Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women's Endocrinology.

PURPOSE: To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process. METHODS: A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes. RESULTS: A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM. CONCLUSION: This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

Resting energy expenditure in women with polycystic ovary syndrome.

STUDY QUESTION: Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories. WHAT IS KNOWN ALREADY: Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting. STUDY DESIGN, SIZE, DURATION: This case-control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp. MAIN RESULTS AND THE ROLE OF CHANCE: REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9 kcal/kgFFM·day, P < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number. LIMITATIONS, REASONS FOR CAUTION: Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Circadian and sex differences in post-ischemic vasodilation and reactive hyperemia in young individuals and elderly with and without type 2 diabetes.

OBJECTIVE: Cardiovascular events show morning preference and sex differences, and are related to aging and type 2 diabetes. We assessed circadian variations and sex differences in vascular conductance (VC) and blood flow (BF) regulations following a brief bout of forearm ischemia. METHODS: Young healthy individuals (H18-30) and elderly without (H50-80) and with type 2 diabetes (T2DM50-80) of both sexes were included. Forearm VC and BF, and mean arterial pressure (MAP) at baseline and following circulatory reperfusion were measured at 6 a.m. and 9 p.m. RESULTS: In the morning compared to evening, following reperfusion, the VC and BF increments were similar in H18-30 (p>.71), but lower in H50-80 (p<.001) and T2DM50-80 (p<.01). VC and BF following circulatory reperfusion were higher in men than women in H18-30 (p<.001), but similar between sexes in the older groups (p>.23). CONCLUSIONS: Forearm vasodilation following reperfusion is attenuated in the morning in the elderly, impairing BF towards an ischemic area. Diabetes does not affect the circadian regulation of VC and BF, but that of MAP. There are sex differences in VC and BF at baseline and after circulatory reperfusion at a young age, being greater in men, which disappear with aging without being affected by diabetes.

Circadian Variations in Sympathetic Vasoconstriction in Older Adults with and Without Type 2 Diabetes.

INTRODUCTION: An impact of the sympathetic nervous system in the higher rate of cardiovascular events in the early morning compared to the evening has been claimed. Augmented sympathetic vasoconstriction increases cardiovascular risk by augmenting pulse pressure and cardiac afterload. Type 2 diabetes (T2DM) further increases sympathetic neurovascular transduction and cardiovascular risk. AIM: We assessed whether peripheral vasoconstriction triggered by a standardized sympathetic stressor is augmented at 6am vs 9pm in adults between 50-80 years with type 2 diabetes (T2DM50-80) vs healthy ones (H50-80). METHODS: Mean values of sympathetic vasoconstrictor responsiveness (SVR), vascular conductance (VC), brachial artery blood flow, and mean arterial pressure were measured on the contralateral forearm over two 5-minute bouts of rest and handgrip-mediated sympathetic stimulation, respectively. RESULTS: Although baseline VC values were lower (p < 0.01) in the morning vs evening in both groups, SVR values in response to sympathoexcitation were similar in H50-80 (- 0.43 ± 12.44 vs - 2.57 ± 11.63 %, p = 0.73) and T2DM50-80 (+6.64 ± 10.67 vs +5.21 ± 7.64 %, p = 0.90), but higher (p < 0.01) in T2DM50-80 vs H50-80 at both day hours. Individuals with T2DM reported positive SVR values and VC change-scores, while healthy individuals reported statistically different (p < 0.02) negative SVR values and VC change-scores. CONCLUSION: Peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of T2DM and different baseline VC values. However, peripheral vasoconstriction responsiveness is blunted in individuals with T2DM as handgrip-mediated sympathoexcitation induces vasodilation in the contralateral forearm in adults with T2DM and vasoconstriction in healthy age-matched controls, highlighting a neurovascular response altered by T2DM.

Circadian and sex differences in carotid-femoral pulse wave velocity in young individuals and elderly with and without type 2 diabetes.

