Decrease In Sex Hormone Binding Globulin Research Articles

Combined effects and potential mechanisms of phthalate metabolites on serum sex hormones among reproductive-aged women: An integrated epidemiology and computational toxicology study

The reproductive age is a crucial stage for women to bear offspring. However, reproductive-aged women are simultaneously exposed to various phthalates, which may pose a threat to their reproductive health. This study employed generalized linear regression and weighted quantile sum (WQS) regression to explore the associations between monoesters of phthalates (MPAEs) and sex hormones in 913 reproductive-aged women in the National Health and Nutrition Examination Survey. Key risk factors driving hormone disruption were identified based on the weights of the WQS models. Interaction models were used to unravel the synergistic or antagonistic effects between MPAEs. The potential toxicological targets of MPAEs interfering with sex hormone-binding globulin (SHBG) levels were revealed based on prior knowledge and molecular docking of hepatocyte nuclear factor 4α (HNF4α). Compared with the first quartile, mono-benzyl phthalate (MBZP) in the second quartile exhibited a decrease in total testosterone (TT) and TT/E2 (estradiol) ratio. Mono-2-ethyl-5-carboxypentyl phthalate (MECPP) in the fourth quartile showed a decrease in SHBG and TT/E2. Additionally, mono-(carboxyoctyl) phthalate and mono-(carboxynonyl) phthalate (MCNP) were negatively associated with SHBG. Each unit increase in the WQS index of MPAE mixtures was associated with 6.73 % lower SHBG levels (95 %CI: −12.80 %, −0.24 %) with mono-(3-carboxypropyl) phthalate, MCNP, MBZP, and MECPP identified as major risk factors. Interaction analyses revealed that the effects of high-risk MPAEs on SHBG were predominantly antagonistic. Molecular docking suggested that MPAEs might compete to bind tryptophan residues of HNF4α. This study provides key information to help develop the most effective phthalate interventions and improve the reproductive health of reproductive-aged women.

Hyperandrogenism after menopause: diagnostic evaluation

Excessive androgen levels in women after menopause often result from an imbalance in ovarian steroid secretion: a rapid decline in estrogen secretion associated with a slow decrease in androgen secretion, compounded by a physiological decrease in sex hormone-binding globulin. Hyperandrogenism is associated with a higher risk of cardiovascular events and gynecological neoplasms, also impacting the emotional well-being of affected women. Therefore, the aim of these guidelines is to guide the clinical physician in the appropriate clinical and biochemical evaluation of hyperandrogenism after menopause, thus optimizing therapeutic outcomes. The most frequent consultation in this stage of life is facial hirsutism associated with hair loss. If the onset of signs is abrupt, severe, associated with virilization and accompanied by serum testosterone levels in the male range, it is necessary to rule out a tumoral origin. A thorough medical history guides the diagnosis. Determination of total testosterone using reliable methods and imaging studies are valid tools to assist when doubts arise in the differential diagnosis.

Effects of 8-week strength training on basal hormone levels, sex hormone binding globulin, insulin-like growth factor binding protein-3, oxidative stress markers, and IL-6 levels in adolescent athletes.

The aim of the study was to investigate how 8-week strength training affects adolescent athletes' basal hormone concentrations, sex hormone binding globulin (SHBG), insulin-like growth factor binding protein-3 (IGFBP-3), cytokine, and oxidative stress markers. Twenty adolescent handball players participated in this study. The participants were randomly divided into the strength training group (ST, n = 10) and the control group (C, n = 10). ST participates in strength training 3 sessions a week for 8 weeks and C participates only in handball training. We quantified serum basal hormone concentration, SHBG, IGFBP3, oxidative stress markers, and IL-6 in each subject's blood samples before and after 8 weeks of strength training. Interestingly, while insulin-like growth factor-1 (IGF-1) concentration declined in group C (p < 0.05), it did not in ST (p > 0.05). Furthermore, the basal concentration of growth hormone (GH), total testosterone (T), cortisol (Cor), total antioxidant status (TAS), and serum-free androgen index (FAI) basal concentration did not change in ST and C. Basal IGFBP-3 and SHBG concentrations decreased only in ST (p < 0.05), but not in C (p > 0.05). Serum-free testosterone (FT) levels increased in ST and C (p > 0.05). Total oxidant status (TOS) and oxidative stress index (OSI) reduced ST and C (p < 0.05). Serum interleukin-6 (IL-6) levels did not alter groups ST and C. Strength training did not affect basal serum concentrations of T, GH, IGF-1, COR, IL-6, and TAS, but it caused a decrease in SHBG and IGFBP3 concentrations in ST. Increased basal FT concentration and improved serum TOS may not depend on strength training.

