Men treated with BEACOPP for Hodgkin lymphoma may be at increased risk of testosterone deficiency.

In the current study, we report the prevalence of male testosterone deficiency in a cohort of 60 male long-term survivors of malignant lymphoma with normal total testosterone but in the lower part of the reference level. Testosterone deficiency was defined as subnormal concentrations of total testosterone or subnormal concentrations of calculated free testosterone. The aim was to clarify whether total testosterone was sufficient for identification of testosterone deficiency in male survivors of malignant lymphoma. Hormonal analyses taken at follow-up were compared with samples taken at diagnosis for a subgroup of 20 survivors, for evaluation of changes in hormones over time. Another group of 83 similar survivors of malignant lymphoma with testosterone in the high end of reference levels were also used for comparison, to identify groups of increased risk of testosterone deficiency. A total group of 143 survivors were therefore included in the study. Our findings indicate that for screening purposes an initial total testosterone is sufficient in some survivors because sexual hormone binding globulin concentration was found stable over time. However, 15% were found with subnormal calculated free testosterone. Survivors intensely treated for Hodgkin lymphoma and older survivors were identified as high-risk groups for testosterone deficiency necessitating endocrinological attention during follow-up. Some evidence of pituitary downregulation was also found, because of uncompensated decreases in testosterone concentration over time. In conclusion, longitudinal measurements of total testosterone alone do not seem adequate for the screening of testosterone deficiency for all long-term lymphoma survivors.

Is there a relationship of cortisol and sex steroid hormones with mental health in middle-aged adults? the FIT-AGEING study.

PURPOSE: Mental health has emerged as a worldwide concern given the rising incidence of anxiety and depression disorders in the last years. Cortisol and sex steroid hormones have been demonstrated to be important regulators of mental health processes in older adults. However, the evidence considering these integrated variables in apparently healthy middle-aged individuals has not been thoroughly addressed. The present study was aimed at investigating the association of plasma cortisol, testosterone, free testosterone, Sex Hormone-Binding Globulin (SHBG) and Dehydroepiandrosterone-sulfate (DHEAS) levels with mental health in middle-aged adults. METHODS: This cross-sectional study included a cohort of 73 middle-aged adults with 45-65 years of age (53% women). Plasma cortisol, testosterone, SHBG, and DHEAS were assessed using a competitive chemiluminescence immunoassay. Free testosterone was calculated from the total testosterone and SHBG. Self-reported depression severity, generic health-related quality of life, hope, satisfaction with life, and optimism-pessimism were evaluated using the Beck Depression Inventory-II (BDI-II), the 36-item Short-Form Health Survey, the Adult Hope Scale (AHS), the Satisfaction with Life Scale (SWLS), and the Life Orientation Test Revised, respectively - higher total scores of these scales indicating greater levels of these variables -. RESULTS: Testosterone and free testosterone levels were inversely associated with BDI-II values in men (all P≤0.042). Cortisol levels were positively related with SWLS scores, whereas testosterone, free testosterone, SHBG, and DHEAS levels were negatively correlated with BDI-II values in women (all P≤0.045). CONCLUSION: In summary, these results suggest that increased levels of steroid hormones - within the normal values - may be associated with better mental health in middle-aged adults.

Trigonelline Chloride Ameliorated Triphenyltin-Induced Testicular Autophagy, Inflammation, and Apoptosis: Role of Recovery.

Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-binding globulin elevation, reduction of inhibin B, free testosterone levels, and sperm count reduction with increased abnormal sperm forms. Moreover, both TG and TPT-Cl withdrawal reduced inflammatory activin A, follistatin, tumor necrosis factor α, interleukin-1ß, and proapoptotic Bax and elevated antiapoptotic Bcl2 in testicular tissues mediated by TPT-Cl. TG and TPT-Cl withdrawal restored the excessive autophagy triggered by TPT-Cl via elevation of mTOR, AKT, PI3K, and P62/SQSTM1 and reduction of AMPK, ULK1, Beclin1, and LC3 mRNA gene expressions and regained the deteriorated testicular structure. In conclusion, TG and TPT-Cl withdrawal had an ameliorative role in partially reversing TPT-Cl-induced testicular toxicity. However, the findings indicated that the use of TG as an adjunctive factor is more favorable than TPT-Cl withdrawal, suggesting the capability of the testis for partial self-improvement.

Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia.