The incidence of cardiovascular events is higher in the morning than in the evening and differs between sexes. We tested the hypothesis that aortic stiffness, a compelling cardiovascular risk factor, increases in the morning than in the evening in young, healthy individuals between 18 and 30 years (H18-30) or in older individuals between 50 and 80 years, either healthy (H50-80) or with type 2 diabetes (T2DM50-80). Sex differences were also investigated. Carotid-femoral pulse wave velocity (cf-PWV) recorded via Doppler Ultrasound, blood pressure and heart rate were checked at 6 a.m. and 9 p.m., at rest and during acute sympathetic activation triggered by handgrip exercise. Cf-PWV values were lower in the morning compared to the evening in all groups (p < 0.01) at rest and lower (p = 0.008) in H18-30 but similar (p > 0.267) in the older groups during sympathetic activation. At rest, cf-PWV values were lower in young women compared to young men (p = 0.001); however, this trend was reversed in the older groups (p < 0.04). During sympathetic activation, the cf-PWV was lower in women in H18-30 (p = 0.001), similar between sexes in H50-80 (p = 0.122), and higher in women in T2DM50-80 (p = 0.004). These data do not support the hypothesis that aortic stiffness increases in the morning compared to the evening within any of the considered groups in both rest and sympathetic activation conditions. There are differences between the sexes, which vary according to age and diabetes status. In particular, aortic stiffness is higher in older women than in men with diabetes during acute stress.

Sympathetic-mediated blunting of forearm vasodilation is similar between young men and women.

BACKGROUND: The in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation. METHODS: 13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated. RESULTS: TPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09). CONCLUSIONS: Although women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.

Clinical Value of Serum Levels of 11-Oxygenated Metabolites of Testosterone in Women With Polycystic Ovary Syndrome.

CONTEXT: Recent data suggested that 11-oxygenated androgens may be the preponderant circulating androgens in women with PCOS. However, the pathophysiological significance of these hormones remains unclear. OBJECTIVE: The aim of this study was to evaluate the relationships between serum 11-OH testosterone (11-OHT) and 11-keto testosterone (11-KetoT) and clinical and biochemical hyperandrogenism, as well as the metabolic parameters, in women with PCOS. METHODS: The main classic and 11-oxygenated androgens were measured by LC-MS/MS and direct equilibrium dialysis in 123 women with PCOS, diagnosed according to the Rotterdam criteria, and 38 healthy controls. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp. RESULTS: Serum 11-oxygenated androgens were higher in women with PCOS than in controls. Elevated levels of 11-OHT and 11-KetoT were found in 28.5% and 30.1% of PCOS women, respectively, whereas free testosterone (FT) was increased in 61.0% of them. Serum 11-oxygenated androgens showed a limited performance in recognizing women with classically defined hyperandrogenism. Unlike FT, 11-oxygenated androgens did not show significant relationships with anthropometric and metabolic parameters, except for a direct association with insulin sensitivity. In multivariable analysis, 11-OHT and 11-KetoT, directly, and FT, inversely, remained significant independent predictors of insulin sensitivity. CONCLUSIONS: Serum levels of 11-oxygenated androgens are higher in women with PCOS than in controls. However, these hormones show a poor performance in recognizing women with hyperandrogenism, as currently defined. The relationships of these androgens with insulin sensitivity strongly differ from that of FT, suggesting a different role of classic and 11-oxygenated androgens in the pathophysiology of PCOS.

The Multiple Functions of Insulin Put into Perspective: From Growth to Metabolism, and from Well-Being to Disease.

Insulin has pleiotropic effects, and is of importance both as a key regulator of glucose metabolism and as a growth factor [...].

Insulin-Mediated Substrate Use in Women With Different Phenotypes of PCOS: the Role of Androgens.

CONTEXT: Few studies have explored in vivo insulin action on substrate use in women with PCOS. In particular, no data are available in women with different PCOS phenotypes. OBJECTIVE: The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, nonoxidative glucose metabolism (Gnonox), and serum free fatty acids (FFAs) in different PCOS phenotypes. METHODS: Participants included 187 nondiabetic women with PCOS diagnosed according to the Rotterdam criteria. Data from a historical sample of 20 healthy women were used as reference values. Whole-body substrate use data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. RESULTS: During hyperinsulinemia, the increase of Gox (ΔGox), Gnonox, as well as the suppression of Lox (ΔLox) and serum FFA (Δ% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Δ% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and ΔGox was lower in women with the classic than in those with the ovulatory phenotype. In multivariable analysis fat mass and free testosterone were independent predictors of ΔGox, Gnonox, and Δ% FFA, whereas only fat mass predicted ΔLox. CONCLUSION: In women with PCOS, regardless of phenotype, insulin-mediated substrate use is impaired. This phenomenon is greater in individuals with the classic phenotype. Free testosterone plays an independent role in insulin action abnormalities in glucose and lipid metabolism.

Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report.

Addison Disease is an uncommon, life-threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.

Current treatment for polycystic ovary syndrome: focus on adolescence.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is associated with an increased rate of infertility. Its etiology remains largely unknown, although both genetic and environmental factors play a role. PCOS is characterized by insulin resistance, metabolic disorders and low-grade chronic inflammation. To date, the treatment of PCOS is mainly symptomatic and aimed at reducing clinical signs of hyperandrogenism (hirsutism and acne), at improving menstrual cyclicity and at favoring ovulation. Since PCOS pathophysiology is still largely unknown, the therapeutic interventions currently in place are rarely cause-specific. In such cases, the therapy is mainly directed at improving hormonal and metabolic dysregulations typical of this condition. Diet and exercise represent the main environmental factors influencing PCOS. Thus, therapeutic lifestyle changes represent the first line of intervention, which, in combination with oral contraceptives, represent the customary treatment. Insulin resistance is becoming an increasingly studied target for therapy, most evidence stemming from the time-honored metformin use. Relatively novel strategies also include the use of thiazolidinediones and GLP1-receptor agonists. In recent years, a nutraceutical approach has been added to the therapeutic toolkit targeting insulin resistance. Indeed, emerging data support inositol and alpha-lipoic acid as alternative compounds, alone or in combination with the aforementioned strategies, with favorable effects on ovulation, insulin resistance and inflammation. Nevertheless, additional studies are required in adolescents, in order to assess the effectiveness of diet supplements in preventing negative impacts of PCOS on fertility in adult age. This review focuses on the main therapeutic options for PCOS to date.

Serum Androgens Are Independent Predictors of Insulin Clearance but Not of Insulin Secretion in Women With PCOS.

CONTEXT/OBJECTIVE: In insulin-resistant individuals, hyperinsulinemia is a key compensatory mechanism, aimed at maintaining glucose homeostasis. Increased secretion and reduced clearance of insulin may both potentially contribute to this phenomenon. Insulin resistance and hyperinsulinemia are common findings in women with polycystic ovary syndrome (PCOS). While there is some information on insulin secretion, very few studies have investigated metabolic clearance rate of insulin (MCRI) in these women. Moreover, there is paucity of data on the relationships between MCRI and the pathophysiological characteristics of PCOS. The aim of the study was to explore these issues. PATIENTS: One hundred ninety women with PCOS, diagnosed according to the Rotterdam criteria, with normal glucose tolerance. DESIGN: Assessment of MCRI and clinical, hormonal, and metabolic characteristics of subjects. MCRI and insulin sensitivity were measured by the hyperinsulinemic euglycemic clamp. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis. A historical sample of healthy women was used to define the corresponding reference intervals. RESULTS: MCRI was impaired in about two-thirds of women with PCOS. Subjects with low MCRI differed from those with normal MCRI for a number of anthropometric, metabolic, and endocrine features. In multivariate analysis, the degree of adiposity, estimates of insulin secretion, and serum androgen concentrations were independent predictors of MCRI. Conversely, age, adiposity, MCRI, and insulin sensitivity, but not serum androgens, were independent predictors of insulin secretion. CONCLUSIONS: In women with PCOS, metabolic clearance of insulin is reduced, contributing to generating hyperinsulinemia. Serum androgens are independent predictors of this phenomenon.

A Case Report of Insulinoma Relapse on Background Nesidioblastosis: A Rare Cause of Adult Hypoglycemia.

Context: Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Case Description: A 63-year-old white woman presented at our institution on April 2017 with a history of distal spleno-pancreatectomy for well-differentiated insulinoma in 2013. Hypoglycemic events did not resolve after surgery, and residual nesidioblastosis near the pancreatic resection margins was identified. Hypoglycemic episodes increased in frequency and severity despite high-dose diazoxide (DZX) therapy. On April 2016, octreotide was introduced but soon discontinued for inefficacy. When the patient arrived at our attention, add-on pasireotide was started and glucose levels monitored by subcutaneous sensor. Compared with DZX, 225 mg/d alone, sensor glucose during pasireotide + DZX 75 mg/d showed occurrence of severe hypoglycemia. Pasireotide was discontinued, and the instrumental workup (68Ga-DOTATOC CT/positron emission tomography, 99mTc-nanocolloid scintigraphy and echo-endoscopy + fine-needle aspiration biopsy) identified an insulinoma relapse. Subtotal pancreatectomy was performed without further recurrence of hypoglycemia over 9 months of follow-up. Conclusions: Although insulinoma relapses on background nesidioblastosis rarely occur, they should be considered as an alternate diagnosis when medical therapy fails to prevent hypoglycemia. Further studies are warranted to test whether the immunophenotypic signature of nesidioblastosis/insulinoma may provide insights for a tailored use of pasireotide.

