Fat intake pattern in women with polycystic ovary syndrome.

RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have a different fat intake pattern to women without PCOS? DESIGN: Case-control study of 276 women between 20 and 35 years old from the Murcia region of Spain. Cases (n = 121) attended the Department of Gynaecology and Obstetrics of the University Clinical Hospital and were diagnosed with PCOS using Rotterdam criteria. Controls (n = 155) were women without PCOS attending the gynaecological outpatient clinic for routine gynaecological examinations. Data from clinical, gynaecological and analytical examinations were collected, including a food frequency questionnaire. Associations between fat intake and presence of PCOS and its phenotypes were examined using multiple logistic regression, adjusting for potential confounding factors. RESULTS: Although no association was found between fatty acid intake and PCOS, significant associations were observed for some PCOS phenotypes. The PCOS phenotype characterized by hyperandrogenism + oligo/amenorrhoea + polycystic ovarian morphology ('H+O+POM') was significantly associated with a higher intake of polyunsaturated fat (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1-14.2; fourth quartile of highest intake [Q4] versus lowest intake quartile as reference [Q1]) and omega-6 fatty acids (OR 3.5; 95% CI 1.01-12.4; Q3 versus Q1). The 'H+O' phenotype was positively associated with saturated fat intake (OR 6.9; 95% CI 1.1-41.6; Q4 versus Q1). CONCLUSION: This exploratory study suggests that higher intakes of specific fatty acids are related to some PCOS phenotypes although no association was found for PCOS on a global basis. It is recommended that studies with larger sample size be performed to further explore these associations, thus contributing to establishing recommendations about fat intake adapted to different PCOS phenotypes.

Associations between urinary concentrations of bisphenol A and sperm DNA fragmentation in young men.

BACKGROUND: Bisphenol A (BPA) is one of the most common endocrine disruptor compounds in our environment, promoting a xenoestrogenic state. Numerous studies have shown a relationship between exposure to BPA and male infertility problems. Spermatic DNA integrity is a critical factor for the correct transmission of paternal genetic material to the embryo. However, only a very few studies have investigated the association between urinary BPA concentrations and human sperm DNA fragmentation (SDF). METHOD: Cross-sectional study conducted with 158 healthy university students (18-23 years), recruited between 2010 and 2011 in the Region of Murcia (Spain). The subjects provided urine and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection, and SDF analysed using the Sperm Chromatin Dispersion test. Statistical analyses were made using linear regression adjusting for potential covariates and confounding factors. RESULTS: No association was found between urinary BPA concentrations and SDF index in the total group. However, in the subgroup of men with SDF index> 30%, significant positive associations across quartiles (p-trend=0.02) and as a continuous BPA levels were observed (ß = 0.055, 95%, CI: 0.002; 0.108). CONCLUSION: Our results show that, within the subgroup of men with relatively high SDF index, the higher the concentration of BPA the greater the SDF index. Nonetheless, more studies are required to confirm these results and draw conclusions in other male populations.

Does the anogenital distance change across pregnancy?

RESEARCH QUESTION: Does the length of the anogenital distance (AGD), an anthropometric biomarker of fetal androgen exposure, change across pregnancy? It has been suggested that AGD remains stable during adulthood with no changes across the menstrual cycle. No studies, however, have been carried out during pregnancy, during which women are exposed to important hormonal and anthropometric variations. DESIGN: A cohort study of 186 singleton pregnant women recruited in the first trimester of pregnancy. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) and body mass index (BMI) were obtained in each trimester. Generalized linear model for repeated measures was carried out to assess differences in AGDs and BMI across the three trimesters of the pregnancy. RESULTS: In crude analyses, AGDAC was progressively and significantly longer as the pregnancy developed (first trimester: 87.69 ± 13.14mm; second trimester: 89.69 ± 13.47mm; third trimester: 91.95 ± 13.25 mm; P < 0.001), whereas AGDAF did not significantly change throughout pregnancy (first trimester: 28.37 ± 6.94 mm; second trimester: 28.09 ± 7.66 mm; third trimester: 28.94 ± 6.7 mm). In the multivariable mixed-effect models for fixed effect (trimester) and time-covariate (BMI), AGDs did not show significant associations with trimesters of pregnancy when BMI was included in the model. CONCLUSIONS: Our results suggest that AGDAF and AGDAC, when adjusted by BMI, do not change throughout gestation despite maternal anthropometric variations during pregnancy. AGDAF may be a meaningful measurement at any time during pregnancy without considering BMI. Therefore, maternal AGDAF may be used as a prenatal biomarker of the mother's in-uteru hormonal exposure even during pregnancy.