Sex Hormone-Binding Globulin as more than a Biomarker of Metabolic Diseases and Reproductive Disorders: What Physicians Should Know?

Until recent years, Sex Hormone-Binding Globulin (SHBG) has been considered of less a priority in the management of metabolic and chronic inflammatory states. However, emerging research highlights the remarkable role of SHBG in the screening and follow-up of patients not only with metabolic disorders but also in influencing reproductive outcomes. The present review aims to consolidate current knowledge on the involvement of SHBG in various clinical conditions. The search was performed using multiple databases to identify original studies measuring SHBG levels in conditions such as type-2 diabetes, metabolic syndrome (MetS), male obesity secondary hypogonadism, Polycystic Ovarian Syndrome (PCOS), male equivalent of PCOS, Nonalcoholic Fatty Liver Disease (NAFLD), infantile obesity, and early puberty. Among a total of 93,735 studies, 62 met the inclusion criteria, encompassing data from 127,771 subjects comprising both patients and controls. Studies were predominantly cross-sectional and observational cohorts, with MetS and NAFLD being the most extensively investigated conditions. Across all clinical conditions, significantly lower SHBG levels were consistently observed among patients compared to matched controls. The decrease in SHBG was found to be significantly associated with adverse reproductive, metabolic, and cardiovascular outcomes. These findings underscore the importance of considering SHBG as a valuable marker in routine clinical practice. Clinicians are encouraged to recognize the potential of SHBG as a useful marker in the assessment and management of various health conditions within their routine practice.

New evidence for the effect of type 2 diabetes and glycemic traits on testosterone levels: a two-sample Mendelian randomization study.

Type 2 diabetes mellitus (T2DM) is an endocrine-related disease with an increasing incidence worldwide. Male sexual dysfunction is common in diabetic patients. Therefore, we designed a Mendelian randomization (MR) study to investigate the association of type 2 diabetes and 3 glycemic traits with testosterone levels. Uncorrelated single nucleotide polymorphisms (SNPs) associated with T2DM (N = 228), fasting insulin (N = 38), fasting glucose (N = 71), and HbA1c (N = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with testosterone levels (total testosterone, TT, bioavailable testosterone, BT, and sex hormone-binding globulin, SHBG) were obtained from the UK Biobank studies and other large consortia. Two-sample MR analysis was used to minimize the bias caused by confounding factors and response causality. Multivariable MR analysis was performed using Body mass index (BMI), Triglycerides (TG), LDL cholesterol (LDL), and adiponectin to adjust for the effects of potential confounders. Type 2 diabetes mellitus was associated with the decrease of total testosterone (β: -0.021,95%CI: -0.032, -0.010, p<0.001) and sex hormone binding globulin (β: -0.048,95%CI: -0.065, -0.031, p<0.001). In males, total testosterone (β: 0.058, 95% CI: 0.088, 0.028, p < 0.001) decreased. In females, it was associated with an increase in bioavailable testosterone (β: 0.077,95%CI: 0.058,0.096, p<0.001). Each unit (pmol/L) increase in fasting insulin was associated with 0.283nmol/L decrease in sex hormone-binding globulin (95%CI: -0.464, -0.102, p=0.002) and 0.260nmol/L increase in bioavailable testosterone (95%CI: -0.464, -0.102, p= 0.002). In males, sex hormone binding globulin decreased by 0.507nmol/L (95%CI: -0.960, -0.054, p= 0.028) and bioavailable testosterone increased by 0.216nmol/L (95%CI: 0.087,0.344, p= 0.001). In females, sex hormone binding globulin decreased by 0.714 nmol/L (95%CI: -1.093, -0.335, p<0.001) and bioavailable testosterone increased by 0.467nmol/L (95%CI: 0.286,0.648, p<0.001). Each unit (%) increase in HbA1c was associated with 0.060nmol/L decrease in sex hormone-binding globulin (95%CI: -0.113, -0.007, p= 0.026). In males, total testosterone decreased by 0.171nmol/L (95%CI: -0.288, -0.053, p=0.005) and sex hormone binding globulin decreased by 0.206nmol/L (95%CI: -0.340, -0.072, p=0.003). Total testosterone increased by 0.122nmol/L (95%CI: 0.012,0.233, p=0.029) and bioavailable testosterone increased by 0.163nmol/L (95%CI: 0.042,0.285, p=0.008) in females. Using MR Analysis, we found independent effects of type 2 diabetes, fasting insulin, and HbA1c on total testosterone and sex hormone-binding globulin after maximum exclusion of the effects of obesity, BMI, TG, LDL and Adiponectin.

