Search

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.Gly146Ala variant is common in individuals with a DSD and has been suggested to act as a susceptibility factor for adrenal disease or cryptorchidism. Since the allele frequency is high in the general population, and the functional testing of the p.Gly146Ala variant revealed inconclusive results, the disease-causing effect of this variant has been questioned. However, a role as a disease modifier is still possible given that oligogenic inheritance has been described in patients with NR5A1/SF-1 variants. Therefore, we performed next generation sequencing (NGS) in 13 DSD individuals harboring the NR5A1/SF-1 p.Gly146Ala variant to search for other DSD-causing variants and clarify the function of this variant for the phenotype of the carriers. Panel and whole-exome sequencing was performed, and data were analyzed with a filtering algorithm for detecting variants in NR5A1- and DSD-related genes. The phenotype of the studied individuals ranged from scrotal hypospadias and ambiguous genitalia in 46,XY DSD to opposite sex in both 46,XY and 46,XX. In nine subjects we identified either a clearly pathogenic DSD gene variant (e.g. in AR) or one to four potentially deleterious variants that likely explain the observed phenotype alone (e.g. in FGFR3, CHD7). Our study shows that most individuals carrying the NR5A1/SF-1 p.Gly146Ala variant, harbor at least one other deleterious gene variant which can explain the DSD phenotype. This finding confirms that the NR5A1/SF-1 p.Gly146Ala variant may not contribute to the pathogenesis of DSD and qualifies as a benign polymorphism. Thus, individuals, in whom the NR5A1/SF-1 p.Gly146Ala gene variant has been identified as the underlying genetic cause for their DSD in the past, should be re-evaluated with a NGS method to reveal the real genetic diagnosis. [ABSTRACT FROM AUTHOR]

Activation of the PPAR gamma 2 gene (PPARG2) improves the action of insulin and its lipid metabolism. We examined the association between Pro12Ala polymorphism of PPARG2, type 2 diabetes mellitus (DM2), and peripheral insulin sensitivity in a population with a high intake of oleic acid. A cross-sectional, population-based study was undertaken in Pizarra, a small town in the province of Malaga in southern Spain. A total of 538 subjects, aged 18-65 y, were selected randomly from the municipal census. All subjects underwent a clinical, anthropometrical, and biochemical evaluation, including an oral glucose tolerance test and Pro12Ala polymorphism of PPARG2. Insulin resistance was measured by homeostasis model assessment. Those subjects with the Ala-12 allele had an odds ratio for impaired fasting glucose of 0.55, for impaired glucose tolerance of 0.59, and for DM2 of 0.30. The intake of monounsaturated fatty acids (MUFA) contributed to the variance of the homeostasis model assessment insulin resistance index (HOMA IR) (P = 0.04), with a 2-way interaction between the Ala-12 allele of PPARG2 and the intake of MUFA (P = 0.005). The results suggest the existence of an interaction between Pro12Ala polymorphism of PPARG2 and dietary MUFA, such that obese people with the Ala-12 allele have higher HOMA IR values, especially if their intake of MUFA is low.

Disorders/differences of sex development (DSD) are the result of a discordance between chromosomal, gonadal, and genital sex. DSD may be due to mutations in any of the genes involved in sex determination and development in general, as well as gonadal and/or genital development specifically. MAMLD1 is one of the recognized DSD genes. However, its role is controversial as some MAMLD1 variants are present in normal individuals, several MAMLD1 mutations have wild-type activity in functional studies, and the Mamld1 -knockout male mouse presents with normal genitalia and reproduction. We previously tested nine MAMLD1 variants detected in nine 46,XY DSD patients with broad phenotypes for their functional activity, but none of the mutants, except truncated L210X, had diminished transcriptional activity on known target promoters CYP17A1 and HES3. In addition, protein expression of MAMLD1 variants was similar to wild-type, except for the truncated L210X. We hypothesized that MAMLD1 variants may not be sufficient to explain the phenotype in 46,XY DSD individuals, and that further genetic studies should be performed to search for additional hits explaining the broad phenotypes. We therefore performed whole exome sequencing (WES) in seven of these 46,XY patients with DSD and in one 46,XX patient with ovarian insufficiency, who all carried MAMLD1 variants. WES data were filtered by an algorithm including disease-tailored lists of MAMLD1 -related and DSD-related genes. Fifty-five potentially deleterious variants in 41 genes were identified; 16/55 variants were reported in genes in association with hypospadias, 8/55 with cryptorchidism, 5/55 with micropenis, and 13/55 were described in relation with female sex development. Patients carried 1-16 variants in 1-16 genes together with their MAMLD1 variation. Network analysis of the identified genes revealed that 23 genes presented gene/protein interactions with MAMLD1. Thus, our study shows that the broad phenotypes of individual DSD might involve multiple genetic variations contributing towards the complex network of sexual development. [ABSTRACT FROM AUTHOR]