Effects of Aerobic and Resistance Training on Circulating Micro-RNA Expression Profile in Subjects With Type 2 Diabetes.

CONTEXT: Structured exercise programs are of great benefit for the treatment of type 2 diabetes (T2DM). However, whether aerobic (AER) or resistance (RES) exercise training exerts specific epigenetic changes through the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown. OBJECTIVE: To assess whether the c-miRNAs profile changes after either AER or RES training in subjects with T2DM. DESIGN: Twenty-four patients with T2DM randomized to AER or RES training protocols were randomly selected from the Resistance vs. Aerobic Exercise in Type 2 Diabetes (RAED2) Trial (NAER = 12; NRES = 12). The baseline and post-training levels of 179 c-miRNAs were initially measured by RT-PCR in 6 individuals (NAER = 3; NRES = 3). C-miRNAs exhibiting ≥40% fold change variation and/or nominal significance from baseline were measured in the whole group. RESULTS: Nineteen c-miRNAs were eventually assessed in the whole group. Compared with baseline, the post-training levels of miR-423-3p, miR-451a, and miR-766-3p were significantly up-regulated, irrespective of exercise type (P < 0.0026; 0.05/19), and targeted upstream pathways relevant to fatty acids biosynthesis and metabolic regulation. MiR-451a and miR-423-3p were significantly correlated with fat loss (ρ = 0.45 and 0.43, respectively) and resulted, alone or in combination, in being predictors of fat loss in generalized linear regression models including exercise type as covariate. Only the association with miR-451a eventually retained significance after further correction for age, sex, body mass index, and HbA1c. CONCLUSIONS: Exercise training in T2DM is associated with substantial c-miRNAs profile changes, irrespective of exercise type and other relevant metabolic covariates. The mechanistic significance of the observed relationship between fat loss and the epigenetic modifications induced by exercise warrants further investigation in larger datasets.

Role of Exercise in Vascular Function and Inflammatory Profile in Age-Related Obesity.

In western countries, aging is often accompanied by obesity and age-related obesity is characterized by vascular dysfunction and a low-grade inflammatory profile. Exercise is a nonpharmacological strategy able to decrease the development and incidence of risk factors for several health-threatening diseases. Nonetheless, its long-term effect on vascular function and inflammation in age-related obesity is still unclear. The aim of this study was to investigate the effect of regular, supervised exercise on inflammatory profile and vascular function in age-related obesity. We also hypothesized that vascular function and inflammatory profile would have been correlated in overweight and obese individuals. Thirty normal weight (NW; 70 ± 5 years, 23.9 ± 2.6 BMI) and forty overweight and obese elderly (OW&OB; 69 ± 5 years, 30.1 ± 2.3 BMI) regularly taking part in a structured, supervised exercise program were enrolled in the study and evaluated for vascular function (flow-mediated dilation; FMD) and inflammatory profile (plasma CRP, IL-1ß, IL-1ra, IL-6, IL-8, IL-10, TNF-α, and MCP-1). Although no differences between groups were found concerning performance and the weekly amount of physical activity, the OW&OB group compared with the NW group demonstrated higher systolic and diastolic blood pressure (+10%, p = 0.001; +9%, p = 0.005, respectively); lower FMD% (-36%, p < 0.001) and FMD/shear rate (-40%, p = 0.001); and higher levels of CRP (+33%, p = 0.005), IL-6 (+36%, p = 0.048), MCP-1 (+17%, p = 0.004), and TNF-α (+16%, p = 0.031). No correlations between vascular function and inflammation were found in OW&OB or NW. Although exercising regularly, overweight and obese elderly exhibited poorer vascular function and higher proinflammatory markers compared with the leaner group. These results support the idea that exercise alone cannot counteract the negative effect of adiposity on vascular function and inflammatory profile in elderly individuals and these two processes are not necessarily related.

