Baseline Testosterone Concentrations Research Articles

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. To clarify associations of sex hormones with these outcomes. Systematic literature review to July 2019, with bridge searches to March 2024. Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. Observational study design, heterogeneity among studies, and imputation of missing data. Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Number of CAG repeats and mortality in middle aged and older men.

The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association. Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI). One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95%CIfor mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats. Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Repeat Microdissection Testicular Sperm Extraction in Azoospermic Men with Nonmosaic Klinefelter Syndrome

Introduction. To investigate the predictive factors for successful repeat microdissection testicular sperm extraction attempts in patients with Klinefelter syndrome. Methods. A total of 28 azoospermic men with nonmosaic Klinefelter syndrome who have received microdissection testicular sperm extraction twice with successful initial microdissection testicular sperm extraction attempts in our institute were studied. Outcome variables (age, serum follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol) of azoospermic men with nonmosaic Klinefelter syndrome and a successful 2nd surgical sperm retrieval attempt (group A) were compared to those with an unsuccessful 2nd sperm retrieval attempt (group B). Results. Twenty-one patients (75%) had successful sperm recovery at the 2nd microdissection testicular sperm extraction attempt. The mean testosterone level at baseline and before the 1st microdissection testicular sperm extraction attempt was higher in group A than in group B (2.7 vs. 0.9 ng/mL, p &lt; 0.01 , and 3.9 vs. 1.1 ng/mL, p = 0.02 ). Receiver operating characteristic curve analysis identified the threshold baseline testosterone concentration (1.5 ng/mL) of patients with Klinefelter syndrome in predicting successful 2nd sperm retrieval attempts and revealed positive and negative predictive values of 94.44% and 60%, respectively. Conclusion. Azoospermic men with Klinefelter syndrome presenting with low testosterone levels and successful sperm recovery during the first microdissection testicular sperm extraction procedure are unlikely to retrieve sperm on the 2nd microdissection testicular sperm extraction attempt. Hence, these patients should be properly counseled before sperm retrieval.

Androgen-armoured amazons: reversed sex roles in coucals are associated with testosterone in females but not males

In some species, sexual selection is stronger in females than males. In classically polyandrous birds, for instance, females compete for mating opportunities and males care for offspring. Sex steroids such as testosterone have been suggested to regulate the behaviours of 'role-reversed' females and males, but comparative studies did not find evidence for a role of testosterone in relation to sex roles. However, the large variability of hormone measurements across laboratories may prevent detecting subtle differences in hormone levels. To circumvent this caveat, I compared sex steroid concentrations of females and males of two closely related and cohabiting species with different mating systems: the classically polyandrous black coucal (Centropus grillii) and the monogamous white-browed coucal (C. superciliosus). Baseline and gonadotropin-releasing hormone (GnRH)-induced testosterone concentrations were twice as high in female black coucals than female white-browed coucals, and the low pre-breeding progesterone concentrations of female black coucals were consistent with progesterone's modulatory role during agonistic interactions in this species. Baseline and GnRH-induced testosterone and progesterone concentrations did not differ between males of both species. This study provides first evidence that elevated testosterone is associated with sex-role-reversed traits in females, whereas low levels of testosterone may not be necessary to facilitate sex-role reversal in males.

Among-species variation in hormone concentrations is associated with urban tolerance in birds.

As cities expand across the globe, understanding factors that underlie variation in urban tolerance is vital for predicting changes in patterns of biodiversity. Endocrine traits, like circulating hormone concentrations and regulation of endocrine responses, might contribute to variation in species' ability to cope with urban challenges. For example, variation in glucocorticoid and androgen concentrations has been linked to life-history and behavioural traits that are associated with urban tolerance. However, we lack an understanding of the degree to which evolved differences in endocrine traits predict variation in urban tolerance across species. We analysed 1391 estimates of circulating baseline corticosterone, stress-induced corticosterone, and testosterone concentrations paired with citizen-science-derived urban occurrence scores in a broad comparative analysis of endocrine phenotypes across 71 bird species that differ in their occurrence in urban habitats. Our results reveal context-dependent links between baseline corticosterone and urban tolerance, as well as testosterone and urban tolerance. Stress-induced corticosterone was not related to urban tolerance. These findings suggest that some endocrine phenotypes contribute to a species' tolerance of urban habitats, but also indicate that other aspects of the endocrine phenotype, such as the ability to appropriately attenuate responses to urban challenges, might be important for success in cities.

Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome.

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.

Menstrual variation in the acute testosterone and cortisol response to laboratory stressors correlate with baseline testosterone fluctuations at a within- and between-person level

Studies have compared HPA and HPG stress reactivity across the follicular and luteal phases to assess the menstrual impact of estradiol and progesterone fluctuations. Ovulatory shifts in baseline and stressor-induced testosterone among athletic women offer a new framework to explore these responses. Here we investigated menstrual variation in baseline testosterone as a predictor of the acute testosterone and cortisol response to laboratory stressors in female athletes. Using a semi-randomized crossover design, thirty athletic women completed a physical (4 × 6-s bike sprints) and psychological (5 × 2-min cognitive tests with social evaluation) stressor on day seven (D7), 14 (D14), and 21 (D21) of a menstrual cycle. Baseline fluctuations and acute changes in salivary testosterone and cortisol were measured. The D14 testosterone response to both stressors (13.7%) exceeded D7 (7.3%) and D21 (7.0%), whereas cortisol was less responsive on D14 (9.8%) than D7 (13.0%) and D21 (12.0%); all moderate to large effect size differences (p < 0.01). Baseline testosterone, which presented large individual and menstrual variation with a D14 peak, was significantly related (moderate correlations) to testosterone and cortisol stress reactivity on a between-person level. Both outcomes were related (weak correlations) to within-person fluctuations in baseline testosterone, but these effects were mediated by testing day. In conclusion, menstrual variation in baseline testosterone concentration correlated with testosterone and cortisol reactivity to a physical and psychological stressor. Thus, gradients of stressor-induced hormonal change showed some dependency to endogenous testosterone, both individual differences and fluctuations over time, among naturally cycling athletic women. Lay summary The female menstrual cycle is accompanied by dramatic shifts in estradiol and progesterone concentration, but less is known about testosterone variability and its role in stress regulation. In this study, menstrual fluctuations in baseline testosterone concentration correlated with acute testosterone and cortisol reactivity to laboratory stressors.

Typological features of the brain in normal conditions and in cerebral hypoperfusion

Relevance. Stress resistance and cognitive abilities of the patient, forming the personal component of the rehabilitation potential, have a significant impact on the course and recovery period after cerebral hypoxia of various origins. The adaptation of rehabilitation measures to the individual characteristics of the patient will significantly increase the effectiveness of rehabilitation measures for stroke and neurodegenerative diseases. The aim of this work is to generalize experimental and clinical studies characterizing the influence of individual characteristics of higher nervous activity on the course of cerebral hypoperfusion. Materials and methods . The study of literary sources of scientometric scientific bases for the last 15 years has been carried out. Results . The level of stress resistance is based on alternative biochemical strategies of neuronal metabolism of macroergs and neurotransmitters. At the organismic level, this is realized in a greater base voltage of the stress-activating system and a smaller reserve capacity of the sympathoadrenal system. In general, this leads to more severe cerebral hypoperfusion in stress-resistant individuals and slower recovery and is correlated with a high baseline sympathetic nervous system tone, insulin and testosterone concentrations. At the same time, a low level of stress resistance determines a greater sensitivity to exogenous corrective influences in cerebral hypoperfusion. The level of cognitive ability is associated with astrocytic responses and the organization of synaptic ensembles. The participation of astrocytes in the regulation of glutamate levels probably has a combined effect on both the state of cognitive mechanisms and damage to the components of neuroglial assemblies during hypoxia. This is also due to the release of S100 +, which, in turn, enhances the coordinated oscillations of neurons in the medial prefrontal cortex and hippocampus and may be the cause of greater damage to the cells of the cerebral hemispheres of the brain in animals with a high level of cognitive abilities in the cerebral hypoperfusion model.

