Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by TMPRSS2:ERG status.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 93-93
Author(s):  
Rebecca E Graff ◽  
Allison Meisner ◽  
Thomas Ahearn ◽  
Michelangelo Fiorentino ◽  
Howard D. Sesso ◽  
...  

93 Background: Experimental studies have shown that androgen receptor stimulation can facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase the risk of developing TMPRSS2:ERG positive prostate cancer specifically. Methods: We conducted a nested case-control study of 200 prostate cancer cases and 1,057 controls from the Physicians’ Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was assessed by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of fusion-positive (n = 94) and, separately, fusion-negative (n = 106) disease. Results: Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05-1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86-1.38) (p-diff: 0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive versus ERG-negative disease. Conclusions: These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG positive prostate cancer but are not associated with prostate cancer that lacks TMPRSS2:ERG.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Felwah S. Al-Zaid ◽  
Abdel Fattah A. Alhader ◽  
Laila Y. Al-Ayadhi

AbstractAndrogens have been implicated in autism pathophysiology as recently, prenatal exposure to elevated androgens has been proposed as risk factor. However, published data on postnatal sex hormone levels in autistic children are controversial and the source of prenatal androgen exposure in autism remains unknown. Therefore, this study investigated postnatal sex hormone levels and dehydroepiandrosterone (DHEA) to shed light on a potential role for the adrenal gland in autism pathophysiology. A case-control study investigating estradiol (E2), DHEA, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was conducted with 31 Saudi males with autism and 28 healthy, age-matched boys plasma. Moreover, correlation analysis with measured hormones and previously measured total testosterone (TT) and free testosterone (FT) in the same group of autism was conducted. DHEA was significantly higher (p < 0.05) in the autism group compared to controls. DHEA positively correlated with previously measured TT (r = + 0.79, p < 0.001) and FT (r = + 0.72, p < 0.001) levels in the same autism group. FSH levels were also significantly higher in the autism group than in the control group (p < 0.01). To the best of our knowledge, this is the first study to report a strong positive correlation between TT, FT and DHEA, suggesting an adrenal source for elevated androgen levels.


2009 ◽  
Vol 160 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Johan Svartberg ◽  
Sigrid K Brækkan ◽  
Gail A Laughlin ◽  
John-Bjarne Hansen

ObjectivesLow testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men.DesignA prospective, population-based study.MethodsSex hormone measurements were available in 1350 men, aged 50–84, participating in the Tromsø study in 1994–1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007.ResultsThere were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19–5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each s.d. increase, hazards ratios (95% CI) were 1.06 (0.83–1.35) for total testosterone, 1.02 (0.79–1.33) for free testosterone, and 1.27 (0.94–1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE.ConclusionsIn this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.


2019 ◽  
Vol 8 (8) ◽  
pp. 1136
Author(s):  
Daniel Castellano-Castillo ◽  
José Luis Royo ◽  
Ana Martínez-Escribano ◽  
Lidia Sánchez-Alcoholado ◽  
María Molina-Vega ◽  
...  

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism. Methodology: 212 young (<45 years) non-diabetic obese (BMI ≥ 30 kg/m2) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal (n = 55, TT > 3.5 ng/mL and FT ≥ 70 pg/mL; EuG), normal FT hypogonadism (n = 40, TT < 3.5 and FT ≥ 70 pg/mL; normal FT HG) and hypogonadism (n = 117, TT < 3.5 ng/mL and TL < 70 pg/mL; HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem). Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) β = 3.28; (AA) β = 12.45) and a decreased of FT levels ((GA) β = −9.19; (AA) β = −18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54). Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.


2006 ◽  
Vol 91 (3) ◽  
pp. 843-850 ◽  
Author(s):  
Varant Kupelian ◽  
Stephanie T. Page ◽  
Andre B. Araujo ◽  
Thomas G. Travison ◽  
William J. Bremner ◽  
...  

Abstract Background: The metabolic syndrome (MetS), characterized by central obesity, lipid and insulin dysregulation, and hypertension, is a precursor state for cardiovascular disease. The purpose of this analysis was to determine whether low serum sex hormone levels or clinical androgen deficiency (AD) predict the development of MetS. Methods: Data were obtained from the Massachusetts Male Aging Study, a population-based prospective cohort of 1709 men observed at three time points (T1, 1987–1989; T2, 1995–1997; T3, 2002–2004). MetS was defined using a modification of the ATP III guidelines. Clinical AD was defined using a combination of testosterone levels and clinical signs and symptoms. The association between MetS and sex hormone levels or clinical AD was assessed using relative risks (RR), and 95% confidence intervals (95% CI) were estimated using Poisson regression models. Results: Analysis was conducted in 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with a body mass index (BMI) below 25 kg/m2 with adjusted RRs for a decrease in 1 sd of 1.41 (95% CI, 1.06–1.87) and 1.65 (95% CI, 1.12–2.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.12–5.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.66–2.24) in men with a BMI of 25 or greater. Conclusions: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, &lt;25). Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men.