Health-related quality of life in women with polycystic ovary syndrome attending to a tertiary hospital in Southeastern Spain: a case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic condition with symptoms affecting many women at reproductive age and evaluating their health-related quality of Life (HRQoL) is an important issue. Moreover, differences in the HRQoL between women with different PCOS phenotypes have never been analyzed. Therefore, the aim of our study was to compare the HRQoL between women with PCOS -and its phenotypes- and controls attending to a tertiary hospital. METHODS: A group of 117 women with PCOS and 153 controls were studied between 2014 and 2016. Controls were women without PCOS attending the gynecological outpatient clinic for routine examinations. Cases were women attending the same setting and diagnosed with PCOS. PCOS diagnose was performed following the Rotterdam Criteria and women were further classified by anovulatory or ovulatory phenotypic subtype. Women underwent physical and gynecological exams and completed health questionnaires including the Short Form-12v2. Eight scales and two component summary scores [Physical (PCS) and Mental (MCS), respectively] were calculated. Bivariate and multivariate analyses were performed to assess differences in HRQoL between women with PCOS and controls. RESULTS: All women with PCOS and anovulatory PCOS presented lower score in PCS compared to controls [mean (95%CI): 53.7 (52.5-54.9) and 52.9 (51.5-54.4) vs. 55.8 (54.8-56.8); p-values< 0.01], as well as lower scores for five out of the eight scales (p-values < 0.05) after adjusting by age, body mass index, infertility, educational level and current occupation. No significant differences were observed for the MCS between women with or without PCOS or its phenotypic subtypes. CONCLUSIONS: HRQoL was significantly decreased in adult women with PCOS and its anovulatory phenotype compared to controls attending the outpatient clinic of a tertiary hospital. These results may have implications for the clinical practice and suggest the need for specific interventions in women with PCOS.

Adherence to diet quality indices in relation to semen quality and reproductive hormones in young men.

STUDY QUESTION: Is adherence to an a priori defined diet quality indices [Alternate Healthy Index 2010 (AHEI-2010), relative Mediterranean diet score (rMED) or dietary approaches to stop hypertension (DASH)] associated with semen quality and reproductive hormone levels in young men? SUMMARY ANSWER: Greater adherence to the DASH diet is related to higher sperm counts. WHAT IS KNOWN ALREADY: Studies assessing the relationship between dietary intake and male reproductive function have mainly been focused on specific nutrients, food groups or data-driven dietary patterns, but the evidence on a priori defined dietary indices is still scarce. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 209 male university students recruited from October 2010 to November 2011 in Murcia Region (Southern Spain). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy young men aged 18-23 years were included in this study. Diet was assessed using a validated food frequency questionnaire and three a priori-defined dietary indices (AHEI-2010, rMED and DASH) were calculated. Linear regression was used to analyze the relation between the three dietary indices and semen quality parameters and reproductive hormone levels accounting for potential confounders and covariates. MAIN RESULTS AND THE ROLE OF CHANCE: We found statistically significant positive associations between the DASH index and sperm concentration (P, trend = 0.04), total sperm count (P, trend = 0.04) and total motile sperm count (P, trend = 0.02). No associations were observed for other semen parameters or male reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: Even though we adjusted for several known and suspected confounders we cannot exclude the possibility of residual or unmeasured confounding or chance findings. Subjects were blinded to the study outcomes thus reducing the potential influence on their report of diet. Our sample size may be too small to rule out associations with other semen parameters or reproductive hormones. Causal inference is limited, as usual with all observational studies. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that greater adherence to the DASH may help improve sperm counts. This study was carried out on young men from the general population. However, results may differ among other populations (e.g. infertile men). Therefore, further research is needed to confirm these findings and extend these results to other populations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Fundación Séneca, grants No 08808/PI/08 and No 19443/PI/14; Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (AES), grants No PI10/00985 and No PI13/01237; and grant P30DK046200 from the National Institutes of Health. Authors have no competing interests to declare.

Are there differences in basal thrombophilias and C-reactive protein between women with or without PCOS?

