-grade inflammation, in total and visceral adiposity, and in markers of cardiovascular health.

Summary Objective Variation in the tumour necrosis factor gene, (TNF) has been associated with insulin resistance traits. We questioned whether the TNF−308G/A polymorphism is associated with birthweight and insulin resistance in children born small for gestational age (SGA), a patient population known to be at risk for insulin resistance. Design A cross-sectional, hospital-based study assessing insulin sensitivity in SGA children. Patients One hundred and ninety-eight school-age children born either SGA (n = 90, age 7·4 ± 4·5 years) or appropriate for gestational age (AGA, n = 108, age 8·7 ± 4·0 years). Measurements All children were genotyped for the TNF−308G/A polymorphism; a biochemical profile was also performed in prepubertal SGA (n = 58) and AGA (n = 57) subjects. Results Genotype frequencies for the TNF−308G/A single nucleotide polymorphisms (SNPs) (GG and GA/AA) differed between SGA and AGA children (86%vs. 72% and 14%vs. 28%, respectively; P = 0·025). The GG genotype was associated with lower birthweight and birth length (2747·0 ± 23·3 g vs. 2851·0 ± 45·7 g, P = 0·045, and 47·0 ± 0·2 cm vs. 48·2 ± 0·4 cm, P = 0·011, respectively) and, in AGA but not in SGA children, with higher systolic blood pressure [103·3 (95% confidence interval (CI) 96·4–110·2) mmHg vs. 92·8 (84·9–100·7) mmHg; P = 0·028], higher blood glucose [4·8 (4·7–5·0) mmol/l vs. 4·5 (4·3–4·8) mmol/l; P = 0·042] and higher homeostasis model assessment for insulin resistance (HOMA-IR) index [1·4 (1·1–1·7) vs. 0·9 (0·4–1·3); P = 0·005]. In multivariate analysis, the TNF−308GG genotype was an independent predictor of HOMA-IR during childhood, explaining 8% of its variance. Conclusion SGA children show increased frequency of the TNF−308G allele, an allele that is associated with prenatal growth and with postnatal insulin resistance. The TNF−308G/A polymorphism may have implications in the growth and metabolic abnormalities that characterise SGA children.

To evaluate deoxypyridinoline as a resorption marker in phenylketonuria (PKU) and to search for a relationship between deoxypyridinoline, calcium/creatinine index (Ca/Cr I), osteocalcin and bone alkaline phosphatase (BAP).This was a transversal analytical study of 46 PKU patients [17.5 (4-38) years]. Deoxypyridinoline and osteocalcin were measured with a chemiluminescent assay and BAP was measured with an immunoradiometric assay.Deoxypyridinoline was significantly increased in patients aged 7-14 and18 years old, being associated with age (r=-0.724, P0.001). Adult patients showed significantly higher Ca/Cr I, which correlates with Phe values for the year prior to the study (P=0.014). Serum BAP was significantly increased in pediatric patients (9-13 years), while it was decreased in adult patients (P=0.003). Decreased osteocalcin levels were found in patients15 years (P=0.028). Altered deoxypyridinoline and BAP values were related (P=0.042).PKU patients excreted increased D-Pyr, suggesting high bone resorption. Bone formation seems active in childhood but deteriorates in adult PKU patients. Periodic measurement of D-Pyr and BAP may be useful in the prevention of osteopenia in PKU patients.

Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor alpha (TNF-alpha) and the high neutrophil/lymphocyte ratio.Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months.The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-alpha levels fell and the high neutrophil/lymphocyte ratio normalized (P0.001). Lean body mass increased (P0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group.Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-alpha, and a normalization of the neutrophil/lymphocyte ratio.