Changes in the Hormonal Profile of Athletes following a Combat Sports Performance

Results Following fighting, the adrenaline concentration was significantly higher in all athletes, most markedly in K (p < 0.001). Baseline cortisol and BDNF levels did not differ among the groups and rose significantly in all the groups after the performance. Baseline testosterone concentration was slightly higher in K than in JSW and rose in all the groups to reach similar levels; the increase in T was significantly higher than in K. Conclusions Despite substantial differences in the characteristics of the combat sports investigated, including the type of physical effort and the required balance between restraint and aggression, the performance in each of them gives rise to similar hormonal changes with a possible exception of karate showing higher stress hormone levels.

Androgens In Men Study (AIMS): protocol for meta-analyses of individual participant data investigating associations of androgens with health outcomes in men

IntroductionThis study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events,...

Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease

BackgroundWhether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. ObjectivesAmong male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. MethodsIn this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL [“low T"] vs. ≥300 ng/dL [“normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. ResultsAmong 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. ConclusionsIn this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. Condensed AbstractIn this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The “low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.

243 The association of sex hormone binding globulin with mortality is mediated by age in men with type 2 diabetes

Hypogonadism (HG), characterised by low serum testosterone and sexual dysfunction, is common in men with diabetes and is independent determinants of CVD risk and mortality. While sex hormone binding globulin (SHBG), lower levels associated with type 2 diabetes (T2DM), was previously considered a passive carrier of sex steroids, recent data suggests that higher levels may be associated with increased mortality. We now describe studies on the relationship between mortality, age and SHBG. We studied 364 men with T2DM not receiving testosterone replacement therapy over a mean 4.2 year; 44 deaths were observed. The primary outcome was all-cause mortality and the association with baseline SHBG levels determined via Cox survival analysis. The statistical model including other factors such as baseline testosterone concentration and other factors associated with SHBG levels. Higher SHBG was seen to be associated with increased body mass index, HbA1c, triglycerides and lower HDL-cholesterol; this finding was expected in our diabetic cohort. SHBG was positively correlated with all-cause mortality (HR: 1.02, 95% CI: 1.01 – 1.04, p=0.007). This association remained significant (HR: 1.03, 95% CI: 1.01 – 1.04, p=0.001) in a model that included other factors associated with mortality such as age, baseline total testosterone (or calculated free testosterone) and triglycerides (all these factors were also associated with mortality suggesting independent effects). We then used pairwise combinations of SHBG and age at recruitment, categorised by median values (age: 66 years, SHBG: 35nmol/l). This analysis showed that association between SHBG and mortality was evident only in men over 66 years; SHBG > 35nmol/l demonstrated higher mortality (mortality: 22.45% , HR: 2.44, 95% CI: 1.05 – 5.56, p=0.077) than SHBG ≤ 35nmol/l (mortality: 15.79%). This effect was independent of both baseline testosterone and triglycerides.

Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys.

Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc.

Testosterone Treatment of Pubertal Delay in Duchenne Muscular Dystrophy.

The outlook for adolescents with Duchenne muscular dystrophy (DMD) has improved greatly as a result of corticosteroid use, but treatment will compromise growth and delay puberty. Whether exogenous testosterone can promote growth, development, and skeletal health is unclear. We collected data retrospectively on growth and pubertal response in 14 adolescents with DMD who were treated with testosterone between 2008 and 2014. A total of 14 boys were treated at a median age of 14.5 years. Eight have finished treatment after a mean age of 3.1 years and the feedback from families was generally positive. The mean testicular volume pretreatment was 2.4 and 3.9 mL posttreatment. The mean baseline testosterone concentrations were < 1.0 and 5.4 nmol/L postintervention. Median height velocity increased from 0.45 cm/y before treatment to 3.6 cm/y after the treatment. The mean height gain was 14.2 cm. A broad range of testosterone preparations was used. Testosterone was generally well-liked, but side effects were experienced by some patients and the pubertal growth increment appears to be compromised. Few subjects had adult endogenous testosterone levels posttreatment. Controlled studies are required to determine the most appropriate treatment regimen and the precise impact of testosterone on key outcomes, such as muscle function and bone integrity. Clinicians will then be better placed to advise families about likely benefits and risks.

