Decreased Sex Hormone-binding Globulin Research Articles

Alleviation of adipose-hepatic glycolipid dysregulation by acetate in experimental PCOS model is associated with NF-κB/NLRP3 repression.

This study hypothesized that acetate breaks the vicious cycle driving adipose-hepatic metabolic dysregulation in a rat model of polycystic ovarian syndrome (PCOS), possibly by suppression of nuclear factor-kappaB (NF-κB)/NOD-like receptor protein 3 (NLRP3) inflammasome. Female Wistar rats (8-week-old) were randomly allocated into four groups of n =6/group, which received vehicle, sodium acetate (200 mg), letrozole (1 mg/kg), and letrozole plus sodium acetate, respectively. The animals were treated by oral gavage, once daily for a period of 21 days. The PCOS animals were insulin-resistant, hyperandrogenic, and hypoestrogenic with decreased sex-hormone binding globulin. In addition, the hepatic tissue had increased lipid profile and decreased glycogen synthesis, while the adipose tissue showed decreased lipid profile with elevated glycogen synthesis. Besides, the results also showed increased malondialdehyde, γ-glutamyl transferase, lactate dehydrogenase, and inflammatory mediators with corresponding decrease in antioxidant defense in the hepatic and adipose tissues. Immunohistochemical evaluation also demonstrated severe expression with Bcl2-associated X protein/NLRP3 antibodies. Nonetheless, concomitant acetate supplementation attenuated these derangements. The present data collectively suggest that acetate ameliorates adipose-hepatic glycolipid dysregulation in experimental PCOS model by attenuating androgen excess and NF-κB/NLRP3 immunoreactivity.

Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism

BackgroundPrenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism.ObjectiveThis study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure.Study designEarly second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure.ResultsIncreased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01–1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04–1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55–0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure.LimitationsThe relative racial and ethnic homogeneity of Utah’s population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power.ConclusionBoth elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.

A cross-sectional study of the association between circulating sex hormone-binding globulin levels and selected adipokines in women with polycystic ovary syndrome.

Changes in the proportion of pro-inflammatory and anti-inflammatory adipokines may reflect the accumulation of lipids in the liver and the development of insulin resistance. Both liver steatosis and insulin resistance result in decreased sex hormone-binding globulin (SHBG) synthesis. This study aimed to analyze associations between circulating SHBG and adipokines levels in women with polycystic ovary syndrome (PCOS). A cross-sectional cohort study involved 87 women with phenotype A of PCOS (39 normal weight and 48 obese). Body mass, height, and waist circumference were measured, and BMI was calculated. In addition, body composition was assessed using the bioimpedance method. Serum SHBG levels and plasma apelin-36 and apelin-12, adiponectin, leptin, omentin-1, and RBP-4 were determined by using the ELISA method. The participants were divided into subgroups with SHBG concentrations above and below this lower limit [N = 35 (40.2%) and N = 52 (59.8%), respectively]. The median adiponectin, apelin-12, and apelin-36 levels were significantly lower, and leptin levels were significantly higher in the subgroup with low SHBG levels than that in the subgroup above the lower limit of the reference range, while there were no differences in median omentin-1 and RBP-4 between the study subgroups. There were positive correlations between SHBG and omentin-1, adiponectin, apelin-36, and apelin-12 levels, as well as negative correlation with leptin levels. However, after adjustment by BMI, waist circumference, and body fat percentage, only the association between SHBG and omentin-1 remained significant. Our results show associations between circulating SHBG and adipokine levels in women with PCOS and support the role of hormonal dysfunction of the adipose tissue in the pathogenesis of PCOS.

AMH as part of the diagnostic PCOS workup in large epidemiological studies.

