Sex Hormone-binding Globulin In Women Research Articles

Abstract P219: Associations Between Endogenous Sex Hormone Levels And Adipokine Levels In The Multi-ethnic Study Of Atherosclerosis (MESA)

Background: Differences in sex hormone levels contribute to sex differences in cardiovascular disease (CVD). Adipokines, which are central to cardiometabolic disease, differ by sex and have divergent associations with CVD. However the link between sex hormones and adipokines is not well established. We hypothesized that an androgenic sex hormone profile is associated with higher leptin & resistin and lower adiponectin levels among postmenopausal women and men. Methods: We performed an analysis of 1822 adults in MESA who had sex hormones and adipokines measured. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG)] were measured at exam 1; free T was estimated. Serum adipokines [leptin, resistin, adiponectin] were measured at visits 2 or 3, an average of 2.6 yrs later. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. Results: The mean age was 63 (10), 48% were women; 41% White, 13% Chinese American, 20% Black, 26% Hispanic. Leptin: After adjusting for demographics (model 1), higher free T & E2 and lower SHBG were associated with greater leptin levels in women and men; higher DHEA was associated with lower leptin in men ( Table ). With full covariate adjustment (model 3), this remained statistically significant for E2 & SHBG in women and for DHEA in men. Adiponectin: With demographic adjustment, higher free T, E2, DHEA & lower SHBG were associated with lower adiponectin in women, and higher free T & lower SHBG with lower adiponectin in men. After full covariate adjustment, these same relationships were slightly attenuated but remained significant for women and men. Resistin: no association in either sex. Conclusion: A more androgenic profile (higher free T & lower SHBG) was independently associated with lower adiponectin in men and women. Higher E2 & lower SHBG in women, and lower DHEA in men, were associated with leptin. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines and CVD risk.

Tree nut consumption is associated with higher sex hormone-binding globulin levels in premenopausal US women

Low levels of sex hormone-binding globulin (SHBG) are associated with many diseases including hypertension, diabetes, and polycystic ovarian syndrome. Walnuts increased circulating SHBG in 31 women complicated with polycystic ovarian syndrome. However, whether tree nuts increase SHBG in women in a general population is unknown. It was hypothesized in this study that consumption of tree nuts was positively associated with SHBG levels in women in a general population. This cohort study included 2699 adult women from the 2013- to 2016 US National Health and Nutrition Examination Survey. Tree nut consumers were defined as those who consumed tree nuts on either of the 2 24-hours recall days. Associations of tree nut consumption with SHBG were assessed using least squares regression. Among the 2699 women, 234 were consuming tree nuts. The median SHBG concentrations were 67.1 and 59.3 nmol/L among tree nut consumers and non-consumers, respectively. Tree nut consumption was positively associated with circulating SHBG (β=0.041, P=.018) but not testosterone nor estradiol after adjustment for all tested confounders. Sub-analyses showed that the positive association of tree nuts with SHBG presented in premenopausal women but not in postmenopausal women. Tree nut consumption remained independently associated with higher circulating levels of SHBG in premenopausal women when tree nut consumption was expressed as percentage of energy derived from tree nuts or when tree nut consumption was defined as a tree nut intake of ≥0.25 ounce per day. Future research will verify the effectiveness of using tree nuts to treat low SHBG in premenopausal women in the general population.