A minority of children born small for gestational age (SGA) maintain a slow weight gain and a short stature (SS). At the other end of the spectrum are SGA children who show rapid postnatal weight gain and catch-up growth; these subjects may develop hyperinsulinemia, exaggerated adrenarche with precocious pubarche (PP), and an associated proinflammatory state with raised IL-6 and reduced adiponectin levels. Metformin therapy in SGA-PP girls attenuates the hyperinsulinemia, the adrenal androgen excess, and the proinflammatory state. In contrast, GH therapy in SGA-SS children promotes height gain but may induce hyperinsulinemia. Both groups are associated with increased risk markers for future cardiovascular disease. Therefore, we studied markers of inflammation in both SGA subpopulations at baseline and after their respectively corrective therapies. SGA-PP girls (n = 33; mean age, 8 yr; body mass index, 18.5 kg/m(2)) were randomized to remain untreated or to receive metformin (425 mg/d) for 6 months. SGA-SS children (n = 29; mean age, 7 yr; body mass index, 14.7 kg/m(2)) were randomly assigned to remain untreated or to receive GH (60 mug/kg/d). In SGA-PP girls, the mean neutrophil count (4.0 x 1000/mm(3)) was more than 2 sd above the mean reference level (2.8 x 1000/mm(3), P < 0.001); this remained stable over 6 months in untreated girls but dropped in metformin-treated girls by -1.1 x 1000/mm(3) (P = 0.002). In SGA-SS children, neutrophil counts were also higher at baseline (3.3 x 1000/mm(3), P < 0.01). This remained stable in untreated children but rose in GH-treated children by +1.1 x 1000/mm(3) (P = 0.004). GH-treated children also showed a rise in circulating IL-6 and dehydroepiandrosterone-sulfate levels and a fall in adiponectin levels. In conclusion, neutrophil counts were elevated in SGA children. In SGA girls with PP, the present results corroborate the antiinflammatory benefits of metformin therapy. In contrast, high-dose GH therapy in short SGA children may increase neutrophil counts and lead to a less favorable adipocytokine profile. Future studies with combined GH plus metformin treatment in short SGA children may clarify whether insulin resistance is a mechanism linking GH therapy to markers of inflammation.

A low-dose combination of flutamide-metformin and ethinylestradiol-drospirenone was recently found to reduce the excess of total and abdominal fat, to diminish the deficit in lean mass, and to attenuate the dysadipocytokinemia of young women with ovarian hyperandrogenism, a variant of polycystic ovary syndrome. We questioned the need to give flutamide, an androgen receptor blocker, together with an oral contraceptive that contains drospirenone, a progestin claimed to have antiandrogen properties. The additive effects of low-dose flutamide (62.5 mg/d) were assessed over 3 months in young patients with hyperinsulinemic ovarian hyperandrogenism (n = 40; age, approximately 17 yr; body mass index, approximately 22 kg/m(2)); all participants started on metformin (850 mg/d) and a fourth-generation contraceptive (ethinylestradiol 30 microg plus drospirenone 3 mg, 21 d/month), and they were randomized to receive flutamide in addition (n = 20) or not (n = 20). Fasting blood glucose, serum insulin, lipid profile, testosterone, adiponectin, and IL-6 were determined at baseline and after 3 months, together with body composition (by dual x-ray absorptiometry) and with Doppler assessment of ovarian arterial resistance. At start, the pulsatility and resistance indices of ovarian arteries were elevated. By comparison of 3-month changes between randomized subgroups, the addition of low-dose flutamide was found to have consistently (more) normalizing effects on low-density lipoprotein cholesterol, IL-6, and adiponectin, lean body mass, total and abdominal fat mass, and arterial flow in the ovaries. In conclusion, low-dose flutamide is herewith identified as a pivotal component within a first contraceptive combination therapy that has been shown to attenuate the hypoadiponectinemia, ovarian vascular hyperresistance, lean mass deficit, and central adiposity of young women with polycystic ovary syndrome. Finally, these data challenge any claim that drospirenone, as currently used in a contraceptive, is a clinically significant antiandrogen.

Among girls with precocious pubarche (PP), those with low birth weight (LBW) are, even if nonobese, at risk for progression to polycystic ovary syndrome (PCOS) including hyperinsulinemic hyperandrogenism, dyslipidemia, dysadipocytokinemia, and central fat excess. Recently, we disclosed the efficacy of insulin sensitization with metformin to disrupt progression from PP to PCOS in formerly LBW girls who were postmenarche. In LBW-PP girls, we have now extended the exploration of early insulin sensitization therapy in two directions: 1) metformin therapy was started before puberty; and 2) we assessed the effects of metformin discontinuation in girls who had started metformin treatment after menarche. Prepubertal LBW-PP girls (n = 33; mean age, 8.0 yr; body mass index, 18.5 kg/m(2)) were randomly assigned to remain untreated or to receive metformin (425 mg/d) for 6 months. Postpubertal LBW-PP girls (n = 24; age, 12.4 yr; body mass index, 21.0 kg/m(2)) had been randomized (at -12 months) to remain untreated or to receive metformin (850 mg/d) for 12 months, at which time (0 month) a treatment cross-over was performed for 6 months. Fasting blood glucose and serum insulin, SHBG, dehydroepiandrosterone sulfate, androstenedione, testosterone, lipid profile, IL-6, and adiponectin were assessed at 0 and 6 months, as was body composition (by dual x-ray absorptiometry). In the prepubertal study (group A), comparisons of untreated vs. treated girls disclosed normalizing effects of metformin on SHBG, androstenedione, dehydroepiandrosterone sulfate, low and high density lipoprotein cholesterol, triglycerides, IL-6, adiponectin, total and abdominal fat mass, and lean body mass. In the postpubertal study (group B), treatment cross-over at 0 month was in each subgroup followed by a striking reversal in the course of the endocrine-metabolic state, adipocytokinemia, and body composition; all changes pointed to normalizing effects of metformin treatment. In conclusion, these two studies provide the first evidence that 1) prepubertal metformin therapy has normalizing effects on PCOS features in high risk girls with a combined history of LBW and PP; and 2) in adolescence, metformin's normalizing effects are reversed as soon as metformin therapy is discontinued.