Reassessing Free-Testosterone Calculation by Liquid Chromatography-Tandem Mass Spectrometry Direct Equilibrium Dialysis.

Context: Assessment of free testosterone (FT) might help evaluate androgen status in patients with borderline total testosterone (T) and/or altered sex hormone-binding globulin (SHBG) levels. However, the validity of different methods to measure FT is debatable. Methods: Serum from 183 women and 146 men was analyzed using equilibrium dialysis (ED), with FT directly measured by liquid chromatography-tandem mass spectrometry. FT calculation was re-evaluated for the mass action law-based equation according to Vermeulen (cFT-V), empirical equations according to Ly (cFT-L), and a proposed calculation based on a multistep, dynamic, allosteric model according to Zakharov (cFT-Z). Results: FT level analyzed by ED [median,13 pmol/L (1.2% of T) in women; 248 pmol/L (1.5% of T) in men] was strongly inversely correlated to SHBG level, significantly to albumin level in women, and only weakly to SHBG level in men. The median [percentile (p) range, 2.5 to 97.5] ratios of calculated FT (cFT) over ED-FT (from European Male Aging Study samples) were 1.19 (0.9 to 1.47), 1.00 (0.69 to 1.42), and 2.05 (1.26 to 3.26) for cFT-V, cFT-L, and cFT-Z, respectively. The ratio for cFT-V was not significantly affected by SHBG, T, or albumin levels (ρ range, 0.17 to -0.01); ratios for cFT-L and cFT-Z were affected (P < 0.05 and P < 0.001, respectively) and strongly correlated with SHBG levels (ρ = 0.72 and 0.75, respectively). Rank correlations between cFT% and ED-FT% (for men) were 0.62, 0.74, and 0.89 for cFT-Z, cFT-L, and cFT-V, respectively. Conclusion: FT results by direct ED confirm prior FT data from indirect ED and ultrafiltration methodologies. Calculations have inherent limitations, with clinically important differences among evaluated equations: cFT-V, although overestimating FT level, appears the most robust approximation, largely independent of SHBG, albumin, and T levels.

Sex differences in the association of psychological status with measures of physical activity and sedentary behaviour in adults with type 2 diabetes.

AIM: To assess the association of psychological variables on leisure-time physical activity and sedentary time in men and women with type 2 diabetes mellitus (T2D). METHODS: In this cross-sectional study, we evaluated 163 patients with T2D, consecutively recruited at the Diabetes Centre of the Verona General Hospital. Scores on depression and anxiety symptoms, psychosocial factors (including self-efficacy, perceived interference, perceived severity, social support, misguided support behaviour, spouse's positive behaviour), physical activity and time spent sitting were ascertained using questionnaires responses to the Beck Depression Inventory-II, Beck Anxiety Inventory, Multidimensional Diabetes Questionnaire, International Physical Activity Questionnaire. RESULTS: Physical activity was significantly associated with higher social support in women and with increased self-efficacy in men. Sedentary time was significantly associated with higher perceived interference, anxiety and depressive symptoms, and with reduced diabetes self-efficacy in women, while it was associated solely with anxiety in men. Depressive symptoms and self-efficacy in women and anxiety symptoms in men were independent predictors of sedentary time when entered in a multivariable regression model also including age, BMI, haemoglobin A1c, diabetes duration, perceived interference and self-efficacy as covariates. CONCLUSIONS: Lower self-efficacy and higher symptoms of depression were closely associated with increased sedentary time in women, but not in men, with T2D. It is possible that individualized behavioural interventions designed to reduce depressive symptoms and to improve diabetes self-efficacy would ultimately reduce sedentary behaviours, particularly in women with T2D.

The free androgen index is inaccurate in women when the SHBG concentration is low.

OBJECTIVE/CONTEXT: The free androgen index (FAI) is known to give erroneous results in men, but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women. DESIGN/PATIENTS: Free serum testosterone T (ED-T) and total serum T (T) were measured by equilibrium dialysis and LC-MS/MS in patients with polycystic ovarian syndrome (n = 130), normal female controls (n = 53) and normal males (n = 120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition, cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism. RESULTS: The cFT showed good agreement with measured ED-T, and the ratio cFT/ED-T was stable across all SHBG concentrations. In contrast, the FAI/ED-T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L. CONCLUSIONS: The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism.