Lower SHBG Research Articles

Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease.

Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD. Baseline assessment of longitudinal cohorts and randomized clinical trials. Nonalcoholic Steatohepatitis Clinical Research Network. Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States. We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression. Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features. Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.

Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice

Obese subjects of all ages and sex have reduced plasma SHBG levels. Whether these low plasma SHBG levels play a role in obesity development is unknown. In the present work we wanted to explore if SHBG overexpression could prevent obesity development induced by high fat diet (HFD). To do so, we fed humanized SHBG transgenic male mice and their wild-type littermates with control diet (CD) or HFD over the course of 8 weeks. The results showed that SHBG overexpression protected against body weight gain and fat accumulation induced by HFD. In addition, SHBG overexpression also abrogated the increase in insulin, leptin and resistin levels, as well as the reduction in adiponectin, induced by HFD. Mechanistically, the SHBG protection against HFD-induced obesity was achieved by stimulating lipolysis in white adipose tissue. Furthermore, we have demonstrated the SHBG cell-autonomous effect using human primary visceral adipocytes. Taking together, our results demonstrate that SHBG overexpression protects against diet-induced obesity and improves the metabolic profile of male mice fed a HFD diet.

Post-Menopausal Sex Hormones in Relation to Type 2 Diabetes Mellitus

Sex Hormone binding globulin is a glyco protein that transports the sex steroids to their target tissue. The concentration of free steroids in the circulation depends upon the availability of serum SHBG. Low SHBG is associated with hyperinsulinemia, T2DM, and cardiovascular risk. Objective: The objective of the study was to determine the correlation of SHBG with hormone levels, insulin and BMI in post- menopausal women with type 2 diabetes mellitus (T2DM). Research Design and methods: One hundred and five post menopausal women with diabetes and eighty five postmenopausal women without diabetes were recruited for the study. Height, weight, BMI, was measured. Insulin,SHBG and sex steroids were measured by enzyme linked immunosorbent assay (ELISA). Results: The mean concentration of SHBG was higher in control group 25.21 (16.1- 43.7), than the diabetic postmenopausal women 20.65 (12.54-33.46) p&lt;0.05. A significant inverse association was observed between insulin resistance, free testosterone and BMI. Conclusion: In postmenopausal women with type 2 diabetes mellitus low levels of SHBG is observed which shows an inverse correlation with insulin resistance, free testosterone and DHEA leading to hyperandrogenecity and hyperinsulinemia .

The impact of metabolically healthy obesity in primary infertile men: Results from a cross‐sectional study

A number of studies showed that obesity may negatively impact on sperm quality and consequently couple's fertility. Recently, specific attention was given to a clinical condition known as metabolically healthy obesity (MHO). To evaluate the effects of MHO on semen and hormonal parameters of men presenting for primary couple's infertility associated with pure male factor infertility (MFI). Data from a homogenous cohort of 512 white-European primary infertile men belonging to couples with pure MFI have been cross-sectionally analyzed. Semen analysis was based on 2010 WHO reference criteria. Patients were segregated into eugonadal, secondary hypogonadal, primary hypogonadal, and compensated hypogonadal. The Harmonized International Diabetes Federation criteria were used to define metabolic syndrome (MetS). Based on BMI and MetS, patients were further segregated into the following: (a) metabolically healthy non-obese (MHNO); (b) metabolically unhealthy non-obese (MUNO) (c) metabolically healthy obesity (MHO); and, (d) metabolically unhealthy obesity (MUHO). Main outcome measures were the prevalence of MHO and the impact of MHO on semen and hormonal parameters in this cohort of MFI primary infertile men. Overall, MHNO, MUNO, MHO, and MUHO were found in 462 (90%), 13 (2.5%), 27 (5.2%), and 10 (1.9%) men, respectively. MHO patients had lower total testosterone and SHBG levels (all P<.05) but higher E2 values (P<.005) compared with MHNO men. Groups did not differ in terms of semen parameters. At multivariable logistic regression, analysis MHO was associated with an increased risk of primary and secondary hypogonadism (all P≤.02) compared with MHNO, after accounting for age and comorbid conditions. Metabolically healthy obesity is threefold more prevalent than unhealthy obesity in primary infertile men. Despite semen parameters are comparable among groups, MHO patients show worse endocrine parameters and a higher risk of primary and secondary hypogonadism compared with metabolically healthy normal infertile men.

Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort.

Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

SUN-077 Do Low Sex Hormone Binding Globulin Levels in Newborns Predict Weight Gain in Infancy and Early Childhood?

Background: SHBG levels are low in obesity, and low SHBG levels are a biomarker for the development of T2DM and the metabolic syndrome. We sought to determine whether low SHBG in newborns will predict childhood obesity. Methods: We studied 94 healthy, singleton, full-term newborns, and measured their length, weight (BW), waist circumference, and skinfold thicknesses. We collected cord blood as well as day 2 venous blood samples for the measurement of SHBG and insulin (ALPCO, Salem NH). Maternal age, pre-pregnancy weight, pregnancy weight gain, and glucose screening test results were obtained from obstetrical records. Mothers with chronic diseases were excluded from the study. When babies were 2 years old, we administered a questionnaire to collect information about their eating, sleeping, screen viewing habits, and anthropometric measurements at ages 6, 12, and 24 months (n=47). Overweight was defined as a BMI SDS of ≥1 and <2.0, and obesity as ≥2 SDS. We used the Shapiro-Wilk test to determine if variables were normally distributed. Data were analyzed using the Mann Whitney U and Wilcoxon signed-rank tests, and by Pearson or Spearman correlation analyses. We report non-normally distributed variables as medians and interquartile ranges (IQR). Because of skewed distributions, log 10 transformed values for SHBG were used in the regression analyses. Results: SHBG levels on day 2 were significantly higher than in cord blood [22.0(28.7-16.9) vs. 19.0(24.6-14.5) nmol/L, p<0.001], whereas insulin levels were higher in cord blood than in day 2 samples [3.2(5.3-2.0) vs. 1.5(2.2-0.8) µIU/mL, p<0.001]. SHBG and insulin levels were similar in male (n=44) and female (n=50) babies at all time points. Babies with Ponderal index values in the highest quartile had lower day 2 SHBG [18.2(22.1-16.7) vs. 24.3(30.3-18.2) nmol/L, p=0.02] and higher cord blood insulin levels [5.0(7.4-2.6) vs. 2.9(4.8-1.5) µIU/mL, p=0.04] than the remainder of the cohort. At age 2 years, 32% (15/47) of babies were overweight or obese, 60% (28/47) were breastfeeding, 58% (27/47) were watching TV or iPads, and 55% (26/47) were eating sweet snacks. Toddlers watching TV or iPads (p=0.008), or eating sweet snacks (p=0.04) were heavier than their peers. Neither cord blood nor day 2 SHBG or insulin levels correlated significantly with any of the anthropometric measurements in the newborns. On the other hand, day 2 SHBG levels correlated positively with weight at 6 (r=0.311, p=0.04) and 24 months (r=0.353, p=0.02) of age. These associations remained significant after adjusting for gender, BW, gestational age, breastfeeding status and fruit juice intake at 6 months (R2=0.28, p=0.048) and for gender, BW, gestational age, breastfeeding status, sweet snack intake and screen viewing habits at 24 months (R2=0.33, p=0.046). Conclusion: Although the heaviest babies had lower SHBG levels at birth, low SHBG did not predict overweight at age 2 years.

Sexual functions in women with focal epilepsy: Relationship to demographic, clinical, hormonal and psychological variables

ObjectivesSexual dysfunctions [SDs] are common in women with epilepsy [WWE] but related studies were neglected in our locality. We aimed to determine the frequencies and severities of SDs and their clinical, hormonal and psychological determinants in WWE.Patients and methods: This study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. Patients and methodsThis study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. ResultsThe majority had occasional/rare frequency of seizures [76.67 %] and well controlled on antiepileptic drugs [AEDs] [81.67 %]. Compared to healthy women, WWE had lower total testosterone and FAI and higher SHBG levels. Compared to women on CBZ, those on OXC had lower frequency and well controlled seizures on medication [P = 0.0001 for both], higher testosterone [P = 0.01] and FAI [P = 0.001] and lower SHBG [P = 0.001] levels. Compared to controls, WWE had significantly higher frequencies and severities of SDs [total sexual function, desire, arousal, lubrication, orgasm, satisfaction and pain] and depression and anxiety symptoms. OXC therapy was associated with lower SDs [FSFI: P = 0.033] and anxiety symptoms [P = 0.025] compared to CBZ therapy. In multiple logistic regression analyses, determinants of SDs were the higher seizures frequency, increasing severities of depression and anxiety but not lower androgen levels or type of epilepsy or AEDs. ConclusionsDifferent aspects of SD and depression and anxiety symptoms were frequent in WWE. Determinants of SDs were the higher frequency of seizures and increasing severities of depression and anxiety. OXC had better control on seizures and thus lower frequencies and severities of SDs and depression and anxiety symptoms. Thus optimizing seizure control is important for psychological state and healthy sexual function in WWE.

Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk.

Women with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women. Reproductive hormones and metabolic parameterswere assessed in 198 women with regular menses and no clinical hyperandrogenism (eumenorrheic [EM]). Hyperandrogenic EM women were compared with 110 women with NIH criteria polycystic ovary syndrome. Twenty-two percent of EM women had HA. Levels of non-sex hormone-binding globulin (SHBG)-bound T were elevated in 68% of women, total T levels were elevated in 43% of women, and dehydroepiandrosterone sulfate levels were elevated in 30% of women. The prevalence of HA increased with BMI category (P = 0.01): 12% for BMI < 25 kg/m2 , 22% for BMI of 25 to 30 kg/m2 , and 31% for BMI ≥ 30 kg/m2 . MetS (adjusted odds ratio 2.9; 95% CI: 1.2-6.9) and dysglycemia risks (adjusted odds ratio 2.7; 95% CI: 1.2-5.8) were increased in hyperandrogenic EM women compared with normoandrogenic EM women, with adjustment for BMI. SHBG levels were independently associated with these metabolic end points (P < 0.001), whereas androgen levels were not. A cluster analysis confirmed that there was a discrete subset of EM women with HA and metabolic abnormalities. HA is common in EM women and is associated with increased risks for MetS and dysglycemia. However, low SHBG levels rather than elevated androgen levels may be the primary predictor of this relationship with metabolic dysfunction.

Early pregnancy metabolic factors associated with gestational diabetes mellitus in normal-weight women with polycystic ovary syndrome: a two-phase cohort study

BackgroundPolycystic ovary syndrome (PCOS) has been consistently associated with subsequent gestational diabetes mellitus (GDM). Women with PCOS showed a high prevalence of obesity, which raises the question regarding the role of obesity or PCOS pe ser in development of GDM. In this study we conducted a 2-phase study to compare the risk of GDM and its associated early pregnancy metabolic factors in women with and without PCOS, stratified by pre-pregnancy body mass index (BMI).MethodsA 2-phase design was used in this study. The initial phase of the study included 566 age- and pre-pregnancy BMI-matched singleton pregnant women (242 with and 324 without PCOS). Risk of GDM and associated early-pregnancy risk factors were explored between women with and without PCOS, after stratification by pre-pregnancy BMI. Stratified analysis was conducted in normal weight (pre-pregnancy BMI < 25 kg/m2) and overweight/obese (pre-pregnancy BMI ≥ 25 kg/m2) groups. Subsequently, the findings was confirmed in a separate cohort study with 18,106 participants (877 with and 17,229 without PCOS).ResultsOverall, prevalence of GDM is higher in women with PCOS. Results from the initial study showed that in normal-weight subjects, there is a significant increase in GDM prevalence in PCOS women than non-PCOS women (26.5% vs. 16.2%, p = 0.02). Additionally, normal-weight PCOS women showed higher triglycerides levels (1.51 ± 0.84 mmol/L vs. 1.30 ± 0.75 mmol/L, p = 0.02), lower SHBG levels (277.8 ± 110.2 nmol/L vs. 330.5 ± 180.4 nmol/L, p = 0.001) and a possible trend towards higher insulin resistance (LogHoMA-IR 0.70 ± 0.55 vs. 0.57 ± 0.57, p = 0.05) during early pregnancy. However, in overweight/obese group, no difference in risk of GDM was observed between PCOS and non-PCOS subjects (p = 0.7). Results from the independent cohort confirmed the risk for GDM associated with PCOS in normal weight women (p < 0.0001).ConclusionConsistent findings from the 2-phase study showed an increased risk of GDM in normal-weight, but not overweight/obese PCOS women. Analysis of early-pregnancy risk factors of GDM suggested that the pathogenesis of GDM in normal weight and overweight/obese women with PCOS may be different.

Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia

BackgroundDepending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation. The latter include life-threatening salt-wasting crises, prenatal virilization of genitalia in women (classic CAH [C-CAH]) as well as milder forms of the disease exclusively presenting with hirsutism, acne or reduced fertility (nonclassic CAH [NC-CAH]), and could influence sexual function and identity. AimThe present study evaluated sexual function, gender identification, and partner preference in women with C-CAH and NC-CAH. MethodsIn a cross-sectional cohort analysis, 35 female patients with CAH were divided into 2 groups: C-CAH (salt-wasting/simple virilizing; n = 17) and NC-CAH (n = 18) according to genotype and phenotype. Sexual function and sexual distress were assessed using established questionnaires, including the Female Sexual Function Index. Phenotype (defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) and with the ovulatory function index. CYP21A2 genotype was determined by Sanger sequencing and multiplex ligation-dependent probe amplification. Sexual function was also separately analyzed in the context of clinical signs of androgenization in women with (n = 13) and without acne (n = 22). OutcomesThe study outcomes were sexual function and sexual distress in relation to genotype, clinical signs of androgenization, and biochemical parameters. ResultsWomen with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism). Indicators of in utero and childhood androgen excess as well as the presence of acne in all patients were related to lower sexual function and higher sexual distress. Clinical signs of hyperandrogenism correlated well with cardiovascular and metabolic risk factors. Clinical TranslationWomen with NC-CAH and women with clinical signs of hyperandrogenism demonstrated higher distress compared to women with C-CAH and women without clinical signs of hyperandrogenism, respectively, regarding different aspects of sexual function. ConclusionsThese data underline the importance of early diagnosis and therapy initiation, especially in patients with NC-CAH.Schernthaner-Reiter MH, Baumgartner-Parzer S, Egarter HC, et al. Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia. J Sex Med 2019;16:1529–1540.

Testosterone and Estrone Increase From the Age of 70 Years: Findings From the Sex Hormones in Older Women Study.

There is a lack of understanding of what is normal in terms of sex steroid levels in older women. To determine whether sex steroid levels vary with age in and establish reference ranges for women >70 years of age. Cross-sectional, community-based study. Included 6392 women ≥70 years of age. Sex steroids measured by liquid chromatography-tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent. The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the samples, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P < 0.001) and lower DHEA (30% less, P < 0.001). Women with overweight and obesity had higher E1 (P < 0.001) and T (P < 0.03) and lower SHBG (P < 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005). From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation.

Physical Activity, Nutrition and Hormone Levels of Postmenopausal Women With and Without Endometrial Cancer [40R

INTRODUCTION: This prospective study evaluated anthropometric data, reported physical activity, nutrition, and hormone levels between postmenopausal women undergoing hysterectomy for endometrial cancer and benign disease. METHODS: After IRB approval, participants completed questionnaires on physical activity, nutrition, menstrual history and hormone use, and provided preoperative blood samples. RESULTS: Of the 77 participants, mean age was 64.5 years, mean BMI was 35.0 kg/m2, and 80.5% had endometrial cancer. Few women (20.8%) achieved recommended weekly exercise and 47.2% did not exercise. Only 44.9% of women ate recommended servings of fruits and vegetables and 55.6% ate fast food weekly. Comparing women with and without cancer, a trend towards higher BMI (36.0 vs 31.1 kg/m2, P=.071) was noted but no significant differences with regard to gravidity, exercise, nutrition, glucose or hormone levels except that estradiol level was significantly lower in women with cancer (45.2 vs 53.8 pg/mL, P=.041). Obese women were significantly less likely to rate their health as excellent/very good (28.6% vs 56.5%, P=.022) and had statistically significant lower FSH (P=.021) and SHBG (P<0.001) but higher C-peptide (P=.019) compared to lean patients. Women were divided into 4 groups (obese or lean with and without cancer) with significant differences found in age (lean women with cancer were older, P=.006), FSH (obese women with cancer had lower levels, P=.012), SHBG (highest in lean women without cancer, P=.02) but not estradiol, androstenedione, C-peptide or diet/exercise. CONCLUSION: Estradiol levels in postmenopausal women with cancer were lower than benign patients and did not correlate with obesity or other diet/exercise habits.