In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 GCKR, rs17496332 PRMT6, rs3779195 BAIAP2L1, rs10454142 PPP1R21, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs440837 ZBTB10, rs12150660 SHBG, and rs8023580 NR2F2 have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 PPP1R21 ([additive genetic model] OR = 1.31; 95%CI = 1.08-1.65; pperm = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 PPP1R21 (included in all nine models, 100%) and four more SNPs-rs7910927 JMJD1C (five models, 55.56%), rs17496332 PRMT6 (four models, 44.44%), rs780093 GCKR (four models, 44.44%), and rs440837 ZBTB10 (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia.

The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway.

Lignan-rich beans, nuts, and various seeds are the main foods with antioxidative and hormone-modulating activities. Although the role of lignans in mediating hormone-dependent cancers and cardiovascular diseases is well characterized, the function of lignans in anti-arthritic activity and its underlying mechanisms remain unknown. Three new lignan derivatives, (-)-nortrachelogenin, trachelogenin, and matairesinol, were extracted from Loranthus parasiticus. After establishing the collagen-induced arthritis (CIA) model by intradermal injection of collagen, rats were treated with three new lignan derivatives ((-)-nortrachelogenin: 37%; trachelogenin: 27%; matairesinol: 25.7%) at a concentration of 50 mg/kg and 100 mg/kg, or methotrexate at 0.3 mg/kg. Mixed lignan derivatives significantly attenuated the immune responses in the joints of CIA rats, leading to lower levels of proinflammatory cytokines (IL-6 and TNF-α) and higher levels of free androgen in the serum compared to the CIA model. The results of molecular docking using AutoDock Vina showed that the lignan derivative (-)-nortrachelogenin was the most effective compound for binding to sex hormone-binding globulin (SHBG), thus inhibiting the activity of NFκB in LPS-stimulated macrophages. In this study, (-)-nortrachelogenin was identified as a novel natural lignan derivative with previously unrecognized anti-inflammatory activity. Its molecular mechanism appears related to the regulation of the NFκB/SHBG pathway. Our findings suggest that further application of sex hormone-like compounds in the treatment of rheumatoid arthritis and the potential clinical applications of (-)-nortrachelogenin are promising.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome.

OBJECTIVE: Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of polycystic ovary syndrome (PCOS). Metformin, Myoinositol and d-chiro-inositol acts as insulin sensitizers and exerts a beneficial effects in PCOS. The objective is to compare the effect of metformin monotherapy versus a combination of metformin with Myoinositol and d-chiro-inositol in PCOS. DESIGN: This study is a randomized controlled trial conducted over a period of 6 months. All overweight and obese women with PCOS with the age group between 18 and 35 were included and randomized into two groups, 27 in the metformin monotherapy arm and 26 in the myoinositol combination arm. PATIENTS AND MEASUREMENTS: The variables assessed were duration of menstrual cycle, anthropometric parameters, modified Ferriman Gallwey score, global acne score, Fasting insulin, HOMA-IR, fasting lipid profile, serum testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, anti-Mullerian hormone, and pelvic ultrasound to assess ovarian volume, PCOS Questionnaire score. Changes in the parameters from baseline at the end of 6 months of treatment were assessed and compared between the groups. RESULTS: Menstrual cycle regularity improved in both groups with significantly greater improvement in the group receiving myoinositol-based therapy (p < .001). Pregnancy rate was equal in both the arms. There was a significant improvement in PCOSQ score in myoinositol-based therapy group (p < .001). However, there was no statistically significant difference in other hormonal, metabolic parameters between two groups in spite of symptomatic benefits. CONCLUSIONS: The addition of myoinositol to metformin exerts additional benefits in improving menstrual cycle regularity, and quality of life in women with PCOS.

Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses.

BACKGROUND: Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASCEMS) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. METHODS: EqASCEMS wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insulin transducers expression were analysed. RESULTS: Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced expression of p53 and p21 pro-apoptotic mediators. Furthermore, SHBG alleviated the oxidative stress caused by EMS and reduced the overaccumulation of intracellular ROS, by reducing ROS + cell percentage and regulating gene expression of endogenous antioxidant enzymes (Sod 1, Cat, GPx), SHBG treatment exhibited antioxidant activity by modulating total nitric oxide (NO) levels in EMS cells as well. SHBG treatment dampened the activation of ER stress sensors and effectors in EqASCEMS cells via the upregulation of MiR-7a-5p, the decrease in the expression levels of ATF-6, CHOP and eiF2A and the restoration of PDIA3 chaperone protein levels. As a consequence, SHBG application substantially improved insulin sensitivity through the modulation of Pi3K/Akt/Glut4 insulin signalling cascades. CONCLUSION: Our results suggest that the SHBG is endowed with crucial beneficial effects on ASCs metabolic activities and could serve as a valuable therapeutic target for the development of efficient EMS treatment protocols. Video Abstract.