2007 ◽  
Vol 156 (6) ◽  
pp. 687-693 ◽  
Author(s):  
Erik Debing ◽  
Els Peeters ◽  
William Duquet ◽  
Kris Poppe ◽  
Brigitte Velkeniers ◽  
...  

Objective: To study the endogenous sex hormone levels in natural postmenopausal women and their association with the presence of internal carotid artery (ICA) atherosclerosis. Design: Case-control study Methods: We compared 56 patients with severe ICA atherosclerosis referred for carotid artery endarterectomy (CEA) with 56 age-matched control subjects free of severe atherosclerotic disease. The presence of atherosclerosis was determined by high-resolution B-mode ultrasound. Metabolic parameters and sex hormones were measured or calculated: total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, insulin, quantitative insulin sensitivity check index, insulin resistance index, IGF-I, DHEA, DHEA sulfate (DHEA-S), free testosterone, total testosterone, estrone, estradiol, androstenedione, and sex hormone-binding globulin. Results: The cases had statistically significant lower levels of both total testosterone (0.23 ± 0.12 vs 0.31 ± 0.20 μg/l, P = 0.043) and free testosterone (3.42 ± 1.94 vs 4.59 ± 2.97 ng/l, P = 0.009) and significantly lower levels of androstenedione (625.3 ± 168.7 vs 697.0 ± 211.9 ng/l, P = 0.017) when compared with controls. Multivariate linear regression analysis, adjusted for traditional cardiovascular risk factors, baseline and physiologic characteristics, showed a significant inverse relationship between both serum free testosterone (β = −0.234, P = 0.028) and androstenedione (β = −0.241, P = 0.028) levels with the presence of severe atherosclerosis of ICA. Conclusions: The study provides evidence of a positive association between low serum androgen levels and severe ICA atherosclerosis in postmenopausal women. It suggests that higher, but physiological, levels of androgens in postmenopausal women have a protective role in the development of atherosclerosis of ICA.


2010 ◽  
Vol 162 (4) ◽  
pp. 747-754 ◽  
Author(s):  
Torkel Vikan ◽  
Henrik Schirmer ◽  
Inger Njølstad ◽  
Johan Svartberg

ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes.DesignPopulation-based prospective cohort study.MethodsFor the analyses, 1454 men who participated in the fourth Tromsø study (1994–1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments.ResultsThere was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54–0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33–0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39–0.79) and when comparing the third (HR 0.38, CI 0.18–0.81) and the fourth quartile (HR 0.37, CI 0.17–0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E2) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26–0.93) and the third (HR 0.51, CI 0.27–0.96) quartile to the highest quartile.ConclusionMen with higher E2 levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.


1990 ◽  
Vol 64 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Timothy J. A. Key ◽  
Liane Roe ◽  
Margaret Thorogood ◽  
John W. Moore ◽  
Graham M. G. Clark ◽  
...  

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation, in comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r–0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.


1986 ◽  
Vol 113 (3) ◽  
pp. 457-462 ◽  
Author(s):  
Ragnar Tegelman ◽  
Pia Lindeskog ◽  
Kjell Carlström ◽  
Åke Pousette ◽  
Rolf Blomstrand

Abstract. The effect of one week of controlled fasting (3 1 of fluid containing 50 g of carbohydrate/day) upon the serum levels of hormones, sex hormone binding globulin, and albumin was studied in healthy subjects. Fasting caused decreased levels of prolactin and T3, no changes in the levels of TSH, FSH, LH, dehydroepiandrosterone, 4-androstene-3,17-dione, total oestrone, and total testosterone, and increased levels of cortisol, dehydroepiandrosterone sulphate and albumin. A significant positive correlation was found between albumin and dehydroepiandrosterone sulphate. Fasting rapidly increased the levels of sex hormone binding globulin and decreased the percentage of free testosterone and the calculated free testosterone level in both sexes. A decreased metabolic clearance of certain steroids (cortisol, dehydroepiandrosterone sulphate) owing to an increased protein binding may be one of the endocrine consequences of fasting. An increased protein binding of testosterone may be outweighed by a decreased gonadal production, thus resulting in an unchanged total testosterone level. The increased sex hormone binding globulin level could not be explained by changes in gonadal and thyroid hormones.


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