Vitamin D supplementation and testosterone concentrations in male human subjects.

A possible association between serum 25-hydroxyvitamin D and testosterone levels has been reported; however, contradictory results have emerged. To investigate a causal link between vitamin D and testosterone status, we studied the effect of vitamin D supplementation on serum testosterone concentrations in three independent intervention studies including male patients with heart failure (study 1), male nursing home residents (study 2) and male non-Western immigrants in the Netherlands (study 3). In study 1, 92 subjects were randomized to either vitamin D (2000 IU cholecalciferol daily) or control. Blood was drawn at baseline, after 3 and 6 weeks. In study 2, 49 vitamin D deficient subjects received either vitamin D (600 IU daily) or placebo. Blood was drawn at baseline, after 8 and 16 weeks. In study 3, 43 vitamin D deficient subjects received either vitamin D (1200 IU daily) or placebo. Blood was drawn at baseline, after 8 and 16 weeks. Serum 25-hydroxyvitamin D levels were measured using LC-MS/MS or radioimmunoassay. Testosterone levels were measured using a 2nd generation immunoassay. Serum 25-hydroxyvitamin D levels significantly increased in all treatment groups (median increase of 27, 30 and 36 nmol/l in studies 1, 2 3, respectively) but not in the control groups. The documented increase in 25-hydroxyvitamin D levels, however, did not affect mean testosterone concentrations at the end of the study (median increase of 0, 0.5 and 0 nmol/l in studies 1, 2 and 3, respectively). In this post hoc analysis of three small clinical trials of limited duration in men with normal baseline testosterone concentrations, vitamin D supplementation was not associated with an increase in circulating testosterone concentrations.

Testosterone dynamics and psychopathic personality traits independently predict antagonistic behavior towards the perceived loser of a competitive interaction

Few studies have investigated the influence of changes in testosterone on subsequent competitive, antagonistic behavior in humans. Further, little is known about the extent to which such effects are moderated by personality traits. Here, we collected salivary measures of testosterone before and after a rigged competition. After the competition, participants were given the opportunity to act antagonistically against the competitor (allocate a low honorarium). We hypothesized that changes in testosterone throughout the competition would predict antagonistic behavior such that greater increases would be associated with the allocation of lower honorariums. Further, we investigated the extent to which personality traits related to psychopathy (fearless dominance, FD; self-centered impulsivity, SCI; and coldheartedness) moderated this relationship. In men (n=104), greater increases in testosterone and greater FD were associated with more antagonistic behavior, but testosterone concentrations did not interact with personality measures. In women (n=97), greater FD and SCI predicted greater antagonistic behavior, but there were no significant endocrine predictors or interactions with personality measures. In a secondary set of analyses, we found no support for the dual-hormone hypothesis that the relationship between baseline testosterone concentrations and behavior is moderated by cortisol concentrations. Thus, results are consistent with previous findings that in men, situation-specific testosterone reactivity rather than baseline endocrine function is a better predictor of future antagonistic behavior. The results are discussed with respect to the Challenge Hypothesis and the Biosocial Model of Status, and the possible mechanisms underlying the independent relations of testosterone and personality factors with antagonistic behavior.

Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo‐controlled trial

High doses of short-term testosterone have been shown to acutely worsen sleep-disordered breathing in men with obstructive sleep apnoea (OSA). The effects of lower, near-conventional doses of testosterone in obese men with OSA may differ over the longer term but have not been systematically studied. We assessed sleep and breathing effects of near-conventional testosterone treatment as an adjunct to weight loss in obese men with severe OSA. An 18-week randomized, double-blind, placebo-controlled, parallel group trial in 67 men. All subjects were placed on a hypocaloric diet and then received intramuscular injections of 1000 mg testosterone undecanoate or placebo at 0, 6 and 12 weeks. Sleep and breathing were measured by nocturnal polysomnography at 0, 7 and 18 weeks. Testosterone, compared to placebo, worsened the oxygen desaturation index (ODI) by 10·3 events/h (95%CI, 0·8-19·8 events/h; P = 0·03) and nocturnal hypoxaemia (sleep time with oxygen saturation <90%, SpO(2) T90%) by 6·1% (95%CI, 1·5-10·6; P = 0·01) at 7 weeks. Testosterone therapy did not alter ODI (4·5, -5·4 to 14·4 events/h; P = 0·36) or SpO(2) T90% at 18 weeks (2·9, -1·9-7·7%; P = 0·23) compared to placebo. The testosterone treatment effects on ODI and SpO(2) T90% were not influenced by baseline testosterone concentrations (testosterone by treatment interactions, all P > 0·35). Blood testosterone concentrations did not correlate with ODI or SpO(2) T90% (all P > 0·19). Testosterone therapy in obese men with severe OSA mildly worsens sleep-disordered breathing in a time-limited manner, irrespective of initial testosterone concentrations. This time-dependency was not related to testosterone concentrations. www.anzctr.org.au Identifier: ACTRN1260-6000404527.

Importance of considering testosterone–cortisol interactions in predicting human aggression and dominance

A novel "field" study recently published in Aggressive Behavior found that individual differences in baseline testosterone concentrations were positively correlated with endorsement of political aggression and that baseline cortisol concentrations were negatively correlated with self-reported aggression among Palestinian boys living in Gaza. Here, we discuss recent evidence indicating that testosterone and cortisol interact to predict competitive, aggressive, and dominant behaviors and urge researchers collecting both hormones to perform and report analyses that formally test for such interaction effects.

Variation in CAG repeat length of the androgen receptor gene predicts variables associated with intrasexual competitiveness in human males

An expanding body of research suggests that circulating androgens regulate the allocation of energy between mating and survival effort in human males, with higher androgen levels promoting greater investment in mating effort. Because variations in the number of CAG codon repeats in the human androgen receptor (AR) gene appear to modulate the phenotypic effects of androgens – with shorter repeat lengths associated with greater androgenic effects per unit androgen – polymorphisms in this gene may predict trait-like individual differences in the degree to which men are calibrated toward greater mating effort. Consistent with this, men in the present study with shorter CAG repeat lengths exhibited greater upper body strength and scored higher on self-report measures of dominance and prestige, all of which are argued to be indices of mating effort. Repeat length failed to predict sociosexual orientation (i.e. pursuit of short-term mating relationships), however, suggesting that the traits correlated with this polymorphism may be primarily associated with intrasexual competitiveness in the service of long-term mating effort. None of these measures of mating effort was related to baseline testosterone concentrations (either as main effects or as interactions with CAG repeat length), implying that long-term androgen exposure associated with AR gene polymorphisms may account for more variance in some androgen-dependent traits than does current testosterone concentration. These findings provide further evidence for the importance of the CAG repeat polymorphism in the AR gene in explaining a broad range of individual differences in human males.

Repeatable intra-individual variation in plasma testosterone concentration and its sex-specific link to aggression in a social lizard

Individual hormone profiles can be important generators of phenotypic variation. Despite this, work on the consequences of hormone profiles has traditionally ignored the large inter-individual variation within natural populations. However, recent research has advocated the need to explicitly consider this variation and address its consequences for selection. One of the key steps in this process is examining repeatability in hormone profiles and their links to behavioral traits under selection. In this study we show that individuals within a free-ranging population of the Australian lizard Egernia whitii exhibit temporal repeatability in their circulating baseline testosterone concentrations as well as their aggressive response towards conspecific intruders. Furthermore, we show significant, sex-specific links between testosterone and aggression. Specifically, testosterone and aggression is negatively linked in males, while there is no relationship in females. As conspecific aggression has significant consequences for fitness-related traits (parental care, mating strategies) in this species, inter-individual variation in testosterone concentrations, through their effects on aggression, could have important implications for individual fitness. We discuss the potential causes and consequences of hormonal repeatability as well as provide explanations for its sex-specific links with aggression. Specifically, we suggest that these patterns are the result of alternative hormonal pathways governing aggression within Egernia and may indicate a decoupling of aggression and testosterone across the sexes.