Resumen Objetivo Comprender las actitudes, comportamientos, creencias y conocimiento de la enfermedad en las personas diagnosticadas de diabetes tipo 2, asi como comprender que esperan de los profesionales sanitarios respecto al soporte y ayuda en el control de su enfermedad Diseno Estudio cualitativo, con un diseno interpretativo de tipo hermeneutico Emplazamiento La investigacion fue realizada en el primer semestre del ano 2001 y la poblacion estudiada procedia de Sabadell, poblacion urbana de la provincia de Barcelona Participantes Un total de 21 pacientes diagnosticados de diabetes tipo 2, atendidos en centros de atencion primaria Metodo Analisis de contenido de 21 entrevistas semiestructuradas realizadas en el domicilio. La validez del analisis fue asegurada mediante su revision por varios miembros del equipo investigador Resultados La diabetes es una enfermedad socialmente aceptada. Los pacientes se sienten mas o menos diabeticos segun sean tratados o no con insulina. La perdida que consideran mas importante es no poder comer ciertas cosas. Los diabeticos diferencian entre los conocimientos que ellos necesitan y los que han de tener los profesionales. El principal apoyo del diabetico es la familia, seguido del de los profesionales sanitarios Conclusiones os planes educativos han de ir muy relacionados con las demandas reales de las personas diabeticas. Estas esperan de los profesionales sanitarios, ademas de los conocimientos propios de la enfermedad, ser atendidas con valores eticos y de apoyo

The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyperandrogenism and insulin resistance. We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16; monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At baseline, there were no endocrine-metabolic differences among treatment groups. Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly ovulation rates increased after 9 months to 75 and 92%, respectively, with metformin alone or with combined therapy, but were unimproved with flutamide alone. All treatments were well tolerated. In conclusion, combined anti-androgen and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia, and dyslipidemia. The data from this small study suggest that dyslipidemia is secondary to excess androgen action in concert with the hyperinsulinemia associated with insulin resistance. In contrast, anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia.

Simple, precise, and low-cost methods for the simultaneous determination of phenolic endocrine disrupting compounds such as bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water samples were developed. The Direct, in situ derivatization methods are based on polydimethylsiloxane rod extraction followed by liquid desorption and chromatographic analysis by liquid chromatography and diode array detection. Several parameters affecting the extraction and desorption of the phenolic compounds and their acetylated derivates were studied, as well as the chromatographic and detection conditions. For the direct method, determination coefficients (r(2) )0.990 and LODs in the 0.6-2 μg/L range were obtained for all compounds except bisphenol A (9.5 μg/L). With the derivatization-based method, based on in situ acetylation, lower limits of detection (0.3-0.9 μg/L) were obtained for all the compounds with r(2)0.988 and RSDs in the 2-9% range. The developed methods were applied to the analysis of spiked water samples obtaining recoveries of between 60.2 and 131.7% for the direct method, and of between 76.6 and 108.2% for the derivatization-based method. The results demonstrate the feasibility of using these two methods for determining bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water.

BACKGROUND Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) -infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values. MATERIALS AND METHODS Plasma tHcy was determined by high-performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein-binding chemiluminescence, and methionine by ion exchange chromatography. RESULTS Significant differences were observed between tHcy concentrations in the HIV-infected patients and the reference values for children of similar ages (P < 0.0001). Folate values were significantly lower in HIV-infected children compared with our reference paediatric population (P < 0.0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = - 0.596; P < 0.0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0.501; P < 0.0001). Plasma tHcy was significantly higher (P = 0.008), while folate values and methionine : tHcy ratios were significantly lower (P = 0.007 and P = 0.042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies. CONCLUSIONS The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV-infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.