Previous studies have shown good correlation between polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels. We evaluated the utility of AMH as a surrogate for PCOM as a part of the polycystic ovary syndrome (PCOS) diagnosis by describing how the use of different AMH cut-off values would change the prevalence of PCOS. A general population-based birth cohort study. Anti-Müllerian hormone concentrations were measured from serum samples taken at age 31 years (n = 2917) using the electrochemiluminescence immunoassay (Elecsys). Anti-Müllerian hormone data were combined with data on oligo/amenorrhoea and hyperandrogenism to identify women with PCOS. The addition of AMH as a surrogate marker for PCOM increased the number of women fulfilling at least two PCOS features in accordance with the Rotterdam criteria. The prevalence of PCOS was 5.9% when using the AMH cut-off based on the 97.5% quartile (10.35 ng/mL) and 13.6% when using the recently proposed cut-off of 3.2 ng/mL. When using the latter cut-off value, the distribution of PCOS phenotypes A, B, C, and D was 23.9%, 4.7%, 36.6%, and 34.8%, respectively. Compared with the controls, all PCOS groups with different AMH concentration cut-offs showed significantly elevated testosterone (T), free androgen index (FAI), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio, body mass index (BMI), waist circumference, and homoeostatic model assessment of insulin resistance (HOMA-IR) values, as well as significantly decreased sex hormone-binding globulin (SHBG) values. Anti-Müllerian hormone could be useful surrogate for PCOM in large data sets, where transvaginal ultrasound is not feasible, to aid the capturing of women with typical PCOS characteristics. Anti-Müllerian hormone measurement from archived samples enables retrospective PCOS diagnosis when combined with oligo/amenorrhoea or hyperandrogenism.

TLANDO, a Novel Oral TRT, Improves Sexual and Mental Domain Outcomes in Hypogonadal Men

Male hypogonadism is characterized by symptoms and deficiency (<300 ng/dL) in levels of in total testosterone (TT), a critical hormone for sexual, cognitive, and body function and development. TLANDO, a testosterone undecanoate (TU) comprising lymphatically delivered oral testosterone replacement therapy (TRT) option not requiring dose titration, treatment has demonstrated effective restoration in hypogonadal men of TT levels to the eugonadal range in multiple clinical studies. TLANDO therapy resulted in decreased sex hormone binding globulin with increased free testosterone (FT). TLANDO’s unique delivery system enables consistent restoration of TT regardless of meal fat content. Moreover, TLANDO has shown potential to improve liver health through resolution of fatty liver disease in hypogonadal men and is not known to have any adverse liver effects. However, it is unclear if fixed dose TLANDO therapy without dose adjustment improves symptoms of psychosexual functions. The objective is to assess key sexual and mental domain Patient Reported Outcomes (PRO) post 52 weeks of treatment using TLANDO on the to-be-marketed dosing regimen in comparison with a widely used topical TRT, Androgel 1.62%. Data analysis was performed in in hypogonadal males post TLANDO treatment without dose adjustment, and in patients on the active control from a randomized, multi-center, open label, active controlled 52-week trial (SOAR, NCT02081300). Sexual and mental domain function PROs were measured at baseline (BL) and end of study (EOS) using Psychosexual Daily Questionnaire (PDQ) and Short Form (SF)-36 surveys and compared between TLANDO and active control. Post treatment with TLANDO dosing regimen not requiring dose titration, key sexual domain function PROs at week 52 were significantly (p<0.05) improved from BL: positive mood (BL:4.5 vs EOS:5.1, p<0.001), negative mood (1.8 vs 1.4, p<0.01), overall sexual desire (2.5 vs 3.7, p<0.001), sexual activity (2.5 vs 4.0, p<0.001), highest pleasure with partner (2.0 vs 2.8, p=0.06), highest pleasure without partner (1.8 vs 2.4, p<0.05), weekly maintained erection (3.3 vs 4.5, p<0.001), and weekly full erection % (50.5% vs 68.9%, p<0.001). Most sexual and mental function PROs were comparable to Androgel 1.62. TLANDO therapy was well tolerated through 52 weeks of treatment exposure. In conclusion, TLANDO, a novel easy to use and prescribe TRT not requiring dose titration, demonstrated improvement in sexual and mental PROs, a significant unmet need in hypogonadal males. Further placebo-controlled studies are warranted to better elucidate these improvements.

