Salivary testosterone measurement in women with and without polycystic ovary syndrome

Clinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P<001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI)(p<0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p<0.05) and insulin resistance(p<0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT(P<0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia

Metabolic comparison of polycystic ovarian syndrome and control women in Middle Eastern and UK Caucasian populations

© 2020, The Author(s). To determine if metabolic characteristics differed in women with and without polycystic ovary syndrome (PCOS) between a Caucasian and Middle East population. Comparative cross-sectional analysis. Demographic and metabolic data from Middle Eastern women from Qatar Biobank (97 with PCOS, 622 controls) were compared to a Caucasian PCOS biobank in Hull UK (108 with PCOS, 69 controls). In both populations, PCOS women showed a worse cardiovascular risk profile of increased systolic and diastolic blood pressure, increased C-reactive protein (CRP), reduced HDL, insulin resistance as well as increased androgens compared to their respective controls without PCOS. UK women without PCOS had higher systolic and diastolic blood pressures, and increased testosterone results (p < 0.01) compared to Middle Eastern women without PCOS who had higher inflammatory markers (WBC and CRP), HDL and insulin resistance (p < 0.001). UK PCOS women had a higher body mass index, systolic and diastolic blood pressures, triglycerides (p < 0.01), whilst Middle Eastern PCOS women showed increased testosterone, free androgen index, HDL and CRP (P < 0.01). There was no difference in insulin or insulin resistance between the two PCOS cohorts. This study highlights ethnic population differences because, whilst cardiovascular risk indices were increased for both PCOS cohorts, this may be for different reasons: BMI, waist and hip measurements, systolic and diastolic blood pressure, and triglycerides were higher in the UK cohort whilst testosterone, HDL and CRP were higher in the Middle East population. Insulin resistance did not differ between the two PCOS populations despite differences in BMI

Estimating Seroprevalence of Herpes Simplex Virus Type 1 among Different Middle East and North African Male Populations Residing in Qatar

HSV-1 epidemiology in the Middle East and North Africa (MENA) remains poorly understood. Our study aimed to measure HSV-1 antibody prevalence (seroprevalence) and its age-distribution among select MENA populations residing in Qatar. Sera were collected from male blood donors attending Hamad Medical Corporation 2013-2015. A total of 2,077 sera were tested for anti-HSV-1 antibodies using HerpeSelect® 1 ELISA IgG kits (Focus Diagnostics, USA). Robust Poisson regression was conducted to estimate adjusted infection prevalence ratios. Country-specific HSV-1 seroprevalence was estimated for 10 national populations: 97.5% among Egyptians, 92.6% among Yemenis, 90.7% among Sudanese, 88.5% among Syrians, 86.5% among Jordanians, 82.3% among Qataris, 81.4% among Iranians, 81.4% among Lebanese, 80.5% among Palestinians, and 77.0% among Pakistanis. Age-specific HSV-1 seroprevalence was estimated for Egypt, the Fertile Crescent (Iraq, Jordan, Lebanon, Palestine, and Syria), and Qatar. Seroprevalence increased with age among Fertile Crescent and Qatari nationals. Seroprevalence increased from 70.0% among those aged ≤24 years up to 98.0% among those aged ≥55 years among Fertile Crescent nationals. Seroprevalence was consistently above 90% for all ages among Egyptians. HSV-1 seroprevalence is high in MENA, though with some variation across countries. The seroprevalence appears to have declined among current young age cohorts compared to its levels a few decades ago

Salivary and serum androgens with anti-Müllerian hormone measurement for the diagnosis of polycystic ovary syndrome

