Evaluation of the Efficacy of Sex Hormone-Binding Globulin in Insulin Resistance Assessment Based on HOMA-IR in Patients with PCOS.

This study aimed to evaluate the efficacy of SHBG in predicting insulin resistance (IR) in newly diagnosed, untreated patients with polycystic ovary syndrome (PCOS). Hundred newly diagnosed, untreated patients with PCOS and 61 subjects without PCOS (41 healthy volunteers with normal BMI and 20 subjects with overweight/obese) were included in the study. Receiver-operating characteristic (ROC) analysis was used to assess the effectiveness of SHBG in predicting IR in overweight/obese and non-overweight PCOS patients and the optimal cut-off values of SHBG. The results showed negative correlations between log-SHBG and log-I0 (r = - 0.372, P < 0.001) and log-SHBG and log-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = - 0.393, P < 0.001) after adjusting for blood pressure, serum lipid, age, and body mass index (BMI) in all of the PCOS patients. In patients with IR (defined as HOMA-IR ≥2.29), the area under the ROC curves (AUCs) of the SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.774 (P = 0.0001), 0.922 (P = 0.0001), and 0.885 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 37 nmol/L with a sensitivity of 97.62% and specificity of 80.85% in the overweight group. In patients with IR (HOMA-IR ≥2.5), the AUCs of SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.741 (P = 0.0003), 0.928 (P = 0.0001), and 0.880 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 30.2 nmol/L with a sensitivity of 97.44% and specificity of 82.69% in the overweight/obese group. In conclusion, this study observed a negative correlation between SHBG and HOMA-IR in PCOS patients after adjustment of confounding factors. SHBG was an independent influential factor of HOMA-IR and can be used as a positive predictive marker for IR in PCOS patients, especially in those who are overweight/obese.

Maternal cholesterol levels during gestation: boon or bane for the offspring?

An increase in cholesterol levels is perceived during pregnancy and is considered as a normal adaptive response to the development of the fetus. In some pregnancies, excessive increase in total cholesterol with high levels of Low-Density Lipoprotein leads to maladaptation by the fetus to cholesterol demands, resulting in a pathological condition termed as maternal hypercholesterolemia (MH). MH is considered clinically irrelevant and therefore cholesterol levels are not routinely checked during pregnancy, as a consequence of which there is scarce information on its global prevalence in pregnant women. Studies have reported that MH during pregnancy can cause atherogenesis in adults emphasizing the concept of in utero programming of fetus. Moreover, Gestational Diabetes Mellitus, obesity and Polycystic Ovary Syndrome are potential risk factors which strengthen combined pathologies in placenta and fetuses of mothers with MH. However, lack of conclusive evidence on cholesterol transport and underlying programming demand substantial research to develop population-based life style strategies for women in their childbearing years. The current review focuses on the mechanisms and outcomes of MH from existing epidemiological as well as experimental data and presents a detailed insight on this novel risk factor of cardiovascular diseases.

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study.

BACKGROUND: To investigate the effectiveness and safety of 3 mg drospirenone and 20 µg ethinyl estradiol tablet (3 mg DRSP/20 µg EE) in the treatment of polycystic ovary syndrome (PCOS). METHODS: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 µg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated. RESULTS: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. CONCLUSIONS: Treatment of PCOS patients with3 mg DRSP/20 µg EE has shown beneficial hormonal and lipid profile along with considerable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022001, March 2019, retrospectively registered.

Prevalence of insulin resistance in Korean women with polycystic ovary syndrome according to various homeostasis model assessment for insulin resistance cutoff values.