Decreased Sex Hormone-Binding Globulin Indicated Worse Biometric, Lipid, Liver, and Renal Function Parameters in Women with Polycystic Ovary Syndrome.

Objective To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. Results In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95–0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695–0.770. SHBG <26.75 mmol/L is the cutoff point with the best Youden index, which has a sensitivity of 0.656 and specificity of 0.698. Conclusions Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081.

The contribution of hyperinsulinemia to the hyperandrogenism of polycystic ovary syndrome

Background: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder of young women.Aim: The proper treatment of PCOS requires a thorough understanding of the underlying cause of disease. In this article, we review the extent to which hyperinsulinemia contributes to the development of PCOS.Setting: The goal of this review was to assess the current literature on the contribution of hyperinsulinemia to the hyperandrogenism of polycystic ovary syndrome in hopes of promoting future research and advancements in clinical treatments for women with PCOS focusing on this major contributing factor, hyperinsulinemia.Method: A review of published peer-reviewed literature was conducted by searching the keywords.Results: Excessive insulin causes both the overproduction of testosterone and decreased sex hormone binding globulin (SHBG) levels seen in PCOS, both of which collaborate in creating an increased testosterone effect.Conclusion: The majority of research and evidence shows that the hyperandrogenism of PCOS is likely caused by hyperinsulinemia. Yet the conventional treatment of hyperandrogenic symptoms in women with PCOS is not directed towards correcting this underlying hyperinsulinemia. Further research is needed to assess how the treatment of the hyperinsulinemia through lifestyle would compare to the current treatment of hyperandrogenemia through testosterone-lowering drugs.

HSD3B1 gene polymorphism and female pattern hair loss in women with polycystic ovary syndrome

Genetic variant of HSD3B1 1245 is known to augment androgen production at peripheral tissue as skin. This study aimed to investigate whether women with polycystic ovary syndrome inheriting this variant exhibit specific androgenic phenotypes. A cross-sectional study of Taiwanese women with polycystic ovary syndrome, defined by Rotterdam criteria, at the reproductive endocrinology outpatient clinic in a university affiliated hospital. The presence of female pattern hair loss in women with polycystic ovary syndrome was significantly associated with an increased body mass index, decreased sex hormone binding globulin and high density lipoprotein cholesterol levels, elevated triglyceride levels, and increased prevalence of hypertension. Using stepwise multivariate logistic regression analysis, body mass index, triglyceride and HSD3B1 1245 AC or CC genotype were significantly related to female pattern hair loss in women with polycystic ovary syndrome after considering other variables. Overweight women with polycystic ovary syndrome had significantly higher risk of female pattern hair loss than normal-weight women with polycystic ovary syndrome. The presence of female pattern hair loss was higher in overweight women with polycystic ovary syndrome who comprised HSD3B1 AC or CC genotype compared with wild type. Carrying the HSD3B1 1245C allele and overweight are associated with the presence of female pattern hair loss in women with polycystic ovary syndrome.

SHBG expression is correlated with PI3K/AKT pathway activity in a cellular model of human insulin resistance

