Impact of flaxseed supplementation and dietary fat restriction on prostate cancer proliferation and other biomarkers: Results of a Phase II randomized controlled trial (RCT) using a presurgical model

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1510-1510 ◽  
Author(s):  
S. L. George ◽  
T. J. Polascik ◽  
D. M. Albala ◽  
P. J. Walther ◽  
J. Moul ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protective Effect ◽  
Dietary Fat ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Sample Mean ◽  
Cell Counts ◽  
Mib 1

1510 Background: Diet may play a key role in the etiology of prostate cancer (PC). Dietary fat restriction (DFR) and flaxseed supplementation (FS) may reduce risk, though results are mixed. We undertook an RCT to test the comparative effects of these dietary regimens on the biology of the prostate and other biomarkers. Methods: PC patients (N=161) scheduled ≥ 21 days prior to prostatectomy were block randomized on race (black vs non-black) and biopsy Gleason sum (<7 vs 7+) to these diets: 1) control; 2) FS (30 g/day); 2) DFR (<20% total energy); or 4) FS+DFR. Blood was drawn upon accrual and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin (SHBG), total testosterone (T), insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), c- reactive protein (CRP), and total and low density lipoprotein cholesterol (TC & LDL-C). Proliferation (MIB-1) and apoptosis (TUNEL) was assessed in the malignant and benign prostate. Results: Complete data were collected on 93% of the sample; mean length on protocol was 30 days. Median MIB-1 positive (+) cells/total nuclei ratios were: 1=2.38;2=1.71;3=2.93;4=1.58. Primary analyses suggest a significant protective effect (p=0.016) of FS. Secondary analyses of MIB-1 + nuclei (controlling for total cell counts) show increased proliferation with DFR (p=.017), and a significant interaction with FS and DFR (p<.0001). No differences were observed between groups with regard to PC apoptosis, and histology of benign tissue. No differences were observed between arms for PSA, SHBG, T, IGF1, IGFBP3 or CRP. Significant differences were observed between arms for changes in serum lipids and body weight [ΔTC = +9/-26/-46/-37 mg/dL; ΔLDLC = -14/-17/-29/-21 mg/dL and Δ weight = +0.3/-1.3/-1.7/-1.1 kg (p’s<.05)]; effects were attributed to DFR and not FS. Side effects did not differ between arms Conclusions: Preliminary findings suggest that FS is safe and exerts a protective effect (main effect or via interaction with DFR) on PC. Data also provide further support of DFR for cardiovascular disease, though its role in PC is less clear. Further controlled analyses and additional studies are needed to confirm findings. No significant financial relationships to disclose.

scholarly journals Serum Omentin Levels in Patients with Prostate Cancer and Associations with Sex Steroids and Metabolic Syndrome

2020 ◽  
Vol 9 (4) ◽  
pp. 1179
Author(s):  
Artur Borowski ◽  
Lucyna Siemińska
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Sex Steroids ◽  
Specific Antigen ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Serum Concentrations ◽  
Prostate Hyperplasia ◽  
Metabolic Characteristics ◽  
Persistent Inflammation

Mechanisms linking obesity and prostate cancer (PC) include increased insulin signaling, persistent inflammation, and altered adipocytokines secretion. Previous studies indicated that omentin may play a potential role in cancerogenesis of different sites, including the prostate. In this study, we focused on the hormonal and metabolic characteristics of men recruited for prostate biopsy. We evaluated serum concentrations of adipocytokines and sex steroids where concentrations are related to the adiposity: omentin, leptin, testosterone, estradiol, and sex hormone-binding globulin (SHBG). Aim: The aim of the study was to assess the concentration of serum omentin in men with PC. We also investigated relationships between omentin, leptin, sex steroids, SHBG, age, and metabolic syndrome (MS). Methods: Our study was conducted on 72 patients with PC and 65 men with benign prostate hyperplasia (BPH). Both groups were compared for body mass index. Results: Comparing men with PC to subjects with BPH there were significantly higher serum concentrations of omentin, estradiol, and prostate specific antigen (PSA) in the former. Estradiol/testosterone ratio, which is a marker of testosterone to estradiol conversion, was also significantly higher in the PC group. MS was diagnosed in 47 men with PC and in 30 men with BPH, the prevalence was significantly higher in the PC group. When the subjects with PC were subdivided into two subgroups, the serum omentin did not differ between those with MS and without MS. In the overall sample serum, omentin was positively associated with age, SHBG, and leptin. A positive correlation was also found between omentin and estradiol/testosterone ratio, and negatively with testosterone/SHBG ratio. Positive correlations were noted between age and SHBG, PSA and estradiol/testosterone ratio. In our study, a drop of total testosterone and testosterone/SHBG ratio, due to age, was also demonstrated. Conclusions: In patients with prostate cancer, serum omentin may be a diagnostic indicator. Omentin levels do not correlate with estradiol or testosterone concentrations but they are related to the testosterone/SHBG ratio. Omentin is not associated with an increased likelihood of having metabolic syndrome in men with prostate cancer.