OBJECTIVE: To investigate the various homeostasis model assessment for insulin resistance (HOMA-IR) cutoff values in a large population of healthy controls and to evaluate the prevalence of IR in women with polycystic ovary syndrome (PCOS). DESIGN: Case control study. SETTING: Reproductive endocrinology center. PATIENT(S): Women with (n = 699) and without PCOS (n = 572). INTERVENTION(S): Blood tests. MAIN OUTCOME MEASURE(S): The upper 75th and 95th percentiles of HOMA-IR in lean controls (n = 522) and the HOMA-IR cutoff that indicates metabolic risk in all participants. RESULT(S): HOMA-IR cutoffs of 1.82 and 3.16 were defined as above the 75th and 95th percentiles in lean controls, and the prevalence of IR in patients with PCOS was 60.7% and 24.5%, respectively. The optimal HOMA-IR for the diagnosis of metabolic syndrome was 2.64; thus, metabolic risk was increased at a lower level of HOMA-IR compared with the 95th percentile cutoff. At HOMA-IR cutoff of 2.64, 34.8% of patients with PCOS had evidence of IR. Metabolic features significantly differed between patients with PCOS with and without IR, and patients with PCOS without IR showed similar or more favorable metabolic features compared with controls. Overweight/obese patients are the most high-risk group, but lean patients also showed a similarly elevated prevalence of IR as overweight/obese controls. A positive correlation was observed between BMI and HOMA-IR in both patients and controls, but the magnitude was significantly greater in patients than in controls. CONCLUSION(S): Although IR is common in women with PCOS, it does not seem to be universal, and patients without IR had reassuring metabolic features.

Assessment of PON1 activity and circulating TF levels in relation to BMI, testosterone, HOMA-IR, HDL-C, LDL-C, CHO, SOD activity and TAC in women with PCOS: An observational study.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most common female endocrinopathy among premenopausal women associated with hyperandrogenism, obesity, dyslipidemia, insulin resistance and inflammation. Oxidative stress is an important component of cardio-metabolic risk seen in PCOS. MATERIAL AND METHODS: A total of 95 women with PCOS and 95 healthy controls were included in this observational study. Serum PON1 activity and stress markers were measured by spectrophotometric methods. Circulating TF level was measured by ELISA. RESULTS: We found decreased PON1 activity and increased TF levels in women with PCOS compared to healthy controls. Fasting insulin, HOMA-IR, testosterone, LDL-C, MDA, PC and SOD activity were significantly increased whereas FGIR, QUICKI, HDLC, CAT and TAC were significantly decreased in PCOS women than controls. We observed a positive association of PON1 activity with FGIR, QUICKI, HDL-C and TAC, and its negative association was observed with LH, testosterone, fasting insulin and HOMA-IR in PCOS women. We further observed a positive association of TF with waist, waist to hip ratio, BMI, glucose 1hr, cholesterol, LDL-C, SGPT, uric acid and SOD activity in PCOS women. CONCLUSIONS: Decreased PON1 activity and raised circulating TF levels are respective indicators of pro-inflammatory and procoagulant status in PCOS women. The imbalanced oxidant/antioxidant status further supports the evidences that PCOS is an oxidant state. Further, the association of PON1 activity and TF levels with the clinical, laboratory findings and stress marker levels suggest that these factors taken together are involved in aggravating the pro-inflammatory status in PCOS women.

Screening for a Simple and Effective Indicator of Insulin Resistance in Chinese Reproductive-Aged Women, with the Insulin Clamp Technique as a Reference.

Background: Applying the hyperinsulinemic-euglycemic clamp to estimate insulin resistance (IR) is accurate but time-consuming, so identifying a simple and effective index for IR is vitally important. The present study aimed to compare the lipid accumulation product (LAP), visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR), and Chinese visceral adiposity index (CVAI) using the hyperinsulinemic-euglycemic clamp as a reference and to screen a simple and effective indicator for IR in Chinese women of childbearing age. Methods: The present study included a cross-sectional study of 537 reproductive-aged women and an interventional study of 90 randomly chosen polycystic ovarian syndrome (PCOS) women. Physical, laboratory, and hyperinsulinemic-euglycemic clamp were completed, and the BMI, WC, LAP, VAI, CVAI, and HOMA-IR were calculated. A linear correlation and a receiver operating characteristic curve were performed. After intervention with metformin, the effects were estimated in the third month. Results: PCOS women had worse glycometabolism, serum lipid metabolism and IR, and higher prevalence rates of metabolic disorders than those without PCOS. The CVAI was strongly associated with the M value (r = -0.6953, P < 0.0001) and outperformed other parameters with the largest area under the curve (0.903) and Youden index (71.07%) for IR diagnosis in Chinese reproductive-aged women, and the diagnostic point was >28.5. After 3 months of metformin therapy, IR improved with remarkable increases in M value and reductions in the CVAI. Conclusion: The CVAI can be used as an appropriate surrogate indicator for the hyperinsulinemic-euglycemic clamp to identify IR in Chinese women of childbearing age. The interventional trial part of this study has been registered as a clinical trial (no. ChiCTR-IIR-16007901).