Decreased sex hormone-binding globulin (SHBG) expression is an independent risk factor for gestational diabetes mellitus(GDM).However, the mechanisms that link low SHBG expression and insulin resistance in GDM is unclear. In this study, we investigated the placenta SHBG in the PI3K/AKT pathway to reveal the mechanism that links decreased SHBG to insulin resistance. A insulin resistance cells model was established by the method of insulin stimulation. Two groups were set up, HTR8/Svneo cells and insulin-resistance cells of HTR8/SVneo. The expression of SHBG and PI3K/AKT associated factors were detected using real-time PCR and western blotting and their correlations were analyzed. The results showed that SHBG protein and mRNA levels in insulin resistance cells were both significantly lower. Along with decreased SHBG expression, the mRNA and protein levels of IRS-1, IRS-2, PI3Kp85α and GLUT-3, GLUT-4 decreased significantly. However, the expression of GLUT-1 increased significantly. Pearson correlation analysis showed that SHBG mRNA expression was positively correlated with IRS-1, IRS-2 and PI3Kp85α mRNA levels. According to the results, low SHBG expression not only participates in the development of local insulin resistance, but may also play an important role in PI3K/AKT pathway-mediated systemic insulin resistance and gestational diabetes.

Sex difference determined the role of sex hormone-binding globulin in obese children during short-term weight reduction program.

The relationship between hyperinsulinemia and decreased sex hormone-binding globulin (SHBG) levels has been observed in obese adults and children. Weight reduction not only increased insulin sensitivity but also elevated serum SHBG levels in obese adults and children. However, the correlation between the changes in insulin resistance indices and serum SHBG concentration during weight reduction program (WRP) is not fully understood, particularly in obese children. This study is to evaluate whether SHBG level is a potential biomarker that can be used to assess insulin resistance in obese children during a short-term WRP. Forty-eight obese Taiwanese children (11.7 ± 2.2 years; 25 boys and 23 girls) participating in 8-week WRP were studied. Anthropometric measurements, lipid profiles, insulin resistance indices, and serum SHBG concentration were recorded at baseline and at the end of the WRP. The results showed body weight (BW), body mass index (BMI), body fat percentage (BF%), body fat weight (BFW), and insulin resistance indices such as fasting insulin, fasting insulin to glucose ratio, homeostasis model assessment (HOMA) of insulin resistance, log (HOMA) all significantly decreased after the 8-week WRP. With respect to lipid profiles, only high-density lipoprotein cholesterol (HDL-C) levels increased in both sexes. At baseline, insulin resistance indices were inversely correlated with SHBG concentrations in girls, but not in boys. The difference in SHBG after WRP was 2.58 nmol/L (95% confidence interval [CI]: −3.51, 8.66) in boys and 0.58 nmol/L (95% CI: −5.23, 6.39) in girls. There was a trend toward increased serum SHBG levels in boys (P = .39) and girls (P = .84) after weight loss, but a significantly negative correlation between the change in SHBG and in each of the insulin resistance indices only in the girls after adjusting age and ΔBFW during WRP.In conclusion, short-term WRP has the potential effects of decreased BW, BMI, BF%, and BFW, as well as increased serum HDL-C levels and insulin sensitivity in obese Taiwanese children. Although serum SHBG levels moderately increased in both sexes during short-term WRP, measuring the change in SHBG concentrations might be a potential biomarker to evaluate improvement in insulin resistance in girls only, and not in boys.

Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome

Background: Decreased sex hormone-binding globulin (SHBG) levels were associated with polycystic ovary syndrome (PCOS). SHBG polymorphisms associated with reduced SHBG production were tested for their association with PCOS, but with inconclusive results. We tested whether altered SHBG levels and SHBG variants were associated with PCOS. Methods: The study subjects included 242 women with PCOS and 238 control women. SHBG genotyping was done by real-time PCR. Results: Higher minor allele frequency of rs13894, rs858521 and rs727428 was seen in PCOS cases, and significant differences in rs858521 and rs727428 genotypes distribution were seen between PCOS cases and controls. Multivariate regression analysis confirmed the association of only rs727428 with PCOS. Though it was not statistically significant, serum SHBG levels were reduced according to rs727428 genotypes in PCOS cases than in controls. Carriage of rs727428 minor allele was associated with significant increases in free/bioactive testosterone in PCOS cases. Seven-locus (rs9898876-rs13894-rs858521-rs1799941-rs6257-rs6259-rs727428) haploview analysis showed increased frequency of GCCGTGA, GTCGTGA and GTCATGG, and reduced frequency of GTCGTGG haplotypes in PCOS cases than in controls, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. Conclusion: Specific SHBG variants affecting serum SHBG levels and SHBG haplotypes are associated with PCOS, suggesting the role for SHBG as PCOS candidate gene.