Association Between Dietary Inflammatory Index and Sex Hormone Binding Globulin and Sex Hormone in U.S. Adult Females

ContextIt is still unknown whether the dietary inflammatory index (DII) is associated with sex hormones and sex hormone binding globulin (SHBG) in adult women.ObjectiveThis study examined the association between DII and sex hormones and SHBG in U.S. adult women.Design and ParticipantsThis was a cross-sectional study. A total of 2,092 female participants (age ≥ 20) from the 2013–2016 National Health and Nutrition Examination Survey were enrolled. Dietary inflammatory potential was assessed by DII based on 24-h dietary recall. SHBG was assessed using immuno-antibodies and chemo-luminescence, whereas sex hormones were measured by ID-LC–MS/MS.ResultsThe average DII was 0.21 ± 1.68, ranging from −4.54 (most anti-inflammatory) to 4.28 (most pro-inflammatory). After adjusting all covariates, a per-unit DII increase in DII tertile 3 was related to an 8.05 nmol/L SHBG decrease compared to DII tertile 1 (P = 0.0366). Subgroup analysis stratified by perimenopausal period found that this negative association remained strong but only existed in women before (β = −3.71, 95% CI: −7.43, −0.12, P = 0.0423) the perimenopausal period. Interaction terms were added to both subgroup analyses and found no significant heterogeneity among different body mass index (BMI) or perimenopausal groups (P > 0.05). Treshold analyses showed that the association of age with SHBG was an inverted U-shaped curve (inflection point: age = 50 yrs).ConclusionA proinflammatory diet caused decreased SHBG. However, more well-designed studies are still needed to validate and verify the causal relationship between DII and sex hormones and SHBG.

Abstract P139: Changes In Sex Hormones In Premenopausal Black And White Women Associated With Childbearing: The Cardia Women’s Study.

Introduction: Sex hormone binding globulin (SHBG) levels in blood are associated with bioavailability of sex hormones, glucose metabolism, and cardiometabolic health of premenopausal women. Low SHBG levels are associated with insulin resistance in women. Pregnancy is characterized by 6-10-fold increase in SHBG levels. This study is designed to evaluate the long-term associations among pregnancy, and SHBG, free and total testosterone levels in premenopausal women. Methods: Premenopausal women, aged 20-32 years, from the CARDIA Women’s Study cohort were tested for levels of serum SHBG, free testosterone, and total testosterone. Hormonal, anthropometric, socio-demographic, and behavioral data, along with self-reported pregnancy and birth data, were collected at baseline (1987-88 [Y0]; n=1,191) and after eight years (Y8; n=809) and 14 years (Y14; n=474) for follow-up. Participants who were pregnant, breastfeeding, had diabetes, hysterectomy, or were using oral contraceptive at any time point were excluded. Participants were divided in parity groups of 0, 1, and 2+births for analyses. Eight-year decrements of SHBG, free and total testosterone were used for primary analyses and 14-year decrements were used for secondary analyses Results: SHBG levels decreased more in parous than nulliparous women in a fully adjusted model including race, CARDIA field center, age, education, alcohol, smoking status, baseline BMI, weight gain and change in waist girth. Total testosterone decreased more in parous women between Y0-Y10 but not thereafter. No significant differences in free testosterone levels were observed among parity change groups in fully adjusted models. Hormone decrement analyses from fully adjusted model Conclusion: Childbearing is associated with a more pronounced long term decrease in SHBG but not with free testosterone levels in premenopausal women. A strong association was observed among parity and total testosterone decrements at 8-year but not 14-year follow-up.

