Alberto Salamanca

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity. Deletions of 11p11–p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224; ref. 2) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 (refs. 3,4) and PFM. Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS.

Subendometrial contractility in menstrual phase visualized by transvaginal sonography in patients with endometriosis

OBJECTIVE To describe the propagation direction of the subendometrial myometrial contractile wave in menstrual phase sonographically assessed in patients with and without endometriosis. DESIGN Prospective study. SETTING Patients and normal volunteers in a university hospital. PATIENTS Sixteen women with (study group) and 21 without (control group) endometriosis. INTERVENTIONS Patients were examined by transvaginal sonography (midsaggital plane of the uterus) and recorded on videotape for a 5-minute period. MAIN OUTCOME MEASURE Direction of propagation of contraction waves. RESULTS The endometriosis group showed a predominant retrograde pattern whereas the control group showed a normal antegrade. CONCLUSION This abnormal cervix-to-fundus myometrial activity could well increase the amount of peritoneal shedding of endometrial menstrual debris, increasing the probabilities of its heterotopic implantation.

Alobar holoprosencephalic embryo detected via transvaginal sonography

The incorporation of high-frequency transvaginal probes in commercial ultrasonic equipment allows now for the earlier detection of fetal malformations and the possibility of interrupting pregnancy when such an anomaly is incompatible with postnatal life. We describe here a case of alobar holoprosencephaly associated with serious facial anomalies, diagnosed via transvaginal sonography during the 10th week of amenorrhea. A cytogenetic study was carried out by transabdominal chorial biopsy and diagnostic confirmation by necropsy was made after termination. In order to be able to counsel patients on the advisability of future pregnancies we stress the importance of making a cytogenetic study of the embryo.

Extended regimens of combined hormonal contraception to reduce symptoms related to withdrawal bleeding and the hormone-free interval: A systematic review of randomised and observational studies

Abstract Objective To assess whether continuous and extended regimens (CRs/ERs) of combined hormonal contraceptives (CHCs) improve symptoms related to withdrawal bleeding or the hormone-free interval and to compare the efficacy, safety, and cost of CRs/ERs to those of conventional 28-day regimens. Study design A literature search of the PubMed database was conducted for randomised clinical trials (RCTs) and observational studies published in any language between 2006 and 2013. Results Sixteen RCTs and 14 observational studies evaluated issues related to our objectives. CRs/ERs, whose efficacy and safety were comparable to those described for conventional regimens, were preferred due to their improvement of symptoms related to withdrawal bleeding or the hormone-free interval and the lower costs resulting from the reduced incidence of these symptoms. Conclusion The contraceptive efficacy and safety of CR/ER use of CHCs is at least equal to that of 28-days conventional regimens, and this use may have some cost savings. CRs/ERs are recommended for women willing to take a CHC for treatment of symptoms related to withdrawal bleeding or the hormone-free interval. Chinese Abstract 摘要 目的 评估复方激素类避孕药（CHCs）连续与扩展周期给药方案能否改善撤 退性出血或停药期间的相关症状，并且与常规28天治疗方案相比较 其有效性、安全性及花费情况。 实验设计 对2006年-2013年间以任何语言发表在Pubmed数据库的随机临 床实验（RCTs）和观察性研究进行文献检索。 结果 针对研究目标，我们对16组随机临床实验和14组观察性研究进行 了评估。在有效性和安全性方面，连续/扩展周期给药方案优于常规方 案，主要是由于撤退性出血或是停药期间相关症状的改善以及由 此导致的成本降低。 结论 复方激素避孕药连续/扩展周期给药方案，其避孕的有效性和安全性至 少与28天常规给药方案等同，并可能节约一定的成本。

Lowering the age at menarche and risk of early menarche in a population of Spanish postmenopausal women during the past two decades.