A phenome-wide association study of genetically mimicked statins

BackgroundBeyond their success in cardiovascular disease prevention, statins are increasingly recognized to have sex-specific pleiotropic effects. To gain additional insight, we characterized associations of genetically mimicked statins across the phenotype sex-specifically. We also assessed whether any apparently non-lipid effects identified extended to genetically mimicking other widely used lipid modifiers (proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) or were a consequence of low-density lipoprotein cholesterol (LDL-c).MethodsWe performed a sex-specific phenome-wide association study assessing the association of genetic variants in HMGCR, mimicking statins, with 1701 phenotypes. We used Mendelian randomization (MR) to assess if any non-lipid effects found were evident for genetically mimicked PCSK9 inhibitors and ezetimibe or for LDL-c.ResultsAs expected, genetically mimicking statins was inversely associated with LDL-c, apolipoprotein B (ApoB), and total cholesterol (TC) and positively associated with glycated hemoglobin (HbA1c) and was related to body composition. Genetically mimicking statins was also inversely associated with serum calcium, sex hormone-binding globulin (SHBG), and platelet count and positively associated with basal metabolic rate (BMR) and mean platelet volume. Stronger associations with genetically mimicked statins were evident for women than men for lipid traits (LDL-c, ApoB, and TC), calcium, and SHBG, but not for platelet attributes, body composition, or BMR. Genetically mimicking PCSK9 inhibitors or ezetimibe was also associated with lower lipids, but was not related to calcium, SHBG, BMR, or body composition. Genetically higher LDL-c increased lipids and decreased BMR, but did not affect calcium, HbA1c, platelet attributes, or SHBG with minor effects on body composition.ConclusionsSimilar inverse associations were found for genetically mimicking statins on lipid traits in men and women as for other lipid modifiers. Besides the positive associations with HbA1c, BMI (which may explain the higher BMR), and aspects of body composition in men and women, genetically mimicking statins was additionally associated with platelet attributes in both sexes and was inversely associated with serum calcium and SHBG in women. This genetic evidence suggests potential pathways that contribute to the effects of statins particularly in women. Further investigation is needed to confirm these findings and their implications for clinical practice.

The role of sex hormones and inflammation in the causal pathway of high bmi to knee oa the role of sex hormones and inflammation in the causal pathway of high bmi to knee OA

Purpose: There is consistent evidence of the high impact of increased BMI on knee OA and knee pain. There is also some evidence that hormone levels are associated to OA, though this relationship is influenced by BMI. We hypothesized that the decreasing hormone levels may play a role in the causal pathway that leads to a higher prevalence and incidence of knee OA and pain at least in women. Therefore, we tested this hypothesis by using Structural Equation Modeling (SEM) in men and women independently. The aim of this study was to explore the causal relationships between sex hormones, inflammation factors and BMI in radiographic knee OA (RKOA) and chronic knee pain (CKP). Methods: We used the Rotterdam Study cohort, a population based prospective study with participants aged 45 and older. The participants underwent an interview on pain questionnaire, blood and radiographic measurements at baseline as well as follow-up radiographic measurements. In our study for prevalent radiographic knee OA (RKOA) we included a total of 12,546 observed knees of which 606 were knee OA cases. For incident radiographic knee OA, from the 11,940 knees without OA, 4,090 were lost to follow-up, so we included 7,850 knees without knee OA at baseline from which 533 developed knee OA during a median follow-up time of 5 years. RKOA was defined as a KL score of 2 or higher. Participants provided answers during a home interview about current musculoskeletal pain in the knees, hips, hands and lower back. If present, the duration was also recorded. We included 5,897 participants in our analysis for prevalent chronic knee pain (CKP). There were 2,349 participants with CKP and 3,548 with no pain in either of their knee joints. CKP was defined as having pain in the knee joint for more than 3 months. We estimated the direct and indirect effects of BMI, CRP, estradiol and sex hormone binding globulin (SHBG) on prevalence and incidence of RKOA and CKP by using SEM. SEM is a multivariate statistical analysis technique that is used to analyze structural relationships. Results: Our results from the SEM analysis on the prevalence of RKOA (Figure 1), show that BMI has a significant association with an effect estimate of 0.1 on RKOA in women. The indirect effects from BMI through estradiol or through SHBG to RKOA were also present only in women but with a much smaller effect estimate (estimate=0.004 through estradiol, estimate=0.01 through SHBG) compared to the direct effect of BMI. In contrast, we found an indirect effect from BMI through CRP to RKOA (estimate=-0.01) only in men. In case of CKP, we did not find indirect effects of BMI though the sex hormones or CRP in neither women nor men. BMI has a strong direct effect on CKP in both women (estimate = 0.18) and men (estimate = 0.15) as shown in Figure 2. The SEM models showed good indices of fit: CFI (Comparative Fit Index) and the RMSEA (Root Mean Square Error of Approximation). CFI should be above 0.95 and RMSEA below 0.05. For the RKOA model: CFI=0.98 and RMSEA=0.046. For the CKP model: CFI=0.98 and RMSEA=0.038. Conclusions: We found indeed indirect effects of BMI on RKOA through estradiol and SHBG in women, but not in men. However, the contribution of the path through sex hormones is negligible to the total effect of BMI on RKOA. In men we found a (small) indirect effect of BMI on RKOA through CRP, a well-known inflammation factor. Curiously, this effect was protective.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Effect of 7‐Day Whey Protein Supplementation on Steroid Hormones and SHBG in Women with Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of child‐bearing age and is associated with obesity, infertility, insulin resistance, and hyperandrogenemia. Sex‐hormone binding globulin (SHBG) is suppressed as a result of hyperinsulinemia leading to an increase in free testosterone levels commonly observed in PCOS women. High levels of free testosterone contributes to hirsutism, acne, and irregular menstrual cycles in this population resulting in the need for interventions aimed at increasing SHBG concentration in PCOS women. Subsequently, estradiol and progesterone levels suffer in this population resulting in irregular menstrual cycles and infertility. Current treatments for PCOS target symptoms of the disease but not the underlying mechanisms, and typically are associated with adverse side effects. Nutritional interventions, therefore, that can ameliorate PCOS‐related issues are warranted. Whey protein has recently been shown to have improved glycemic homeostasis, reduced chronic inflammation and enhanced protein anabolism effects in people with or without insulin resistance. The purpose of this study was to examine changes in SHBG and free testosterone concentrations following 7 days of whey protein supplementation and to examine differences in baseline measurements of progesterone and estradiol between PCOS women and healthy controls (CON). Women with PCOS and CON consumed 35g of whey protein for 7 days. Baseline and Day 7 concentrations were measured via plasma and serum collection. Progesterone and estradiol concentrations were measured at baseline only whereas free testosterone and SHBG concentrations were measured at baseline and Day 7. Protocols used in this study were approved by the TWU Institutional Review Broad (IRB). Initial analyses indicate progesterone levels were lower in the PCOS group compared to CON. Currently, no other statistical differences are reported at baseline nor over time in any other variable. Additional analyses are currently being conducted. Seven days whey protein supplementation is not a viable intervention to increase fertility in PCOS women by enabling changes in steroid hormone and globulin binding concentrations. Future studies will include a prolonged intervention period to establish potential changes in the aforementioned hormones following chronic whey protein supplementation.Support or Funding InformationGlanbia Nutritionals, Inc., TWU Research Enhancement Program, TWU Human Nutrition Research funds

Sex Hormone-binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes: A Longitudinal Study and Meta-analysis.

Objective:This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM.Methods:We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18–40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10–14, 15–26, 23–31, and 33–39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk.Results:SHBG levels at gestational weeks 10–14 were significantly inversely associated with fasting insulin (r = −0.17, P = 0.01) and insulin resistance as measured by HOMA-IR (r = −0.17, P = 0.01) at gestational week 15–26. SHBG at gestational weeks 10–14 and 15–26 was lower in cases than controls (mean ± standard deviation: (204.0 ± 97.6) vs. (220.9 ± 102.5) nmol/L, P = 0.16 and (305.6 ± 124.3) vs. (322.7 ± 105.1) nmol/L, P = 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, P < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76–0.95, P = 0.01) for GDM.Conclusion:Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.

Association between CYP19A

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A <G rs700518 variants on sex hormones level and the risk of AV. In this case-control study, 181 patients with AV and 144 healthy individuals from Western Iran were investigated. The CYP19 variants were detected by PCR-RFLP method. The frequency of GG genotype in all patients (27.1%) was significantly higher than the controls (10.4%, P<0.001), which increased the relative risk of AV by 1.96 times. Also, the presence of this genotype was associated with 1.5-fold (P=0.005), 1.89-fold (P=0.011) and 3.33-fold (P=0.019) increased risk of mild, moderate and severe AV, respectively. A significantly higher serum level of estradiol was observed in women in the presence of AA genotype (107.3±72.1 pg/ml) in comparison with GG genotype (73.2±58.8 pg/ml) (P=0.009). Our study demonstrated that the GG genotype of CYP19 rs700518 polymorphism increased the risk of AV and the severity of the disease, and also was associated with lower levels of estradiol in females. Significantlydecreased serum level of sex hormone-binding globulin in women with AV in comparison with healthy individuals could be related to increasing level of androgen that was observed in women with AV.

TESTOSTERONE AND SEX HORMONE-BINDING GLOBULIN IN DYSGLYCEMIC WOMEN AT HIGH CARDIOVASCULAR RISK: A REPORT FROM THE OUTCOME REDUCTION WITH AN INITIAL GLARGINE INTERVENTION TRIAL

The role of testosterone and sex hormone-binding globulin (SHBG) in female cardiovascular disease and dysglycemia is debated. The present objective was to investigate the prognostic impact of total (TT) and free testosterone (FT) and SHBG in women at high cardiovascular risk and dysglycemia.

Testosterone Levels in Third Trimester in Polycystic Ovary Syndrome: Odense Child Cohort.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism. In pregnancy, testosterone levels may be higher in women with PCOS compared with controls. To compare total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) levels in third-trimester pregnant women with PCOS and controls and to establish reference ranges for TT, FT, and SHBG in PCOS and controls. The study was part of the prospective study, Odense Child Cohort. PCOS was diagnosed by questionnaires and/or patient records. Fasting blood samples were collected at gestational week 28 and plasma TT was measured by liquid chromatography-tandem mass spectrometry in women with PCOS (n = 145) and in women without PCOS (controls, n = 1341). Levels of TT (mean, 2.4 vs 2.0 nmol/L) and FT (mean, 0.005 vs 0.004 nmol/L) were higher, whereas SHBG levels (mean, 447 vs 477 nmol/L) were lower in women with PCOS vs controls (all P < 0.001). Reference intervals for TT, FT, and SHBG in women with PCOS and controls were overlapping, and partitioning of reference intervals was an ambiguous decision. In multiple regression analyses, TT and FT levels were positively associated with PCOS status and BMI and inversely associated with age and parity. Offspring sex did not predict maternal TT and FT. TT and FT levels were higher in third-trimester pregnant women with PCOS compared with controls. Separate reference interval for FT in women with PCOS should be considered.

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

Sex hormone-binding globulin has no effect on salivary testosterone.

We would like to follow up our 2014 publication in this journal by submitting further validation data to support the measurement of salivary testosterone (T), highlighting its independence from variations in circulating sex hormone-binding globulin (SHBG), unlike serum total T which is positively correlated with SHBG. All analyses were performed as previously described. In addition, further samples were collected from, 48 males and 38 females, healthy volunteers (mean age 32 y, range 18–66). Ethical committee approval was granted from Ghent University Hospital. These samples were analysed for salivary T, total T and equilibrium dialysis using liquid chromatography-tandem mass spectrometry. Figure 1 shows that: (i) serum total T is significantly and positively correlated with SHBG in both men (n1⁄4 93) and women (n1⁄4 86); (ii) serum calculated free T is not correlated with SHBG in men but negatively correlated with SHBG in women; (iii) salivary T is not correlated with SHBG in either men or women; (iv) serum-free T measured using equilibrium dialysis is not correlated with SHBG in men (n1⁄4 48) but, like calculated free T, is inversely correlated with SHBG in women (n1⁄4 38). These results demonstrate that salivary T is not influenced by variations in serum SHBG, unlike the analogue serum free T direct assay. The sexually dimorphic relationship between free T, whether calculated or measured by equilibrium dialysis, and SHBG, is an interesting observation which, to the best of our knowledge, has not been previously reported.

The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial

BackgroundFindings from observational studies suggest that sex hormone-binding globulin (SHBG) and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels.FindingsAfter a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42) were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group) per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate].No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone.ConclusionsOur data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.

Postmenopausal Sex Hormones in Relation to Body Fat Distribution

Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate whether a woman's body fat distribution shows a BMI-independent association with these breast cancer-related biomarkers. Performing cross-sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist-to-hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI < 30 kg/m(2) but not in women with a BMI ≥ 30 kg/m(2). The latter suggests that in obese women, a possibly unique effect of abdominal fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG-related sex hormones (free estradiol and free testosterone) independently of BMI.

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome

Background This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS). Study Design Forty women with PCOS (age 16–35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS). Results In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20–50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD. Conclusions Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism.

Differences in Sensitivity to Cold in Japanese Men and Postmenopausal Women Aged ≥50 Years