Sexual function and metabolic/hormonal changes in women using long-term hormonal and non-hormonal contraceptives: a pilot study

BackgroundFemale sexual dysfunction is a common condition that negatively impacts the emotional health and quality of life of the affected individuals. Long-acting reversible contraceptives (LARCs) are becoming increasingly popular due to their effectiveness and convenience. LARCs can be hormonal (etonogestrel releasing implant—ENG and Levonorgestrel intrauterine system—LNG) or non-hormonal (copper intrauterine device—CuIUD and copper-silver intrauterine device—SIUD). There are very few studies that assess the influence on LARCS on sexual function are lacking. This study aimed to assess changes in sexual function as well as metabolic and hormonal parameters in women after implantation with LARCs.MethodsIn this prospective cohort study, we assessed 80 women who visited the Military Police Hospital in Brazil for LARCs placement. The study participants were divided into 4 groups according to the type of LARC received: ENG n = 17; LNG n = 22, CuIUD n = 18 and SIUD n = 23. The four groups were evaluated twice (prior to LARC placement and approximately 3 months later) for sexual function, using the Female Sexual Function Index (FSFI) and Female Sexual Quotient (QS-F) questionnaires. Metabolic and hormonal parameters were also assessed using blood tests.ResultsENG worsened sexual function according to FSFI and QS-F, across all domains. A decrease in sex hormone-binding globulin (SHBG) between stages was observed for all groups. We observed an improvement in sexual function for non-hormonal LARCs, specially SIUD. However this improvement was not statistically significant.ConclusionThe use of non-hormonal LARCS improved sexual function. Etonogestrel implants, had a negative influence on sexual function, probably by blocking ovarian function, and thus reducing the production of androgens and estrogens.

Testosterone administration increases leukocyte-endothelium interactions and inflammation in transgender men

To evaluate the effect of testosterone treatment on metabolic and inflammation parameters and leukocyte-endothelium interactions in transgender men (TGM). Prospective observational study. University hospital. One hundred fifty-seven TGM. Administration of testosterone undecanoate (1,000 mg, intramuscular) every 12 weeks. Endocrine parameters, adhesion molecules (vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and E-selectin), proinflammatory cytokines interleukin-6, and tumor necrosis factor alpha were evaluated in serum before and after treatment using Luminex's xMAP technology. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear leukocytes were assessed by flow chamber microscopy. Testosterone treatment led to an increase in leukocyte-endothelium interactions due to an increase in polymorphonuclear leukocytes rolling and adhesion and decreased rolling velocity. It also boosted levels of vascular cell adhesion molecule-1, E-selectin, interleukin-6, and tumor necrosis factor alpha. As expected, testosterone also produced a significant increase in free androgenic index, androstenedione, total testosterone, and atherogenic index of plasma and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol. Treatment of TGM with testosterone induces an increase in leukocyte-endothelium interactions and adhesion molecules and proinflammatory cytokines. These effects are a reason to monitor cardiovascular risk in these patients.

Major determinants of circulating myostatin in polycystic ovary syndrome.

The present study was designed to investigate the possible impact of hormonal and demographic parameters of patients with polycystic ovary syndrome (PCOS) on the circulating levels of myostatin. The study cohort comprised 46 patients with PCOS and 42 healthy female controls, and all subjects were of normal weight. Multiple regression analysis was applied to investigate the possible associations between serum myostatin levels and other laboratory parameters. Evaluation of the levels of myostatin revealed no significant differences between the PCOS and control groups (P>0.05). In the control group, no significant correlations were identified between the myostatin levels and any other laboratory parameters. Only low-density-lipoprotein cholesterol (LDL-C) levels in the PCOS group were revealed to be significantly, although negatively, associated with myostatin levels (P=0.018). In the regression model of the PCOS group, an increase in LDL-C and prolactin (PRL) were associated with a decrease in myostatin (P=0.001 and P=0.013, respectively). Furthermore, a decrease in sex hormone-binding globulin (SHBG), fasting blood glucose (FBG) and monocytes were associated with an increase in myostatin (P=0.028, P<0.001 and P=0.026, respectively). An increase in triglycerides was also associated with an increase in myostatin (P=0.001). In the regression model of the control group, a decrease in LDL-C was associated with an increase in myostatin (P=0.003) and a decrease in thyroid-stimulating hormone was associated with a decrease in myostatin (P=0.028). These results indicated that the normal range of myostatin levels in patients with PCOS is regulated by changes in the circulating levels of PRL, LDL-C, SHBG, triglycerides, monocytes and FBG.