RESEARCH QUESTION: Polycystic ovary syndrome (PCOS) women have increased cardiovascular risks, although it is unclear whether the haemostatic system and coagulation contribute to that increased risk. DESIGN: Women attending the Gynecology Unit of the 'Virgen de la Arrixaca' University Hospital (Murcia, Spain) for routine gynaecological examinations between September 2014 and May 2016 were assessed for PCOS using the Rotterdam criteria (hyperandrogenism [H], oligo/amenorrhoea [O] and polycystic ovarian morphology [POM]) and were classified into four phenotypic. In total, 126 cases were identified and 159 control women were selected. All women underwent physical and gynaecological examinations, and blood tests between the second and fifth day of the menstrual cycle. Differences in hormonal, basal thrombophilia and metabolic parameters, and C-reactive protein (CRP) between PCOS and controls were analysed. RESULTS: After adjusting by BMI and age, PCOS women had higher LH (P < 0.001), testosterone (P < 0.001), free testosterone (P = 0.01) and anti-Müllerian hormone (P < 0.001) and lower FSH (P = 0.03) compared with controls, whereas sex hormone-binding globulin was no different. Cases showed significantly higher protein S, glucose, insulin and insulin resistance (HOMA-IR) compared with controls (P < 0.05). There were no differences in protein C levels, antithrombin III, prothrombin time, homocysteine, D-dimer, factor V Leyden, prothrombin G20210A polymorphism or CRP. The H+O phenotype showed the poorest results for insulin and HOMA-IR (P = 0.04 and 0.05). CONCLUSIONS: The results suggest that there are no differences in the basal thrombophilias between women with and without PCOS. However, PCOS with H+O shows the poorest metabolic profile.

Meat intake in relation to semen quality and reproductive hormone levels among young men in Spain.

The aim of this study was to assess the associations of intake of different types of meat with semen parameters and reproductive hormones in healthy young men. This cross-sectional study included 206 men, 18-23 years, from Southern Spain. All men completed a validated FFQ, underwent a physical examination, and provided blood and semen samples. Multivariable linear regression was used to evaluate the associations between meat intake with semen quality parameters and reproductive hormones. Total meat intake was unrelated to semen quality or reproductive hormone levels. When subgroups of meat were separately considered, however, shellfish intake was positively related to progressive motility. The adjusted percentages of progressively motile spermatozoa for men in increasing quartiles of shellfish intake were 45·2, 42·0, 49·4 and 53·2 % with a significant linear trend across quartiles (P trend≤0·001). In contrast, men who consumed organ meats had significantly lower progressive sperm motility (51·5 v. 42·8 %; P = 0·001) and higher luteinising hormone levels (4·0 v. 4·6 IU/l; P = 0·03) compared with men who did not consume organ meats. Intake of shellfish and organ meats was low in this population, however. Given the scarcity of data on the relation between specific types of meat with semen quality and reproductive hormone levels, additional research is needed to confirm or refute these findings.

Assessment of anogenital distance as a diagnostic tool in polycystic ovary syndrome.

RESEARCH QUESTION: Is anogenital distance (AGD) a useful clinical tool for predicting polycystic ovarian syndrome (PCOS) and its main National Institutes of Health (NIH) phenotypes? DESIGN: Case-control study conducted between September 2014 and May 2016 at the Department of Obstetrics and Gynecology of the University Clinical Hospital 'Virgen de la Arrixaca' in the Murcia region (south-eastern Spain). One hundred and twenty-six cases of PCOS and 159 controls without PCOS were included. AGD measurements were taken from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Parametric and non-parametric tests and receiver operating characteristic (ROC) curves were used to assess associations between AGD and the presence of PCOS and its phenotypes. RESULTS: AGDAC, but not AGDAF, was associated with PCOS and all its phenotypes (P-values < 0.001 to 0.048). The highest area under the curve (0.62; 95% confidence interval 0.55 to 0.71) was obtained for all PCOS with AGDAC with a sensitivity and specificity of 50.0% and 73.0%, and positive and negative predictive value of 59.0% and 64.4%, respectively. CONCLUSIONS: AGDAC could moderately discriminate the presence of PCOS and may be a useful clinical tool.

Comparability between adult female anogenital distance and perineal measurements standardized by POP-Q system (GH and PB).