To determine the predictive value of a raised androgen level with an elevated anti-Müllerian hormone (AMH) for the diagnosis or exclusion of polycystic ovary syndrome (PCOS), a prospective cross-sectional study of 170 women (105 with PCOS type A and 65 normal) was undertaken. AMH was combined with one of, total serum testosterone (T); calculated free androgen index; salivary testosterone (salT); serum androstenedione (A); salivary androstenedione (salA). The diagnostic sensitivity and specificity of AMH (>35 pmol/l) alone for PCOS were 55% and 79% respectively. The diagnostic sensitivity and specificity of AMH (>35 pmol/l) with either an elevated T or raised FAI level for PCOS showed 100% specificity and a 100% positive predictive value. Conversely, diagnostic exclusion of PCOS was shown by an AM

Herpes Simplex Virus Type 2 Seroprevalence among Different National Populations of Middle East and North African Men

© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association. Background There are limited data on herpes simplex virus type 2 (HSV-2) seroprevalence in the Middle East and North Africa (MENA). We examined country- and age-specific HSV-2 seroprevalence among select MENA populations residing in Qatar. Methods Sera were collected from male blood donors attending Hamad Medical Corporation between June 2013 and June 2016. Specimens were screened for anti-HSV-2 IgG antibodies following a 2-test algorithm: HerpeSelect 2 ELISA was used to identify HSV-2-positive specimens, and Euroline-WB was used to confirm positive and equivocal specimens for final HSV-2 status. Trends and associations with HSV-2 seropositivity were assessed. Results Of the 2077 tested sera, 61 were found and confirmed positive. The proportion of those confirmed positive increased steadily with HerpeSelect 2 ELISA index value, ranging from 16.3% for index values of 1.101 to 1.999 to 92.9% for index values of 4 or greater. Nationality-specific seroprevalence was 6.0% (95% confidence interval [CI], 4.1%-8.8%) in Qataris, 5.3% (95% CI, 2.5%-11.1%) in Iranians, 4.2% (95% CI, 1.8%-9.5%) in Lebanese, 3.1% (95% CI, 1.2%-7.7%) in Sudanese, 3.0% (95% CI, 1.4%-6.4%) in Palestinians, 2.2% (95% CI, 1.1%-4.3%) in Egyptians, 2.0% (95% CI, 1.0%-5.0%) in Syrians, 1.0% (95% CI, 0.3%-3.6%) in Jordanians, 0.7% (95% CI, 0.1%-3.7%) in Yemenis, and 0.5% (95% CI, 0.1%-2.8%) in Pakistanis. There was evidence for higher seroprevalence in older age groups. Conclusions The seroprevalence of HSV-2 was in the range of few percentage points. There were no major differences in seroprevalence by nationality. These findings add to our understanding of HSV-2 epidemiology in MENA and indicate unmet needs for sexual health and control of sexually transmitted infections.Funding text #1 From the *Infectious Disease Epidemiology Group, Weill Cornell Medicine—Qatar, Cornell University, Qatar Foundation—Education City; †Department of Biomedical Science, College of Health Sciences, and ‡BioMedical Research Center, Qatar University, Doha, Qatar; and §Department of Healthcare Policy and Research, Weill Cornell Medi-cine, Cornell University, Ithaca, NY Acknowledgments: The authors gratefully acknowledge the administrative support of Ms Adona Canlas. They are also grateful to Dr Asmaa Al-Marwani, Ms Maria Samatti, and Ms Sana Abohasera for their work on blood specimen collection. The authors are further grateful for sup-port provided by the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine—Qatar. Funding text #2 Funding: Testing kits were provided through pilot funding by the Biomedical Research Program at Weill Cornell Medicine—Qatar. Funding text #3 G.K.N. acknowledges support by Qatar University internal grant No. QUST-CHS-SPR-15/16-7. L.J.A. and S.R.D. acknowledge study conception and design support through NPRP grant number 9-040-3-008 from the Qatar National Research Fund (a member of Qatar Foundation), and G.K.N. acknowledges support from the Qatar National Research Fund UREP grant number UREP18-001-3-001. The findings achieved herein are solely the responsibility of the authors

The effect of high dose isoflavone supplementation on serum reverse T3 in euthyroid men with Type 2 Diabetes and post-menopausal women

