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This article presents a rare case of postmenopausal hyperandrogenism, which is characterized by an excess of male hormones in women after menopause. The condition can be caused by various factors, including ovarian or adrenal neoplasia, Cushing's syndrome, or polycystic ovary syndrome. The article emphasizes the importance of thorough endocrine investigation and diagnostic tools such as serum hormone levels, imaging, and venous sampling. The case study discussed in the article highlights the challenges in diagnosing and localizing the source of hyperandrogenism and suggests the potential usefulness of venous sampling in certain patients. The study was conducted by a team of medical professionals, including radiologists, a histopathologist, an endocrine surgeon, and a gynecologist. [Extracted from the article]

Objective: As part of the update of the International Evidence‐Based Guidelines for the Assessment and Management of polycystic ovary syndrome (PCOS), a systematic review was performed to inform evidence‐based recommendations. Design: Systematic review. Only randomised controlled trial were included. Patients: Women with PCOS; the use of combined oral contraceptive pills (COCP) was compared with no medical treatment. Measurements: Outcomes were designed in collaboration with clinical experts, researchers, and consumers. Critical outcomes included hirsutism, irregular cycles, quality of life, body mass index (BMI), and weight. Results: 1660 publications were identified, but only four studies were included. No studies could be combined for meta‐analysis. COCP treatment improved cycle regularity compared with no medical treatment (100% vs. 0%, with low certainty of evidence). COCP showed no difference in improvement of hirsutism or BMI compared with placebo or lifestyle; a lower weight after COCP compared with no treatment (mean difference [MD] −8.0 (95% confidence interval, CI −11.67); −4.33 kg); and improvement in quality of life (MD 1.2 [95% CI 0.96]; 1.44), but these results were all very low certainty of evidence. Conclusion: Results show that COCP benefit cycle regulation, but other benefits or potential adverse effects were only identified with very low certainty of evidence. The COCP is frontline medical treatment in PCOS, but this is still based on established efficacy in the broader general population. Our results show that research in PCOS is seriously lacking and should be prioritised to capture core reproductive, metabolic and psychological outcomes important in PCOS. [ABSTRACT FROM AUTHOR]

Objective: A nonclassic form of 11β‐hydroxylase deficiency (NC11β‐OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11‐deoxycortisol (11‐DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11‐DOC level cutoffs. One of the accepted references for 11‐DOC levels for the paediatric population was published in 1991 by Lashansky et al. Aim: To determine the correlation between 11‐DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β‐OHD. Design: A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients' medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11‐DOC cut‐off levels according to Lashansky for sex and age, and according to commercial kit cut‐offs. Results: Data were complete at presentation for 136 patients. Long‐term clinical data were documented for 98 patients, mean follow‐up duration of 3.1 years (1.37–5.09). There was no statistically significant difference in the number of cases with elevated 11‐DOC according to both cut‐offs and early puberty, premature adrenarche nor acne. Follow‐up data demonstrated no statistically significant difference in the number of cases with elevated 11‐DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism. Conclusions: Basal and corticotropin stimulated 11‐DOC levels were not significantly elevated above the 1.5 times cut‐offs according to paediatric‐specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β‐OHD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of continuous (CA) and intermittent (IA) aerobic training on hormonal and metabolic parameters and body composition of women with polycystic ovary syndrome (PCOS). Design: Prospective, interventional, randomized study. Methods: Randomized controlled training (RCT) with sample allocation and stratification into three groups: CAT (n = 28) and IAT (n = 29) training and no training [control (CG), n = 30]. Before and after 16 weeks of intervention (CAT or IAT) or observation (CG), hormonal and metabolic parameters, body composition and anthropometric indices were evaluated. Aerobic physical training on a treadmill consisted of 30‐ to 50‐minute sessions with intensities ranging from 60% to 90% of the maximum heart rate. Results: In the CA group, there was reduction in waist circumference (WC) (P =.045), hip circumference (P =.032), cholesterol (P ≤.001), low‐density lipoprotein (P =.030) and testosterone (P ≤.001). In the IAT group, there was a reduction in WC (P =.014), waist‐to‐hip ratio (P =.012), testosterone (P =.019) and the free androgen index (FAI) (P =.037). The CG showed increases in WC (P =.049), total body mass (P =.015), body fat percentage (P =.034), total mass of the arms (P ≤.001), trunk fat percentage (P =.033), leg fat percentage (P =.021) and total gynoid mass (P =.011). Conclusion: CAT and IAT training reduced anthropometric indices and hyperandrogenism in PCOS, whereas only IAT training reduced the FAI. Furthermore, only CAT training improved the lipid profile. [ABSTRACT FROM AUTHOR]

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone‐insulin‐like growth factor‐1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH‐dependent and ACTH‐independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is a complex disorder with diverse metabolic implications. Diagnosis typically relies on oligo-amenorrhoea (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). However, the role of polymenorrhoea in PCOS remains understudied. Additionally, limited information exists regarding metabolic disturbances in women with partial PCOS phenotypes that do not meet diagnostic criteria. This extensive database aims to provide substantial evidence on the metabolic implications of polymenorrhoea and partial PCOS phenotypes., Design: Prospective observational study., Patients and Measurements: In this single-centre study, 6463 women with PCOS-like characteristics and 3142 age-matched healthy women were included. The study compared clinical (anthropometry, modified Ferriman Gallwey [mFG] score), hormonal (serum testosterone), and metabolic (plasma glucose, serum lipids, insulin) characteristics between women diagnosed with PCOS, those with partial PCOS phenotypes, and the healthy control group RESULTS: In all, 5174 women met Rotterdam criteria for PCOS diagnosis, while 737 were classified as Pre-PCOS, including HA (n = 538), OA (n = 121), or PCOM (n = 78). Common clinical features included oligomenorrhoea (75.5%), hirsutism (82.9%), obesity (27.2%), hypertension (1.6%), metabolic syndrome (19.6%), and diabetes mellitus (5.6%). Women diagnosed with PCOS, HA only, and OA only exhibited higher average body mass index, plasma glucose levels (both fasting and 2 h after the oral glucose tolerance test), and lipid fractions in comparison to those with PCOM and the healthy controls. However, indices of insulin resistance were similar among women with PCOS, HA, PCOM, and OA, albeit higher than in the healthy controls. The polymenorrhoea subgroup (5.9%) had lower BMI and serum testosterone, but similar mFG score, plasma glucose, insulin, and lipid levels as the oligomenorrhoea subgroup., Conclusion: The metabolic disturbances observed in Pre-PCOS women highlight the need to reassess diagnostic criteria. Including the polymenorrhoea subcategory in PCOS criteria is recommended due to similar metabolic dysfunctions as the oligomenorrhoea group., (© 2023 John Wiley & Sons Ltd.)