AIMS: Anogenital distance (AGD) has been proposed as a marker of the prenatal hormonal milieu and potential environmental insults. The measures of the Pelvic Organ Prolapse-Questionnaire (POP-Q) system is being widely used in the evaluation of the perineum in women with POP pathologies. Genital hiatus (GH) and perineal body (PB) lengths have been related to both prolapse incidence and recurrence and for pessary treatment failure. The use of AGD in female human studies is now emerging and its comparability with other anthropometric measurements could be relevant. The aim of the study was to compare AGD and POP-Q system in adult females. METHODS: The study included 155 pregnant women in the first stage of labor. Perineal measurements were performed on women in the lithotomy position: AGD from the anus to the clitoris (AGDAC ); AGD from the anus to the fourchette (AGDAF ); GH from the external urethral meatus to the posterior midline hymen, and length of the PB from the posterior midline hymen to the mid-anal opening. Coefficients of variations (CV) were calculated. Intraclass correlation coefficients (ICC) and Bland-Altman graphs were used to compare both set of measurements. RESULTS: CV were below 15% for AGDAC and GH + PB, though higher for AGDAF and PB (20% and 17%, respectively). ICCs for each pair of measurements were above 80%, (excellent agreement between methods). Concordance between measurements was confirmed by Bland-Altman graphs. CONCLUSIONS: Comparable measurements were obtained using AGDs and POP-Q system. Further studies are needed to explore clinical and epidemiological implications of these findings.

Urinary bisphenol A concentrations are associated with reproductive parameters in young men.

Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region). All subjects provided urine, blood serum and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, concentration, motility, morphology and total sperm count (TSC). Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B and estradiol. Relationships between urinary BPA concentrations and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders and covariates. Ninety-five percent of the men had detectable urinary BPA concentrations with unadjusted median (5th-95th) of 2.8 (0.16-11.5) ng/mL. After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (ß = 0.07, 95%CI: 0.02;0.12, p-value < 0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (ß = - 0.04, 95%CI: - 0.07;- 0.02, p-value < 0.01) and TSC (ß = - 0.05, 95%CI: - 0.08;- 0.02, p-value < 0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Our results support the hypothesis that BPA exposure may be associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm counts in young men.

Anogenital Distance, a Biomarker of Prenatal Androgen Exposure Is Associated With Prostate Cancer Severity.

BACKGROUND: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Experimental studies have shown that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The aim of this study is to assess the relationship between anogenital distance (AGD), as an indirect marker of prenatal hormonal environment, and prostate cancer (PCa) severity. MATERIALS: We conducted a cross-sectional study with a total of 120 PCa patients with confirmed biopsy of the tumour from April 2007 to July 2015. Two variants of the anogenital distance were assessed, from the anus to the posterior base of the scrotum (AGDAS ) and to the cephalad insertion of the penis (AGDAP ). We compared differences in groups to evaluate the association between AGD measurements and severity of the preoperative biopsy and clinical scores. RESULTS: Longer AGDAS was significantly associated with the highest Gleason score (P = 0.015) and D'Amico nomogram (P = 0.048). In contrast, no statistical differences were found in the AGDAP and severity of the preoperative biopsy. CONCLUSIONS: These findings are consistent with the hypothesis that a higher prenatal androgen exposure is associated with higher severity of PCa. Prostate 77: 406-411, 2017. © 2016 Wiley Periodicals, Inc.

