scholarly journals Free testosterone and malignant melanoma risk in men: prospective analyses of testosterone and SHBG with 19 cancers in men and postmenopausal women UK Biobank

2020 ◽  
Author(s):  
Eleanor L. Watts ◽  
Aurora Perez-Cornago ◽  
Anika Knuppel ◽  
Konstantinos K. Tsilidis ◽  
Timothy J. Key ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Malignant Melanoma ◽  
Liver Cancer ◽  
Postmenopausal Women ◽  
Multiple Testing ◽  
Cox Regression ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Uk Biobank

AbstractWe investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank.Risk was estimated using multivariable-adjusted Cox regression in up to 182,608 men and 122,112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within two years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate.In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase=1.35, 95% CI 1.14-1.61 and 1.10,1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L=2.45,1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L=1.56,1.31-1.87) and a lower risk of prostate cancer (0.93,0.91-0.96); associations with liver cancer were attenuated after excluding early follow-up. In postmenopausal women, higher free and total testosterone and lower SHBG were associated with elevated risks of endometrial (HR per 10 pmol/L=1.59,1.32-1.90; HR per 0.5 nmol/L=1.34,1.18-1.52 and HR per 25 nmol/L=0.78,0.67-0.91, respectively) and breast cancer (1.32,1.22-1.43;1.24,1.17-1.31 and 0.88,0.83-0.94, respectively).We report a novel association of free testosterone with malignant melanoma in men; our findings also support known associations between sex hormones and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.

Sex-specific associations of circulating testosterone levels with all-cause and cause-specific mortality

2021 ◽  
Author(s):  
Jiayu Wang ◽  
Xikang Fan ◽  
Mingjia Yang ◽  
Mingyang Song ◽  
Kai Wang ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Cancer Mortality ◽  
Multiple Testing ◽  
Cox Regression ◽  
Positive Association ◽  
Total Testosterone ◽  
Critical Determinant ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Risk Of Cancer

Objective: Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined. Methods: We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154,965 men and 93,314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. Results: Over a median follow-up of 8.9 (inter-quartile range, 8.3-9.5) years, we documented 5,754 deaths in men, including 1,243 (21.6%) from CVD and 2,987 (51.9%) from cancer. In postmenopausal women, 2,435 deaths occurred, including 346 (14.2%) from CVD and 1,583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75-0.91) and 0.80 (95% CI: 0.73-0.87) for the highest (Q5) versus the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 versus Q1 = 1.20, 95% CI: 1.06-1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03). Conclusions: Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.

scholarly journals Lung function changes over 8 years and testosterone markers in both sexes: UK Biobank

2020 ◽  
Vol 6 (3) ◽  
pp. 00070-2020
Author(s):  
Alexandra Lenoir ◽  
Elaine Fuertes ◽  
Francisco Gómez-Real ◽  
Benedicte Leynaert ◽  
Diana A. van der Plaat ◽  
...  
Keyword(s):  
Lung Function ◽  
Free Testosterone ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Uk Biobank ◽  
Lung Function Decline ◽  
Cross Sectional ◽  
Physically Active

Higher levels of testosterone have been associated with better lung function in cross-sectional population-based studies. The role of testosterone in lung function in women and in lung function decline in men or women is unclear.We studied 5114 men and 5467 women in the UK Biobank with high-quality spirometry at baseline (2006–2010) and 8.4 years later. We studied cross-sectional associations of total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI) and sex hormone-binding globulin (SHBG) with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using linear regression and associations of baseline markers with lung function decline using linear mixed-effects regression.Men with higher levels of TT had higher FEV1 (27.56 mL per interquartile range increase TT, 95% CI 5.43–49.68) and FVC (48.06 mL, 95% CI 22.07–74.06) at baseline. Higher cFT levels were associated with higher FEV1 and FVC among physically active men only. In women, higher FAI and cFT levels were associated with lower lung function at baseline and higher levels of TT, cFT and FAI were associated with slightly attenuated FEV1 and FVC decline. Higher levels of SHBG were associated with better lung function in both sexes but slightly accelerated decline in men.In this population-based sample, higher levels of TT were associated with better lung function in men and higher levels of cFT with better lung function in physically active men. A small attenuation of lung function decline with higher levels of TT, cFT and FAI was seen in women only.

scholarly journals Plasma androgens and the presence and course of depression in a large cohort of women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anouk E. de Wit ◽  
Erik J. Giltay ◽  
Marrit K. de Boer ◽  
Fokko J. Bosker ◽  
Aviva Y. Cohn ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Depressive Disorders ◽  
Geometric Mean ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Physiological Range ◽  
Statistical Equivalence ◽  
Androgen Levels

AbstractMajor depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27–1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.

Serum levels of androgens and migraine in postmenopausal women

2002 ◽  
Vol 103 (5) ◽  
pp. 487-491 ◽  
Author(s):  
Peter MATTSSON
Keyword(s):  
Serum Level ◽  
Postmenopausal Women ◽  
Screening Program ◽  
International Headache Society ◽  
Conditional Logistic Regression ◽  
Free Testosterone ◽  
Serum Levels ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
The Mean