Correlation between sex hormone binding globulin and type 2 diabetes retinopathy

Objective To investigate the relationship between sex hormone binding globulin (SHBG) in serum and diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM). Methods A total of 160 hospitalized people with T2DM was enrolled into the study. The patients were divided into two groups with or without merged DR. Clinical and laboratorial data were collected, and the correlation was analyzed between sex hormone binding globulin and diabetic retinopathy. Results ⑴ Compared to the group without DR, patients in T2DM with DR had significant lower SHBG concentration, triglyceride (TG) and total cholesterol (TC) concentration were increased significantly (P<0.01) . ⑵ The level of SHBG was associated with waist circumference, body weight, fasting blood glucose, and glycosylated hemoglobin (P<0.05). ⑶ While the level of SHBG was significantly increased from Quartile 1 to Quartile4 , the prevalence of DR was also significantly decreased (A: 70%, B: 51.2%, C: 40.5%, D: 29.7%) (P<0.01). ⑷ Logistic regressing analysis shows that with the decrease of SHBG level, the increase of triglyceride levels, the risk of DR was significantly increased (SHBG: OR: 0.616, 95% CI: 0.447-0.850, P<0.01; TG: OR: 1.323, 95% CI: 1.025-1.707, P<0.05). Conclusions With the decrease of SHBG, the prevalence of DR is significantly increased, lower SHBG may be one of the hazards of T2DM patients with DR. Key words: Sex hormone-binding globulin/ME; Diabetes mellitus, type 2/ME/CO; Diabetic retinopathy/ME/CO

The frequency of polycystic ovary syndrome in young reproductive females in Qatar.

This was a prospective cross-sectional study in which 126 female students between the ages of 18 and 30 years were evaluated for the frequency of polycystic ovary syndrome (PCOS) through clinical interview, questionnaire, and anthropometric measurements. The diagnostic criteria of the US National Institutes of Health criteria were used. Menstrual irregularities (MI) were identified, and clinical hyperandrogenism was evaluated by self-assessment of hirsutism using modified Ferriman–Gallwey score. Blood analysis was done for measurement of prolactin, thyroid-stimulating hormone, and the androgen hormones. Of all the students, 37 (30.8%) had MI, 38 (31.7%) had clinical hirsutism, 37 (30.8%) had acne, and 76 (63.3%) had a family history of type 2 diabetes. The estimated frequency of PCOS was 18.33% according to the US National Institutes of Health definition. Hormonal analysis demonstrated a significant increase in androgens (total testosterone, dehydroepiandrosterone sulfate, and free testosterone), and a significant decrease in sex hormone-binding globulin in our PCOS group, with a P-value <0.05. This study revealed a higher level of the androgen hormones among PCOS subjects with a frequency of PCOS (18.33%) similar to the global estimates of 10%–20%.

Mitochondrial Impairment and Oxidative Stress in Leukocytes after Testosterone Administration to Female-To-Male Transsexuals