Presence of polycystic ovary syndrome is associated with longer anogenital distance in adult Mediterranean women.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker of fetal androgen exposure, in adult Mediterranean women? SUMMARY ANSWER: Longer AGD is associated with PCOS in adult Mediterranean women. WHAT IS KNOWN ALREADY: AGD is a biomarker of prenatal androgen milieu. Human observational studies have reported that associations between AGD and reproductive parameters in both sexes. Exposure of the female fetus to intrauterine androgens may be a risk factor for PCOS in adulthood. STUDY DESIGN, SIZE, DURATION: This was a case-control study of 126 women with PCOS and 159 controls between September 2014 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases were attending the gynecology unit of the 'Virgen de la Arrixaca' University Clinical Hospital (Murcia, Spain), and were diagnosed following the Rotterdam criteria. Phenotypic subtypes of PCOS were also assessed. Both prevalent and incident (newly diagnosed) cases were included. Controls were women without PCOS attending the gynecological outpatient clinic for routine gynecological exams. All women completed health questionnaires, and underwent physical and gynecological examinations, including transvaginal ultrasound and blood draw. We obtained measures from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Gynecologists performing the AGD measures were blind to the status of the patients. We used unconditional multiple logistic regression to evaluate the association between AGD measurements and PCOS while accounting for relevant covariates and confounders, such as BMI, age and episiotomy. MAIN RESULTS AND THE ROLE OF CHANCE: Cases showed significantly longer AGDAF and AGDAC compared to controls in bivariate analyses (P-values < 0.05). In the final adjusted models, AGDAC, but not AGDAF, was associated with the presence of PCOS (P-values = 0.002-0.008). Women with AGDAC in the upper compared to the lowest tertile were 2.9-times (95% CI 1.4-5.9; P-trend = 0.008) more likely to have PCOS. AGDAC measures were also significantly associated with all of the different phenotypic subtypes of PCOS (ORs = 3.1-5.1; P-values < 0.05). LIMITATIONS REASONS FOR CAUTION: We took into account known and suspected covariates and confounders, but the possibility of chance findings or residual confounding should be noted. As with all observational studies, causal inference is limited, and study selection and information bias should not be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the hypothesis that PCOS has an intrauterine origin, and that the hormonal environment in which the fetus develops may be highly relevant. STUDY FUNDING/COMPETING INTEREST: This work was supported by the Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII) (AES, Acción Estratégica en Salud), grant No. PI13/01237, and The Seneca Foundation, Murcia Regional Agency of Science and Technology, grant No. 19443/PI/14. There are no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Investigation of anogenital distance as a diagnostic tool in endometriosis.

An association between anogenital distance (AGD) and endometriosis has been reported, suggesting that AGD may be a useful clinical tool in endometriosis. The predictive ability of AGD of women in discriminating presence and type of endometriosis was examined. A case-control study was conducted at the University Hospital 'Virgen de la Arrixaca', Murcia, Spain, between 2014 and 2015. A total of 114 participants diagnosed with endometriosis using ultrasound findings and 105 controls were recruited. Two AGD measurements were obtained: one from the anterior clitoral surface to the upper verge of the anus (AGDAC), and another one from the posterior fourchette to the upper verge of the anus (AGDAF). Parametric and non-parametric tests andreceiver operator characterstic analyses were used to determine relationships between AGD and presence of endometriosis and subgroups (ovarian endometriomas or deep infiltrating endometriosis [DIE]). The AGDAF, but not AGDAC, was associated with presence of endometriomas, DIE (P-values, <0.001-0.02), or both. The highest area under curve (0.91; 95% CI 0.84 to 0.97) was obtained for the DIE subgroup with the AGDAF measurement, with a sensitivity and specificity of 84.4% and 91.4%, respectively. AGDAF can therefore efficiently discriminate the presence of DIE and may be a useful clinical tool.

Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment.

STUDY QUESTION: Is the length of the anogenital distance (AGD), a biomarker of the in-utero prenatal hormonal environment, associated with the presence of endometriomas and deep infiltrating endometriosis (DIE)? SUMMARY ANSWER: Shorter AGD is associated with presence of endometriomas and DIE. WHAT IS KNOWN ALREADY: It is debated whether hormonal exposure to estrogens in utero may be a risk factor for endometriosis in adulthood. AGD is a biomarker of prenatal hormonal environment and observational studies have shown an association between AGD and reproductive parameters in both sexes. STUDY DESIGN, SIZE, DURATION: This case-control study of 114 women with endometriosis (endometriomas and/or DIE) and 105 controls was conducted between September 2014 and May 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases were attending the Endometriosis Unit of the Hospital. Prevalent as well as incident cases, diagnosed by transvaginal ultrasound (TVUS), were included. Controls were women without endometriosis attending the gynecological outpatient clinic for routine gynecological exams. Participants completed health questionnaires, followed physical and gynecological examinations, including TVUS. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) were obtained in all subjects. Unconditional multiple logistic regression was used to estimate the association between AGD measurements and presence of endometriomas and/or DIE while accounting for important confounders and covariates, including age, body mass index, vaginal delivery or episiotomy. MAIN RESULTS AND THE ROLE OF CHANCE: AGDAF was related to presence of endometriomas and/or DIE. For all cases of endometriosis (endometriomas and DIE), women in the lowest tertile of the AGDAF distribution, compared with the upper tertile, were 7.6-times (95% CI 2.8-21.0; P-trend < 0.001) more likely to have endometriosis. With regard to DIE, women with AGDAF below the median, compared with those with AGDAF above the median, were 41.6-times (95% CI 3.9-438; P-value = 0.002) more likely to have endometriosis. LIMITATIONS, REASONS FOR CAUTION: In case-control studies, information and selection bias has to be ruled out. Physicians conducting the measurement were blind to the status of the patients. Controls came from the same population as the cases. We adjusted for known and suspected confounders and covariates, but the possibility of residual confounding or chance findings should always be considered. As with all observational studies, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that endometriosis, especially the DIE, might have a prenatal origin that may be traced back to the hormonal milieu in which the fetus develops. STUDY FUNDING/COMPETING INTEREST: This work was supported by the Ministry of Economy and Competitiveness, ISCIII (AES), grant no. PI13/01237 and the Seneca Foundation, Murcia Regional Agency of Science and Technology, grant no. 19443/PI/14. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Associations between urinary organophosphate pesticide metabolite levels and reproductive parameters in men from an infertility clinic.