Sensitivity to cold is associated with several factors, such as aging, sex, and body composition. However, no previous studies have examined the differences in sensitivity to cold in men and women or the association of hormonal levels with sensitivity to cold. The aim of the present study was to clarify both the change in sensitivity to cold with aging and the difference in sensitivity to cold between men and women. Associations were also examined between circulating hormonal concentrations and the changes with aging and differences in sensitivity. This population-based cohort study enrolled healthy Japanese men and women aged > or = 50 years. A standardized 210-item health questionnaire was used to obtain information on symptoms of sensitivity to cold. Serum concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin (SHBG) were measured. Of the 154 men and 180 women enrolled in this study, more women than men had sensitivity to cold. Whereas the percentage of men who had sensitivity to cold significantly increased with aging (P < 0.05), the percentage of women who had sensitivity to cold was already high (23.7%) at 50 to 60 years of age and did not change with aging. In men, advancing age and low body mass index (BMI) were significantly associated with sensitivity to cold (P < 0.05); however, age and BMI in women were not similarly associated. In addition, the effect of sex after adjustment for age was significant (P < 0.05), and there was also a numeric but nonsignificant effect of sex after adjustment for BMI. In men, low serum levels of the gonadal hormone FSH were significantly associated with sensitivity to cold in logistic analysis, but this association was nonsignificant after multivariate analysis. Serum concentrations of gonadal hormones and SHBG in women were not associated with sensitivity to col. The association of age with sensitivity to cold was different in men and women; the association of BMI with sensitivity to cold might be different in men and women. In addition, these changes in sensitivity to cold were not associated with circulating hormonal concentrations.

Differences in Free Estradiol and Sex Hormone-Binding Globulin in Women with and without Premenstrual Dysphoric Disorder

Over the years, different hypotheses involving the ovarian steroid hormones have been proposed to explain the luteal phase occurrence of severe premenstrual syndrome symptoms. Although it had been strongly suspected that differences in the concentrations of the ovarian steroids may underlie the mood and psychological imbalance of this disorder, the evidence for this hypothesis has been inconsistent and remains controversial. Our objective was to measure the ovarian steroid hormones across the menstrual cycle in women with and without luteal phase symptoms consistent with premenstrual dysphoric disorder (PMDD). We measured estradiol (E2), progesterone, and SHBG in women with and without PMDD using a cross-sectional and prospective experimental design. Participating women underwent 2-month self-assessment symptom screening and 1-month hormonal evaluation. Overall means for LH, progesterone, E2, peak E2, and free E2 were not different between groups. Across the menstrual cycle, overall percent free E2 was significantly lower and SHBG significantly greater in the PMDD group compared with controls (1.39 +/- 0.26 vs. 1.50 +/- 0.28, P = 0.03; 61.4 +/- 25.1 vs. 52.4 +/- 21.3 nmol/liter, P = 0.046, respectively). During the luteal phase, free E2 was significantly lower in the PMDD group compared with controls (PMDD 7.6 +/- 7.0 vs. controls 8.9 +/- 8.4 pmol/liter; P = 0.032). For both follicular and luteal phases, SHBG was significantly higher in the PMDD group (follicular phase 60.5 +/- 31.7 vs. 51.4 +/- 38.2 nmol/liter, P = 0.047; luteal phase 65.1 +/- 32.3 vs. 55.1 +/- 38.9 nmol/liter, P =0.03). In both groups, SHBG significantly increased from the follicular to luteal phase. Luteal phase concentrations of free E2, percent free E2, and SHBG differ significantly between women with and without PMDD.

Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS

Decreased high-density lipoprotein cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels, and the metabolic syndrome, are all closely associated with a higher prevalence of atherosclerotic cardiovascular disease. We investigated the association between HDL-C, SHBG and the metabolic syndrome in women with polycystic ovary syndrome (PCOS). Among 106 young Taiwanese women (mean age +/- SD, 24.9 +/- 4.8 years) with PCOS, 69 (65.1%) women had an HDL-C level <50 mg dl(-1). The level of HDL-C was highly correlated with that of serum SHBG (gamma = 0.6034, P < 0.0001). The SHBG level was significantly lower in subjects with an HDL-C <50 mg dl(-1) than that in subjects with an HDL-C > or =50 mg dl(-1). Using multiple linear regression models with adjustment for age, BMI and other anthropometric, metabolic, liver function and hormonal variables, we showed serum SHBG to be independently correlated with HDL-C. Based on logistic regression analysis with adjustment for age, the SHBG level was significantly lower in women with PCOS with the metabolic syndrome (odds ratio = 0.92, P = 0.003). Low levels of SHBG in women with PCOS were associated with low levels of HDL-C, independent of insulin resistance and obesity. The SHBG level was inversely related to the occurrence of metabolic syndrome, further strengthening the potential link between SHBG levels and cardiovascular disease in women with PCOS.

Is sex hormone‐binding globulin associated with glucose tolerance?