An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma.

OBJECTIVES: Sex hormone binding globulin (SHBG) is a hormone binding protein which plays an important role in regulating the transport and availability of biologically active androgens and estradiol to target cells and used to calculate free testosterone concentrations. METHODS: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, featuring an albumin removal step followed by a tryptic digestion. After a reduction step with dithiothreitol and alkylation with iodoacetamide three signature peptides were used for the quantification of SHBG. RESULTS: The method enables the quantification of serum and plasma SHBG over the clinically relevant range of 200-20,000 ng/mL and was validated according to the most recent guidelines. The LC-MS/MS method correlates well with the Abbott Alinity immunoassay (R2>0.95), but the LC-MS/MS results are on average 16-17% lower than the immunoassay results, which is consistent for all three signature peptides. CONCLUSIONS: The LC-MS/MS method which includes an albumin depletion step allows quantification of SHBG in serum and plasma without an immunocapture step at clinically relevant SHBG levels, thus contributing to better lab-to-lab consistency of results.

The influence of growth and sex hormones on risk of alzheimer's disease: a mendelian randomization study.

Alzheimer's disease is more prevalent in women, possibly due to sex or growth hormones but existing evidence is inconclusive. We investigated whether genetically predicted sex and growth hormones are associated with risk of Alzheimer's disease. Genetic variants strongly and independently predicting insulin-like growth factor 1 (IGF-1), testosterone and sex hormone-binding globulin (SHBG) were obtained from large, published genome wide associations studies (GWAS) and applied to GWAS of Alzheimer's disease based on clinical diagnosis (cases = 21,982, control = 41,944) from the International Genomics of Alzheimer's Project and the UK Biobank parental (maternal cases = 27,696; paternal cases = 14,338) and siblings' diagnosis (cases = 2,171) as proxy cases. Published GWAS summary statistics were used in our analyses. Estimates were obtained from inverse variance weighting with sensitivity analysis (i.e., MR-Egger, weighted median and MR-PRESSO). Multivariable analyses adjusted for pleiotropic effects and possible sources of selection bias were also performed. Genetically predicted higher total testosterone may reduce the risk of paternal Alzheimer's disease (odds ratio (OR) 0.86, 95% confidence interval (CI) 0.76 to 0.97, per SD increase in testosterone) and in meta-analysis for women (OR 0.92, 95% CI 0.87, 0.98) with directionally similar results from other analyses. SHBG were not associated with Alzheimer's disease. IGF-1 in women was inversely associated with risk of clinical Alzheimer's disease in sensitivity analysis but not in the main analysis. These results suggest genetically predicted higher total testosterone may lower risk of Alzheimer's disease. The role of testosterone and the immune system in Alzheimer's disease could be further investigated.

Is elevated baseline SHBG associated with increased ovulation?

Sexual hormone binding globulin (SHBG) is associated with the endocrine and reproductive systems. We aimed to investigate the role of SHBG in the reproductive process. Therefore, we conducted a secondary analysis of the PCOSAct (Polycystic Ovary Syndrome and Acupuncture Clinical Trial) study, which involved 21 sites in China and a total of 1000 women with PCOS. Out of these, 954 women with SHBG were included in the analysis. Through multivariate analysis of ovulation predictors, we found that age, BMI, estradiol, testosterone, and SHBG all showed a positive predictive value for ovulation (p = 0.0211, 0.0011, 0.0211, 0.0029, 0.0434, respectively). However, the LH to FSH ratio had a negative predictive value (p = 0.0539). Higher quartiles of SHBG were associated with a higher rate of ovulation, and per quartile increased was statistically significant (HR = 1.138, 95%CI [1.054,1.229]). The association remained significant even after adjusting for testosterone (HR = 1.263, 95%CI [1.059, 1.507]). On the other hand, quartiles of testosterone and estradiol did not exhibit any significant tendency toward ovulation. SHBG demonstrated predictive ability for ovulation, conception, pregnancy, and live birth (p < 0.05), and this correlation remained significant after adjusting intervention. Kaplan-Meier curves illustrated that increased levels of SHBG were a factor in high rates of ovulation, conception, and pregnancy. In comparison to other sexual hormones, a higher baseline level of SHBG was related to increased ovulation.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Usefulness of routine assessment of free testosterone for the diagnosis of functional male hypogonadism.

OBJECTIVE: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional hypogonadism. METHODS: Total and free testosterone (calculated on SHBG levels) were determined in 188 patients with sexual symptoms and 184 with infertility. RESULTS: Hypogonadism (calculated free testosterone <63 pg/ml) was found in 47/188 (25.0%) patients with sexual symptoms and in 21/184 (11.4%) with infertility. Total testosterone determination misdiagnosed hypogonadism in 8.4% (12/143) of men with sexual symptoms and in 2% (3/152) with infertility. In subjects with borderline total testosterone, only 24.7% (19/77) had hypogonadism confirmed by free testosterone levels. Free testosterone levels significantly correlated with age, haematocrit, gonadotropins, gynecomastia, BMI, and number of co-morbidities, whereas total testosterone associated only with the latter two. Furthermore, age, haematocrit, BMI, and the presence of erectile dysfunction and of low libido were significantly different between men with normal and low free testosterone, whereas only BMI and low libido were significantly different between patients with normal and low total testosterone. CONCLUSION: Routine assessment of free testosterone allows a more accurate diagnosis of functional hypogonadism, especially in men with sexual symptoms. Free testosterone levels associate with clinical and biochemical parameters of androgen deficiency better than total testosterone levels.

Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay.

BACKGROUND: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. AIM: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged < 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. METHODS: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. RESULTS: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p < 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p < 0.0001) or cFT (9.5% vs 7%, p < 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. CONCLUSIONS: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency.

The effects of long-term testosterone treatment on endocrine parameters in hypogonadal men: 12-year data from a prospective controlled registry study.

Testosterone therapy (TTh) is the primary treatment for aging men with functional hypogonadism. Whilst the benefits of testosterone (T) replacement are well-evidenced, the long-term data for TTh on metabolic and endocrine parameters is limited. Here we present the effect of TTh on endocrine parameters in hypogonadal men at a 12-year follow-up. In this single-centre, cumulative, prospective, registry study, 321 hypogonadal men (mean age: 58.9 years) received testosterone undecanoate injections in 12-week intervals for up to 12 years. Blood samples were taken at every other visit to measure levels of total T (TT), calculated free T, sex hormone-binding globulin (SHBG), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and prolactin. We observed an increase in TT of 15.5 nmol/L (p < 0.0001), a reduction in SHBG of 10.5 nmol/L (p < 0.0001) and an increase in calculated free T of 383.04 pmol/L (p < 0.0001) over the study period. This was accompanied by an increase in estradiol levels by 14.9 pmol/L (p < 0.0001), and decreases in progesterone (0.2 ng/mL, p < 0.0001), LH (10.4 U/L, p < 0.0001) and FSH (8.4 U/L, p < 0.0001) were demonstrated at 12-years. The levels of prolactin remained unchanged. Long-term TTh altered hormonal parameters to predictably modify the endocrine system. These effects were sustained during the entire observation time of 12 years.

Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men.

PURPOSE: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function. METHODS: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score ≤ - 2.5SD and T-score between - 1 and - 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels. RESULTS: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs. CONCLUSION: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD.

ß-Carotene regulates glucose transport and insulin resistance in gestational diabetes mellitus by increasing the expression of SHBG.

The aim of this work was to study the effect and mechanism of ß-carotene on insulin resistance and glucose transport in gestational diabetes mellitus (GDM). Placental tissue and venous blood of 26 GDM patients and 18 normal women were collected. Mice fed a high-fat diet were established as GDM models and treated with ß-carotene, from which peripheral blood and placenta tissue were collected. HTR-8/SVneo cells were treated with 10-7  mol/L insulin for 48 h and established as insulin resistance cell models. The expression of SHBG, GLUT1, GLUT3, GLUT4, IRS-1, IRS-2, PI3Kp85α, and p-CREB/CREB in placental tissues and HTR-8/SVneo cells was detected. Insulin resistance index was calculated from the values of fasting blood glucose and fasting insulin. The glucose consumption of insulin-resistant cells was calculated by detecting the glucose content of the supernatant. The cyclic adenosine monophosphate (cAMP) kit was applied to measure the concentration of cAMP in cells. SHBG was lowly expressed in GDM. ß-Carotene treatment upregulated SHBG in the placenta of GDM mice and in insulin-resistant HTR-8/SVneo cells. Overexpression of SHBG upregulated GLUT3, GLUT4, and IRS-1 and enhanced glucose consumption in insulin-resistant cells. ß-Carotene treatment promoted the expression of SHBG, GLUT4 and IRS-1 and increased glucose consumption in insulin-resistant cells underexpressing SHBG. Silencing of SHBG decreased the levels of cAMP and pCREB/CREB but ß-carotene treatment increased their expression despite SHBG silencing in insulin-resistant cells. ß-Carotene promotes glucose transport and inhibits insulin resistance in GDM by increasing the expression of SHBG.