OBJECTIVE Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dyslipidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP. PATIENTS AND DESIGN We obtained fully longitudinal data from 51 girls with a history of PP and compared normal-birthweight (n = 26) with low-birthweight (n = 25) girls (birthweight SD score 0·0 ± 0·2 vs. − 2·4 ± 0·2) for measurements obtained at diagnosis of PP (mean age 7·0 years), in early puberty (10·4 years) and after menarche (14·3 years). MEASUREMENTS Fasting serum lipids and lipoproteins, together with insulin responses to an oral glucose load, were assessed at diagnosis of PP, in early puberty and after menarche; serum gonadotropins were measured in early puberty and after menarche; ovarian function was examined postmenarche. RESULTS Comparisons of endocrine-metabolic results between normal- and low-birthweight PP girls showed no detectable differences before puberty. The hypertriglyceridaemia and elevated LDL-cholesterol levels characterizing low-birthweight PP girls became detectable by early puberty; reduced insulin sensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal- and low-birthweight subgroups were identical in early puberty and postmenarche. CONCLUSIONS These longitudinal data show that, in PP girls, the endocrine-metabolic risk conferred by prenatal growth restraint is not readily detectable until puberty or postmenarche, and is not attributable to a higher body mass index.

Even nonobese girls with precocious pubarche may develop a variant of polycystic ovary syndrome (PCOS) characterized by hyperinsulinism, hyperandrogenism, abnormal lipids, and persistent anovulation. Insulin-sensitizing treatment has limited hyperinsulinism and hyperandrogenism and restored eumenorrhea in women with PCOS. Extrapolating from observations in obese women with PCOS who receive an insulin-sensitizing agent such as metformin or troglitazone and become more likely to ovulate, this study examined the effects of metformin in 18 nonobese adolescent girls with a mean age of 16½ years who were 3 to 7 years past menarche. All were anovulatory and met clinical and hormonal criteria for ovarian hyperandrogenism. The participants also had a history of precocious pubarche caused by exaggerated adrenarche. All the girls were hyperinsulinemic but had normal glucose tolerance. Anovulation was confirmed twice by obtaining four consecutive serum progesterone levels below 4 ng/ml at 1-week intervals. Metformin was given for 6 months in a daily dose of 1275 mg. Hirsutism scores decreased with metformin therapy, as did levels of fasting serum insulin, luteinizing hormone, total testosterone, androstenedione, dehydroepiandrosterone sulfate, and the free androgen index. Serum levels of sex hormone-binding globulin increased at the same time, and the lipid profiles became less atherogenic. There were no changes in body mass index, fasting glycemia, or serum levels of estradiol or follicle-stimulating hormone. All but 2 of the 18 girls reported regular menses within 4 months of the start of metformin therapy and, after 6 months, all were eumenorrheic. Ovulation induction failed in 4 of the 18 girls (Fig. 1), including the 2 with the most severe hyperandrogenism. Abdominal discomfort in 4 girls resolved spontaneously within 2 weeks. Metformin treatment tends to normalize endocrine-metabolic function in nonobese adolescent girls with anovulatory hyperandrogenism and induces ovulation in many of them.

The aim of the study was to observe the influence of carbamazepine and valproic acid on plasma total homocysteine and B-vitamin status and the gene-drug interaction with the 677C--T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Plasma total homocysteine concentrations were determined in 136 epileptic children taking anti-epileptic drugs as monotherapy. Nutritional (folate, B12 and B6 vitamins) and genetic (MTHFR 677 C--T) determinants of plasma homocysteine were studied in a random sample of 59 of the 136 epileptic children. Total homocysteine concentrations were significantly increased (p0.05) and folate and vitamin B6 levels were significantly decreased (p0.01) in the children taking anti-epileptic drugs compared with our reference ranges. In the carbamazepine-treated group, significantly positive correlation was found between duration of treatment and homocysteine concentration (p0.01). Homocysteine concentrations showed a significantly negative correlation with vitamin levels (folate: p = 0.002, and vitamin B12: p = 0.017) only in the carbamazepine treated group. In children treated with carbamazepine up to 3 years, total homocysteine concentration correlated negatively only with folate (p = 0.003), while in patients treated for more than 3 years, total homocysteine correlated negatively only with vitamin B12 values (p = 0.007). The lowering action of carbamazepine treatment on folate levels seems to be associated with hyperhomocysteinaemia, which seems to be related to the homozygous condition for the MTHFR 677C--T mutation. Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype.

