Serum Sex Hormone Binding Globulin Concentration as a Predictor of Ovarian Response During Controlled Ovarian Hyperstimulation.
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ABSTRACT:
SUBMITTER: Zhai J
PROVIDER: S-EPMC8600072 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The objective of the present study was to compare sex hormone-binding globulin (SHBG) levels according to sex (healthy male and female volunteers) and age to determine reference values. Serum SHBG expression levels in patients with breast cancer with different tumor burden states were also determined. A total of 109 samples were obtained from 34 patients in 3 different disease states (non-tumor, localized tumor and systemic metastasis) during follow-up. A sandwich ELISA was conducted to measure SHBG, cancer antigen (CA)15-3 and CA125 expression levels. Wilcoxon rank-sum tests were performed on non-normally distributed data and an unpaired t-test was used for normally distributed variables. SHBG expression levels were higher in females compared with males (P<0.0001). When SHBG expression levels were compared by sex, the difference was maintained in the age groups <30, 30-39 and ≥50 years, but not in the 40-49 years group. In males, SHBG expression levels increased until the age of 49 and then decreased (P=0.01). In females, SHBG expression levels exhibited a decreased trend until the age of 49 (P=0.66). In patients with breast cancer, the SHBG expression levels revealed a decreasing trend after the age of 50, which was different compared with the healthy females. There was a decreasing trend of SHBG expression levels from pre-menopause to post-menopause healthy volunteers (P=0.74). CA15-3 (r2=0.07; P=0.59) and CA 125 (r2=-0.18; P=0.17) levels did not exhibit any significant correlation with SHBG expression levels. There was a significant difference in the SHBG expression levels between male and female healthy volunteers. SHBG expression levels also revealed different patterns between healthy female volunteers and female patients with breast cancer ≥50 years of age. The present study demonstrated that SHBG does not have value as a biomarker, but different reference values according to age and sex may aid in predicting high-risk groups for hormone-dependent cancer and guide treatment direction for post-menopausal breast cancer.
| S-EPMC7285803 | biostudies-literature
Project description:The access of testosterone and estradiol to target tissues is regulated by sex hormone-binding globulin (SHBG) in human blood. Serum SHBG levels are low in patients with hyperandrogenism, especially in association with polycystic ovarian syndrome (PCOS) and in individuals at risk for diabetes and heart disease. Here, we identify SHBG coding region variations from a compound heterozygous patient who presented with severe hyperandrogenism during pregnancy. Serum SHBG levels in this patient measured 2 years after her pregnancy were exceptionally low, and her non-protein-bound testosterone concentrations greatly exceeded the normal reference range. A single-nucleotide polymorphism within the proband's maternally derived SHBG allele encodes a missense mutation, P156L, which allows for normal steroid ligand binding but causes abnormal glycosylation and inefficient secretion of SHBG. This polymorphism was identified in four other patients with either PCOS, ioiopathic hirsutism, or ovarian failure. The proband's paternal SHBG allele carries a single-nucleotide deletion within exon 8, producing a reading-frame shift within the codon for E326 and a premature termination codon. CHO cells transfected with a SHBG cDNA carrying this mutation fail to secrete the predicted truncated form of SHBG. To our knowledge, these are the first examples of human SHBG variants linked to hyperandrogenism and ovarian dysfunction.
| S-EPMC150924 | biostudies-literature
Project description:This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960-1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.
| S-EPMC4814971 | biostudies-literature
Project description:Sex hormone-binding globulin (SHBG) is a circulating glycoprotein that transports testosterone and other steroids in the blood. Interest in SHBG has escalated in recent years because of its inverse association with obesity and insulin resistance, and because many studies have linked lower circulating levels of SHBG to metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, and early puberty. The purpose of this review is to summarize molecular, clinical, endocrine, and epidemiological findings to illustrate how measurement of plasma SHBG may be useful in clinical medicine in children.
| S-EPMC4805039 | biostudies-literature
Project description:BackgroundEstrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.MethodsFour biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.ResultsAge, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p=0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.ConclusionSome common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.
| S-EPMC2615755 | biostudies-literature
Project description:The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH).This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced. We also investigated a polymorphism (rs4073366 G?>?C) that was 142 bp from insLQ. The association of the insLQ and rs4073366 alleles and outcome to COH (number of mature follicles, estradiol level on day of human chorionic gonadotropin (hCG) administration, the number of eggs retrieved and ovarian hyperstimulation syndrome (OHSS)) was determined.Increasing age and higher day 3 (basal) FSH levels were significantly associated with poorer response to COH. We found that both insLQ and rs4073366 were in linkage disequilibrium (LD) and no patients were homozygous for both recessive alleles (insLQ/insLQ; C/C). The insLQ variant was not significantly associated with any of the main outcomes to COH. Carrier status for the rs4073366 C variant was associated (P?=?0.033) with an increased risk (OR 2.95, 95% CI?=?1.09-7.96) of developing OHSS.While age and day 3 FSH levels were predictive of outcome, we found no association between insLQ and patient response to COH. Interestingly, rs4073366 C variant carrier status was associated with OHSS risk. To the best of our knowledge, this is the first report suggesting that LHCGR genetic variation might function in patient risk for OHSS.
| S-EPMC3727944 | biostudies-literature
Project description:Sex hormone-binding globulin (SHBG) transports androgens and estrogens in blood and regulates their access to target tissues. Hepatic production of SHBG fluctuates throughout the life cycle and is influenced primarily by metabolic and hormonal factors. Genetic differences also contribute to interindividual variations in plasma SHBG levels. In addition to controlling the plasma distribution, metabolic clearance, and bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts novel effects on androgen and estrogen action. In mammals, the gene-encoding SHBG is expressed primarily in the liver but also at low levels in other tissues, including the testis. In subprimate species, Shbg expression in Sertoli cells is under the control of follicle-stimulating hormone and produces the androgen-binding protein that influences androgen actions in the seminiferous tubules and epididymis. In humans, the SHBG gene is not expressed in Sertoli cells, but its expression in germ cells produces an SHBG isoform that accumulates in the acrosome. In fish, Shbg is produced by the liver but has a unique function in the gill as a portal for natural steroids and xenobiotics, including synthetic steroids. However, salmon have retained a second, poorly conserved Shbg gene that is expressed only in ovary, muscle, and gill and that likely exerts specialized functions in these tissues. The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction.
| S-EPMC4480437 | biostudies-literature
Project description:Sex hormone-binding globulin (SHBG) has emerged as one of the multiple genetic and environmental factors that potentially contribute to the pathophysiology of type 2 diabetes mellitus (T2DM). In addition to epidemiologic studies demonstrating a consistent relationship between decreased levels of serum SHBG and incident T2DM, recent genetic studies also reveal that transmission of specific polymorphisms in the SHBG gene influence the risk of T2DM. At the molecular level, the multiple interactions between SHBG and its receptors in various target tissues suggest physiologic roles for SHBG that are more complex than the simple transport of sex hormones in serum. Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM.
| S-EPMC3351377 | biostudies-literature
Project description:Findings from observational studies suggest that sex hormone-binding globulin (SHBG) and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels.After a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42) were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group) per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate]. No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone.Our data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.
| S-EPMC3502342 | biostudies-literature
Project description:The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.
| S-EPMC4755786 | biostudies-literature