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Sex hormone binding globulin and verbal memory in older men.

ABSTRACT: Cognitive function in older adults may be affected by multiple factors, such as sex hormone levels, metabolic disturbances, and neuropsychiatric illness. However, relatively few studies have tested the associations between these factors and cognitive function in a single sample. A cross-sectional analysis was conducted to examine the association between sex hormones, metabolic parameters, and psychiatric diagnoses with verbal memory in nondemented older men.Participants were 112 men (mean age: 61.3 years) from the Baltimore Epidemiologic Catchment Area Follow-Up Study who completed measures of blood sex hormone levels, metabolic parameters (e.g., lipid profiles), and verbal memory.Higher levels of serum sex hormone binding globulin (SHBG) were associated with lower delayed verbal memory scores (standardized coefficients [beta]=-0.19, t=-2.07, df=1, 105, p=0.04), and higher body mass index (BMI) was associated with better immediate (beta=0.21, t=2.41, df=1,105, p=0.02) and delayed (beta=0.22, t=2.46, df=1,105, p=0.02) verbal memory performance after adjustment for age, education, and psychiatric disorders. There was an inverse correlation between SHBG levels and BMI (Pearson's r=-0.37, N=112, p<0.001). Estimated free testosterone levels revealed curvilinear associations with verbal memory performance.Our data suggest that higher SHBG levels are associated with worse verbal memory, whereas a higher BMI is associated with better verbal memory in older men. Higher SHBG levels due to lower adiposity may be a risk factor for cognitive dysfunction. The mechanisms linking SHBG to cognitive function have yet to be elucidated.

SUBMITTER: Takayanagi Y

PROVIDER: S-EPMC3785559 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Sex hormone binding globulin and verbal memory in older men.

Takayanagi Yoichiro Y Spira Adam P AP McIntyre Roger S RS Eaton William W WW

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20130622 3

<h4>Objective</h4>Cognitive function in older adults may be affected by multiple factors, such as sex hormone levels, metabolic disturbances, and neuropsychiatric illness. However, relatively few studies have tested the associations between these factors and cognitive function in a single sample. A cross-sectional analysis was conducted to examine the association between sex hormones, metabolic parameters, and psychiatric diagnoses with verbal memory in nondemented older men.<h4>Methods</h4>Part ...[more]

PMID: 23800538

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Project description:In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

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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Sex hormone binding globulin and verbal memory in older men.

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Sex hormone binding globulin and verbal memory in older men.

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