Evaluation of Tamoxifen and Anastrozole in the Prevention of Gynecomastia and Breast Pain Induced by Bicalutamide Monotherapy of Prostate Cancer

2005 ◽  
Vol 23 (4) ◽  
pp. 808-815 ◽  
Author(s):  
F. Boccardo ◽  
A. Rubagotti ◽  
M. Battaglia ◽  
P. Di Tonno ◽  
F.P. Selvaggi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Sexual Functioning ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Sex Hormone Binding Globulin ◽  
Breast Pain ◽  
Testosterone Levels ◽  
Tamoxifen Group

Purpose To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. Patients and Methods A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. Results Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by ≥ 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone–binding globulin levels. Conclusion Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

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.

Hormonal Predictors of Prostate Cancer: A Meta-Analysis

2000 ◽  
Vol 18 (4) ◽  
pp. 847-847 ◽  
Author(s):  
Terrence Shaneyfelt ◽  
Rozita Husein ◽  
Glenn Bubley ◽  
Christos S. Mantzoros
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Population Distribution ◽  
Serum Insulin ◽  
Meta Analysis ◽  
Prostate Cancer Risk ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone

PURPOSE: Although there is strong circumstantial evidence that androgens are implicated in the etiology of prostate cancer, epidemiologic investigations have failed to demonstrate consistently that one or more steroid hormones are implicated. In contrast, recent epidemiologic studies unequivocally link serum insulin-like growth factor 1 (IGF-1) levels with risk for prostate cancer. METHODS: We have performed the first meta-analysis of all previously published studies on hormonal predictors of risk for prostate cancer. RESULTS: A meta-analysis restricted to studies that performed mutual adjustment for all measured serum hormones, age, and body mass index indicated that men whose total testosterone is in the highest quartile are 2.34 times more likely to develop prostate cancer (95% confidence interval, 1.30 to 4.20). In contrast, levels of dihydrotestosterone and estradiol do not seem to play a role of equal importance. The only study that provides multivariably adjusted sex hormone–binding globulin data indicates that this binding protein is inversely related to prostate cancer risk (odds ratio, 0.46; 95% confidence interval, 0.24 to 0.89). Finally, all three studies that examined the role of serum IGF-1 have consistently demonstrated a positive and significant association with prostate cancer risk that is similar in magnitude to that of testosterone. CONCLUSION: Men with either serum testosterone or IGF-1 levels in upper quartile of the population distribution have an approximately two-fold higher risk for developing prostate cancer.

Correlation Between Testosterone and PSA Kinetics in Metastatic Prostate Cancer Patients Treated With Diverse Chemical Castrations

2014 ◽  
Vol 9 (5) ◽  
pp. 430-434 ◽  
Author(s):  
Leonardo O. Reis ◽  
Fernandes Denardi ◽  
Eliney F. Faria ◽  
Elcio Dias Silva
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Linear Correlation ◽  
Specific Antigen ◽  
Rank Correlation ◽  
Total Testosterone ◽  
Psa Kinetics ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Group 2

To assess total testosterone and prostatic-specific antigen (PSA) kinetics among diverse chemical castrations, advanced-stage prostate cancer patients were randomized into three groups of 20: Group 1, Leuprolide 3.75 mg; Group 2, Leuprolide 7.5 mg; and Group 3, Goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients’ levels of serum total testosterone and PSA were evaluated at two time periods: before the treatment and 3 months after the treatment. Spearman’s rank correlation coefficient was utilized to verify the hypothesis of linear correlation between total testosterone and PSA levels. At the beginning the patients’ age, stage, grade, PSA, and total testosterone were similar within the three groups, with median age 72, 70, and 70 years in Groups 1, 2, and 3, respectively. Three months after the treatment, patients who received Leuprolide 7.5 mg presented significantly lower median total testosterone levels compared with Goserelin 3.6 mg and Leuprolide 3.75 mg (9.5 ng/dL vs. 20.0 ng/dL vs. 30.0 ng/dL, respectively; p = .0072), while those who received Goserelin 3.6 mg presented significantly lower PSA levels compared with Leuprolide 7.5 mg and Leuprolide 3.75 mg (0.67 vs. 1.86 vs. 2.57, respectively; p = .0067). There was no linear correlation between total testosterone and PSA levels. Overall, regarding castration levels of total testosterone, 28.77% of patients did not obtain levels ≤50 ng/dL and 47.80% did not obtain levels ≤20 ng/dL. There was no correlation between total testosterone and PSA kinetics and no equivalence among different pharmacological castrations.

scholarly journals Dynamics of Prostate-Specific Antigen Levels During Treatment with Testosterone Undecanoate in Patients with Type 2 Diabetes Mellitus

2012 ◽  
Vol 19 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Rucsandra Dănciulescu Miulescu ◽  
Suzana Dănoiu ◽  
Denisa Margină ◽  
Sorin Păun ◽  
Cătălina Poiană
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Total Testosterone ◽  
Testosterone Replacement Therapy ◽  
Testosterone Undecanoate ◽  
History Of

AbstractObjectives. Prostate-specific antigen (PSA) is the most used and validated marker ofprostate cancer risk. The aim of this study was to assess PSA levels during treatmentwith testosteronum undecanoat in patients with type 2 diabetes (T2DM). Material and Methods. We evaluated 38 T2DM patients aged between 48 and 61 years withconfirmed hypogonadism. 1000 mg testosterone undecanoate was injectedintramuscular every 10 to 14 weeks. Total testosterone and PSA levels were assessedat baseline and after 6, 12, 24 months of treatment. Results. The average age was55.03 ± 2.40 years and 3 patients (7.89%) had a family history of prostate cancer.Treatment with testosterone undecanoate generated significant changes in serumtotal testosterone (482.29±50.78 ng/dl vs. 246.66±51.50 ng/dl, p < 0.001) but not inserum PSA levels (2.11±.0.49 ng/ml vs. 2.09±0.47 ng/ml, p - NS). Conclusion.Testosterone replacement therapy may normalize serum androgen levels but appearsto have little effect on PSA levels.

scholarly journals Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

2009 ◽  
Vol 27 (30) ◽  
pp. 4986-4993 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Elisabeth I. Heath ◽  
Janet R. Walczak ◽  
William G. Nelson ◽  
Helen Fedor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Prostate Tissue ◽  
Localized Prostate Cancer ◽  
Double Blind ◽  
Ki 67 ◽  
End Points ◽  
Cox 2

Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.

scholarly journals Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

2021 ◽  
Author(s):  
Bryony L Hayes ◽  
Timothy Robinson ◽  
Siddhartha P. Kar ◽  
Katherine S Ruth ◽  
Konstantinos K Tsilidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Risk ◽  
Protective Effect ◽  
Sex Hormones ◽  
Prostate Cancer Risk ◽  
Total Testosterone ◽  
Testosterone Levels ◽  
Bioavailable Testosterone ◽  
Breast And Prostate Cancer