Summary: Objective: Hirsutism affects 5%‐10% of reproductive‐aged women worldwide and exhibits clinical importance as a cutaneous manifestation of underlying hyperandrogenism. Racial and genetic factors play roles in manifestation of hirsutism, and the prevalence of hirsutism seems to be low in East Asians. However, the reference value of the modified Ferriman‐Gallwey (mFG) score to diagnose hirsutism and the prevalence of hirsutism have not been determined in Korean populations to date. We aimed to investigate the distribution of the mFG score and establish its reference value for defining hirsutism and to examine its relationship with metabolic and reproductive traits in reproductive‐aged Korean women. Design, patients and measurements: We enrolled 2139 female volunteers of reproductive age (15‐39 years). We recorded mFG scores from 0 to 4 on 9 different body locations (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back and thighs). Hirsutism was defined as >95th percentile of mFG score. In addition, a 75‐g oral glucose tolerance test was performed, and the homoeostasis model assessment of insulin resistance (HOMA‐IR) was calculated. Results: The mFG values of the 50th, 75th, 90th and 95th percentiles were 0, 1, 4 and 6, respectively. Therefore, the mFG score was indicative of hirsutism when the score was 6 or greater, which represents the 95th percentile. In the correlation analysis, total testosterone, free testosterone, fasting plasma insulin and HOMA‐IR were positively correlated with mFG score (all Ps <0.05). Multiple linear regression analysis revealed that HOMA‐IR (β = 0.081) was positively associated with mFG score after adjustments for age, body mass index, total testosterone and the number of menses per year (P < 0.001). Conclusions: In conclusion, setting the 95th percentile of the mFG score as normal, the reference value to define hirsutism was 6 in reproductive‐aged Korean women. HOMA‐IR was positively associated with the mFG score even after adjustment for biochemical hyperandrogenism. [ABSTRACT FROM AUTHOR]

Summary: Objective: Polycystic ovary syndrome (PCOS) is associated with increased obesity with a greater propensity to weight gain and a lack of sustainable lifestyle interventions. Altered brown adipose tissue (BAT) thermogenesis is a potential contributor to obesity in PCOS. BAT activity and modulation have not been studied in PCOS. This observational study explored BAT thermogenesis and its associations in women with and without PCOS. Participants and methods: Cutaneous temperature was recorded from supraclavicular (indicator of BAT activity) and upper arm regions using dataloggers (SubCue, Calgary, Canada) in a cross‐sectional substudy, nested within a randomized control trial, of community‐recruited premenopausal women with (n = 47, Rotterdam diagnostic criteria) and without (n = 11) PCOS. Results: Complete temperature data were available in 44 PCOS (mean age: 30.0 ± 6.2, mean BMI: 29.3 ± 5.5) and 11 non‐PCOS (mean age: 33.0 ± 7.0, mean BMI: 25 ± 3) women. Women with PCOS had lower supraclavicular skin temperature compared to controls overall (33.9 ± 0.7 vs 34.5 ± 1, P < 0.05) and during sleep (34.5 ± 0.6 vs 35.2 ± 0.9, P < 0.001). In the PCOS group, supraclavicular skin temperature overall and over sleep and waking hours correlated inversely with testosterone (r = −0.41 P < 0.05, r = −0.485 P < 0.01 and r = −0.450 P < 0.01 respectively). Testosterone levels explained approximately 15%, 30% and 20% of the variability in supraclavicular skin temperature overall and over sleep and waking hours in women with PCOS, respectively. Conclusion: Women with PCOS have lower BAT activity compared to controls. BAT thermogenesis is negatively associated with androgen levels in PCOS. [ABSTRACT FROM AUTHOR]

Summary: Objective: The aim of this study was to develop a simple phenotypic algorithm that can capture the underlying clinical and hormonal abnormalities to help in the diagnosis and risk stratification of polycystic ovary syndrome (PCOS). Methods: The study consisted of 111 women with PCOS fulfilling the Rotterdam diagnostic criteria and 67 women without PCOS. A Firth's penalized logistic regression model was used for independent variable section. Model optimism, discrimination and calibration were assessed using bootstrapping, area under the curve (AUC) and Hosmer‐Lemeshow statistics, respectively. The prognostic index (PI) and risk score for developing PCOS were calculated using independent variables from the regression model. Results: Firth penalized logistic regression model with backward selection identified four independent predictors of PCOS namely free androgen index [β 0.30 (0.12), P = 0.008], 17‐OHP [β = 0.20 (0.01), P = 0.026], anti‐mullerian hormone [AMH; β = 0.04 (0.01) P < 0.0001] and waist circumference [β = 0.08 (0.02), P < 0.0001]. The model estimates indicated high internal validity (minimal optimism on 1000‐fold bootstrapping), good discrimination ability (bias corrected c‐statistic = 0.90) and good calibration (Hosmer‐Lemeshow χ2 = 3.7865). PCOS women with a high‐risk score (q1 + q2 + q3 vs q4) presented with a worse metabolic profile characterized by a higher 2‐hour glucose (P = 0.01), insulin (P = 0.0003), triglycerides (P = 0.0005), C‐reactive protein (P < 0.0001) and low HDL‐cholesterol (P = 0.02) as compared to those with lower risk score for PCOS. Conclusions: We propose a simple four‐variable model, which captures the underlying clinical and hormonal abnormalities in PCOS and can be used for diagnosis and metabolic risk stratification in women with PCOS. [ABSTRACT FROM AUTHOR]

Background and objective: While has been well demonstrated that clinical characteristics of polycystic ovary syndrome (PCOS) are associated with an impaired quality of life (QoL) in patients, it is unclear that whether the biochemical aspects of PCOS can influence their QoL. We aimed to investigate the relationship between clinical and biochemical characteristics, and various domains of QoL in patients with PCOS. Design: A cross‐sectional study. Patients and Measurements: We assessed the association between clinical and biochemical characteristics and QoL domains (psychosocial–emotional, fertility, sexual function, and obesity–menstrual) in a total of 211 women with PCOS using a specific health‐related quality‐of‐life questionnaire for PCOS patients. Results: Our findings showed positive significant association of QoL with age, and its negative significant associations with BMI, hirsutism and infertility (P < 0.05). We also found a negative association between FAI and total QoL (r = −0.14; P = 0.042) and domains of hirsutism (r = −0.14; P = 0.045) and obesity–menstrual (r = −0.23; P = 0.001). DHEAS was positively associated with the sexual function aspect of QoL (r = 0.20; P = 0.043). There were no significant associations between QoL and other hormonal parameters including LH to FSH ratio and total testosterone (tT). Significant associations were found between triglycerides (TG), total cholesterol (TC), LDL and HDL cholesterol, and domain of obesity–menstrual of QoL. HOMA‐IR was significantly related to all QoL domains except self‐image and hirsutism. Conclusion: Although biochemical markers can influence QoL in patients with PCOS, clinical manifestations of this syndrome such as obesity, infertility and hirsutism seem to play roles in worsening QoL, in particular for psychosocial domains. Hence, clinicians should regularly assess the clinical and psychosocial dimensions of PCOS as well as biochemical aspects. [ABSTRACT FROM AUTHOR]

Summary: Objective: The purpose of this narrative review was to summarize available data on testosterone levels in normal, healthy adult males and females, to provide a physiologic reference framework to evaluate testosterone levels reported in males and females with conditions that elevate androgens, such as disorders of sex development (DSD), and to determine the separation or overlap of testosterone levels between normal and affected males and females. Methods: A literature review was conducted for published papers, from peer reviewed journals, reporting testosterone levels in healthy males and females, males with 46XY DSD, and females with hyperandrogenism due to polycystic ovary syndrome (PCOS). Papers were selected that had adequate characterization of participants, and description of the methodology for measurement of serum testosterone and reporting of results. Results: In the healthy, normal males and females, there was a clear bimodal distribution of testosterone levels, with the lower end of the male range being four‐ to fivefold higher than the upper end of the female range(males 8.8‐30.9 nmol/L, females 0.4‐2.0 nmol/L). Individuals with 46XY DSD, specifically those with 5‐alpha reductase deficiency, type 2 and androgen insensitivity syndrome testosterone levels that were within normal male range. Females with PCOS or congenital adrenal hyperplasia were above the normal female range but still below the normal male range. Conclusions: Existing studies strongly support a bimodal distribution of serum testosterone levels in females compared to males. These data should be considered in the discussion of female competition eligibility in individuals with possible DSD or hyperandrogenism. [ABSTRACT FROM AUTHOR]