Precocious pubarche in girls is often preceded by low weight at birth and followed by hirsutism, ovarian hyperandrogenism, and oligomenorrhea in adolescence, the latter usually being accompanied by dyslipidemia and hyperinsulinism, which are, in turn, two major risk factors for cardiovascular disease in later life. We hypothesized that insulin resistance may be a key pathogenetic factor in this sequence. We tested the hypothesis by assessing the effects of an insulin-sensitizing agent, metformin, given at a daily dose of 1275 mg for 6 months to 10 nonobese adolescent girls (mean age, 16.8 yr; body mass index, 21.9 kg/m2; birth weight, 2.7 kg) with hirsutism, ovarian hyperandrogenism (diagnosis by GnRH agonist test), oligomenorrhea, dyslipidemia, and hyperinsulinemia after precocious pubarche. Before the metformin trial, longitudinal studies in these girls had shown that hyperinsulinism was present at prepubertal diagnosis of precocious pubarche, and that it increased markedly in late puberty or early postmenarche. Metformin treatment was well tolerated and was accompanied by a marked drop in hirsutism score, insulin response to oral glucose tolerance test, free androgen index, and baseline testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate levels (all P < 0.01). During metformin treatment, the LH and 17-hydroxyprogesterone hyperresponses to GnRH agonist were attenuated (P < 0.01); serum triglyceride, total cholesterol, and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol rose. All girls reported regular menses within 4 months. Withdrawal of metformin treatment was followed, within 3 months, by a consistent reversal toward pretreatment conditions. In conclusion, metformin treatment reduced hyperinsulinemia, hirsutism, and hyperandrogenism; attenuated the LH and 17hydroxyprogesterone hyperresponses to GnRH agonist; improved the atherogenic lipid profile; and restored eumenorrhea in nonobese adolescent girls with a history of precocious pubarche. These observations corroborate the idea that insulin resistance may indeed be a prime factor underpinning the sequence from reduced fetal growth, through precocious pubarche, to adolescent endocrinopathies that are reminiscent of so-called polycystic ovary syndrome.

Objective: To assess the recovery, maintenance, and quality of ovarian function by comparing the success of autotransplantation in intraperitoneal (IP) and SC locations over a 6-month period in syngeneic Lewis rats. Design: Experimental animal study. Setting: Unit of Experimental Research at the Barcelona University School of Medicine. Animal(s): Female syngeneic Lewis rats. Intervention(s): The animals were randomized to one of three groups: group A, control group with ovariectomy (n = 15); group B, ovariectomy and IP autologous heterotopic transplant of ovarian tissue without vascular pedicle (n = 14); and group C, ovariectomy and SC autologous heterotopic transplant (n = 15). Main Outcome Measure(s): Serum levels of FSH and 17β-E 2 and vaginal cytology. Result(s): In groups B and C, E 2 serum concentrations from day 7 and day 10 onward remained comparable to basal levels, and significantly higher than in group A, throughout the 6-month period. In group B from day 7 after surgery onward, and in group C from day 10 after surgery onward, FSH concentrations remained low (comparable to basal levels) throughout the follow-up period. Vaginal cytology of groups B and C showed trophic maturation between days 4 and 10 after ovariectomy and insertion of the ovarian tissue implant, whereas the control group remained atrophic. There were no statistically significant differences between IP and SC implants. Conclusion(s): A heterotopic autotransplant of ovarian tissue without vascular pedicle in syngeneic Lewis rats is successful for ≥6 months.

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.