Testosterone undecanoate (T) treatment is common in female-to-male transsexuals (FtMs) but can induce impairment of mitochondrial function and oxidative stress. The effect of T treatment on the mitochondrial function and redox state of leukocytes of FtMs subjects was evaluated. This was an observational study conducted in a university hospital. Fifty-seven FtMs were treated with T (1,000 mg) for 12 weeks, after which anthropometric and metabolic parameters and mitochondrial function were evaluated. Anthropometric and metabolic parameters were evaluated. Mitochondrial function was studied by assessing mitochondrial oxygen (O2) consumption, membrane potential, reactive oxygen species (ROS) production, glutathione levels (GSH), and the reduced glutathione/oxidized glutathione (GSH)/(GSSG) ratio in polymorphonuclear cells. T treatment led to mitochondrial impairment in FtMs as a result of a decrease in mitochondria O2 consumption, the membrane potential, GSH levels, and the (GSH)/(GSSG) ratio and an increase in ROS production. Mitochondrial O2 consumption and membrane potential negatively correlated with T levels, which was further confirmed that the T treatment had induced mitochondrial dysfunction. T also produced a significant increase in total testosterone, free androgenic index, and atherogenic index of plasma, and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol. Treatment of FtMs with T can induce impairment of mitochondrial function and a state of oxidative stress. This effect should be taken into account in order to modulate possible comorbidities in these patients.

Effects of Smoking Cessation on Hormonal Levels in Men

Chronic smoking can cause imbalance in endocrine homeostasis and impairment of fertility in both sexes. The male reproductive system is more resilient, still the literature provides conflicting results about the influence of smoking on the steroid hormone levels. The data about smoking cessation are limited; there has not yet been a study primarily focused on changes in steroids levels. In our study, we analyzed levels of testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), cortisol and sex hormone-binding globulin (SHBG) in male smokers and during smoking cessation. Monitored analytes were determined by RIA. The free testosterone index was calculated. Basal samples of men successful and unsuccessful in smoking cessation did not differ and monitored hormones could hardly predict success of smoking cessation. After one year without smoking, a significant BMI increase and SHBG decrease in former smokers was observed. The decrease in total testosterone was non-significant. Changes in SHBG and testosterone did not correlate with BMI, presumably due to the direct effect of smoking cessation.

SHBG in GDM maternal serum, placental tissues and umbilical cord serum expression changes and its significance

AimsTo compare the expression of sex hormone binding globulin (SHBG) in normal placental tissues and serum with placental tissues from patients with gestational diabetes mellitus (GDM) and to deduce the mechanism affecting placental SHBG in GDM. MethodsEnzyme-linked immunosorbent assay (ELISA) method were used to detect SHBG levels changes in normal and GDM maternal serum, umbilical cord serum and placental. We measured SHBG mRNA and protein using reverse-transcription polymerase chain reaction, and Western blotting, respectively, in normal and GDM placental tissues. ResultsIn maternal serum, compared with the control group, GDM group: glucose, insulin increased, SHBG decreased. In the placenta, compared with the control group, GDM group: SHBG, SHBG mRNA and SHBG protein decreased. There is no correlation between placenta SHBG and maternal serum SHBG respectively in control and GDM group, but in GDM group maternal serum insulin and placenta SHBG are linear correlation. ConclusionsGDM serum and placental SHBG levels are reduced, hyperinsulinemia may lead to a reduction of SHBG in circulating blood, but also damage the placenta cells which led to placental synthesis and secretion of SHBG decrease.

Endogenous sex hormones impact the progression of subclinical atherosclerosis in women during the menopausal transition

ObjectiveTo determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife. Methods249 Pre- or early peri-menopausal women (42–57 years) from the Study of Women's Health Across the Nation (SWAN) were followed for up to 9 years (median = 3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity. ResultsIn final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression (P = 0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression (P = 0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression (P = 0.003). T and SHBG were not associated with progression or level of AD. ConclusionsIndependent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife.

