Endogenous Testosterone Concentrations Research Articles

Testosterone and the risk of incident atrial fibrillation in older men: further analysis of the ASPREE study

A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men. Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression. Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR=1.91; 95%CI=1.29-2.83 and Q5:Q3HR=1.98; 95%CI=1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up. Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations. National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth.

Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study

Objective This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. Methods The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography–tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. Results The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7–77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). Conclusions In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Effect of cosmetic hair treatment and natural hair colour on hair testosterone concentrations.

Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments. Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose. The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected. The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women.

Wound inflammation post-orchiectomy affects the social dynamic of Nelore bulls

BackgroundConfinement of cattle imposes spatial restrictions and predisposes to aversive social encounters that can lead to contusions, wounds, pain, stress, fright, and reduced productivity. Although endogenous testosterone concentrations are linked to agonistic dominance behaviors in males, it is unknown whether decreased blood testosterone concentrations after castration alter social hierarchy rank in Nelore bulls. Therefore, in this study, we investigated the impact of the surgical would inflammation post-orchiectomy on social dynamics in a group of Nelore bulls (Bos indicus). Fourteen Nelore (Bos indicus) bulls were castrated and assessed pre- and post-surgically. Parameters evaluated were agonistic (mounting, headbutting, and fighting) and affiliative (head-play) behavior, plasma testosterone concentrations, average daily weight gain (ADG), and a score for severity of post-surgical infection. Exploratory statistics included social network analysis (SNA), hierarchy rank delta (Δ), and principal component analysis (PCA). Furthermore, statistical inferences included the Wilcoxon test, multiple logistic regression models, and Spearman's correlation.ResultsThe social dynamic of Nelore bulls was modified after castration based on the findings of the SNA and the PCA. The moderate correlation between the postoperative inflammation level with the Δ, and the significant effect of this level in the logistic model post-castration were partially attributed to effects of pain on social relations.ConclusionsOur findings suggest the severity of post-surgical inflammation, which has an association with pain intensity, was closely associated with changes in the social hierarchy.

Testosterone and psychophysiological aspects of personality in sports

Recent studies have shown that testosterone, in addition to its well-known anabolic effect, has a relationship with a number of psychological and psychophysiological characteristics. The purpose of the study is to generalize information about the relationship between psychophysiological aspects of personality and the level of testosterone in athletes. Methodology: analysis and generalization of data of modern scientific and methodological literature from scientometric bases and resources of Google Scholar, PubMed, Web of Science, Scopus. Research results and their discussion. Research by scientists has shown that high concentrations of basal testosterone are associated with a number of character traits and behavior. Competition, rivalry, competitions affect changes in testosterone levels and cause behavior modification. Scientists express the opinion that the basal level of testosterone before competitions can be an individual biopsychophysiological marker that interacts in the regulation of the hypothalamic-pituitary hormonal axis (HPA) under stress conditions and reflects the degree of dominance, the level of power motivation and obtaining a winning status. In separate studies, the positive effect of testosterone on cognitive functions and visual-spatial abilities was established, the relationship of this hormone with the propensity to take risks, reducing the feeling of fear, increasing attention in the face of threat, which can contribute to the combat readiness of the athlete and the desire to win, was established. Scientists have observed a connection between testosterone and such personality traits as fearless dominance, impulsiveness. Conclusions. According to literary sources, the level of testosterone is associated with a number of psychophysiological and psychological characteristics of an athlete, namely, it increases aggression, the motivation to dominate, which contributes to the motivation to achieve success in sports. High endogenous concentrations of testosterone can provide both a physiological and a psychological advantage in sports. The study of hormonal and psychophysiological parameters can provide an opportunity for a more complete assessment of human stress reactions in the conditions of sports competition.

Intake of Fluted Pumpkin Seeds Rebalances Oxidative Stress Parameters in the Aged Rat’s Testes

The effect of fluted pumpkin seeds (FPS) consumption on the antioxidant status of the testes of aged Wistar rats was evaluated in this study. Sixty (50 aged, 6 months old, and 10 young, 2 months old) rats were divided into six groups of 10 per each group. Testosterone (15 mg kg-1 body weight, once weekly for 40 days) was injected intraperitoneally and used as positive control. FPS intake (50, 100, and 200 mg kg-1 body weight) or vehicle control (corn oil) were administered orally, twice weekly for 40 days and compared with the untreated aged and young control rats. Changes in antioxidant status in the testis of the aged rats was reflected as increased superoxide dismutase and catalase activities and glutathione and decreased lipid peroxidation levels which were attenuated more efficiently by the lowest dose FPS (50 mg kg-1 body weight). Additionally, nitrite concentration that was found to be diminished in the aged rats was raised to the young control values after intake of the FPS (50 mg kg-1 body weight). As expected, testosterone injection increased endogenous testosterone concentration and also remained higher in the untreated aged animals than in young control and treated aged rats. In conclusion, compromised antioxidant defense system of the testes that is associated with ageing could be reversed to the status of the young control by the intake of FPS.