An extraction and preconcentration procedure for the determination in water samples of several halogenated flame retardants (FRs), nine brominated diphenyls ethers (BDEs) and seven non-BDE FRs, was developed and validated. The optimised procedure is based on polydimethylsiloxane (PDMS) rods as sorptive extraction material, followed by liquid desorption and gas chromatography coupled to negative chemical ionisation-mass spectrometry (GC-NCI-MS) determination, rendering an efficient and inexpensive method. The final optimised protocol consists of overnight extraction of 100mL of sample solutions containing 40% MeOH and 4% NaCl, followed by a 15-min sonication-assisted desorption with 300μL of ethyl acetate, solvent evaporation and GC-NCI-MS analysis. Under these conditions, extraction efficiencies in the 9 to 70% range were obtained, leading to enrichment factors between 108 and 840, detection limits in the range from 0.4 to 10ngL-1and RSD values in the 2-23% range. After method validation, different real water samples, including river, ria, sea, landfill leachate, influent and effluent wastewater from an urban sewage treatment plant (STP) and effluent wastewater from a textile industry, were analysed. BDE-47, BDE-99, BDE-100 and BDE-197 were detected in wastewater and landfill leachate samples at concentration levels up to 2887ngL-1. Among the non-BDE FRs, bis (2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (DEHTBP) was detected in surface water samples (sea, river and ria) between 1.3 and 2.2ngL-1 and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) in the landfill leachate (64ngL-1) This work was supported by the Spanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovacion) and FEDER funds, project no. CTQ2009-08377 and CTM2011-28765-C02-02, and Xunta de Galicia, project no.10MDS700006PR. R. Rodil and J.B. Quintana (Ramon y Cajal research program), E. Villaverde-de-Sdaa (FPI grant, ref. BES-2011-047887) and C. Valls-Cantenys (FPI grant, ref. BES-2009-024892) extend their gratitude to the Spanish Ministry of Science and Innovation

Phosphorus is a key nutrient and in natural environments regulates trophic status and consequently water quality. Therefore monitoring of phosphorus content in natural and wastewater is essential. Although several phosphorus species can be found in the environment, the majority of the methods developed are for orthophosphate determination. High performance liquid chromatography (HPLC) coupled with inductively coupled plasma with atomic emission spectroscopy (ICP-AES) has been first used in this study for the speciation of the most common phosphorus oxoanions in aquatic environments: orthophosphate, phosphite, hypophosphite, pyrophosphate and tripolyphosphate. The chromatograms have been obtained by registering the phosphorous 213.618 nm emission intensity variation with time. The pH and the ionic strength of the mobile phase have been the most critical variables of the chromatographic separation. Moreover, methanol addition promotes the elution of the most retained species. Finally, by using ammonium nitrate and a gradient elution, increasing ionic strength and decreasing the pH, the separation has been achieved in 12 min. Limits of detection have been included within the 1–5 mg L −1 range. The developed methodology has been tested with spiked tap water and effluent water of a wastewater treatment plant (WWTP) obtaining recoveries in the range of 91.5–114.1% for a 20 mg P L −1 spike concentration.

Background/Aims: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Unequal crossing over or gene conversion between the active CYP21A2 gene and the inactive CYP21A1P pseudogene accounts for 95% of mutations, but many non-pseudogene-derived mutations have been described. It is important for these new mutations to be assigned to a specific phenotype. Case Report and Results: We report a young boy diagnosed with the classical simple virilizing phenotype in whom the CYP21A2 genetic analysis disclosed that he was a compound heterozygous for p.His38Leu and the c.290-13A/C>G mutations. The p.His38Leu mutation has been recently described, but has not been associated with a specific phenotype thus far. Residue 38 is the only charged amino acid of a hydrophobic patch that interacts closely with the membrane. This mutation leads to a non-charged amino acid, suggesting a much more hydrophobic continuous domain. This patch is highly conserved through different mammals indicating the importance of this domain in the protein-membrane interaction. Conclusion: Our results support p.His38Leu as a severe mutation causing a classical simple virilizing phenotype.

Las vías de entrada de la contaminación ambiental en el cuerpo humano se establecen a través de la respiración, de la vía digestiva y de la piel. La entrada a través del aire, agua, alimentos y cosméticos hacen a veces imperceptible para los humanos la exposición a productos cuya toxicidad les puede perjudicar. Muchos de los tóxicos ambientales, insecticidas, disolventes o metales pesados pueden acumularse en el cuerpo, en especial en el de las mujeres por su mayor contenido en células grasas. El cuerpo de la mujer actúa, pues, como un bioacumulador químico y sufre consecuencias como las alteraciones de la salud reproductiva, la aparición de enfermedades emergentes como la Fibromialgia, la Sensibilidad Química Múltiple y la Fatiga Crónica y el incremento del Cáncer de Mama. La creciente influencia de la contaminación ambiental en la salud de las mujeres hace que el ecofeminismo no pueda ser ajeno a su investigación. Environmental pollution can enter the human body via the respiratory or digestive systems or through the skin. As pollution enters the body via air, water, food and cosmetics, we often do not realize that we are exposed to toxic products which may be prejudicial to our health. Many toxic insecticides, solvents and heavy metals can accumulate in our bodies, and in particular in women's bodies due to their higher concentration of fat cells. Women´s bodies can act as chemical bio accumulators and suffer consequences such as changes in reproductive health and the appearance of new illnesses such as fibromyalgia, multiple-chemical sensitivity, chronic fatigue syndrome and an increase in breast cancer. The growing influence of environmental pollution on women's health means that that eco-feminism can no longer neglect the need for research in this area.

Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin.In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23.7 kg/m(2)], all of whom started on Flu (62.5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7.5 mg/day; n = 19) on the same 21/28 days.Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year.PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P0.001), and reduced visceral fat and IMT by a mean 22% and 31% (both P0.001). Low-dose Pio accounted for about half of the PioFluMet effects on IMT, visfatin and HMW adiponectin.In hyperinsulinaemic women with androgen excess, low-dose polytherapy with PioFluMet evoked striking rises in both circulating visfatin and HMW adiponectin, while lowering IMT and reducing visceral adiposity within 1 year.

Summary Background Discontinuation of metformin therapy, if started beyond menarche in adolescents or young women with hyperinsulinaemia following low birthweight, is rapidly followed by rebound deteriorations in body fat, insulin resistance and blood lipid profile. Objective We hypothesized that early commencement of metformin and its continuation throughout puberty might have more persisting benefits. Patients and measurements We followed up on a previously reported randomized study cohort at 12 months and 18 months after treatment discontinuation, including body composition by absorptiometry, fasting insulin, glucose and blood lipids. In that open-labelled, prospective study, 22 low birthweight girls with early normal puberty (Stage 2 breast development at age 8–9 years) were randomized to remain untreated (N = 12] or to receive metformin (850 mg/day; N = 10) for 36 months (between time –36 months to 0 month). Results The significant improvements previously reported at the end of the 36-month active treatment period in per cent body fat, abdominal fat mass, fasting insulin sensitivity, high density lipoprotein (HDL) cholesterol and triglyceride levels all persisted at follow-up 12 months after treatment discontinuation. Further anthropometry at 18 months off therapy confirmed the persistence of benefits in height, body mass index (BMI) and waist circumference in the previously metformin-exposed girls. Conclusion In low birth weight girls with early normal onset of puberty, metformin treatment for 3 years across puberty resulted in auxological, endocrine and metabolic benefits that persisted for at least 1 year after metformin withdrawal. Further follow-up and longer-term studies are needed to explore the possibility that insulin sensitization therapy during puberty might reprogramme predisposition to metabolic disease.

Girls with precocious pubarche (PP, pubic hair at8 yr of age) are at high risk for early onset and rapid progression of puberty, in particular if their prenatal growth was restrained, i.e. low birth weight (LBW), and followed by rapid postnatal catch-up of weight gain. We postulated that insulin resistance contributes to early onset and rapid progression of puberty in LBW-PP girls and thus explored the puberty-delaying effects of insulin sensitization with metformin initiated shortly after PP diagnosis.The study population consisted of 38 prepubertal LBW girls with PP attributed to exaggerated adrenarche [mean body weight, 2.4 kg; age, 7.9 yr; body mass index (BMI), 18.4 kg/m(2)]. These girls were randomly assigned to remain untreated (n = 19) or to receive metformin (n = 19; 425 mg/d) for 2 yr.Pubertal staging, age at menarche, body composition by absorptiometry, fasting insulin, glucose, lipids, leptin, IGF-I, IGF-binding protein-1, testosterone, dehydroepiandrosterone sulfate, and SHBG were the main outcome measures.Metformin treatment was associated with a less adipose body composition (and lower serum leptin levels) and with a 0.4-yr delay in the clinical onset of puberty (Tanner B2; 9.5 vs. 9.1 yr; P0.01). These findings were corroborated by a delay of at least 1 yr in the puberty-associated rise of circulating IGF-I (P0.01). Available results also point to a metformin-associated delay of menarche (P0.02). Gain in height and lean mass was not divergent between study subgroups.The efficacy of early metformin treatment in PP girls is here extended to include not only a less adipose body composition after 2 yr but also a less advanced onset of puberty, whereas height gain is maintained. These findings open the perspective that, ultimately, metformin treatment may also prove to heighten the short adult stature of LBW-PP girls.