Copyright of Adicciones is the property of Sociedad Cientifica Espanola de Estudios sobre el Alcohol and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH. 本文报道一名36岁女性，因21-羟化酶缺乏患有先天性肾上腺皮质增生症（congenital adrenal hyperplasia，CAH），且于出生后接受皮质醇替代治疗。因未长期坚持治疗，患者表现为持续男性化特征及高睾酮水平。近来，患者求助于本性别中心，希望进行生殖整形手术。检查中我们发现患者左卵巢有一肿物，病理检验结果为卵巢门细胞瘤，故建议患者行左卵巢切除术。后患者睾酮水平降至正常且男性化特征消失，但ACTH水平未降低。此病例中出现的卵巢原位肿瘤极其罕见，但当发现CAH女性出现男性化症状时，应予以警惕。 [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate the usefulness of the Bem Sex Role Inventory (BSRI; Bem, 1974), an overall measurement of the cultural construct of masculinity and femininity, in the psychological assessment of Spanish transsexuals. Seventy male-to-female transsexuals (MF), 51 female-to-male transsexuals (FM), 77 control men, and 79 control women completed the Spanish version of the BSRI. Statistically significant differences between groups were only found on the femininity scale, on which MF transsexuals and control women scored significantly higher than FM transsexuals and control men. The results indicate that (a) only the femininity scale of the BSRI appears to be useful today for evaluating differences in the sex-role identification in Spanish controls and transsexuals; and (b) MF and FM transsexuals score as a function of their gender identity instead of their anatomical sex on the BSRI femininity scale. [ABSTRACT FROM AUTHOR]

Variants of NR5A1 are often found in individuals with 46,XY disorders of sex development (DSD) and manifest with a very broad spectrum of clinical characteristics and variable sex hormone levels. Such complex phenotypic expression can be due to the inheritance of additional genetic hits in DSD-associated genes that modify sex determination, differentiation and organ function in patients with heterozygous NR5A1 variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the NR5A1 gene. We tested the transactivation activity of novel NR5A1 variants. We additionally included six of these patients in a targeted diagnostic gene panel for DSD and identified a second genetic hit in known DSD-causing genes STAR, AMH and ZFPM2/FOG2 in three individuals. Our study increases the number of NR5A1 variants related to 46,XY DSD and supports the hypothesis that a digenic mode of inheritance may contribute towards the broad spectrum of phenotypes observed in individuals with a heterozygous NR5A1 variation. [ABSTRACT FROM AUTHOR]

Objective. To provide a bibliometric and contents analyses of the Spanish research in the field of gender dysphoria based on a literature review. Method. Five international and four national databases, and two platforms were used to retrieve publications using the keyword "gender dysphoria" and related terms. The results were combined with Spain and with the name of the Spanish cities' names with a hospital. The articles published from the Gender Identity Units (GIU) being part of the National Health System were selected. The number of citations was assessed using the Science Citation Index (SCI) and Google Scholar. Results. A total of 179 articles were included. Production shows a progressive increase from 1999 to 2015 and a slight decrease in the following years. 34.6% were published in English, 45.8% were based on set of cases, and the most frequent topic is psychology and mental health (58.1%). The 75 publications indexed in the SCI had received 1,252 citations, and the 152 found in Google Scholar reached 3,105 citations. The highest SCI average citation per article corresponds to those published in English (22.2), based on set of cases (21.1), in the field of neuroimaging (52), and coming from the Catalonia GIU (25.7). Conclusions. The Spanish research on gender dysphoria produced from the GIUs has had a progressive growth, covers many topics, includes a high number of studies based on set of cases, and the number of citations reflect an impact on the scientific community and international leadership in some areas such as neuroimaging. [ABSTRACT FROM AUTHOR]