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome.

The purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615-0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

Assessment of oxytocin level, glucose metabolism components and cutoff values for oxytocin and anti-mullerian hormone in infertile PCOS women.

OBJECTIVE: Comparing oxytocin level and some other parameters between infertile women with or without polycystic Ovary Syndrome (PCOS), to evaluate the correlation between oxytocin with anti-mullerian hormone (AMH), Body Mass Index (BMI) and insulin resistance (IR). MATERIALS AND METHODS: This cross-sectional study was performed on 80 PCOS and 81 non-PCOS women as the control group. Oxytocin, various hormones, Oral glucose tolerance test (OGTT) and Homeostatic model assessment of insulin resistance (HOMA-IR) were compared between two groups. Correlations between parameters were assessed by the spearman's rank correlation coefficient. Cutoff values for oxytocin and AMH in PCOS were calculated by the ROC-Curve and DeLong method. RESULTS: The mean oxytocin level was statistically lower in the case group (p ≤ 0.001). The mean BMI, AMH, HOMA-IR, fasting insulin and insulin 2-h after 75-g glucose were significantly higher in the PCOS group. Oxytocin was negatively correlated to AMH when evaluated for all participants or only among controls. Moreover oxytocin was negatively correlated to HOMA-IR among all participants. However the relationship between oxytocin and BMI was not statistically significant. The calculated cutoff value for oxytocin was 125 ng/L and for AMH was 3.6 ng/mL in the PCOS group. CONCLUSION: The mean oxytocin level in the PCOS infertile women was lower than non-PCOS women. Oxytocin showed a significant reverse correlation with AMH and HOMA-IR.

Establishing the cut off values of androgen markers in the assessment of polycystic ovarian syndrome.

INTRODUCTION: Hyperandrogenism remains as one of the key features in Polycystic Ovarian Syndrome (PCOS) and can be assessed clinically or determined by biochemical assays. Hirsutism is the most common clinical manifestation of hyperandrogenism. The clinical assessment is subjected to wide variability due to poor interobserver agreement and multiple population factors such as ethnic variation, cosmetic procedures and genetic trait. The difficulty in resolving the androgen excess biochemically is due to a lack of consensus as to which serum androgen should be measured for the diagnosis of PCOS. The aim of the study was to compare and establish the diagnostic cut off value for different androgen biomarker for the diagnosis of PCOS. MATERIALS AND METHODS: A total of 312 patients classified to PCOS (n = 164) and non PCOS (n = 148) cohorts were selected from the Laboratory Information System (LIS) based on serum total testosterone (TT) and sex hormone binding globulin (SHBG) from the period of 1st April 2015 to 31st March 2016. PCOS was diagnosed based on Rotterdam criteria. Clinical hyperandrogenism and ultrasound polycystic ovarian morphology were obtained from the clinical records. The other relevant biochemical results such as serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and albumin were also obtained from LIS. Free androgen index (FAI), calculated free testosterone (cFT) and calculated bioavailable testosterone (cBT) were calculated for these patients. Receiver Operating Characteristic (ROC) curve analysis were performed for serum TT, SHBG, FAI, cFT, cBT and LH: FSH ratio to determine the best marker to diagnose PCOS. RESULTS: All the androgen parameters (except SHBG) were significantly higher in PCOS patients than in control (p<0.0001). The highest area under curve (AUC) curve was found for cBT followed by cFT and FAI. TT and LH: FSH ratio recorded a lower AUC and the lowest AUC was seen for SHBG. cBT at a cut off value of 0.86 nmol/L had the highest specificity, 83% and positive likelihood ratio (LR) at 3.79. This is followed by FAI at a cut off value of 7.1% with specificity at 82% and cFT at a cut off value of 0.8 pmol/L with specificity at 80%. All three calculated androgen indices (FAI, cFT and cBT) showed good correlation with each other. Furthermore, cFT, FAI and calculated BT were shown to be more specific with higher positive likelihood ratio than measured androgen markers. CONCLUSIONS: Based on our study, the calculated testosterone indices such as FAI, cBT and cFT are useful markers to distinguish PCOS from non-PCOS. Owing to ease of calculation, FAI can be incorporated in LIS and can be reported with TT and SHBG. This will be helpful for clinician to diagnose hyperandrogenism in PCOS.