Summary: Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting reproductive‐aged women with adverse reproductive, metabolic and psychological outcomes. It has a complex pathophysiology and therefore requires a multidiscipline clinical approach. However, there remains limited research synthesizing the broad clinical implications of PCOS which would assist clinicians in the management of PCOS. Objective: To summarize and appraise methodological quality of systematic reviews and meta‐analyses evaluating complications and comorbidities associated with PCOS. Methods: A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15 September 2017. Article selection, data extraction and quality appraisal of included reviews using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the findings was conducted. Results: Twenty‐three reviews were included. All reviews were of low (n = 2) to moderate quality (n = 21). PCOS was associated with adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7), endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates many of these outcomes. Conclusions: There is a large body of reliable evidence for adverse metabolic outcomes and smaller, but consistent evidence for psychological issues in PCOS. We identified a shortage of systematic reviews regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the association between PCOS and subclinical hyperthyroidism, vitamin D levels and cancers which future studies could aim to address. [ABSTRACT FROM AUTHOR]

Summary: Objective: Episodes of acute adrenal insufficiency (AI)/adrenal crises (AC) are a serious consequence of congenital adrenal hyperplasia (CAH). This study aimed to assess morbidity from acute illness in CAH and identify factors associated with use of IV hydrocortisone, admission and diagnosis of an AC. Method: An audit of acute illness presentations among children with CAH to paediatric hospitals in New South Wales, Australia, between 2000 and 2015. Results: There were 321 acute presentations among 75 children with CAH. Two‐thirds (66.7%, n = 214) of these resulted in admission and 49.2% (n = 158) of the patients received intravenous (IV) hydrocortisone. An AC was diagnosed in (9.0%). Prior to presentation, 64.2% (n = 206) had used oral stress dosing and 22.1% (n = 71) had been given intramuscular (IM) hydrocortisone. Vomiting was recorded in 61.1% (n = 196), 32.7% (n = 64) of whom had used IM hydrocortisone. Admission, AC diagnosis and use of stress dosing varied significantly between hospitals. IM use varied from 7.0% in one metropolitan hospital to 45.8% in the regional hospital. Children aged up to 12 months had the lowest levels of stress dosing and IV hydrocortisone administration. Higher numbers of prior hospital attendances for acute illness were associated with increased use of IM hydrocortisone. Conclusion: Prehospital and in‐hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self‐management of CAH in the context of acute illness in educated patient populations. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study aimed at investigating the association of serum vitamin D (25(OH)D) and anti‐Mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) as well as non‐PCOS healthy ovulatory women and the possible confounding effects of adiposity and androgen. Method: This was a cross‐sectional study conducted on serum samples collected from 451 women diagnosed with PCOS as well as 244 age‐matched healthy ovulatory women in a tertiary gynaecology out‐patient clinic and a family planning clinic. Results: Serum 25(OH)D level was significantly higher in women recruited during summer and autumn than those recruited in winter and spring. Both serum 25(OH)D and AMH levels peaked during summer in women with PCOS. In ovulatory women, only serum 25(OH)D but not AMH level showed such seasonal variation. Serum 25(OH)D level in women with PCOS significantly correlated positively with AMH, AMH/antral follicle count (AFC) ratio, serum total testosterone, sex‐hormone‐binding globulin and quantitative insulin‐sensitivity check index and inversely with body mass index (BMI), insulin, triglycerides and homeostatic model assessment of insulin resistance. After controlling for BMI, 25(OH)D level remained significantly correlated positively with serum AMH, AMH/AFC and total testosterone, and inversely with triglycerides. 25(OH)D level was an independent predictor of serum AMH level after controlling for age, BMI and free androgen index in women with PCOS. Conclusion: Serum 25(OH)D level is an independent factor significantly associated with AMH level in women with PCOS but not in ovulatory women. [ABSTRACT FROM AUTHOR]

Summary: Objective: Insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic low‐grade inflammation may act together in a vicious cycle in the pathophysiology of PCOS. However, the inter‐relationships of these components are not fully understood. We aimed to study these mechanisms in the pathophysiology of PCOS. Participants and methods: Premenopausal women with PCOS (Rotterdam diagnostic criteria) and without PCOS were recruited from a community setting into a cross‐sectional substudy within a randomized control trial. Insulin resistance (fasting insulin and glucose), hyperandrogenism (testosterone, sex hormone‐binding globulin [SHBG] and Free Androgen Index [FAI]), muscle sympathetic nerve activity (MSNA) and markers of chronic low‐grade inflammation (high sensitivity C‐reactive protein [hs‐CRP] and high molecular weight adiponectin [HMW‐adiponectin]) were measured. Results: Forty‐nine women with PCOS (mean age 30 ± 6 mean BMI 29 ± 5) and 23 controls (mean age 29 ± 8 mean BMI 33 ± 7) with included in this analysis. MSNA and testosterone level were most significantly associated with PCOS status, after adjustment for age and BMI. In women with PCOS, markers of sympathetic activity correlated inversely with HMW‐adiponectin and HMW‐adiponectin correlated inversely with FAI. Testosterone and FAI both correlated positively with insulin resistance in women PCOS. Conclusion: Sympathetic dysfunction and hyperandrogenism are significantly associated with PCOS. Chronic low‐grade inflammation potentially mediates the effect of sympathetic dysfunction on hyperandrogenism and insulin resistance. [ABSTRACT FROM AUTHOR]

Summary: Background: Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown. Objective: To summarize and appraise the methodological quality of systematic reviews and meta‐analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS. Methods: A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted. Results: This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill (COCP) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions. Conclusions: There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCPs for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Although the Rotterdam 2003 polycystic ovarian syndrome (PCOS) diagnostic criteria is widely used, the need to consider multiple variables makes it unwieldy in clinical practice. We propose a simplified PCOS criteria wherein diagnosis is made if two of the following three items were present: (i) oligomenorrhoea, (ii) anti‐mullerian hormone (AMH) above threshold and/or (iii) hyperandrogenism defined as either testosterone above threshold and/or the presence of hirsutism. Design setting and participants: This prospective cross‐sectional study consists of healthy women (n = 157) recruited at an annual hospital health screen for staff and volunteers from the university community, and a patient cohort (n = 174) comprising women referred for suspected PCOS. Main outcome measures: We used the healthy cohort to establish threshold values for serum testosterone, antral follicle counts (AFC), ovarian volume (OV) and AMH. Women from the patient cohort, classified as PCOS by simplified PCOS criteria, AMH alone and Rotterdam 2003, were compared with respect to prevalence of oligomenorrhoea, hyperandrogenism and metabolic indices. Results: In healthy women, testosterone ≥1.89 nmol/L, AFC ≥22 follicles and OV ≥8.44 mL, best predicted oligomenorrhoea and were used as threshold values for PCOS criteria. An AMH level ≥37.0 pmol/L best predicted polycystic ovarian morphology. AMH alone as a single biomarker demonstrated poor specificity (58.9%) for PCOS compared to Rotterdam 2003. In contrast, there was a 94% overlap in women selected as PCOS by the simplified PCOS criteria and Rotterdam 2003. The population characteristics of these two groups of PCOS women showed no significant mean differences in androgenic, ovarian, AMH and metabolic (BMI, HOMA‐IR) variables. Conclusions: Our data recommend the simplified PCOS criteria with population‐specific thresholds for diagnosis of PCOS. Its ability to replace ovarian ultrasound biometry with the highly correlated variable AMH, and use of testosterone as a single marker for hyperandrogenaemia alongside the key symptoms of oligomenorrhoea and hirsutism confers significant clinical potential for the diagnosis of PCOS. [ABSTRACT FROM AUTHOR]