Organophosphate (OP) pesticides are compounds used for pest control at home or in agriculture activities. Almost all OP pesticides are metabolized to at least one of six possible dialkylphosphates (DAPs). Despite wide use, their potential effects on human reproductive health have not yet been fully characterized. The aim of this study was to evaluate the associations between urinary concentrations of six DAP metabolites and reproductive parameters in men. All men were attended an infertility clinic and provided urine, serum and semen samples on the same day. Six DAP metabolites were measured in urine (dimethylphosphate [DMP], dimethylthiophosphate [DMTP], dimethyldithiophosphate [DMDTP], diethylphosphate [DEP], diethylthiophosphate [DETP], and diethyldithiophosphate [DEDTP]). Sperm quality was assessed by measuring volume, concentration, total sperm count (TSC), motility and morphology, and serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin and estradiol. Pearson correlations were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. All men presented detectable concentrations of at least one urinary OP metabolite. After adjustment by important covariates, there was a significant positive association between DEDTP concentrations and LH [(ß)=11.4; 95% CI 0.81-22.1] as well as FSH levels [(ß)=3.2; 95% CI 0.08-6.2]. Sperm concentration and TSC were both significantly inversely associated with DMP, DMDP, DMDTP and ∑DAP in multivariate analysis. Besides, there was a significant inverse association between percentage of motile sperm and DMTP, DMDTP and DEP metabolite concentrations. Our results suggest that exposure to OP pesticides may be associated with decreased sperm counts and motility and altered reproductive hormone levels in male partners of couples seeking for infertility treatment. However, further studies are warranted to confirm and extent these findings.

Trans fatty acid intake is inversely related to total sperm count in young healthy men.

STUDY QUESTION: Is intake of fatty acids related to semen quality among young men? SUMMARY ANSWER: The intake of trans fatty acids is inversely related to total sperm count in healthy young men. WHAT IS KNOWN ALREADY: Spain has seen an increase in the proportion of calories consumed as fat over the same period that a downward trend in semen quality has been observed. In addition, rodent models suggest that trans fat intake may severely affect testicular function. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 209 men recruited between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 209 healthy young university students 18-23 years of age provided a semen sample and completed a previously validated food frequency questionnaire. The association between intake of fatty acids with semen quality parameters (sperm concentration, motility, morphology and total count) was assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF THE CHANCE: Trans fatty acid intake was inversely related to total sperm count after adjusting for potential confounders (P, trend = 0.03). The multivariate adjusted mean (95% confidence interval) total sperm count in increasing quartiles of trans fat intake was 144 (110-190), 113 (87-148), 100 (18-130) and 89 (69-117). There also was an inverse association between cholesterol intake and ejaculate volume (P, trend = 0.04). No other statistically significant relations were observed. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional design of the study limits causal inference, we cannot exclude the possibility of unmeasured confounding and there was insufficient statistical power to identify modest associations. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study, together with previous experimental work in rodents and biomarker studies among infertility patients, suggest that intake of trans fatty acids may be related to lower semen quality. Although the data provide further evidence that diet is a modifiable factor that could impact male fertility, it is not known whether the observed differences in sperm count translate into differences in fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Seneca Foundation, Regional Agency of Science and Technology, grant no 00694/PI/04, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (FIS), grant no PI10/00985, and grant P30 DK46200 from the National Institutes of Health. The authors have no competing interests to declare.

Anogenital distance of women in relation to their mother's gynaecological characteristics before or during pregnancy.