Metabolic risk assessment of Indian women with polycystic ovarian syndrome in relation to four Rotterdam criteria based phenotypes.

OBJECTIVES: Though polycystic ovarian syndrome (PCOS) is associated with multiple metabolic abnormalities, the metabolic risk profile of various PCOS phenotypes is still debated. Here we sought to compare the clinical, biochemical and metabolic parameters among the different PCOS phenotypes and controls. STUDY DESIGN: A total of 394 newly diagnosed PCOS women and 108 controls were enrolled consecutively. PCOS women were divided into four phenotypes based on the presence of two of the following Rotterdam criteria: oligo/anovulation (O), hyperandrogenism (H), and polycystic ovaries (P): A (O + H + P), B (O + H), C (H + P), D (O + P). RESULTS: Phenotype A (55.8%) was the most common phenotype in the PCOS cohort. Prevalence of metabolic syndrome was highest in phenotype A and B compared to other two phenotypes and controls. The clinical, biochemical and metabolic characteristics, of phenotypes A and B, were similar, but phenotype A had higher hirsutism score and androgen level. Phenotype C had intermediate metabolic characteristics between A and controls whereas phenotype D had the mildest metabolic abnormalities among the four phenotypes. Significant predictors for metabolic syndrome within the PCOS cohort are waist circumference >80 cm, hypertension, fasting glucose >100 mg/dL, HDL-cholesterol <50 mg/dL and triglyceride >150 mg/dL (p < 0.001). CONCLUSIONS: Indian PCOS women with Phenotype A and B lie at increased metabolic risk compared to other phenotypes. Phenotypic classification of PCOS women may facilitate more effective application of screening and treatment strategies for high-risk metabolic phenotypes.

Polycystic ovarian syndrome: Assessment of approaches to diagnosis and cardiometabolic monitoring in UK primary care.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age. We examined the specific tests that are done in primary care to lead to the diagnosis of PCOS, and to support the diagnosis once made. METHODS: One thousand seven hundred and ninety-seven women were identified from a pooled GP practice database. The search included all patients defined with PCOS or related terms. Records included demographic information, medical history (diagnoses), blood test results and whether a pelvic ultrasound scan had been performed. RESULTS: The most common age of PCOS diagnosis was 20-29 years; 67.7% of the women had at least one concomitant Read-coded diagnosis. Most pelvic ultrasound scans were performed in the month immediately prior to diagnosis. In the 12 months prior to the diagnosis of PCOS being made, 30.5% of women underwent a measurement of their serum total testosterone level while 29.6% had their serum SHBG measured. For serum oestradiol, the corresponding statistics were 28.4%, LH 45.3% and for FSH 45.5% checked before diagnosis. Fasting blood glucose, random glucose and HbA1c were checked in 10.2%, 18.8% and 4.2%, of women before diagnosis, respectively, but in only 7.9%, 6.0% and 3.4% of women in the 24 months after diagnosis. There was a tendency for endocrine testing (oestradiol, LH, FSH, testosterone, SHBG) to peak in the weeks before diagnosis. For plasma glucose, testing was performed more evenly over time as for serum cholesterol. Of all women diagnosed with PCOS, 32.8% were prescribed metformin, 3.7% antihypertensives, 2.2% statins and 63.5% an oestrogen-containing contraceptive pill or HRT. CONCLUSION: The underlying pathophysiology of PCOS is still not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome itself. Robust laboratory led protocols would provide the necessary information to enable an appropriate diagnostic evaluation/cardometabolic monitoring.