Relationships between endogenous and exogenous testosterone and cardiovascular disease in men.

In this narrative review, we discuss the evidence about the controversy about the cardiovascular effects of endogenous and exogenous testosterone in men. Prospective cohort studies with follow-up of ~5-15years generally indicate no association or a possible inverse relationship between serum endogenous testosterone concentrations and composite major cardiovascular events, cardiovascular deaths and overall mortality. Pharmacoepidemiological studies of large databases generally show no association between testosterone therapy and incident major cardiovascular events, and some pharmacoepidemiological studies demonstrate an association with decreased overall mortality. Randomized, placebo-controlled trials indicate that there is no increased incidence of overall major cardiovascular events with 1-3years of testosterone therapy. These placebo-controlled trials have major limitations including small numbers of participants, short duration of testosterone therapy and follow-up, and lack of systematic adjudication of cardiovascular events. Overall, the evidence indicates that endogenous testosterone concentrations and testosterone therapy at physiological dosages confer no or minimal effects on the incidence of cardiovascular outcomes. There is insufficient evidence to make conclusions about testosterone therapy for patients at high risk of cardiovascular events (e.g., men with recent myocardial infarctions or stroke and men with recurrent idiopathic deep venous thromboses). In general, clinicians should avoid prescribing supraphysiological testosterone therapy to hypogonadal men or men with slightly low to low-normal serum testosterone concentrations and no identified disorder of the hypothalamus-pituitary-testicular axis because of the uncertain cardiovascular risks and the lack of proven health benefits. For most men with bona fide hypogonadism, benefits of testosterone therapy exceed the potential risk of adverse cardiovascular effects.

The positive relationship between androgens and hematocrit levels in the Japanese quail (Coturnix japonica).

Studies have confirmed the involvement of androgens in bird erythropoiesis, suggesting its potential function as a mediator thereof. However, little is known on whether anti-androgenic treatment reduces erythropoiesis and whether changes in endogenous androgen levels are reflected in red blood cell (RBC) indices in birds. Clarifying such issues would highlight the importance of androgens in mediating avian erythropoiesis and bring attention to the effects of endocrine-disrupting chemicals with anti-androgenic activity on their ecology. The present study focused on hematocrit levels among the RBC indices, as well as the relationship between androgens and hematocrit levels in the Japanese quail (Coturnix japonica). In experiment 1, daily injections (i.m.) of testosterone propionate administered to immature quails for a week dose-dependently increased their hematocrit levels. In experiment 2, daily injections (i.m.) of flutamide, a general antagonist of the androgen receptor (AR), administered to adult male quails for a week dose-dependently decreased their hematocrit levels. In experiment 3, weekly blood collection from male quails through the immature to mature stages revealed that changes in endogenous testosterone concentrations were correlated with changes in hematocrit levels along with sexual maturation. The aforementioned results suggested that androgen stimulates erythropoiesis via the ARs and further highlighted the biological importance of androgens on erythropoiesis in quails. Moreover, given that hematocrit is considered a key determinant of aerobic performance related to migration in birds, these findings highlight the need for investigating the effects of anti-androgenic chemicals on the hematology of migratory species for their conservation.

Systematic review and meta-analyses on associations of endogenous testosterone concentration with health outcomes in community-dwelling men

ObjectivesThe overall study aim is to clarify the relation of endogenous sex hormones with major health outcomes in men. This paper reports a systematic review focusing on published estimates for...