Sex Differences in Effects of Obesity on Reproductive Hormones and Glucose Metabolism in Early Puberty.

Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty. To assess sex differences in effects of obesity on reproductive hormones and their relation to insulin sensitivity and secretion. Cross-sectional study including anthropometrics, serum and urine reproductive hormone concentrations, and intravenous glucose tolerance testing (IVGTT) to assess acute insulin response to glucose (AIRg), and insulin sensitivity (Si). Outpatient academic clinical research center. Girls (52%) and boys (48%) who were normal weight (NW; n = 51, BMI-Z score = -0.11 ± 0.77, age = 11.5 ± 1.7 years) and obese (n = 53, BMI-Z score = 2.22 ± 0.33, age = 10.9 ± 1.5 years), Tanner stage 2 to 3. Boys with obesity had lower total testosterone (P < 0.0001) and higher concentrations of the urinary estradiol metabolite, E1c, (P = 0.046) than boys with NW. Girls with obesity had higher free androgen index (FAI; P = 0.03) than NW girls. Both boys and girls with obesity had lower sex hormone-binding globulin (SHBG; P < 0.0001) than NW. AIRg was inversely related to SHBG in boys (R = 0.6, P < 0.0001) and girls (R = 0.53, P = 0.0001). Si correlated with higher SHBG in boys (R2 = 0.67, P < 0.0001) and girls (R = 0.5, P = 0.0003), higher total testosterone for boys (R = 0.39, P = 0.01), and lower FAI for girls (R = -0.2, P = 0.04). Youth with obesity have lower SHBG than youth with NW, but obesity has differential effects on reproductive hormones in girls versus boys, which are apparent early in puberty. Ongoing longitudinal studies will evaluate the impact of obesity on reproductive hormones in girls and boys as puberty progresses.

Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later.

Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). Province of Uusimaa and Northern Finland. At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

Male PCOS equivalent and nutritional restriction: Are we stepping forward?

Polycystic ovarian syndrome (PCOS) is an endocrine disorder characterized by alteration of menses, polycystic ovaries, clinical and or biochemical signs of hyper-androgenism in the context of metabolic abnormalities such as obesity and insulin resistance that play a fundamental role in pathogenesis of the disease as well as in development of long-term complications including cardiovascular disease (CVD) and type II diabetes mellitus (DM II). Latest evidence supports the hypothesis of a genetic component in the aetiology of PCOS that seems to be inherited through an oligo-genic mechanism and cluster in families. Recent studies identified the existence of a male PCOS correspondent syndrome in which the genes responsible for PCOS susceptibility in women may be inherited by male relatives of women with PCOS. The same hormonal, clinical and metabolic alterations of women with PCOS have been found in their male relatives suggesting a relation between the syndrome in its male equivalent.Considering clinical manifestations of male PCOS equivalent, the early onset andro-genetic alopecia (AGA) is considered a clinical marker of insulin resistance, supported by the findings of a case-control study that reported an increased prevalence of hyperinsulinemia and insulin-resistance-associated disorders such as dyslipidaemia, hypertension and obesity, in men with early onset of alopecia (<35), compared with age-matched controls. Moreover, AGA and insulin resistance show higher levels of active androgens, highlighting that low SHBG levels occur in both the diseases and that the two conditions may concur to a worsening of the disease. With regards to the existence of a male PCOS equivalent syndrome, in particular with refer to its phenotypic hallmark of early onset AGA, our hypothesis supposes a beneficial effect of diet restriction used for PCOS as therapy for male patients affected by PCOS equivalent syndrome. Several observational studies and some randomized trials reported that modest reductions of body weight decrease the risk of development of many diseases, including diabetes and cardiovascular disease and contributes to increase insulin sensitivity in PCOS women. Weight reduction may be adopted for men affected by PCOS equivalent syndrome in order to reduce both levels of circulating androgens, insulin resistance and related-complications such as CVD and DM II.