Aim. The purpose of this study is to confirm in our population the decreasing secular trend in the age of menarche (AAM) observed in other European countries. Another aim is to investigate the association between early menarche and breast cancer, metabolic disorders risk or early menopause. Materials and Methods We conducted a nationwide population-based study of 1980 Caucasoid Spanish postmenopausal women from 2003 to 2006 to investigate the AAM, the duration of the fertile period and the relation of early menarche with breast cancer and some metabolic disorders. Results Regression analysis of AAM demonstrates a trend towards the younger AAM in our population during the past decades (P > 0.001). Parallel to this decrease we observe a significant increase in the fertility period and the height of our population (P < 0.001). In the women with AAM less than 11 years, there is an increased risk of hypercholesterolaemia, being overweight and obesity. However, early menarche does not raise the risk of adult onset diabetes, hypertension or breast cancer. Conclusions These data indicate a decreasing secular trend of AAM in a Spanish population in the last decades. Furthermore, hypercholesterolaemia and obesity, but not breast cancer, appears to be influenced by younger AAM. Only women who have their menarche at the age of nine years or less are more likely to have an earlier menopause.

Multigenic combination of estrogen-related genes is associated with age at natural menopause in a Spanish population

Objective Age at natural menopause (ANM) can be considered a complex parameter that depends on the interaction of multiple factors. In the present study, the role of interaction between genetic variants within estrogen synthesis and signalling pathways in the ANM in Spanish women is studied. Material and methods Nine single nucleotide polymorphisms (SNPs) located at different candidate genes related to the estrogen signalling pathway were analysed in 1980 Spanish postmenopausal women. Results Independently, none of the nine markers were significantly associated with early ANM. Only heterozygosis at the NRIP rs2229741 locus could be associated with early menopause; however, this marker does not maintain statistical significance. In contrast, linear regression analysis suggests several epistatic interactions including these markers in relation to ANM, especially between ESR2, NRIP1 and BMP15. The genetic variant that appears most in these interactions is that of the BMP15 rs3897937. It was observed that AA-TC combined genotype for NRIP-BMP15 (rs3897937), respectively, appears to be associated with a lower ANM than other possible combinations of these SNP (46.1±5.9 versus 50.4±3.3; P = 0.002). In the multilocus analysis, the multigenic interaction formed by ESR2 (AA), BMP15 rs3897937 (TC) and NRIP1 (AA) has the lower ANM (45.37±6.8 versus 48.69±5; P = 0.038). Conclusions The results suggest that epistatic interactions of estrogen-related alleles may contribute to variance in ANM in Spanish women. Moreover, BMP15 and NRIP1 also appear as attractive candidate genes for premature menopause but require further investigation to confirm them.

Transvaginal sonographic evaluation of subendometrial–myometrial contractility in women using a copper-releasing intrauterine device

BACKGROUND The aim of this study was to determine the effects of a copper-releasing intrauterine device (IUD) on myometrial contractility midway through the menstrual cycle. STUDY DESIGN Uterine peristalsis was studied midway through the cycle with transvaginal sonography in two groups of women, a control group and women in whom a copper-releasing IUD had been inserted. RESULTS The results showed that 12 months after insertion, no uterine motility could be detected with sonography in any of the women with an IUD, but motility did occur in all the controls. CONCLUSIONS Subendometrial-myometrial contractility midway through the menstrual cycle had been abolished in patients with a copper-releasing IUD. The loss of motility may inhibit sperm transport from the cervix to the oviduct and account for at least part of the contraceptive effect of these devices.

Spanish consensus on vulvar disorders in postmenopausal women

INTRODUCTION The consequences of vulvar disorders in terms of health, sexuality, and quality of life are usually undervalued, with disparities in the conceptual, diagnosis and treatment criteria. AIM The objective of this guide will be to analyse the factors associated with the diagnosis and treatment of vulvar disorders and to provide recommendations for the most appropriate diagnostic and therapeutic measures. METHODOLOGY A panel of experts from various Spanish scientific societies related to sexual health (Spanish Menopause Society [SMS] and the Asociación Española de Patología Cervical y Colposcopia [AEPCC]) met to reach a consensus on these issues and to decide the optimal timing and methods based on the best evidence available. RESULTS We recommend a biopsy of all vulvar lesions with an uncertain diagnosis, especially with asymmetry, irregular borders, variegated and irregular colour and diameter >6mm. For vulvodynia, we recommend the use of lubricants or topical treatments with lidocaine or bupivacaine, amitriptyline, baclofen or triamcinolone. For vulvar epithelial disorders, we recommend beginning with topical corticosteroids of moderate to high potency. For sexual dysfunction, a multidisciplinary approach is the best management strategy in these patients.