Women with a reduced concentration of sex hormone-binding globulin (SHBG) in the first trimester of pregnancy are at increased risk of developing gestational diabetes. Furthermore, a lower concentration of SHBG in women with gestational diabetes identifies women at increased likelihood of requiring insulin treatment. The aim of this study was to explore the relationship of SHBG concentration in pregnancy to insulin resistance and glucose tolerance. Prospective cohort study of 220 pregnant women who attended The Royal North Shore Hospital in Sydney, Australia between August 2002 and June 2003 for their 75-g glucose tolerance test. All tests were performed in the morning after the women had fasted for at least 10 h. To test for differences between patients with or without gestational diabetes, t-tests and chi-square tests were used. Stepwise linear regression was used to determine the independent predictors of SHBG. The mean concentration of SHBG increased linearly with gestational age. Statistically significant predictors of SHBG from the stepwise regression were gestational age (P < 0.001), insulin resistance (P < 0.001) and body mass index (P = 0.003). Glucose tolerance as assessed by either a fasting or 2-h glucose tolerance test did not predict SHBG concentration in this population. In addition, there was no significant difference in the concentration of SHBG between patients categorized as normal glucose tolerance or gestational diabetes (P = 0.77). This remained the case when SHBG was expressed as SHBG/insulin ratio as suggested by Bartha et al. (Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scanda 2000; 79: 839-845) (P = 0.10). In a cross-sectional study of pregnant women, we find no association between SHBG concentration and glucose tolerance.

Hormonal status and NIDDM in the European and Melanesian populations of New Caledonia: a case-control study. The CALedonia DIAbetes Mellitus (CALDIA) Study Group.

To assess ethnic differences in androgenic status related to non insulin-dependent diabetes mellitus (NIDDM) in male and female Melanesians and Europeans of New Caledonia. This is a case-control study nested in a prevalence study for diabetes mellitus in the multiracial population of New Caledonia. 186 male subjects were included in the survey (77 Melanesians and 16 Europeans in each case and control group). Each case and control group included 104 female Melanesian subjects (69 premenopausal and 35 postmenopausal). Diabetic subjects were matched for age, gender, ethnic group and location, with healthy normoglycaemic subjects. Testosterone levels in men and sex hormone-binding globulin (SHBG) levels in women (measured by radioimmunoassay, RIA) were compared between NIDDM and control subjects in relation to obesity, central adiposity and insulin levels. In both ethnic groups, NIDDM was associated with lower testosterone levels but there was a marked difference among Europeans. Testosterone was negatively associated with the body mass index (BMI) (r= -0.35, P <0.01) and fasting insulin (r= -0.37, P <0.001) in control Melanesians only. In Melanesian women, NIDDM was associated with lower SHBG levels in pre- and postmenopausal women (P <0.001). SHBG mean level was not associated with menopausal status. Our results confirm in a Pacific population that NIDDM is associated with low levels of testosterone in men and low levels in SHBG in women. In contrast to white populations, Melanesian women have a more androgenic profile, whatever their menopausal status.

Sex hormone—binding globulin and insulin resistance in African-American women

Sex hormone—binding globulin (SHBG) binds testosterone, determining the level of free, biologically active hormone, and is a sensitive indicator of androgen status in women. SHBG is strongly correlated with high-density lipoprotein (HDL), central obesity, and insulin sensitivity in Caucasian and Mexican-American women, thereby acting as a biologic marker for cardiovascular disease risk. The purpose of this study was to determine if SHBG was a significant correlated of metabolic cardiovascular risk factors in African-American women. Eighty-one nondiabetic, normotensive African-American women were enrolled (mean age, 30 years). After excluding women on oral contraceptives (n = 19), 62 women were examined during the follicular phase of the menstrual cycle. All subjects underwent an oral glucose tolerance test (OGTT) and a euglycemichyperinsulinemic insulin clamp, and the lipid and sex hormone levels were measured. Correlation analyses showed a significant correlation between SHBG and the following variables in women; central obesity, body mass index (BMI), HDL cholesterol, apolipoprotein B (apoB), insulin sensitivity adjusted for lean mass (M'), and the sum of insulin during the OGTT. The strongest correlates of SHBG in women were measures of insulin resistance ( r = .421, P < .001). SHBG appears to be a biologic marker for insulin resistance, which is linked to cardiovascular risk, in African-American women.