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women.

The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk. We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis. LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54kg, women with LBW (<2.72kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.) LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.

Epidemiologic investigation of polycystic ovarian syndrome (PCOS) in Han ethnic women of reproductive age in Liaoning Province, China

Objective: To determine the incidence of polycystic ovary syndrome (PCOS) among Han women of reproductive age in Liaoning Province in Northeastern China, based on the Revised Rotterdam 2003 criteria. Materials and Methods: A retrospective cohort study was carried out on 1,600 women using questionnaires, physical examination, ultrasonography, and biochemical indices (aged = 19 to 45 years; n = 1,600). PCOS patients were identified using the Revised Rotterdam 2003 criteria. Results: A total of 132 Han women of reproductive age were diagnosed with PCOS, with a prevalence of 8.25%. The prevalence of menstrual dysfunction was as follows: 97 patients (73.48%) had abnormal menstruation, three (2.27%) had polymenorrhea, and 94 (71.21%) had oligomenorrhea. Up to 64 patients (48.48%) had androgen excess, 42 (31.82%) had biochemical evidence of androgen excess, and 34 (25.76%) had clinical androgen excess. Up to 34 patients (25.76%) were obese (body mass index [BMI] ≥ 25) and 19 (14.39%) had hirsutism (F-G scoring ≥ 6). A total of 127 patients (96.22%) were diagnosed with PCOS via ultrasonography, 67 of whom (50.76%) had a unilateral polycystic ovary and 60 (45.46%) had bilateral polycystic ovaries. Conclusions: The prevalence of PCOS in this study population was 8.25%, with an infertility rate of 27.8%. The classical manifestation of PCOS is PCO, abnormal menstruation, and obesity. The high-risk factors of PCOS include high free testosterone index, homeostasis model assessment-insulin resistance (HOMA-IR), increased serum testosterone and androstenedione, decreased sex hormone-binding globulin, long history of infertility, menarche later than 16 years old, and failure to have regular menstruation within two years.

Effects of Testosterone Replacement on Response to Sildenafil Citrate

Letters2 April 2013Effects of Testosterone Replacement on Response to Sildenafil CitrateMatthew Spitzer, MD, Shehzad Basaria, MD, Thomas G. Travison, PhD, and Shalender Bhasin, MDMatthew Spitzer, MDFrom Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, Shehzad Basaria, MDFrom Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, Thomas G. Travison, PhDFrom Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.Search for more papers by this author, and Shalender Bhasin, MDFrom Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-7-201304020-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Dr. Smoger's comment that testosterone measurements vary because of multiple factors, including assay variation, diurnal and pulsatile secretory rhythms, and variations in sex hormone–binding globulin levels. We measured testosterone between 7:30 and 10:00 a.m. by liquid chromatography–tandem mass spectrometry, which is widely considered the reference method with the highest sensitivity and specificity. However, we concur that additional measurements of testosterone during screening would have been valuable.Obesity is associated with decreased sex hormone–binding globulin, and we agree that it might have played some role in the low levels of total testosterone (1). As such, we ...