Total testosterone is not associated with lean mass or handgrip strength in pre-menopausal females

The aim of this study was to examine the relationship between endogenous testosterone concentrations and lean mass and handgrip strength in healthy, pre-menopausal females. Testosterone has been positively associated with lean mass and strength in young and older males. Whether this relationship exists in pre-menopausal females is unknown. Secondary data from the 2013–2014 National Health and Nutrition Examination Survey were used to test this relationship. Females were aged 18–40 (n = 716, age 30 ± 6 years, mean ± SD) and pre-menopausal. Multivariate linear regression models were used to examine associations between total testosterone, lean mass index (LMI) and handgrip strength. Mean ± SD testosterone concentration was 1.0 ± 0.6 nmol L−1 and mean free androgen index (FAI) was 0.02 ± 0.02. In pre-menopausal females, testosterone was not associated with LMI (β = 0.05; 95%CI − 0.04, 0.15; p = 0.237) or handgrip strength (β = 0.01; 95%CI − 0.11, 0.12; p = 0.926) in a statistically significant manner. Conversely, FAI was associated with LMI (β = − 0.03; 95%CI − 0.05, − 0.02; p = 0.000) in a quadratic manner, meaning LMI increases with increasing FAI levels. Handgrip strength was not associated with FAI (β = 0.06; 95%CI − 0.02, 0.15; p = 0.137). These findings indicate that FAI, but not total testosterone, is associated with LMI in pre-menopausal females. Neither FAI nor total testosterone are associated with handgrip strength in pre-menopausal females when testosterone concentrations are not altered pharmacologically.

Role of Endogenous Testosterone Concentration in Pediatric Stroke

The androgen testosterone is synthesized in the mitochondrion from its precursor steroid cholesterol by cleavage via 20,22?desmolase into pregnenolone, with subsequent conversion of pregnenolone into testosterone. Testosterone determines the male phenotype during sexual differentiation, and promotes sexual maturation during puberty in boys. The measurement of circulating testosterone is clinically relevant in 1) diagnosis and treatment of androgen disorders, 2) gender assignment in newborns with ambiguous genitalia, and 3) determination of pubertal stage in children with delayed or precocious puberty. Apart from circadian and seasonal variations, preanalytical factors influencing circulating testosterone concentration include diet (eg, fasting, intake of low or high glycemic meals, alcohol consumption), plasma volume (eg, hemoconcentration, hemodilution), illness, stress, and sexual activity.

Testosterone effects on functional amygdala lateralization: A study in adolescent transgender boys and cisgender boys and girls

The influence of testosterone on the development of human brain lateralization has been subject of debate for a long time, partly because studies investigating this are necessarily mostly correlational. In the present study we used a quasi-experimental approach by assessing functional brain lateralization in trans boys (female sex assigned at birth, diagnosed with Gender Dysphoria, n = 21) before and after testosterone treatment, and compared these results to the functional lateralization of age-matched control groups of cisgender boys (n = 20) and girls (n = 21) around 16 years of age. The lateralization index of the amygdala was determined with functional magnetic resonance imaging (fMRI) during an emotional face matching task with angry and fearful faces, as the literature indicates that boys show more activation in the right amygdala than girls during the perception of emotional faces. As expected, the lateralization index in trans boys shifted towards the right amygdala after testosterone treatment, and the cumulative dose of testosterone treatment correlated significantly with amygdala lateralization after treatment. However, we did not find any significant group differences in lateralization and endogenous testosterone concentrations predicted rightward amygdala lateralization only in the cis boys, but not in cis girls or trans boys. These inconsistencies may be due to sex differences in sensitivity to testosterone or its metabolites, which would be a worthwhile course for future studies.

Association of endogenous testosterone concentration with depression in men: a systematic review protocol.

The objective of this review is to examine the association between serum testosterone concentration and the presence and severity of depression in men. Cross-sectional and longitudinal cohort studies examining the relationship between serum testosterone concentration and depression in men have produced mixed results. There has not, however, been any prior attempt to systematically interrogate the data. Clarification of the relationship has clinical importance because depression may be under-diagnosed in men. This review will consider studies involving community-dwelling men who are not receiving testosterone replacement therapy. The exposure of interest reviewed will include endogenous testosterone concentration measured through validated assays. Studies measuring total and testosterone fraction concentration will be included. This review will include studies with depression or incident depression outcomes as defined by either clinical diagnosis of depression or validated self-administered questionnaire assessing depression symptomatology. This review will follow the JBI approach for systematic reviews of etiology and risk. The following sources will be searched: PubMed, PsycINFO, Embase, the Cochrane Central Register of Controlled Trials, Australian New Zealand Clinical Trials Registry and the ISRCTN Registry. Analytical observational studies including prospective and retrospective cohort studies, case control studies and analytical cross-sectional studies published in English or other languages with English translation will be considered. Retrieval of full-text studies, assessment of methodological quality and data extraction will be performed independently by two reviewers. Data will be pooled in statistical meta-analysis, where possible. PROSPERO CRD42018108273.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels.

ObjectivePharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile function, mood, and lean body mass for each group were compared. In a subset of patients with very low baseline endogenous testosterone levels (<100 ng/dL), we investigated whether TNG is a suitable treatment option.Materials and MethodsPatients with testosterone deficiency (serum TT <300 ng/dL) were treated with TNG for 3 months, followed by safety extension periods of 90 and/or 180 days. Pharmacokinetic parameters were calculated from serum hormone levels on days 30 and 90, along with efficacy measurements, which were analyzed by comparison with baseline values. Baseline and/or predose TT values were used for patient stratification.ResultsPrestudy and predose endogenous testosterone concentrations correlated. The maximal concentration of TT was nearly identical across all cohorts at days 30 and 90, whereas the average concentration over 24 hours had a slight positive dependence relative to predose levels. LH levels remained in the normal range but were decreased more in patients with higher starting baseline levels. These findings indicate that TNG works with an active hypothalamic-pituitary-gonadal axis that responds to each dose of TNG throughout the treatment period. Patients with the lowest endogenous testosterone levels received maximum exposure impact from each TNG dose. Patients with severe testosterone deficiency had similar efficacy improvements as the remainder of the study population.ConclusionAll testosterone-deficient cohorts were successfully treated with TNG.

Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy.

BackgroundOestradiol with or without an anti-androgen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy; however, there is no evidence to guide optimal treatment choice.ObjectiveWe aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals.DesignRetrospective cross-sectional study.MethodsWe analysed 114 transfeminine individuals who had been on oestradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; oestradiol alone (n = 21), oestradiol plus cyproterone acetate (n = 21) and oestradiol plus spironolactone (n = 38). Secondary outcomes included serum oestradiol concentration, oestradiol valerate dose, blood pressure, serum potassium, urea and creatinine.ResultsMedian age was 27.0 years (22.5–45.1) and median duration of hormone therapy was 1.5 years (0.9–2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8 nmol/L (0.6–1.20)) compared with the spironolactone group (2.0 nmol/L (0.9–9.4), P = 0.037) and oestradiol alone group (10.5 nmol/L (4.9–17.2), P < 0.001), which remained significant (P = 0.005) after adjustments for oestradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily oestradiol dose, blood pressure, serum oestradiol, potassium or creatinine.ConclusionsThe cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.

Plasma total testosterone and risk of incident atrial fibrillation: The Atherosclerosis Risk in Communities (ARIC) study

ObjectiveWhether endogenous testosterone concentrations are associated with atrial fibrillation (AF) development is not well established. We assessed the association between plasma total testosterone concentrations and incident AF in a population-based longitudinal study. Study designUsing data from the prospective Atherosclerosis Risk in Communities (ARIC) study, we identified incident AF among 9282 participants who had plasma total testosterone measured by liquid chromatography tandem mass spectrometry at Visit 4 (1996–1998). Main outcome measuresAF cases were identified by electrocardiograms performed during study visits, hospital records/discharge codes, and death certificates through 2013. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident AF across quartiles of plasma total testosterone, stratified by sex, with multivariable Cox models. ResultsThe mean age of the participant sample at ARIC Visit 4 was 63 years (range 52–75); 54.5% were women. Mean (SD) plasma total testosterone levels were 537 ng/dL (213) for men and 27.6 ng/dL (34.7) for women. Over a mean of 13.7 years of follow-up, 1664 incident cases of AF were identified. Comparing those in the highest quartile of plasma total testosterone concentration to those in the lowest quartile and after adjustment for potential confounding variables, there was a positive association between plasma total testosterone and incident AF in men (HR 1.33, 95% CI 1.07, 1.66), but no such association in women (HR 0.99, 95% CI 0.80, 1.22).Conclusion A higher plasma total testosterone concentration was associated with a modestly greater incidence rate of AF in men.

Endogenous circulating testosterone and sex hormone-binding globulin levels and measures of myocardial structure and function: the Framingham Heart Study.