Background: The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action.Materials and Methods: We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3′,5′-tri-iodothyronine; rT3) in two studies comprising 400 patients: 200 men (study 1; 3 months) and 200 post-menopausal women (study 2; 6 months) who were randomized to consume 15 g soy protein with 66 mg of isoflavones (SPI) daily, or 15 g soy protein alone without isoflavones (SP) daily.Results: SPI supplementation increased rT3 serum concentration in both men 0.41 (0.12) vs. 0.45 (0.14) nmol/L and women 0.33 (0.12) vs. 0.37 (0.09) nmol/L at 3 months compared to SP that was not seen at 6 months. Thyroid stimulating hormone (TSH) serum concentrations increased while free thyroxine (fT4) concentrations decreased with 3 months of SPI compared to SP supplementation for both men and women. rT3 correlated with TSH in both studies (p = 0.03) but not with either fT3 or fT4. fT3 levels did not differ between the SPI and SP preparations.Conclusion: Soy isoflavones transiently increased rT3 levels within 3 months though reverted to baseline at 6 months. The mechanism for this would be either rT3 degrading deiodinase 1 and/or deiodinase 2 activities are transiently inhibited at 3 months, or inhibition of deiodinase 3, which generates rT3 from T4 is induced at 6 months. These changes were mirrored in the TSH concentrations, suggesting that short-term high dose isoflavone transiently impairs thyroid function in the first 3 months and may impact on general health during this period

Soy isoflavones improve cardiovascular disease risk markers in women during 1 the early menopause 2 1

BackgroundHormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers.MethodsThe expected 10-year risk of cardiovascular disease and mortality were calculated as a secondary endpoint from a double blind randomised parallel study involving 200 women (mean age 55 years, Caucasian, Hull, UK, 2012) in the early menopause who were randomised to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (depleted of all isoflavones; SP) given as a snack bar between meals daily for 6 months. Age, diabetes, smoking, blood pressure and lipid profiles were used to calculate CVR using the Framingham CVR engine.ResultsSPI treatment resulted in a significant reduction in the metabolic parameters and systolic blood pressure compared to SP (p < 0.01). There were no changes in fasting lipid profile and diastolic blood pressure with either treatment. At 6 months, changes in these parameters with SPI treatment were reflected in a calculated 27% (p < 0.01) reduction in 10 year coronary heart disease risk, a 37% (p < 0.01) reduction in myocardial infarction risk, a 24% (p < 0.04) reduction in cardiovascular disease and 42% (p < 0.02) reduction in cardiovascular disease death risk.ConclusionsSupplementation with soy protein with isoflavones for 6 months significantly improved CVR markers and calculated CVR at 6 months during early menopause compared to soy protein without isoflavones

Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS

Background: Plasma elevated levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) have been associated with obesity and insulin resistance, but their relationship to stimulated insulin resistance (IR) in PCOS and in response to exercise is unknown. Indeed, it is unknown whether the mechanism of IR in PCOS is mediated through changes in the metabolome.Methods: Twelve women with polycystic ovary syndrome (PCOS) and ten age and body mass index matched controls completed an 8 week supervised exercise program at 60% maximal oxygen consumption. Before and after the exercise program, all participants underwent maximal IR stimulation with intralipid infusions followed by insulin sensitivity (IS) measurement by hyperinsulinaemic euglycaemic clamps. Amino acid profiles and metabolites were taken at baseline and at maximal insulin resistance stimulation before and after the exercise program.Results: At baseline, PCOS subjects showed increased leucine/isoleucine, glutamate, methionine, ornithine, phenylalanine, tyrosine and proline (p &lt; 0.05) that, following exercise, did not differ from controls. While compering within the groups, no significant changes in the amino acid levels before and after exercise were observed. Exercise improved VO2 max (p &lt; 0.01) but did not alter weight. Amino acid profiles were unaffected by an acute increase in IR induced by the lipid infusion. IS was lower in PCOS (p &lt; 0.001) and was further decreased by the lipid infusion in both PCOS and controls. Although, exercise improved IS in both PCOS and in controls, the IS remained compromised in PCOS.Conclusion: The baseline amino acid profile in PCOS reflected that seen in obese subjects and differed to controls. After exercise, and despite no change in weight in either group, there were no differences in the amino acid profile between PCOS and controls. This shows that exercise may normalize the amino acid metabolome, irrespective of weight.ISRCTN number: ISRCTN4244881