Objective. To provide a bibliometric and contents analyses of the Spanish research in the field of gender dysphoria based on a literature review. Method. Five international and four national databases, and two platforms were used to retrieve publications using the keyword “gender dysphoria” and related terms. The results were combined with Spain and with the Spanish cities’ names with a hospital. The articles published from the Gender Identity Units (GIUs) being part of the National Health System were selected. The number of citations was assessed using the Science Citation Index (SCI) and Google Scholar. Results. A total of 179 articles were included. Production shows a progressive increase from 1998 to 2015, and a slight decrease in the following years. 34.6% were published in English, 45.8% were based on set of cases, and the most frequent topic is psychology and mental health (58.1%). The 75 publications indexed in the SCI had received 1,252 citations, and the 152 found in Google Scholar reached 3,105 citations. The highest SCI average citation per article corresponds to those published in English (22.2), based on set of cases (21.1), in the field of neuroimaging (52), and coming from the Catalonia GIU (25.7). Conclusions. The Spanish research on gender dysphoria produced from the GIUs has had a progressive growth, covers many topics, includes a high number of studies based on set of cases, and the number of citations reflect an impact on the scientific community and international leadership in some areas such as neuroimaging [ABSTRACT FROM AUTHOR]

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Objective: The aim of this study was to undertake a prospective study of the changes in certain risk factors for cardiovascular disease occurring during menopause., Methods: A longitudinal cohort study of 475 women was followed up for 6 years (Pizarra Study). The final menstrual period was defined after at least 6 months of amenorrhea. The women were classified into three groups: group 1, no menopause at either the first or second study; group 2, no menopause at the first study but menopause at the second study (6 y later); and group 3, menopause at the first study (and also at the second). The following are the main outcome measures used: age; body mass index; waist circumference; waist-to-hip ratio; skinfold thickness; arm circumference; intake of macronutrients (quantitative questionnaire); systolic and diastolic blood pressures; cholesterol, triglycerides; high-density lipoprotein cholesterol; uric acid; homeostasis model assessment of insulin resistance; and the prevalence of obesity, hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose., Results: None of the cardiovascular risk factors studied changed during the passage from premenopause to postmenopause, independently of age or physical activity., Conclusions: Menopause is a biological condition of the human species, for which has recently received attempts at medicalization that were not always justified. If menopause is not accompanied by any other cardiovascular risk factor independently of age, the stigma of menopause being considered a risk factor should cease. Although the results have the strength of a prospective study, the sample size forced us to consider these findings as preliminary.

For more than a decade the pedicled island neurovascular flap of the glans penis has been the standard procedure for clitoroplasty in intersex anomalies and in male-to-female genital sex reassignment surgery. Most authors focusing on genitoperineal reconstructions have used the island neurovascular flap of the dorsal shaft of the penis, including a variable-sized dorsal chip of the glans penis as the distal and functional portion of the flap. Although this dorsal glans clitoroplasty technique for neoclitoral reconstruction is well known, it nevertheless deserves scientific revision, with a view to improving several neglected aesthetic and functional points. The authors describe a new method for reconstruction of the neoclitoris in male-to-female transsexuals, the corona glans clitoroplasty. It is based on a modification of the original pedicled island neurovascular flap of the glans penis. The main difference compared with the dorsal glans clitoroplasty is that, distally, this method includes a bifid dorsolateral coronal flap designed in the shape of an open lotus flower or a bull's horns. Furthermore, a semicircular preputial flap is retained, attached to the bifid coronal flap of the glans, to improve the cosmetic appearance of the vestibulum and avoid growth of hair around the neoclitoris. Finally, a small dorsal flap of the spongiomucosa urethra designed in the shape of a pencil tip is added to improve the cosmetic appearance of the vestibulum between the neoclitoris and the urethral neomeatus. Since October of 1999, the authors have performed more than 30 genital sex reassignment surgeries in male-to-female transsexuals, of whom 16 underwent their technique of corona glans clitoroplasty. The authors describe and discuss the anatomic basis and clinical implications of this technique and its cosmetic and potential functional advantages. They also consider the anatomic differences among four distal designs of the pedicled island neurovascular flap of the glans penis: dorsal, lateral, ventral, and corona glans clitoroplasty in male-to-female transsexuals.

Background and Objective: Our purpose was to evaluate in a cross-section, populational study the association between daily physical activity and various metabolic and cardiovascular disease risk factors., Patients and Method: A total of 1226 randomly selected persons (aged 18-65 years) from a town in southeast Spain were evaluated for studying the association between the level of daily physical activity, both in and out of working hours, and the following variables: body mass index, plasma lipids, hypertension, obesity, altered baseline glycemia, and abnormal glucose tolerance., Results: The intensity of the physical activity at work was related negatively with insulin resistance and levels of LDL cholesterol, and positively with HDL cholesterol. The probability of hypertension, altered baseline glycemia, and abnormal glucose tolerance was greater in those undertaking less daily physical activity., Conclusions: Daily physical activity, considered as part of the lifestyle, is related with the presence of components of the metabolic syndrome. An increase in daily physical activity should contribute to improve preventible cardiovascular risk factors.