Aims: To study the value of interleukin (IL)-8, IL-6 and IL-1β in vaginal wash as predictors of preterm delivery. Methods: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1β, IL-6 and IL-8 concentrations. Results: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1β, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1β, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. Conclusion: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1β, IL-6 and IL-8 as a predictor clinically.

To determine the relation between weight deficit at birth and IGF-I, IGFBP-I, Leptin, and AFP levels in amniotic fluid after 14-18 weeks; to assess the diagnostic usefulness of these biochemical markers.Longitudinal, prospective study. Amniocentesis was performed in pregnant women after 14-18 weeks of gestation.86 controls, 18 IUGR10 percentile, and 17 IUGR5 percentile.No significant correlation was found between severity of IUGR and IGF-I, IGFBP-I, or Leptin. AFP was inversely correlated with severity of IUGR; results for the IUGR10 percentile were: S: 65.7%, SP: 56.9%, PPV: 38.3%, NPV: 80.3%, and an overall diagnostic capacity of 65.6%. Results for the IUGR5 percentile were: S: 76.4%, SP: 54.8%, PPV: 21.6%, NPV: 93.4% were obtained, and an overall capacity of 70.6%.Elevated values of AFP in amniotic fluid may help early detection of populations at risk of developing IUGR.

Objective: To evaluate the role of inhibin in elevated base levels of FSH and follicular hyperplasia in ovarian autotransplantation in rats. Design: Experimental animal study. Setting: Unit of Experimental Research at the Barcelona University School of Medicine. Animal(s): Female syngeneic Lewis rats aged 16 weeks. Intervention(s): The animals were randomized into two groups: group A, control group undergoing only laparotomy (n = 5) and group B, oophorectomized with SC autologous heterotopic transplant (n = 5). The animals were killed and their ovaries removed for histologic, morphometric, and immunohistochemical analysis at 28 days after surgery in both groups. Main Outcome Measure(s): Serum levels of E-2 and FSH were determined on day 0 (the day of surgery or baseline) and days 4, 7, 14, 21, and 28. Morphometric analysis of ovarian structure for evaluation of antral follicles and their granulosa cell area and immunohistochemistry for inhibin staining were also done. Result(s): The endocrinological function recovered at 28 days, and the FSH levels for the transplant group were significantly higher than for the group with normoinsert ovary. Morphometric analysis showed that the mean granulosa cell area was greater in group B when compared with the control group. Immunohistochemistry revealed almost null inhibin staining of the stroma in transplanted ovarian tissue. Conclusion(s): Tissue damage brought on by ischemia in the transplant of nonvascularized ovaries may bring about an inhibin deficit in the ovarian stroma, which might explain the increased levels of FSH. These increased levels, in turn, would be responsible for the follicular hyperplasia seen in this tissue when it recovers its function. (Fertil Steril((R)) 2003;79(Suppl 1):743-8. (C) 2003 by American Society for Reproductive Medicine.).

Prenatal growth restraint, as reflected in a low birthweight for gestational age, is a risk factor for postpubertal FSH hypersecretion and for reduced gonadal size. The ontogeny of the low-birthweight effect on the FSH-inhibin B feedback loop is unknown. Infancy is an episode of choice to study the possibility of an early low-birthweight effect on the FSH-inhibin B loop because this phase is characterized by high activity within the gonadal axis. We assessed serum concentrations of FSH and inhibin B in 46 infants [26 girls and 20 boys; mean age, 4 months; range, 3–6 months; 17 appropriate for gestational age (AGA), 29 small for gestational age (SGA); mean birthweight, 3.2 kg for AGA vs. 2.3 kg for SGA], together with circulating levels of LH, E2, and free androgen index. In SGA girls and boys, serum FSH levels were 2- and 4-fold higher (P < 0.001), respectively, than in AGA controls of the same gender (7.3 ± 0.9 vs. 3.8 ± 0.4 IU/ml and 2.9 ± 0.5 vs. 0.7 ± 0.2 IU/ml). Serum LH, inhibin B, and free androgen index/E2 concentrations were similar in AGA and SGA infants. In conclusion, prenatal growth restraint was found to be followed by elevated serum FSH concentrations in infant girls and boys. SGA infants seem to need an augmented FSH drive to fulfill inhibin B requirements on the afferent side of the feedback loop. The late-endocrine correlates of early growth restraint are herewith extended to include the main axis of reproduction in both genders. It remains to be studied whether FSH hypersecretion in infancy is a marker of subsequent subfertility.