Female hormones are thought to be of importance in the aetiology of migraine, which is more common in women than in men. Little attention has been paid to androgens. This study investigates the associations between migraine and serum levels of androgens in postmenopausal women not taking oestrogens. A case-control study was carried out among women participating in a mammography screening program. A neurologist clinically assessed the participants. Headache criteria proposed by the International Headache Society were used. Each of the 15 women with migraine was matched to three controls by time since menopause and by body mass index. Serum levels of androstenedione and total testosterone were measured by radioimmunoassays. Free testosterone was calculated from total testosterone, immunoassayed sex hormone-binding globulin and albumin. The mean±S.D. serum level of androstenedione was 2.7±1.1nmol/l and 3.4±1.9nmol/l in cases and controls respectively. The mean serum level of testosterone was 0.8±0.4nmol/l and 1.0±0.5nmol/l in cases and controls respectively. The mean serum level of free testosterone was 12.5±8.5pmol/l and 14.0±7.9pmol/l in cases and controls respectively. Conditional logistic regression analysis was used to test for differences in serum levels of androstenedione, total testosterone and free testosterone between cases and controls. No statistically significant differences were found. To conclude, there was no evidence in this study that differences within normal levels of androgens play an important role in the aetiology of migraine in postmenopausal women not taking oestrogens.

scholarly journals No association between circulating levels of testosterone and sex hormone-binding globulin and risk of COVID-19 mortality in UK biobank

2020 ◽  
Author(s):  
Xikang Fan ◽  
Jing Yang ◽  
Jiayu Wang ◽  
Cheng Yin ◽  
Meng Zhu ◽  
...  
Keyword(s):  
Free Testosterone ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Uk Biobank ◽  
Hormone Binding ◽  
Disaggregated Data ◽  
Death Cases ◽  
Circulating Levels

Background: Sex-disaggregated data suggest that men with coronavirus disease 2019 (COVID-19) are more likely to die than women. Whether circulating testosterone or sex hormone-binding globulin (SHBG) contributes to such sex differences remains unknown. Objective: To evaluate the associations of circulating total testosterone (TT), free testosterone (FT), and SHBG with COVID-19 mortality. Design: Prospective analysis. Setting: UK Biobank. Participants: We included 1306 COVID-19 patients (678 men and 628 women) who had serum TT and SHBG measurements and were free of cardiovascular disease or cancer at baseline (2006-2010). Main outcome measures: The death cases of COVID-19 were identified from National Health Service death records updated at 31 July 2020. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CI) for mortality. Results: We documented 315 deaths of COVID-19 (194 men and 121 women). After adjusting for potential confounders, we did not find any statistically significant associations for TT (OR per 1-SD increase = 1.03, 95% CI: 0.85-1.25), FT (OR per 1-SD increase = 0.95, 95% CI: 0.77-1.17), or SHBG (OR per 1-SD increase = 1.09, 95% CI: 0.87-1.37) with COVID-19 mortality in men. Similar null results were observed in women (TT: OR per 1-SD increase = 1.10, 95% CI: 0.85-1.42; FT: OR per 1-SD increase = 1.10, 95% CI: 0.82-1.46; SHBG: OR per 1-SD increase = 1.16, 95% CI: 0.89-1.53). Conclusions: Our findings do not support a significant role of circulating testosterone or SHBG in COVID-19 prognosis.

scholarly journals The Association Between Dietary Inflammatory Index and Sex Hormones Among Postmenopausal Women in the US

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-Yu Chen ◽  
Yan-Peng Fu ◽  
Wen Zhong ◽  
Min Zhou
Keyword(s):  
Linear Regression ◽  
Postmenopausal Women ◽  
Sex Hormones ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Dietary Inflammatory Index ◽  
Inflammatory Index ◽  
Underlying Mechanisms ◽  
Stratified Analysis

AimsDiet has been found to have an important effect on sex hormones. The effect of diet-induced inflammation on sex hormones has not been studied in detail among women. Therefore, we aimed to investigate the association between energy-adjusted dietary inflammatory index (E-DII) and sex hormones among postmenopausal women.MethodsThis study used data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 waves. A total of 1183 postmenopausal women who provided information on two 24-hour dietary intake recalls, sex hormones including total testosterone (TT), estradiol (E2), TT/E2, sex hormone-binding globulin (SHBG), free estradiol (FE2) and free testosterone (FT), as well as selected covariates were included. Linear regression and restricted cubic spline evaluated the association between E-DII and sex hormones. Effect modification by body mass index (BMI) and type of menopause was then examined in stratified analysis.ResultsAfter adjusting for covariates, linear regression showed that E-DII was positively associated with TT (P=0.035), FT (P=0.026) and TT/E2 (P=0.065). TT (P-nonlinear = 0.037) and TT/E2 (P-nonlinear = 0.035) had significant nonlinear association with E-DII. E2 (P-nonlinear = 0.046) and FE2 (P-nonlinear = 0.027) depicted a nonlinear U-shaped significant association with E-DII, the two inflection points were found at the E-DII score of -0.22 and 0.07, respectively, the associations in natural menopausal women were more pronounced.ConclusionsOur study indicates that several indicators of androgen and estrogen were associated with E-DII in postmenopausal women. Further research is needed to understand the underlying mechanisms.

scholarly journals Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

2020 ◽  
Vol 123 (12) ◽  
pp. 1808-1817
Author(s):  
Aurora Perez-Cornago ◽  
Georgina K. Fensom ◽  
Colm Andrews ◽  
Eleanor L. Watts ◽  
Naomi E. Allen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Incidence ◽  
Multiple Testing ◽  
Cox Regression ◽  
Future Research ◽  
Cancer Death ◽  
Uk Biobank ◽  
Prostate Cancer Incidence ◽  
Incidence And Mortality

Abstract Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

scholarly journals Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Biologically Active ◽  
Free Form ◽  
Total Testosterone ◽  
The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

scholarly journals Hypogonadism and liver fibrosis in HIV-infected patients

2021 ◽  
Author(s):  
E. Quiros-Roldan ◽  
T. Porcelli ◽  
L. C. Pezzaioli ◽  
M. Degli Antoni ◽  
S. Paghera ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Univariate Analysis ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Cross Sectional ◽  
Pituitary Dysfunction ◽  
Consequent Reduction ◽  
Secondary Hypogonadism ◽  
The Relationship

Abstract Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

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