Expression changes of sex hormone binding globulin in GDM placental tissues

To compare the expression of sex hormone binding globulin (SHBG) in normal placental tissues with placental tissues from patients with gestational diabetes mellitus (GDM) and to deduce the mechanism affecting placental SHBG in GDM. We detected SHBG localization and measured SHBG mRNA and protein using immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blotting, respectively, in normal and GDM placental tissues. The distribution of SHBG in placental cells was examined using immune electron microscopy. Compared to controls, placental tissues from patients in the GDM group displayed disordered cell surface microvilli that were decreased in quantity, swollen, and had narrowed and broken gap junctions. Intracellular abnormalities included expanded rough endoplasmic reticula, swollen mitochondria, and irregular nuclear morphologies with non-uniform chromatin. SHBG localized primarily to trophoblast cell membranes and cytoplasm. SHBG was strongly expressed on the microvilli side and weakly expressed on the basement membrane with uneven staining. SHBG also was expressed in villous stromal cells and vascular endothelial cells. Compared to the controls, placental tissues from the GDM group displayed significantly decreased immunostaining rates for SHBG, as well as significantly lower levels of SHBG mRNA and protein expression (P<0.05). SHBG was detected in placental trophoblast cells from patients with GDM, and the synthesis and secretion of SHBG were reduced when trophoblast cells were irregular. A decrease in SHBG could affect placental function or aggravate GDM. Our results suggest that placental SHBG plays an important role in the pathogenesis of GDM.

Effects of Tomato- and Soy-Rich Diets on the IGF-I Hormonal Network: A Crossover Study of Postmenopausal Women at High Risk for Breast Cancer

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.

Reproductive hormones and obesity: 9 years of observation from the Study of Women's Health Across the Nation.

The effect of change in reproductive hormones and menopause on incident obesity (body mass index > or =30 kg/m(2)) and severe obesity (body mass index > or =35 kg/m(2)) was evaluated over 9 years in 3,260 US women recruited in the multiethnic Study of Women's Health Across the Nation in 1996-1997. After 9 years, cumulative incidences of obesity and severe obesity reached 21.8% and 12.3%, respectively. In multivariate analysis, hormone changes, chronic health conditions, lower physical activity, race/ethnicity, and age were significantly associated with incident obesity and/or severe obesity. The odds of incident severe obesity increased with surgical menopause (odds ratio (OR) = 5.07, 95% confidence interval (CI): 2.29, 11.20; P < 0.001) and initiation of hormone therapy prior to 12 months of amenorrhea (OR = 2.94, 95% CI: 1.14, 7.58; P = 0.03). Predictors of obesity included an increase in free androgen index (OR = 1.37, 95% CI: 1.12, 1.68; P = 0.002) and a decrease in sex hormone-binding globulin (OR = 0.60, 95% CI: 0.45, 0.80; P = 0.0005). Similar results were found for severe obesity. Obesity rates varied by race, but no hormone-by-race interactions were observed. These longitudinal data demonstrate that higher androgens, lower sex hormone-binding globulin, surgical menopause, and early hormone therapy use predict incident obesity and/or severe obesity in a multiracial cohort of women transitioning into menopause.

Sex Hormone-Binding Globulin as an Independent Predictor of Incident Type 2 Diabetes Mellitus in Men

Low levels of sex hormone-binding globulin (SHBG) and total testosterone (T) in men have been associated with increased risk of type 2 diabetes mellitus (T2DM). As total T and SHBG levels are highly correlated, we determined whether SHBG influences the risk of T2DM through T or whether SHBG is an independent predictor of T2DM. Longitudinal analyses were conducted on men participating in the Massachusetts Male Aging Study, a population-based study of men aged 40-70 years. Of 1,709 men enrolled in 1987-1989, 1,156 were evaluated 7-10 years later and 853 after 15-17 years. Analyses were restricted to 1,128 men without T2DM at baseline. Ninety new cases of T2DM were identified. After adjustment for age, body mass index, hypertension, smoking, alcohol intake, and physical activity, the hazard ratio (HR) for incident T2DM was 2.0 for each 1 SD decrease in SHBG (95% confidence interval [CI], 1.42-2.82, p < .001) and 1.29 for each 1 SD decrease in total T (95% CI, 1.01-1.66, p = .04). Free T was not associated with T2DM (HR = 1.03, 95% CI, 0.81-1.31, p = .79). The strong association of T2DM risk with SHBG persisted even after additional adjustment for free T (HR = 2.04, 95% CI, 1.44-2.87, p < .0001) or total T (HR = 1.95, 95% CI, 1.34-2.82, p = .0004). SHBG is an independent predictor of incident T2DM even after adjusting for free T or total T. Free T is not significantly associated with T2DM. SHBG may contribute to the risk of T2DM through nonandrogenic mechanisms, which should be investigated as they may provide novel targets for diabetes prevention.