Human Reproductive Health in Relation to Thyroid Alterations

Background: Thyroid alterations have adverse effects on other health systems in the body, and reproductive system is one of the most affected organs. Here, we perform a comprehensive analysis on the effects of different thyroid abnormalities on sexual and reproductive-related hormones in both men and women in different age groups. Method: A comprehensive analysis was performed on 15,043 subjects within the reproductive age (15 - 49 years). They were tested for thyroid markers (TSH, FT4, anti-TPO, anti-Tg) and 13 reproductive hormones in Vibrant America Clinical Laboratory between March 2016 to July 2018. The alterations of each reproductive hormone in hypothyroidism, hyperthyroidism, anti-TPO+ anti-Tg+ groups were evaluated. Results: A total of 10,626 women was tested. Women with hypothyroidism had elevated cortisol and low SHBG and DHEA-S. Women with hyperthyroidism showed elevated total testosterone and SHBG. Women seropositive for anti-TPO had elevated total testosterone and low cortisol. Women seropositive for anti-Tg had low parathyroid hormones. Similarly, a total of 4417 men was tested. Men with hypothyroidism had low IGF-I. Similarly, men with hyperthyroidism had low DHEA-S, but elevated estradiol, FSH, LH and prolactin. Men seropositive for anti-TPO had elevated SHBG and low progesterone. Men seropositive for anti-Tg had elevated progesterone. The reproductive and related hormone levels of age group 36 - 49 showed the most variations. Conclusion: Our results clearly show that individuals with different thyroid alterations have different effects on reproductive health, especially in the age group 36 - 49. Hence, routine testing and follow-up checkups on reproductive system would be beneficial for individuals in the age group 36 - 49 with thyroid disorders.

PO-289 Lipidomic analysis of blood serum from prepubertal boys with different BMI

Objective Childhood obesity is a worldwide health problem which may causes metabolic diseases such as hyperglycemia, hyperlipidemia, hypertension and hyperuricemia. It is well know that lipid metabolites regulate fatty acid and glucose homeostasis. Lipidomics is the comprehensive analysis of lipid metabolites which include their quantitation and metabolic pathways. The intention of this study is to identify the circulating lipid species which are altered in obese prepubertal boys.&#x0D; Methods A total number of 72 boys aged 10.28 ±0.69 years old were included into this study, and divided into normal(NC), overweight(OW) and obese group(OB). The degree of maturation of all boys were measured by bone age and sex hormones. Then we measured the form indexes, blood lipids, blood glucose level to identify the current state of all boys. Serum indexes were detected by CLIA and ELISA methods. A lipidomic method was established by using a Waters Acquity UPLCI-Class liquid system combined with Waters Xevo G2-SQ-TOF mass spectrometry system. The identification and analysis of lipid metabolites were complished by using MassLynx 4.1, Progenesis QI software and LipidMaps database. Statistical analyzes were performed using SPSS22.0 software.&#x0D; Results (1)The waist-to-hip ratio, bone age and HDL-c levels ware significant lower in OW and OB groups. The TG level was significant higner in OB group. The DHEA and SHBG levels was significant higner in OW and OB groups and the other sex hormones are not .&#x0D; (2) In this study, 153 most significant different lipid metabolites were founded, incluing 3 diacylglycerol, 32 triglyceride, 1 Phosphatidyl cholines, 1 Phosphatidylinositol, 3 Sphingomyelin, 1 Ceramide which significant higher in OW&amp;OB group; 4 diacylglycerol, 17 Phosphatidic acid, 32 Phosphatidyl cholines, 4 Phosphatidylinositol, 13 Phosphatidylserine, 18 Phosphatidyl ethanolamine, 3 Phosphoglycerides, 13 Sphingomyelin and 6 Ceramide which significant lower in OW&amp;OB group.&#x0D; Among all this metabolites, 8 lipids (fold change ≥5) were founded as the significant biomarkers related prepubertal obesity , including 1 Phosphatidyl cholines, 1 phosphatidylserine, 2 sphingomyelin and 4 Triglyceride. What’s more, the level of SM(d16:1/24:0) and TG(15:0/17:1/20:3) which measured by UPLC-QTOF/MS are highly positive correlated with the level of serum SHBG; PC(18:0/0:0) and TG(16:1/18:0/20:3) are highly negtive correlated with serum SHBG.&#x0D; Conclusions Overweight and obese prepubertal boys showed disorder in lipid metabolism and bone growth. The lipidomic results showed lower SHBG level is related with the disorder of lipid metabolism. We suggest that further studies on these metabolites could help us gain a better understanding of the relationship between obesity and growth disorder.