Summary: Although there is a growing body of literature reporting that pregnancies in women with polycystic ovary syndrome (PCOS) are associated with greater complications than those without PCOS, methodological differences across studies make these results difficult to consolidate. This narrative review outlines potential mechanisms involved in adverse pregnancy outcomes in PCOS and the nature of the complications. It covers limitations of current evidence and future research directions. Future research should include prospective studies with phenotypic stratification of PCOS and matching or consideration of specific PCOS manifestations and risk factors specific to each pregnancy complication. This review also emphasizes the importance of following a healthy lifestyle for women with PCOS and of individualized care according to overall risk factors for pregnancy complications. [ABSTRACT FROM AUTHOR]

Postmenopausal hyperandrogenism can be tumour- or non-tumour-related, with pathology residing either in the ovary or adrenal gland(s). The tempo of investigation is determined by the clinical severity of hyperandrogenism (presence/absence of actual virilisation) and degree of serum testosterone elevation. When clinical or biochemical hyperandrogenism is severe, rapidly developing, or associated with hypercortisolism, screening for adrenocortical or ovarian carcinoma with cross-sectional imaging should be prioritised over detailed biochemical evaluation. Adrenal hyperandrogenism is readily characterised, both biochemically and radiologically. By contrast, even a combination of high-resolution imaging with laboratory evaluation, including dynamic endocrine testing, often cannot distinguish between ovarian hyperthecosis (OH) and virilising ovarian tumour (VOT); a definitive diagnosis usually emerging only after histological examination of excised ovaries. VOTs are typically below the resolution-limit of current imaging modalities and exhibit suppression of gonadotropin-dependent androgen secretion with GnRH-analogue therapy. Thus, for well-characterised ovarian hyperandrogenism, laparoscopic bilateral salpingo-oophorectomy may serve both as a diagnostic and therapeutic procedure. Nevertheless, women unable or unwilling to undergo ovarian surgery can be reassured that malignant VOTs are exceedingly rare and that long-term medical therapy with oral antiandrogens or GnRH-analogues is safe and well-tolerated. OH is strongly associated with insulin-resistance, with hyperinsulinaemia acting synergistically with raised gonadotropin levels to stimulate thecal cell hyperplasia and androgen secretion by the postmenopausal ovary, which lacks granulosa cell aromatase activity and thus cannot convert testosterone to 17 beta estradiol. Thus, features of metabolic syndrome may indicate OH, and significant reductions in androgens can thereby potentially be achieved with lifestyle measures and/or insulin-sensitising drugs. [ABSTRACT FROM AUTHOR]

Objective To compare age-associated changes in cardiovascular risk markers in lean and obese reproductive-aged women with polycystic ovary syndrome ( PCOS) with community controls. Design Longitudinal study at an academic medical centre Patients Patients diagnosed with PCOS by 2004 Rotterdam criteria in a multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS cohort study and subsequently agreed to participate in a longitudinal study. The comparison controls were from the prospective, longitudinal Ovarian Aging ( OVA) study, which consists of healthy women with regular menstrual cycles recruited from 2006 to 2011. Measurements Cardiovascular risk markers and hormone parameters at baseline and follow-up. Results Obese and lean PCOS (n = 38) and control women (n = 296) completed two study visits. The follow-up time (3.5 ± 1.5 vs 4.0 ± 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m2/y [−0.11, 0.36] vs +0.26 [−0.18, 0.87] P = .19) did not differ between obese and lean PCOS and controls. In PCOS subjects, total testosterone decreased in both obese and lean, but the decrease was greater in obese subjects (−0.09 nmol/L per year; 95% CI: −0.16, −0.02 vs −0.04 nmol/L per year; 95% CI: −0.11, 0.03). Compared to their respective controls, obese and lean PCOS saw worsening triglyceride ( TG) levels ( P < .05) and HOMA- IR ( P < .05) over time, but there was no difference in change in LDL, HDL, fasting glucose, C-reactive protein or ALT. Conclusions In a longitudinal study, reproductive-aged women with PCOS demonstrated declines in biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced steeper increases in cardiovascular risk factors associated with insulin resistance, including triglycerides and HOMA- IR. [ABSTRACT FROM AUTHOR]

Objective Hyperandrogenism, hyperinsulinaemia and obesity, known characteristics of polycystic ovary syndrome ( PCOS), may influence bone mineral density and biochemical markers of bone turnover ( BTMs) can provide a noninvasive assessment of bone turnover. To this end, the serum concentrations of BTMs and 25-hydroxyvitamin D (25 OHD) were analysed in women with PCOS, and their possible associations with metabolic parameters of PCOS were determined. Subjects and methods Bone formation markers procollagen type I amino-terminal propeptide ( PINP) and osteocalcin ( OC), and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen ( CTX), along with 25 OHD, were measured in 298 women with PCOS and 194 healthy controls. Results Serum levels of PINP (47.0 ± 20.2 vs 58.1 ± 28.6 μg/L, P < .001) and OC (18.2 ± 7.5 vs 20.6 ± 9.8 μg/L, P < .001) were decreased in women with PCOS compared with controls, whereas no significant differences were found in CTX and 25 OHD levels. Age-stratified analyses suggested that PINP (50.5 ± 21.7 vs 68.2 ± 26.6 μg/L, P < .001) and OC levels (20.4 ± 7.6 vs 25.5 ± 9.6 μg/L, P < .001) were decreased only in the younger age group (≤30 years) women with PCOS compared with controls. The formation markers and resorption marker decreased with age in both study groups. Conclusions Bone formation markers were decreased in younger women with PCOS when compared with healthy women, which may affect bone mass in these women. [ABSTRACT FROM AUTHOR]

Objective Nonclassic congenital adrenal hyperplasia ( NCAH) is common among Ashkenazi Jews (1:400). It is associated with various degrees of postnatal virilization, irregular menses and infertility. Therapy of symptomatic subjects consists of physiologic doses of glucocorticoids. The objective of this study was to evaluate the effect of glucocorticoid treatment on fertility and on pregnancy outcome in women with NCAH. Design, Setting and Patients This retrospective study included 75 women diagnosed with NCAH who were followed in our clinic and sought fertility between 2008 and 2015. Results Seventy-two women succeeded in conceiving (187 pregnancies). Time to conception was 4.0 ± 7 months without and 3.3 ± 3 months with glucocorticoid therapy ( P = .43). Seventeen pregnancies were achieved by glucocorticoid therapy after failure to conceive spontaneously. Time to conception before therapy initiation was 10.2 ± 11.4 months compared to 3.3 ± 3.4 months after therapy initiation ( P = .02). Of 187 pregnancies, 135 (72%) resulted in live births, 38 (20.3%) ended in spontaneous miscarriages during the first trimester, seven (3.7%) were electively terminated, three (1.6%) were ectopic and four (2.1%) were ongoing during the study with similar rate in glucocorticoid treated and untreated pregnancies. Conclusions The 96% pregnancy rate among our cohort of NCAH females was similar to the 95% rate reported for the normal population. Glucocorticoid therapy may shorten the time to conceive in a subgroup of women with NCAH. Glucocorticoid therapy did not affect the rate of first trimester miscarriage. Our 77% live birth rate was similar to the 72% live birth rate in the current healthy US population. [ABSTRACT FROM AUTHOR]

Background/Objectives Polycystic ovary syndrome ( PCOS) is a heterogeneous disorder characterized by chronic anovulation, hyperandrogenism, polycystic ovary morphology ( PCOM) and metabolic disturbances including insulin resistance and type 2 diabetes mellitus. Although insulin resistance could be associated with PCOM, recent studies have shown controversial results. The aim of this study was to determine the relationship between PCOM and insulin resistance. Subjects/Methods This was a cross-sectional clinical study. A total of 679 women with PCOS who were diagnosed using the National Institute of Child Health and Human Disease ( NICHD) criteria and 272 control women were analysed. We measured fasting glucose and insulin levels, 75 g oral glucose tolerance test-derived glucose and insulin levels, testosterone levels, ovarian volume and follicle number. Results Polycystic ovary morphology was described in 543 women (80.0%) with PCOS. Women with PCOS had significantly higher 2 hours postload glucose, fasting and 2 hours postload insulin levels, ovarian volume, ovarian follicle numbers and lower insulin sensitivity compared with those of the controls (all P<.01). In women with PCOS, ovarian volume and ovarian follicle number were negatively associated with the quantitative insulin sensitivity check index after adjusting for age, body mass index and total testosterone; however, this association was not observed in the controls. In the logistic regression analysis, increased ovarian follicle number was associated with decreased insulin sensitivity in women with PCOS. Conclusions In PCOS, enlarged ovarian volume and follicle excess were associated with insulin resistance, and the number of ovarian follicles could be a predictor of insulin resistance. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome ( PCOS) is the most prevalent endocrine disorder in women of reproductive age. PCOS is associated with multiple comorbidities including, obesity, insulin resistance and type 2 diabetes, as well as mood disorders and impaired quality of life (QoL). Obstructive sleep apnoea ( OSA) is also a common medical condition that is often undiagnosed, particularly in women. OSA is associated with a similar spectrum of comorbidities to that observed in PCOS, including manifestations of the metabolic syndrome and impaired QoL, whilst obesity frequently constitutes a common denominator in the pathophysiology of both OSA and PCOS. Hence, it is not surprising that OSA and PCOS may coexist in women of reproductive age, and the current clinical guidelines on the management of PCOS recommend screening for OSA symptoms in overweight/obese women with PCOS. In this review, we examine the relationship between OSA and PCOS and explore the potential underlying mechanisms that link these two conditions. [ABSTRACT FROM AUTHOR]

Background and Objective A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism ( HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters ( BHPs) and Ferriman-Gallwey ( FG) score in patients with polycystic ovary syndrome ( PCOS). Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000-2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used. Results Fifty-five study groups with a total of 6593 PCOS patients were analysed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) ( P=.034) and dehydroepiandrosterone sulphate ( DHEAS) ( P=.012), whereas it showed no association with total testosterone ( tT), free testosterone ( fT), sex hormone bonding globulin ( SHBG) and free androgen index ( FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity. Conclusion This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome ( PCOS) is characterized by a combination of hormonal and metabolic disturbances, such as insulin resistance, glucose intolerance, anovulation and hyperandrogenism. Clinical phenotypes of PCOS show different patterns of steroid hormones that have been investigated to some extent. This study aimed to establish a liquid chromatography-tandem mass spectrometry ( LC- MS/ MS) method for the quantification of salivary testosterone and androstenedione and to describe the salivary testosterone-to-androstenedione (T/A4) ratio as a new tool for the assessment of hyperandrogenism and metabolic health. Material and methods Saliva and serum samples of 274 patients with PCOS and 51 healthy women were used for the quantification of steroid hormones. A comprehensive clinical and metabolic assessment was performed. Salivary testosterone and androstenedione were measured via LC- MS/ MS. The salivary T/A4 ratio was calculated and correlated with hormones and metabolic parameters. Results Salivary testosterone ( P < 0·001), androstenedione ( P < 0·001) and the salivary T/A4 ratio ( P < 0·001) were significantly higher in patients with patients compared to healthy women. In patients with PCOS, a high salivary T/A4 ratio was associated with an adverse metabolic phenotype, that is glucose intolerance ( P = 0·019), insulin resistance ( P < 0·001), metabolic syndrome ( P < 0·001), obesity ( P < 0·001) and oligo-/anovulation ( P = 0·001). Significant correlations of the salivary T/A4 ratio with adverse metabolic parameters were found. Conclusion Quantification of salivary androgens provides an attractive alternative to serum analysis and helps in characterizing metabolic health in women with PCOS. Our data show a strong link between a high salivary T/A4 ratio and an adverse metabolic phenotype in patients with PCOS. [ABSTRACT FROM AUTHOR]

Objective To examine the relationship between anti-Müllerian hormone ( AMH) and the severity of the phenotype of patients with polycystic ovary syndrome ( PCOS) and whether AMH can act as a diagnostic marker for PCOS? Design A prospective diagnostic utility study of AMH as a marker of PCOS. Patients A consecutive series of women presenting to a tertiary infertility clinic ( n = 164) plus a second series of women prepared for assisted conception treatments ( n = 89) recruited between June 2012 and May 2013. Measurements Polycystic ovary syndrome was diagnosed using the Rotterdam criteria. AMH was measured using the Generation II assay (Beckman Coulter). The diagnostic utility of AMH was established using receiver operator characteristic ( ROC) curves. Cut-off values for the individual features of PCOS are proposed. Results There was a significant difference in serum AMH concentration in women with normal ovaries (13·2 pmol/l), polycystic ovary morphology ( PCOM) alone (37·8 pmol/l) and PCOS (53·2 pmol/l). Follicle number, increasing cycle length and evidence of hyperandrogenism were all independently associated with serum AMH concentration ( P < 0·01). AMH was significantly affected by the different phenotypic presentations of PCOS with those with all components ( PCOM, HA and OA) having the highest mean value [72·7 pmol/l ( P < 0·01)]. Conclusions Serum AMH has the capacity to act as a diagnostic test for PCOS. Moreover, since its value rises with the more marked phenotypes, different cut-off values need to be used to differentiate those patients with polycystic ovarian morphology ( PCOM), hyperandrogenism ( HA) and oligoanovulation ( OA). [ABSTRACT FROM AUTHOR]

Objective Hyperandrogenism in congenital adrenal hyperplasia ( CAH) provides an in vivo model for exploring the effect of androgens on erythropoiesis in women. We investigated the association of androgens with haemoglobin (Hb) and haematocrit (Hct) in women with CAH. Design Cross-validation study. Patients Women with CAH from Sheffield Teaching Hospitals, UK (cohort 1, the training set: n = 23) and National Institutes of Health, USA (cohort 2, the validation set: n = 53). Measurements Androgens, full blood count and basic biochemistry, all measured on the same day. Demographic and anthropometric data. Results Significant age-adjusted correlations ( P < 0·001) were observed for Ln testosterone with Hb and Hct in cohorts 1 and 2 (Hb r = 0·712 & 0·524 and Hct r = 0·705 & 0·466), which remained significant after adjustments for CAH status, glucocorticoid treatment dose and serum creatinine. In the combined cohorts, Hb correlated with androstenedione ( P = 0·002) and 17-hydroxyprogesterone ( P = 0·008). Hb and Hct were significantly higher in cohort 1 than those in cohort 2, while there were no group differences in androgen levels, glucocorticoid treatment dose or body mass index. In both cohorts, women with Hb and Hct in the highest tertile had significantly higher testosterone levels than women with Hb and Hct in the lowest tertile. Conclusions In women with CAH, erythropoiesis may be driven by androgens and could be considered a biomarker for disease control. [ABSTRACT FROM AUTHOR]

Objective To investigate serum interleukin-1 receptor antagonist ( IL-1Ra) levels in women with polycystic ovary syndrome ( PCOS). Subjects and methods Serum IL-1Ra levels were measured at baseline in 73 women with PCOS and 45 control subjects (18-47 years), and in 27 women with PCOS who underwent oral and intravenous glucose tolerance tests ( OGTTs and IVGTTs). Results IL-1Ra concentrations predicted OGTT 2-h glucose levels independently of BMI and insulin resistance ( P ≤ 0·001) in women with PCOS. Serum IL-1Ra concentration was elevated in women with PCOS compared with controls [mean ( SD): 309·5 (208·8) vs 199·1 (81·4) ng/l, P < 0·001], but the difference disappeared after adjusting for BMI. An increment of five BMI units raised IL-1Ra levels by 108·5 ng/l [95% confidence interval ( CI): 85·5-131·5, r2 = 0·603] in women with PCOS and only by 77·0 ng/l (95% CI: 50·5-103·5, r2 = 0·512) in controls when adjusted for BMI and age. Levels of IL-1Ra in obese women with PCOS reflected decreasing OGTT-derived insulinogenic index ( P = 0·032) and disposition index ( P = 0·046) independently of BMI. Increased levels of IL-1Ra correlated with indices showing increasing insulin resistance and AUC insulin ( P ≤ 0·002). Conclusions Increased IL-1Ra levels in women with PCOS were largely explained by increasing adiposity. However, serum IL-1Ra concentrations predicted 2-h glucose levels independently of BMI suggesting that increased IL-1Ra may be associated with disturbed glucose metabolism. [ABSTRACT FROM AUTHOR]

Objective As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. Patients and methods Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25.4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5.1 and 29.9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. Results The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. Conclusion The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing. [ABSTRACT FROM AUTHOR]

Objective Polycystic ovary syndrome (PCOS) affects 12 21% of women. Women with PCOS exhibit clustering of metabolic features. We applied rigorous statistical methods to further understand the interplay between PCOS and metabolic features including insulin resistance, obesity and androgen status. Design Retrospective cross-sectional analysis. Patients Women with PCOS attending reproductive endocrine clinics in South Australia for the treatment of PCOS (n = 172). Women without PCOS (controls) in the same Australian region (n = 335) from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a national population-based study (age- and BMI-matched within one standard deviation of the PCOS cohort). Measurements The factor structure for metabolic syndrome for women with PCOS and control groups was examined, specifically, the contribution of individual factors to metabolic syndrome and the association of hyperandrogenism with other metabolic factors. Results Women with PCOS demonstrated clustering of metabolic features that was not observed in the control group. Metabolic syndrome in the PCOS cohort was strongly represented by obesity (standardized factor loading = 0.95, P < 0.001) and insulin resistance factors (loading = 0.92, P < 0.001) and moderately by blood pressure (loading = 0.62, P < 0.001) and lipid factors (loading = 0.67, P = 0.002). On further analysis, the insulin resistance factor strongly correlated with the obesity (r = 0.70, P < 0.001) and lipid factors (r = 0.68, P < 0.001) and moderately with the blood pressure factor (loading = 0.43, P = 0.002). The hyperandrogenism factor was moderately correlated with the insulin resistance factor (r = 0.38, P < 0.003), but did not correlate with any other metabolic factors. Conclusions PCOS women are more likely to display metabolic clustering in comparison with age- and BMI-matched control women. Obesity and insulin resistance, but not androgens, are independently and most strongly associated with metabolic syndrome in PCOS. [ABSTRACT FROM AUTHOR]

Objective The psychosocial implications of polycystic ovary syndrome (PCOS) phenotypes have been investigated in different patient populations, but little attention was paid to adolescent and young women. The aim of this study was to evaluate the psychosocial correlates of PCOS and other hyperandrogenic states in a population of late adolescent and young females and to provide a psychological characterization of specific clinical hyperandrogenic phenotypes. Design This was a cross-sectional study. Patients High school female students, aged 16 19 years. Measurements The study protocol was designed with three possible levels of participation characterized by an increased level of commitment. For the specific purposes of this investigation, we focused on the subsamples of students whose clinical state was assessed by medical examination (n = 835) and for whom additional laboratory tests were available (n = 394). Psychological evaluation encompassed psychological distress, levels of stress, well-being, illness behaviour and quality of life (as measured by the Symptom Questionnaire, the Psychosodal Index and the Psychological Well-Being scales). Results Significantly higher levels of psychological distress and impaired well-being and quality of life were found among late adolescent and young women with isolated clinical hyperandrogenism compared to their normal counterparts. Furthermore, females with PCOS showed significantly greater hostility/irritability compared to healthy control subjects. Conclusions These findings highlight the importance of early recognizing and adequately managing psychological distress in such patients. [ABSTRACT FROM AUTHOR]

Keywords: complications; hyperandrogenism; menstruation disturbances; obesity; polycystic ovary syndrome; type 1 diabetes EN complications hyperandrogenism menstruation disturbances obesity polycystic ovary syndrome type 1 diabetes 265 266 2 07/30/21 20210801 NES 210801 In recent decades, improvements in type 1 diabetes (T1D) therapy have led to an increasingly positive outlook for persons living with this condition. Complications, hyperandrogenism, menstruation disturbances, obesity, polycystic ovary syndrome, type 1 diabetes. [Extracted from the article]

Objective PCOS is associated with obesity and insulin resistance. Efforts have focused on whether an abnormal energy homeostasis contributes to the development of obesity in these patients. There are conflicting results in the literature regarding whether women with PCOS have an altered basal metabolic rate ( BMR), thereby leading to difficulties in weight loss. The objective of this study is to compare basal metabolic rate ( BMR) in women with PCOS and controls. Design Cross-sectional study. Patients One hundred and twenty-eight PCOS patients diagnosed by original NIH consensus criteria and 72 eumenorrheic, non-hirsute controls were recruited from an academic medical centre. Measurements Assessment of BMR using the InBody portable bioelectrical impedance analysis ( BIA) device and insulin resistance by HOMA-IR indices. Results PCOS women were younger than controls. As expected, PCOS subjects had higher body mass index ( BMI), serum androgens and estimated insulin resistance. After adjusting for age and BMI, there was no significant difference in BMR between PCOS subjects (adjusted mean 5807 kJ/day, 95% CI 5715-5899) and controls (adjusted mean 5916 kJ/day, 95% CI 5786-6046) ( P = 0·193). BMR was also comparable in a secondary analysis comparing PCOS women with and without insulin resistance. Conclusions After adjusting for age and BMI, there was no difference in BMR between PCOS women and controls. [ABSTRACT FROM AUTHOR]

Objective To compare insulin resistance ( IR) and metabolic characteristics of different phenotypes of polycystic ovary syndrome ( PCOS) and healthy controls in a representative sample of reproductive-aged Iranian women. Design Cross-sectional community-based study. Patients Of 915 participants, 136 met Rotterdam criteria for PCOS and were divided in four subgroups: ovulatory dysfunction with polycystic ovaries (Anovu + PCO), hyperandrogenism with PCO ( HA + PCO), hyperandrogenism with ovulatory dysfunction ( HA + Anovu) and full Rotterdam ( HA + Anovu + PCO). Also 423 subjects served as normal controls, and the rest of participants were analysed as isolated HA, Anovu or PCO subgroups. Measurements Anthropometric measures, biochemical parameters and IR were compared between different groups. IR was defined using the homeostatic model assessment- IR ( HOMA- IR). Results Overall prevalence of IR in PCOS and normal women were 26·5% and 23·9%, respectively ( P = 0·03). After age and BMI adjustment, there was no difference regarding metabolic characteristics between different PCOS phenotypes. Also metabolic characteristics, fasting insulin and HOMA- IR were comparable in PCOS subjects with hyperandrogenism and the nonhyperandrogenic phenotype (Anovu + PCO). In regression analysis, only overweight and obesity ( BMI ≥ 25 kg/m2) had an independent association with IR ( OR: 2·49, CI: 1·06-5·82, P = 0·03). Conclusions In a representative sample of an Iranian PCOS population, there is no significant difference between different PCOS phenotypes or between PCOS women and normal subjects regarding their metabolic characteristics. These findings suggest that overall metabolic screening may not always be required for all women diagnosed with PCOS. Larger-scale population-based studies are needed to further assess these issues. [ABSTRACT FROM AUTHOR]

Objective Quality of life is impaired in polycystic ovary syndrome ( PCOS). In this study, we compared the time to first prescription of antidepressants ( ADM) in PCOS vs two control groups. Design Register-based cohort study. Patients One thousand and one hundred and twenty-four premenopausal women with hirsutism and/or PCOS, premenopausal women with hypertension ( HT, n = 301), and age- and sex-matched population controls (controls, n = 4110). Measurements Prescriptions for ADM on secondary care contacts from regional registers. Results The median age at cohort entry in PCOS, HT and controls was 29, 34 and 29 years, respectively. Among PCOS, HT and controls, 227 (20%), 74 (25%) and 633 (15%), respectively, had prescriptions of ADM. The median time to first prescription of ADM in the PCOS, HT and control cohorts was 6·8, 6·6 and 7·2 years, respectively. The adjusted hazard ratio for time to prescription of ADM for HT vs PCOS was 1·36 [95% CI (1·02-1·82)], P = 0·039, and for controls vs PCOS, it was 0·75 [95% CI (0·64-0·88)], P < 0·001. Within patients with PCOS, hyperandrogenism contributed significantly to the model, likelihood ratio test P = 0·009. The adjusted hazard ratio for hyperandrogenism vs no hyperandrogenism was 1·97 (1·12-3·45), P = 0·018. Conclusion Patients with PCOS had moderately but significantly decreased time to first prescription of ADM compared with age-matched healthy women, whereas patients with HT had the shortest time to prescription. In PCOS, prescription of ADM was associated with the presence of hyperandrogenism. [ABSTRACT FROM AUTHOR]

Objective To examine the association between glycaemic control, insulin resistance and hyperandrogenism on cardiac autonomic function in peripubertal girls with type 1 diabetes. Design Prospective, clinic-based study of 125 girls with diabetes and 46 age-matched nondiabetic girls. Measurements Heart rate variability ( HRV) parameters derived from a 10-min ECG recording using LabChart Pro were as follows: standard deviation of mean NN intervals ( SDNN), where NN = adjacent QRS complexes; root mean squared difference of successive NN intervals ( RMSSD) - estimates of overall HRV; and low-/high-frequency ( LF: HF) ratio - an estimate of the sympathovagal balance. Androgens and sex hormone binding globulin ( SHBG) were measured in girls with diabetes, and free androgen index ( FAI) calculated. HRV and anthropometry were measured in nondiabetic controls. Results Adolescents with diabetes (median age 15·1 years [13·3-16·0], diabetes duration 7·0 years [4·6-10·0] and median Hb A1c 8·4% [7·5-9·3]) had higher HR and lower HRV compared with controls. Using multivariate models in the diabetes group, higher HR was associated with higher Hb A1c, total daily dose insulin/kg body weight and systolic BP standard deviation scores ( SDS), whilst reduced HRV was associated with higher HbA1c ( SDNN, RMSSD and LF: HF ratio), lower SHBG ( SDNN and RMSSD) and higher weight SDS ( LF: HF ratio). Higher FAI was associated with higher HR and reduced HRV measures in the univariate analyses only. Conclusions In adolescent girls with diabetes, reduced HRV parameters are associated with worse glycaemic control, lower SHBG and higher weight SDS. SHBG should be considered in the cardiac risk models for this population. [ABSTRACT FROM AUTHOR]

Background Precocious adrenarche ( PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome ( PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age ( AGA) to healthy body mass index ( BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. Subjects and methods We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance ( HOMA- IR), insulin sensitivity index ( ISIcomp) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. Results Precocious adrenarche girls had greater height and bone age-adjusted uterine length ( UL; P = 0·01) and UL standard deviation score ( SDS) ( P = 0·02) than BMI-matched peers. Mean ovarian volume ( MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups ( P > 0·05). MOV and MOV SDS correlated with ISIcomp ( r = −0·683, P < 0·001; r = −0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance ( P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS ( R2 = 0·731, β = −4·784, P = 0·001). Conclusions Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS. [ABSTRACT FROM AUTHOR]

Objective Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea ( OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features. Design/Patients/Measurements A total of 1174 young women (aged 19-39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index ( ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome ( PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40-60 days). Results In normal-weight women ( BMI < 23 kg/m2), the degrees of insulin resistance and hyperandrogenaemia are the highest in PCOS and higher in severe OM compared with mild OM. In overweight or obese women, PCOS was more insulin resistant and hyperandrogenaemic, but there was no difference between severe and mild OM. After excluding PCOS, women with severe OM showed a twofold increased risk of metabolic syndrome compared with regular cycling women (odds ratio 2·4, 95% confidence interval 1·1-5·6). By linear regression analysis, a longer menstrual cycle length was associated with ISI after adjustment for age, BMI, metabolic risk factors and testosterone. Conclusions Women with a menstrual cycle length over 60 days should be more closely monitored for the metabolic syndrome than women with a menstrual cycle length of 40-60 days, even if they have no PCOS. [ABSTRACT FROM AUTHOR]