The relation between endogenous testosterone concentrations and myocardial mass and function remains incompletely understood. To determine the cross-sectional association between endogenous hormone levels with cardiac magnetic resonance measures of myocardial mass, structure, and function in community-dwelling men across a wide age range. A total of 720 men from the Framingham Heart Study Offspring Cohort (age range 37-82, mean=59.6years) who underwent cardiac magnetic resonance imaging and had hormone levels measured. Total testosterone (measured using liquid chromatography-tandem mass spectrometry), sex hormone-binding globulin (measured using an immunofluorometric assay), and calculated free testosterone levels were assessed in male participants of the Framingham Heart Study Offspring Cohort at examination 7. Cardiac magnetic resonance imaging was performed between examinations 7 and 8 (2002-2006). Age-adjusted linear regression models showed statistically significant association between total testosterone levels and left ventricular mass (p=0.009), left ventricular mass index (p=0.006), cardiac output (p=0.001), and main pulmonary artery diameter (p=0.008); the association between total testosterone and these cardiac magnetic resonance measures was weak and was not significant after adjustment for established risk factors-age, body mass index, diabetes, and hypertension. Furthermore, calculated free testosterone level was not significantly associated with any measure of myocardial mass or function. Sex hormone-binding globulin level was significantly associated with left ventricular mass (p=0.002), left ventricular mass index (p=0.004), cardiac output (p=0.003), left ventricular ejection fraction (p=0.039), and main pulmonary artery diameter (p=0.042) in age-adjusted models; these associations were also rendered non-significant after adjusting for cardiovascular risk factors. Neither testosterone nor sex hormone-binding globulin levels in men are associated significantly with myocardial mass and function independent of established cardiovascular risk factors.

High sex hormone-binding globulin concentration is a risk factor for high fibrosis-4 index in middle-aged Japanese men.

Low endogenous testosterone and sex hormone-binding globulin (SHBG) concentrations have been reported to be associated with metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationships between testosterone or SHBG and liver fibrosis in NAFLD. Thus, we aimed to clarify the relationships between serum testosterone or SHBG concentration and fibrosis-4 (FIB-4) index, a marker of liver fibrosis. Serum testosterone was assayed in various forms (total testosterone [TT], calculated free testosterone [cFT], calculated bioavailable testosterone [cbT], and SHBG) and metabolic markers were also measured in 363 Japanese men (mean age 51.1 ± 8.7 years) at routine health examinations. We then attempted to identify the factors contributing to liver fibrosis by investigating the associations between the metabolic markers, including testosterone, and FIB-4 index. People with a relatively high FIB-4 index (≥1.3) demonstrated lower cFT, cbT, homeostasis model assessment (HOMA)-β, low-density lipoprotein-cholesterol, and blood urea nitrogen, but higher SHBG, than those with a lower FIB-4 index (<1.3). There were no significant differences in HbA1c, fasting glucose concentration, HOMA-R, or metabolic syndrome prevalence between the two groups. Binary regression analysis revealed that SHBG ≥52 nmol/L and cFT <8.0 ng/dL were statistically significant risk factors for FIB-4 index ≥1.3. Receiver operating characteristic analysis revealed that cFT <7.62 ng/dL (area under the curve [AUC] = 0.639) and SHBG ≥49.8 nmol/L (AUC = 0.649) were the strongest risk factors for FIB-4 index ≥1.3. In contrast to previous findings showing low SHBG concentrations in NAFLD, we provide evidence that high SHBG and low bioactive testosterone are associated with liver fibrosis.

Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study.

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Codeine influences the serum and urinary profile of endogenous androgens but does not interact with the excretion rate of administered testosterone.

Today's doping tests involve longitudinal monitoring of urinary steroids including the testosterone glucuronide and epitestosterone glucuronide ratio (T/E) in an Athlete Biological Passport (ABP). The aim of this study was to investigate the possible influence of short-term use of codeine on the urinary excretion of androgen metabolites included in the steroidal module of the passport prior to and after the co-administration with testosterone. The study was designed as an open study with the subjects being their own control. Fifteen healthy male volunteers received therapeutic doses of codeine (Kodein Meda) for 6 days. On Day 3, 500 mg or 125mg of testosterone enanthate (Testoviron®-Depot) was administered. Spot urine samples were collected for 17 days, and blood samples were collected at baseline, 3, 6, and 14days after codeine intake. The circulatory concentration of total testosterone decreased significantly by 20% after 3days' use of codeine (p=0.0002) and an atypical ABP result was noted in one of the subjects. On the other hand, the concomitant use of codeine and testosterone did not affect the elevated urinary T/E ratio. In 75% of the individuals, the concentration of urinary morphine (a metabolite of codeine) was above the decision limit for morphine. One of the participants displayed a morphine/codeine ratio of 1.7 after codeine treatment, indicative of morphine abuse. In conclusion, our study shows that codeine interferes with the endogenous testosterone concentration. As a result, the urinary steroid profile may lead to atypical findings in the doping test.