Assessment of insulin resistance in Chinese PCOS patients with normal glucose tolerance.

The study aimed to investigate insulin resistance (IR) status in polycystic ovary syndrome (PCOS) women with normal glucose tolerance (NGT), and further to evaluate feasible diagnostic method for those patients. Three hundred and twenty-five PCOS women with NGT and ninety-five healthy age-matched controls were recruited with Rotterdam criterion and 75 g oral glucose tolerance test (OGTT). IR status was estimated following a glycemic and insulinemic OGTT (0, 30, 60, 120, and 180 min). A modified HOMA-IR formula was applied to each time-course value of glycemia and insulinemia. The predictive performance of each IR index was analyzed with the use of ROC curves. Compared with healthy controls, both non-obese and obese PCOS patients with NGT had a higher BMI, serum glucose, insulin value (p < .05). The best predictive index of IR in non-obese PCOS-NGT was a HOMA-M30 value of 20.36 or more (AUC: 0.753). In obese PCOS-NGT population, the best predictive performance was obtained by a HOMA-M60 value of 32.17 or more (AUC: 0.868). IR was common in Chinese PCOS women with NGT, and the early assessment of IR should be heeded. We recommended HOMA-M30 (Cutoff: 20.36) and HOMA-M60 (Cutoff: 32.17) as the best predictive parameters for non-obese and obese PCOS-NGT patients, respectively.

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome.

OBJECTIVE: To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. METHODOLOGY: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value <2 in adults and hyperinsulinemia based on fasting insulin levels ≥12 µIU/ml. RESULTS: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 ±5.5 years. Mean HOMA-IR of women was 3.1 ±1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 ±5.8 µIU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. CONCLUSION: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR.

Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Assessment of the body composition of patients with polycystic ovary syndrome using dual-energy X-ray absorptiometry.

OBJECTIVE: To compare the body composition among patients with polycystic ovary syndrome (PCOS) and patients without PCOS. METHODS: A cross-sectional study enrolled patients aged 12-39 years, with body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 18.5 but below 25, who attended the Endocrine Gynecology Clinic of Santa Casa de Sao Paulo School of Medical Sciences, Brazil, between January 1, 2014, and July 31, 2015. Anthropometric measurements, metabolic and androgenic profiles, and dual-energy X-ray absorptiometry measurements were compared between patients with PCOS and those without PCOS. RESULTS: In total, 102 eligible patients attended the study clinical during the study period; 43 were excluded owing to not meeting the inclusion criteria or declining to undergo complete study testing, and 15 withdrew from the study. Of the 44 participants, 28 had PCOS and 16 were included in the control group. Serum 17-hydroxyprogesterone concentration (P=0.046), leg-fat (P=0.031), and truncal-fat (P=0.001) were all higher among patients with PCOS. CONCLUSION: The present study demonstrated increased truncal and leg fat among women with PCOS. The study did not detect any difference in insulin parameters but larger studies could be more suitably powered to investigate this. CLINICALTRIALS.GOV: NCT02467751.

Gender and Sexual Health: Infertility.

Infertility is common in the United States, with up to 15% of heterosexual couples experiencing difficulty in achieving conception. Family physicians often are the first physicians to evaluate couples attempting to conceive. Evaluation begins with assessment of ovulation, evaluation of anatomic abnormalities, and semen analysis. Many etiologies of anovulation can be managed by family physicians, and clinicians can offer counseling on timing of intercourse and assist patients with lifestyle changes to promote fertility. Ovulation induction for women with polycystic ovary syndrome and treatment of hypothyroidism also can be managed in the family physician's office. For couples who are referred to a reproductive endocrinology subspecialist, clinicians can provide emotional support, screen for depression and anxiety, and provide education about procedures and behaviors that can affect success rates.

Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome.

OBJECTIVE: To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome. METHODS: This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods. RESULTS: Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0-29.9 kg/m(2)) and 22 had normal weight (BMI = 18.5-24.9 kg/m(2)). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls. CONCLUSION: Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.

Assessment of Anti-Müllerian Hormone Level in Management of Adolescents with Polycystic Ovary Syndrome.