Objective To develop and internally validate a prognostic score to predict the risk of metastases or recurrence in patients with adrenal cortical carcinomas ( ACC). Design Clinical, laboratory and pathological data from 129 ACC patients, treated in a tertiary centre, were retrospectively reviewed. Results Using a multivariate binary logistic regression analysis, we developed a prognostic score with five covariates: a functional pattern other than isolated hyperandrogenism, a tumour size >7·5 cm, a primary tumour classified as T3/T4, the presence of microscopic venous invasion and a mitotic index >5/50 high-power fields. The prognostic score was calibrated according to the Hosmer-Lemeshow goodness-of-fit test ( P = 0·9329) and exhibited excellent overall performance (Brier score = 0·0738). Finally, the discriminatory ability of the model, determined by the area under the ROC curve ( AROC), was near perfect ( AROC, 0·9611; 95% CI, 0·92676-0·99552). The prediction model was internally validated with 200 bootstrap resamples and achieved excellent performance for estimating the risk of metastasis and recurrence in eight additional patients with apparently localized disease at diagnosis. Conclusion We developed and internally validated a prognostic score based on the clinicopathological data that are readily available to any attending physician. Our model can be used to accurately estimate the risk of unfavourable outcomes in ACC patients. This score could be beneficial for both patient counselling and the identification of patients in whom adjuvant mitotane is justified. [ABSTRACT FROM AUTHOR]

Objective To investigate the frequencies of three paraoxonase ( PON)1 polymorphisms in Greek polycystic ovary syndrome ( PCOS) and non- PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance. Design Case-control genetic association study. Setting University Hospital Endocrine Unit. Patients A total of 142 PCOS cases (NIH criteria) and 112 controls. Main Outcome Measure Genotyping of the c.-108C>T ( PON1-108), the c.163T>A ( PON1-55) and the c.575A>G ( PON1-192) polymorphisms and measurement of baseline androgen and insulin resistance profile. Results The PON1-108 TT and PON1-192 RR genotypes were more frequently encountered in the PCOS than in the control group. The PON1-192 R allele frequency was greater in the PCOS than in the control group. Comparing the PCOS and the control groups, statistical significances favoured a recessive and a dominant genetic model, respectively, for the single PON1-108 T and PON1-192 R alleles. Free Androgen Index ( FAI) levels were higher in patients with PON1-108 TT, whereas Testosterone, FAI and Dehydroepiandrosterone sulphate ( DHEAS) levels were higher in patients with PON1-192 RR than patients with the wild or the heterozygous genotype. Conclusions The decreased PON1 activity-associated PON1-108 TT and the PON1-192 RR genotypes are more frequently found in Greek PCOS women and are associated with hyperandrogenaemia. Hyperandrogenaemia must depend also on other genetic factors because the same genotypes were not associated with hyperandrogenaemia in the control group. Through identification of the involved polymorphisms, women with PCOS could potentially have a better therapeutic screening. [ABSTRACT FROM AUTHOR]

Context Bisphenol A, one of the highest-volume chemicals currently available, is known to act as endocrine disruptor and alters several metabolic functions, including inflammatory pathways. Elevated serum levels of bisphenol A have been found in women with polycystic ovary syndrome ( PCOS) and a role of low-grade chronic inflammation has been recently reported in the pathogenesis of this syndrome. Increased spleen volume, a reliable and stable index of chronic inflammation, was strictly associated with the severity of hepatic steatosis ( HS) in obese subjects, determining the so-called liver-spleen axis. Objective To evaluate the contribution of increased serum bisphenol A levels to low-grade chronic inflammation, HS and hyperandrogenism in women with PCOS. Design, setting and participants Forty lean and overweight/obese premenopausal women with PCOS and 20 healthy age-matched women were consecutively enrolled in a cross-sectional study from 2009 to 2011 at the Federico II University Hospital in Naples. Measurements Bisphenol A, homoeostasis model assessment of insulin resistance ( Ho MA- IR), laboratory liver tests, testosterone, sex hormone-binding globulin, free androgen index ( FAI), C-reactive protein, interleukin-6, and the ultrasound quantification of HS and spleen longitudinal diameter. Results Independently of body weight, higher bisphenol A levels in PCOS women were associated with higher grades of insulin resistance, HS, FAI and inflammation, spleen size showing the best correlation. At multivariate analysis, spleen size and FAI were the best predictors of bisphenol A (β coefficients 0·379, P = 0·007 and 0·343, P = 0·014, respectively). Conclusions In premenopausal women with PCOS, we evidenced an association of serum bisphenol A levels with HS and markers of low-grade inflammation, in particular with spleen size, unravelling the presence of the liver-spleen axis in this syndrome. [ABSTRACT FROM AUTHOR]

Objective Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders ( PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome ( PCOS) are at higher risk of PDDs. Design Longitudinal case-control study. Patients Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby. Measurements Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children's versions of the Autism- Spectrum Quotient ( AQ- C), the Empathy Quotient ( EQ- C) and Systemizing Quotient ( SQ- C) tests were administered. Results Total AQ- C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ- C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ- C and SQ- C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy non- PCOS controls. AQ- C, EQ-C and SQ- C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels. Conclusions Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common in women with polycystic ovary syndrome ( PCOS), with the 67-85% of women with PCOS having serum concentrations of 25-hydroxy vitamin D (25 OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25 OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population. [ABSTRACT FROM AUTHOR]

Objective To report genotype-phenotype correlation in a large cohort of patients. Context Study of the CYP21A2 gene in 866 unrelated chromosomes of 21-hydroxylase deficiency in Argentinean patients with classic and nonclassic (NC) forms of congenital adrenal hyperplasia (CAH). Methods Eleven most common mutations were analysed by allele-specific polymerase chain reaction, restriction fragment length polymorphism (RFLP) or southern blot analysis. Gene sequencing was performed when no mutation was detected in one allele or the genotype-phenotype correlation was lacking . Results The 11-most-common-mutation screening allowed for the detection of 88·1% of affected alleles (80·3% in the NC and 95·2% in the classic forms). p.V281L, IVS2-13A/C>G (In2) and gene deletions and large gene conversions were the most prevalent mutations. In2 (35·2%) in salt wasting (SW), p.I172N (37·3%) in simple virilizing and p.V281L (54·1%) in NC CAH were the most prevalent mutations within the clinical forms. In 7/15 p.P30L mutation alleles, a chimeric CYP21A1P/CYP21A2 gene [PromCYP21A1P; p.P30L] was detected, while 6/15 represented a single-nucleotide substitution, and in 2/15 linkage with mutations, p.[P30L; V281L] and [p.P30L; IVS2-13A/C > G; p.Q318X] was found. In two SW patients, a novel nonsense mutation, p.Q41X, was observed. In three p.V281L mutation patients, the phenotype was more severe than predicted by genotype. Sequence analysis revealed an intronic alteration in the allele carrying the p.V281L mutation [IVS2 + 5G > A; p.V281L]. An aberrant splicing in this p.V281L mutated allele explains the clinical phenotype. Conclusions A high percentage of CYP21A2 affected alleles is detected by the 11-mutation screening study. Genotype-phenotype correlation was high, but when the phenotype is more severe than predicted by genotype, presence of two alterations in one allele should be ruled out. [ABSTRACT FROM AUTHOR]