Favorable Changes in Serum Estrogens and Other Biologic Factors After Weight Loss in Breast Cancer Survivors Who are Overweight or Obese

BackgroundObesity is associated with an increased risk for recurrence and all-cause mortality in breast cancer survivors. Excess adiposity is associated with increased estrogen, insulin, and leptin, and with decreased sex hormone binding globulin (SHBG) concentrations, which may promote breast cancer progression and recurrence. This study aimed to assess the effects of weight loss on these factors. Patients and MethodsBreast cancer survivors who were overweight or obese (n = 220) and who were enrolled in a weight loss intervention study provided baseline and follow-up blood samples and weight data. Serum estrogens, SHBG, insulin, and leptin were measured at baseline, 6 months, and 18 months. ResultsWeight loss of ≥5% of initial weight decreased leptin and insulin compared with those who did not achieve that amount of weight loss (P < .0001). Weight loss also increased SHBG at 6 and 18 months (P < .01). Postmenopausal women who lost ≥5% of body weight at 6 months had lower estrone (P = .02), estradiol (P = .002), and bioavailable estradiol (P = .001) concentrations than women who did not lose at least 5% of body weight, and weight loss at 18 months was significantly related to a change in serum bioavailable estradiol concentration (P = .02). ConclusionsFavorable changes in estrogens, SHBG, insulin, and leptin were observed in association with weight loss in these women who were overweight or obese and who had been diagnosed and treated for breast cancer. Weight loss appears to have favorable effects on hormonal and biologic factors associated with increased risk for recurrence and poorer prognosis.

The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone-binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total-cholesterol and low-density lipoprotein-cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.

Increased free androgen index is associated with hypertension in premenopausal women

Objective: Increased testosterone and decreased sex hormone-binding globulin (SHBG) are associated with a number of adverse cardiovascular risk factors in postmenopausal women. The aim of this population-based study of women aged 25 to 50 was to assess the relationship between free androgen index (FAI) and cardiovascular risk factors in premenopausal women. Methods: A population-based survey of 396 premenopausal women with no hormonal treatment was undertaken as part of the Northern MONICA study. The study involved questionnaires, anthropometry and assays of testosterone and SHBG. Results: Increased FAI was associated with a number of cardiovascular risk factors in premenopausal women but this relationship was strongly affected by body mass index (BMI). After adjustment for age and BMI, FAI was significantly associated with increased systolic and diastolic blood pressures. Conclusion: Hyperandrogenism is associated with increased blood pressure and these findings emphasize the need to assess cardiovascular risk factors in women with hyperandrogenism of all ages.

Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation

Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation. The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18-44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles. Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005). These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome.

Effects of Testosterone Administration on Nocturnal Cortisol Secretion in Healthy Older Men

In animal studies, testosterone decreases, whereas estrogen increases, cortisol production. In one clinical study, short-term testosterone replacement attenuated corticotrophin-releasing hormone-stimulated cortisol secretion during leuprolide-induced hypogonadism in young men. The effects of longer term testosterone treatment on spontaneous cortisol secretion in younger or older men are unknown. In a randomized, double-masked placebo-controlled study, we assessed the effects of testosterone supplementation (100 mg intramuscular every 2 week) for 26 weeks on nocturnal cortisol secretory dynamics in healthy older men. Testosterone administration increased early morning serum concentrations of free testosterone by 34%, decreased sex hormone-binding globulin by 20%, and did not alter early morning concentrations of cortisol-binding globulin or cortisol compared with placebo treatment. Testosterone did not significantly alter nocturnal mean and integrated cortisol concentrations, cortisol burst frequency, mass/burst, basal secretion, pulsatile cortisol production rate, pattern regularity, or approximate entropy. We conclude that low-dose testosterone supplementation for 26 weeks does not affect spontaneous nocturnal cortisol secretion in healthy older men.

Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS

There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone <2.5 mIU/l and ≥2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone ≥2.5 mIU/l had a significantly higher body mass index ( P = 0.003), higher fasting insulin concentrations ( P = 0.02) and altered insulin resistance indices ( P = 0.007), higher total testosterone ( P = 0.009) and free androgen indices ( P = 0.001) and decreased sex hormone–binding globulin concentrations ( P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5 mIU/l. Generally, all of these parameters correlated significantly ( P < 0.05) with thyroid-stimulating hormone only in women with thyroid-stimulating hormone ≥2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone ≥2.5 mIU/l had significantly altered endocrine and metabolic changes.