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Cross-sectional study of factors influencing sex hormone-binding globulin concentrations in normally cycling premenopausal women.

ABSTRACT: To assess the relationship between SHBG and 18 other hormonal and metabolic parameters in well characterized, normally cycling premenopausal women.Cross-sectional study.University general clinical research center.A total of 319 young healthy women with ovulatory menstrual cycles.None.Midfollicular serum SHBG concentrations.In our final linear regression model, SHBG was negatively associated with bioavailable T and positively associated with adiponectin, associations that were independent from other parameters. SHBG was also positively associated with estrone sulfate, but only when taking into account confounding variables. Unexpectedly, there was no straightforward relationship between SHBG and insulin resistance according to homeostasis-model assessment.Our results highlight the link between androgen action, as reflected by bioavailable T, and circulating SHBG concentrations in all premenopausal women and speak to the importance of the relationship between SHBG and adiponectin, which is at least in part independent from androgen action.NCT00393172.

SUBMITTER: Crawford TN

PROVIDER: S-EPMC4663171 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Cross-sectional study of factors influencing sex hormone-binding globulin concentrations in normally cycling premenopausal women.

Crawford Talia N TN Arikawa Andrea Y AY Kurzer Mindy S MS Schmitz Kathryn H KH Phipps William R WR

Fertility and sterility 20150916 6

<h4>Objective</h4>To assess the relationship between SHBG and 18 other hormonal and metabolic parameters in well characterized, normally cycling premenopausal women.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>University general clinical research center.<h4>Subject(s)</h4>A total of 319 young healthy women with ovulatory menstrual cycles.<h4>Intervention(s)</h4>None.<h4>Main outcome measure(s)</h4>Midfollicular serum SHBG concentrations.<h4>Result(s)</h4>In our final linear regression mo ...[more]

PMID: 26385402

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Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 ?g mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Project description:BackgroundCirculating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain.MethodsWe performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls).ResultsAmong women, higher plasma levels of sex hormone-binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone-binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone-binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex hormone-binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex hormone-binding globulin may have a causal role in the risk of type 2 diabetes.ConclusionsLow circulating levels of sex hormone-binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination.

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Cross-sectional study of factors influencing sex hormone-binding globulin concentrations in normally cycling premenopausal women.

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Cross-sectional study of factors influencing sex hormone-binding globulin concentrations in normally cycling premenopausal women.

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