Expression of microRNA in follicular fluid in women with and without PCOS

© 2019, The Author(s). Several studies have shown the expression of small non-coding microRNA (miRNA) changes in PCOS and their expression in follicular fluid has been described, though the number of studies remains small. In this prospective cohort study, miRNA were measured using quantitative polymerase chain reaction (qPCR) in 29 weight and aged matched anovulatory women with PCOS and 30 women without from follicular fluid taken at the time of oocyte retrieval who were undergoing in vitro fertilization (IVF); miRNA levels were determined from a miRNA data set. 176 miRNA were detected, of which 29 differed significantly between normal women and PCOS women. Of these, the top 7 (p < 0.015) were miR-381-3p, miR-199b-5p, miR-93-3p, miR-361-3p, miR-127-3p, miR-382-5p, miR-425-3p. In PCOS, miR-382-5p correlated with age and free androgen index (FAI), miR-199b-5p correlated with anti-mullerian hormone (AMH) and miR-93-3p correlated with C-reactive protein (CRP). In normal controls, miR-127-3p, miR-382-5p and miR-425-3p correlated with the fertilisation rate; miR-127-3p correlated with insulin resistance and miR-381-3p correlated with FAI. Ingenuity pathway assessment revealed that 12 of the significantly altered miRNA related to reproductive pathways, 12 miRNA related to the inflammatory disease pathway and 6 were implicated in benign pelvic disease. MiRNAs differed in the follicular fluid between PCOS and normal control women, correlating with age, FAI, inflammation and AMH in PCOS, and with BMI, fertilization rate (3 miRNA), insulin resistance, FAI and inflammation in control women, according to Ingenuity Pathway Analysis

Increased MicroRNA Levels in Women With Polycystic Ovarian Syndrome but Without Insulin Resistance: A Pilot Prospective Study

© Copyright © 2020 Butler, Ramachandran, Cunningham, David, Gooderham, Benurwar, Dargham, Hayat, Sathyapalan, Najafi-Shoushtari and Atkin. Background: Small noncoding microRNA (miRNA) have regulatory functions in polycystic ovary syndrome (PCOS) that differ to those in women without PCOS. However, little is known about miRNA expression in women with PCOS who are not insulin resistant (IR). Methods: Circulating miRNAs were measured using quantitative polymerase chain reaction (qPCR) in 24 non-obese BMI and age matched women with PCOS and 24 control women. A miRNA data set was used to determine miRNA levels. Results: Women with PCOS showed a higher free androgen index (FAI) and anti-mullerian hormone (AMH) but IR did not differ. Four miRNAs (miR-1260a, miR-18b-5p, miR-424-5p, and miR let-7b-3p) differed between control and PCOS women that passed the false discovery rate (FDR) out of a total of 177 circulating miRNAs that were detected. MiRNA let-7b-3p correlated with AMH in PCOS (p < 0.05). When the groups were combined, miR-1260a correlated with FAI and let-7b-3p correlated with body mass index (BMI) (p < 0.05). There was no correlation to androgen levels. Ingenuity pathway analysis showed that nine of the top 10 miRNAs reported were associated with inflammatory pathways. Conclusion: When IR did not differ between PCOS and control women, only four miRNA differed significantly suggesting that IR may be a driver for many of the miRNA changes reported. Let-7b-3p was related to AMH in PCOS, and to BMI as a group, whilst miR-1260a correlated with FAI. Androgen levels, however, had no effect upon circulating miRNA profiles. The expressed miRNAs were associated with the inflammatory pathway involving TNF and IL6