OBJECTIVE: This study was oriented to investigate the benefit of anti-Müllerian hormone (AMH) level in the management of polycystic ovary syndrome (PCOS). To assess the impact of metformin and oral contraceptives (OC) on serum AMH levels in a cohort of adolescents with PCOS. METHODS: Forty-nine adolescents with PCOS were recruited to the study. Twenty-nine patients without insulin resistance were treated with OC (group 1), and 20 patients with insulin resistance were treated with metformin and OC (group 2). AMH and androgen levels were measured prior to and 6 months after the initiation of treatment. RESULTS: AMH levels were significantly decreased with treatment in both group 1 (p=0.006) and group 2 (p=0.0048). There was a significant correlation between pre- and post-treatment AMH and left ovarian volume (pretreatment: rho=0.336, p=0.018; post-treatment: rho=0.310, p=0.034). CONCLUSION: This study investigated two different treatment regimens in adolescents with PCOS and revealed that AMH levels decreased with treatment. AMH levels were correlated with ovarian volume.

Comparative assessment of five serum antimüllerian hormone assays for the diagnosis of polycystic ovary syndrome.

OBJECTIVE: To determine whether the different antimüllerian hormone (AMH) immunoassays on the market offer the same performance for the diagnosis of polycystic ovary syndrome (PCOS). DESIGN: A total of 95 serum AMH samples were retrospectively evaluated for a period of 3 months in the same laboratory. SETTING: Academic center laboratory. PATIENT(S): Forty-eight control women with regular menses and no hyperandrogenism and 47 patients with classic PCOS (i.e., hyperandrogenism plus oligoanovulation) attending our department for infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): AMH measurement using five commercial assays. Method comparison and evaluation of the diagnostic performance by receiver operating characteristic analysis. RESULT(S): Values obtained with Gen II and AL-105i ELISAs were similar to those provided by EAI AMH/MIS, whereas automatic assays generated lower values. A significant mean difference was observed between Access Dxi (1.35 ng/mL) or Cobas (1.73 ng/mL) and EIA AMH/MIS ELISA. By ROC analysis each assay displayed similar efficiency for PCOS diagnosis. Sensitivities varied from 49% to 74% when setting the specificity at 92%. Cluster analysis run in the control group identified a subgroup of asymptomatic women with polycystic ovary morphology (PCOM). After exclusion of PCOM, the 95th percentile of controls was 4.2 ng/mL (30 pmol/L) with the automatic assays and 5.6 ng/mL (40 pmol/L) with the manual assays. CONCLUSION(S): Performance of the different AMH assays for PCOS diagnosis is comparable, providing that different threshold values are used for manual and automatic assays. Measurement of serum AMH level appears as a robust tool for the definition of PCOM.

Head-To-Head Assessment of Diagnostic Performance of Testosterone Immunoassays in Patients With Polycystic Ovary Syndrome.

BACKGROUND: Determination of plasma testosterone is critical for the proper diagnosis of polycystic ovary syndrome (PCOS), but the interpretation of biochemical tests is hampered by inadequate specificity and precision of available immunoassays. We here compared the diagnostic performance of three testosterone immunoassays (Advia Centaur, Immulite 2000 XPi, Cobas e411) in PCOS patients using receiver operator characteristics curve analysis. METHODS AND RESULTS: Plasma levels of testosterone, androstendione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, estradiol, progesterone, steroid hormone binding globulin, luteinizing hormone, and follicular stimulating hormone were determined in 188 patients with PCOS and 202 controls. Free testosterone (fT) levels and free androgen index (FAI) were calculated. Testosterone levels measured on Advia Centaur, Immulite 2000 XPi, and Cobas e411 showed clear linear relationship to each other. Testosterone measured with Advia Centaur showed discriminatory performance superior to Immulite 2000 XPi and Cobas e411. Calculation of fT or FAI improved the performance of Advia Centaur and Immulite 2000 XPi, which nevertheless performed better than Cobas e411. The performance of other parameters was inferior to that of testosterone, fT, and FAI. CONCLUSION: Present study documents striking differences between testosterone immunoassays with respect to their capacity to identify PCOS patients and favors the use of calculated parameters reflecting active testosterone in plasma.