Body weight and fat mass across the menopausal transition: hormonal modulators.

BACKGROUND: The role of the menopause in weight gain is an understudied yet important field, given the rising prevalence of obesity and its associated risk of disease. OBJECTIVE: To review the current evidence regarding the impact of the menopausal transition on changes in body composition and fat accrual in women and the hormonal mechanisms underlying the process. METHODS: A critical appraisal of the current literature by experts in the field. RESULTS: Menopause is associated with an overall increase in fat mass, which tends to accumulate around the waist. There is also a decrease in lean mass, particularly evident in the lower limbs. Reduced energy expenditure (EE) has been confirmed in parallel with increased food intake, the latter being more evident in experimental models. A prominent role has been found for the estrogen receptor (ER) alpha isoform in fat accrual. Human studies suggest a role for androgens in central fat accumulation and type 2 diabetes. FSH is a key factor in the process of fat accumulation, but only in rodents. Clinical studies suggest that these endocrine alterations are insufficient to explain the observed changes. CONCLUSIONS: The menopausal transition is associated with an increase in adiposity, which accumulates preferentially in the abdominal area. Hypoestrogenism and the imbalance of the androgen/estrogen ratio are strong candidates to explain the phenomenon, although other hormonal factors probably also play a role. The impact on risk of disease is still insufficiently known, although an association with risk factors, such as an unfavorable lipid profile or insulin resistance seems likely.

The association between serum sex hormone-binding globulin changes during progestin-primed ovarian stimulation and embryo outcomes: a retrospective cohort study.

Objective: This study is aimed to examine the associations between embryo outcomes and serum sex hormone-binding globulin (SHBG) changes during progestin-primed ovarian stimulation (PPOS) protocols in IVF/ICSI cycles.Research methods: This study included 2790 eligible consecutive cycles of patients aged 21-53 years undergoing PPOS treatment. Multivariable linear regression analysis was performed to explore the association between SHBG changes and embryo outcomes.Results of the study: Our results showed that the SHBG-increase rate on the HCG day and in the late follicular phase were positively and linearly correlated with available embryos in day3, with adjusted regression coefficients (ß) for the SHBG-increase rate on the HCG day, in the late follicular phase were 0.6 (0.4, 0.9), 0.4 (0.2, 0.6), but in the middle follicular phase and in the early follicular phase, this correlation was not significant (p > 0.05).Conclusion: Our results indicate that serum SHBG increment may serve as a biomarker of the developmental potential of the oocytes from patients undergoing the PPOS protocol.

First trimester sex hormone-binding globulin predicts gestational diabetes mellitus in a population of Nigerian women.

There has been a steady rise in the disease burden of Gestational Diabetes Mellitus (GDM) in the sub-Saharan African region over time. Diagnostic testing for GDM is currently recommended at 24 - 28 weeks of gestation, leaving a narrow window for intervention before delivery. Hence the need for early prediction and preventive intervention. The performance of first trimester serum sex hormone-binding globulin (SHBG) assay as a predictor of GDM was determined by binary logistic regression. Women with GDM (n = 49) had a significantly lower mean first trimester SHBG level (104.7 ± 61.6 nmol/L) than did those without GDM (n = 180; 265.2 ± 141.5 nmol/L; p < .001). First trimester SHBG was significantly negatively correlated (rpb = -0.460, p value = <.001) with subsequent development of GDM and an area under receiver operator characteristics (ROC) curve of 0.874 (p < .001). A cut-off value of 158.0 nmol/L predictive of GDM had a diagnostic sensitivity of 81.5%, a specificity of 80.1%, and an overall diagnostic efficiency of 80.3%.IMPACT STATEMENTWhat is already known on this subject? GDM is associated with high risk of various complications and is commonly diagnosed at 24-28 weeks of gestation, leaving a narrow window for intervention. The performance of current maternal clinical and demographic risk factor-based prediction approaches is unreliable. Thus, more favourable prediction approaches need to be developed. Previous studies have suggested that SHBG, a readily assessable marker, has potential to predict GDM; however, these studies have mostly involved Caucasian and other non-African populations.What the results of this study add? SHBG may serve as a reliable first trimester screening tool for GDM development in Nigerian women with singleton pregnancies. This study demonstrates that first trimester SHBG can predict GDM development in sub-Saharan African women despite racial, ethnic and geographical differences.What are the implications of these findings for clinical practice and/or further research? Effective first trimester prediction of GDM using SHBG may enable preventive interventions, thereby mitigating the high burden of the disease in the sub-Saharan African region. It may also provide relevant information that may guide adaptation of current management guidelines to ensure effective management of GDM in the region.