BACKGROUND Previous research has demonstrated that a morning-preference chronotype is protective against both breast and prostate cancer. Sex hormones have been implicated in relation to both chronotype and the development of both cancers. This study aims to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer risk using a Mendelian Randomization (MR) framework. METHODS We obtained genetic variants strongly (p<5x10-8) associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), and oestradiol from previously published genome-wide association studies (GWAS) that had been undertaken in UK Biobank and 23andMe (n=244,207 females and n=205,527 males). These variants were used to investigate causal relationships with risk of breast and prostate cancer using summary data from the largest available consortia in breast (nCases/nControls=133,384/ 113,789) and prostate cancer (nCases/nControls=79,148/61,106). This was achieved using a series of MR approaches: univariable, bidirectional and multivariable. Results Overall, we found evidence for a protective effect of genetically predicted tendency towards morning preference on both breast (OR=0.93, 95% CI:0.88, 1.00) and prostate (OR=0.90, 95% CI:0.83, 0.97) cancer risk. There was evidence that an increased tendency to morning preference reduces bioavailable testosterone levels in both females (mean SD difference=-0.08, 95% CI:-0.12, -0.05) and males (mean SD difference=-0.06, 95% CI:-0.09, -0.03), and reduces total testosterone levels in females (mean SD difference=-0.07, 95% CI:-0.10, -0.03). We also found evidence to support higher total and bioavailable testosterone increasing the risk of breast cancer (OR=1.15, 95% CI:1.07, 1.23, OR=1.10, 95% CI:1.01, 1.19 respectively) and higher bioavailable testosterone increasing prostate cancer risk (OR=1.22, 95% CI:1.08, 1.37). While findings from univariable and bidirectional MR analyses indicated that testosterone may lie on the causal pathway between chronotype and cancer risk, there was evidence for a bidirectional association between chronotype and testosterone in females, implicating testosterone as both a confounder and mediator of the chronotype effect on breast cancer risk. However, the effects of chronotype remained largely unchanged when accounting for testosterone in multivariable MR, suggesting that any confounding or mediating effect is likely to be minimal. Conclusions This study has extended previous findings regarding the protective effect of chronotype on breast cancer and found evidence to suggest that morning preference also reduces prostate cancer risk in men. While testosterone levels were found to be closely linked with both chronotype and cancer risk, there was inconsistent evidence for the role of testosterone in mediating the effect of morning preference chronotype on both breast and prostate cancer. Findings regarding the potential protective effect of chronotype on both breast and prostate cancer risk are clinically interesting. However, this may not serve as a direct target for intervention, since it is difficult to modify someone's morning/evening preference. Given this, further studies are needed to investigate the mechanisms underlying this effect and to identify other potential modifiable intermediates.

scholarly journals What are the possible reasons for urethral PSA varieties after radical prostatectomy?

2010 ◽  
Vol 57 (2) ◽  
pp. 31-35 ◽  
Author(s):  
T. Pejcic ◽  
J. Hadzi-Djokic ◽  
B. Markovic ◽  
N. Lalic ◽  
B. Glisic
Keyword(s):  
Prostate Cancer ◽  
Body Mass Index ◽  
Bladder Cancer ◽  
Standard Deviation ◽  
Radical Prostatectomy ◽  
Specific Antigen ◽  
Total Testosterone ◽  
Androgenic Alopecia ◽  
Group A ◽  
Group B

Objective: To examine the possible reasons for great varieties in urethral prostate specific antigen (urPSA) levels, in patients after radical prostatectomy (RP). Materials and methods: In 46 patients with prostate cancer, PSA, urPSA, total testosterone, body-mass index (BMI) and the stage of androgenic alopecia (AGA) were determined. Forty-five patients underwent retropubic RP, while one underwent cystoprostatectomy with orthotopic bladder construction, due to bladder cancer. Results: Average patients age prior to surgery plus or minus standard deviation was 65.2+5.8 years. Average urPSA was 20.9+47.5 ng/ml (0.05 to 212 ng/ml, median 2.24 ng/ml). With urethral PSA cut-off of 2.0 ng/ml, two groups were formed: A (urPSA < 2.0 ng/ml) and B (urPSA = 2.0 ng/ml). Patients in the group A had significantly lower average AGA score, than the patients from the group B (2.4+1.3 vs. 4.4+2.2, p=0.0003). In addition, patients from the group A had significantly lower postoperative PSA (0.07+0.08 ng/ml vs. 0.14 + 0.06 ng/ml, p=0.0014). Conclusions: The patients with higher urPSA have higher AGA scores and higher postoperative PSA. This phenomenon is probably the consequence of higher local dihydrotestosterone activity in the scalp and PSA-secreting urethral glands.

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.

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