Animal models suggest that anogenital distance (AGD) at birth reflects androgen concentrations during in-utero development and predicts adult AGD. Several human observational studies show an association between menstrual cycle irregularities and a hyperandrogenic environment and that may result in a potential alteration of the female reproductive tract during in-utero development. This study examined associations between AGD of young women and their mother's gynaecological characteristics before or during pregnancy. This is cross-sectional study of 100 college-age volunteers in southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. Linear regression analysis was used to examine the association between AGD measurements (anus-fourchette (AGDAF) and anus-clitoris (AGDAC)) of women and their mother's gynaecological characteristics. Longer AGDAF was associated with the presence of mother's menstrual cycle irregularities before pregnancy (P=0.03). Longer female AGD has been related to excess androgen exposure in utero in toxicological studies. The current findings may be consistent with studies in which an association between menstrual cycle irregularities and an hyperandrogenic environment has been reported, which therefore may result in a potential modification of the female offspring's reproductive tract during in-utero development, including AGD. Rodent models suggest that perineal length at birth reflects male hormone concentrations (androgens) during in-utero development and predicts adult perineal length. Several human studies show a relationship between menstrual cycle irregularities and an excessive androgen environment. We hypothesize that androgen excess may result in a potential alteration of the female reproductive tract during in-utero development. Our aim was to examine associations between perineal length of young women and their mother's gynaecological characteristics before or during pregnancy. This is a study of 100 college-age volunteers in Southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. We used multivariate analyses to assess the association between perineal length of women and their mother's gynaecological characteristics. Longer perineal length was associated with the presence of mother's menstrual cycle irregularities before pregnancy. Longer female perineal length has been related to excess androgen exposure in utero in rodent studies. Our findings may be consistent with previous studies in which an association between menstrual cycle irregularities and an excess of androgen has been reported, which therefore may result in a potential modification of the female offspring's reproductive tract during in-utero development, including perineal length.

Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: A chemical mixtures approach.

People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of -5.5 % [95 % CI: -10.7, -0.3] for those in percentile 50, and - 5.4 % [95 % CI: -10.8, -0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.

The Spanish version of the reflective functioning questionnaire: Validity data in the general population and individuals with personality disorders.

INTRODUCTION: Mentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children's attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders. METHODS: 602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants. RESULTS: Exploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group. DISCUSSION: This study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders.

Dietary intake of antioxidant nutrients is associated with semen quality in young university students.

STUDY QUESTION: What are the associations between the dietary intake of antioxidant nutrients and semen parameters in young men? SUMMARY ANSWER: Our study suggests that some sperm parameters are sensitive to dietary intake of antioxidant nutrients. WHAT IS KNOWN ALREADY: A few reports have suggested that some dietary factors might be related to semen quality. However, the relationship between the intake of antioxidant nutrients and semen quality in young men remains unexplored. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, 215 young men were included between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy university students with complete dietary and semen quality data were analyzed. Dietary intake was recorded using a validated food frequency questionnaire. The associations between the energy-adjusted nutrient intake of antioxidants in quartiles and the semen volume, sperm concentration, sperm motility, sperm morphology, total sperm count and total motile sperm count were assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 240 students who contacted us, 223 (92.9%) were eligible to participate in this study, and 215 attended the clinical appointment. In the multivariate adjusted linear regression models, there was a positive association between dietary intakes of cryptoxanthin (P(trend) = 0.03), vitamin C (P(trend) = 0.04), lycopene (P(trend) = 0.03) and ß-carotene (P(trend) = 0.04) and total motile sperm count. The semen volume increased with higher intakes of vitamin C (P(trend) = 0.04). LIMITATIONS, REASONS FOR CAUTION: Only one sample of semen was taken for each subject. However, there are indications that one semen sample may be sufficient to characterize the semen quality of the individuals in epidemiological studies. Bias due to measurement errors may also occur since there is no perfect method to assess diet. However, any bias due to measurement error would be non-differential and would reduce, not increase, the strength of the associations. Although selection bias in cross-sectional studies might not always be ruled out, our subjects were university student volunteers who were rewarded for their participation and the study was not advertised as a fertility study. WIDER IMPLICATIONS OF THE FINDINGS: Previous articles in this area have focused mainly on men attending fertility clinics, thus our study brings generalizability to young men of the general population with unknown or untested fertility. Some of our results are in agreement with the previously reported papers.