Relationship between umbilical cord sex hormone binding globulin, sex steroids, and age at menarche: a prospective cohort study

To study the role of the prenatal environment in regulating reproductive development by measuring the prospective association between umbilical cord concentrations of sex hormone binding globulin (SHBG; principal regulator of sex steroid activity), bioavailable sex steroids, and age at menarche. Prospective population-based cohort. Not applicable. In 286 female members of the Western Australian Pregnancy (Raine) cohort, concentrations of SHBG and steroids (estrogens: estrone, estradiol, estriol and estetrol [E4]; androgens: total testosterone, Δ4-androstenedione, androstenedione and dehydroepiandrosterone) were measured by liquid chromatography-tandem mass spectrometry from archived umbilical cord blood samples collected at birth. Bioavailable concentrations of testosterone and estradiol were calculated along with total composite measures of androgen and estrogen bioactivity. SHBG was measured by ELISA. None. Age of menarche was calculated from date of menarche, collected prospectively by questionnaire sent home with participants at the year 10 follow-up. Higher maternal education, higher body mass index, and the presence of antepartum hemorrhage were all significantly associated with earlier age at menarche. The bioavailable sex steroid measures accounted for 8.3% of the variance in age at menarche. Further, both SHBG and E4 concentrations accounted for a significant proportion of unique variance in age at menarche. Lower SHBG and higher E4 concentrations in umbilical cord blood were associated with earlier age at menarche. These results suggest that the prenatal sex steroid environment contributes toward pubertal development and age at menarche.

Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis.

Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones. To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP. Cohort study. Cross-sectional sample included 2371 postmenopausal women and 2688 men free of CVD, of which 2041 women and 2348 men were included longitudinally. NT-proBNP at baseline (2000 to 2002) and one or more repeat NT-proBNPs (through 2012). Analyses adjusted for CVD risk factors. Women had higher NT-proBNP than men (median 79.9 vs 38.5 pg/mL). Cross-sectionally, higher bioavailable T, free T, DHEA, and lower SHBG levels were independently associated with lower NT-proBNP among both women and men (all P < 0.05). Higher total T in women and estradiol in men were also associated with lower NT-proBNP (both P < 0.05). Longitudinally, in women, higher total T, bioavailable T, free T, DHEA, and lower estradiol and SHBG were associated with greater 10-year increase in NT-proBNP (all P < 0.05). In men, higher free T and estradiol were associated with greater NT-proBNP increase (both P < 0.05). A more androgenic sex hormone pattern was inversely associated with NT-proBNP cross-sectionally and may contribute to sex differences in NT-proBNP. Longitudinally, a more androgenic sex hormone pattern was associated with greater increase in NT-proBNP in women, which may reflect a mechanism for CVD risk after menopause.

Testosterone level in aging male with different glucose tolerance state and its association with osteocalcin

Objective: To investigate the relationship of testosterone and different glucose tolerance state, and its association with osteocalcin.Methods: A cross-sectional study was conducted of 1176 males aged 60–97 years who were arranged for an annual regular checkup from March to May 2012 in Chinese PLA general hospital in Beijing.Results: Individuals categorized as having prediabetes or diabetes were more likely to have lower osteocalcin, testosterone, and SHBG levels compared to those with normal glucose tolerance (p < .05 in males). In aging males, after adjusting for age, the negative association between osteocalcin and BMI, waist circumference, FPG, 2hPBG, or TG were significant. And serum TT was negatively associated with BMI, waist circumference, FPG, 2hPBG, or TG independent of age, ALP, Ca, P, VitD, and PTH.Conclusions: It showed that serum osteocalcin and TT were closely related with BMI, blood glucose, and TG, which supported the hypothesis that regulation of bone remodeling, energy metabolism, and reproduction are linked.