Baseline Testosterone Research Articles

Osteocalcin and its forms respond similarly to exercise in males and females.

Acute exercise increases osteocalcin (OC), a marker of bone turnover, and in particular the undercarboxylated form (ucOC). Males and females differ in baseline levels of total OC and it is thought the hormonal milieu may be driving these differences. Males and females adapt differently to the same exercise intervention, however it is unclear whether the exercise effects on OC are also sex-specific. We tested whether the responses of OC and its forms to acute High Intensity Interval Exercise (HIIE) and High Intensity Interval Training (HIIT) differed between males and females. Secondly, we examined whether sex hormones vary with OC forms within sexes to understand if these are driving factor in any potential sex differences. Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 96 healthy participants from the Gene SMART cohort (74 males and 22 females) at rest, immediately after, and 3h after a single bout of HIIE, and at rest, 48h after completing a four week HIIT intervention. Baseline testosterone and estradiol were also measured for a subset of the cohort (Males=38, Females=20). Linear mixed models were used to a) uncover the sex-specific effects of acute exercise and short-term training on OC forms and b) to examine whether the sex hormones were associated with OC levels. At baseline, males had higher levels of tOC, cOC, and ucOC than females (q<0.01). In both sexes tOC, and ucOC increased to the same extent after acute HIIE. At baseline, in males only, higher testosterone was associated with higher ucOC (β=3.37; q<0.046). Finally, tOC and ucOC did not change following 4weeks of HIIT. While there were no long-term changes in OC and its forms. tOC and ucOC were transiently enhanced after a bout of HIIE similarly in both sexes. This may be important in metabolic signalling in skeletal muscle and bone suggesting that regular exercise is needed to maintain these benefits. Overall, these data suggest that the sex differences in exercise adaptations do not extend to the bone turnover marker, OC.

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.

Recent testosterone drop-off and risk of cardiovascular events

Low baseline testosterone level has been associated with the development of risk factors for cardiovascular disease such as insulin resistance and obesity. In addition to the absolute testosterone level, remarkable changes in testosterone level may have an acute effect on cardiovascular disease development and progression, which has been rarely investigated. In this study, we used a clinical dataset of 376 hypogonadal men whose testosterone levels were measured every six months for up to 11 years from a registry study in Germany, and conducted survival analyses to investigate the effect of testosterone changes since the last visit (time-varying) on the risk of cardiovascular events. Given the potential discrepancies in comorbidity conditions among patients with prior cardiovascular events and those without, all the analyses were stratified by patients’ prior cardiovascular event status. We found the effects were not different among patients with prior cardiovascular events and those without. Regardless of patients’ prior cardiovascular event status, patients with larger testosterone declines (≥3.12 nmol/L, 90th percentile) since the last visit were more likely to experience myocardial infarction. In conclusion, recent pronounced testosterone drop-offs may affect the risk of cardiovascular events among hypogonadal men. Future longitudinal studies are needed to confirm our exploratory study findings.

Linking human male vocal parameters to perceptions, body morphology, strength and hormonal profiles in contexts of sexual selection

Sexual selection appears to have shaped the acoustic signals of diverse species, including humans. Deep, resonant vocalizations in particular may function in attracting mates and/or intimidating same-sex competitors. Evidence for these adaptive functions in human males derives predominantly from perception studies in which vocal acoustic parameters were manipulated using specialist software. This approach affords tight experimental control but provides little ecological validity, especially when the target acoustic parameters vary naturally with other parameters. Furthermore, such experimental studies provide no information about what acoustic variables indicate about the speaker—that is, why attention to vocal cues may be favored in intrasexual and intersexual contexts. Using voice recordings with high ecological validity from 160 male speakers and biomarkers of condition, including baseline cortisol and testosterone levels, body morphology and strength, we tested a series of pre-registered hypotheses relating to both perceptions and underlying condition of the speaker. We found negative curvilinear and negative linear relationships between male fundamental frequency (fo) and female perceptions of attractiveness and male perceptions of dominance. In addition, cortisol and testosterone negatively interacted in predicting fo, and strength and measures of body size negatively predicted formant frequencies (Pf). Meta-analyses of the present results and those from two previous samples confirmed that fonegatively predicted testosterone only among men with lower cortisol levels. This research offers empirical evidence of possible evolutionary functions for attention to men’s vocal characteristics in contexts of sexual selection.

Clinical Characteristics and Spermatogenesis in Patients with Congenital Hypogonadotropic Hypogonadism Caused by FGFR1 Mutations.

Objective The aim of this study was to investigate the clinical characteristics of patients diagnosed with congenital hypogonadotropic hypogonadism (CHH) caused by FGFR1 (fibroblast growth factor receptor 1) gene mutations and to evaluate the effect of gonadotropin or pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis. Methods A retrospective study was conducted on CHH patients admitted to Peking Union Medical College Hospital from January 2012 to March 2020. Clinical features and laboratory results were recorded. Testicular volume and sperm count responding to gonadotropin and pulsatile GnRH therapy were compared between the FGFR1 mutation group and the mutation-negative group. Results (1) FGFR1 mutation group included 14 patients who received sperm-induction therapy, and the mutation-negative group enrolled 25 CHH patients. (2) The incidence of cryptorchidism was 50.0% (7/14) and 12.0% (3/25) in the FGFR1 group and the mutation-negative group, respectively (p=0.019). The baseline testicular volume of the FGFR1 mutation group was smaller than that of the mutation-negative group, 1.6 (0.5–2.0) mL vs. 2 (1.75–4) mL (p=0.033). The baseline luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and testosterone levels were similar between the two groups. (3) Using the Kaplan–Meier and log-rank tests for the analysis of spermatogenesis, it was found that there was no significant difference in the first sperm appearance between the FGFR1 mutation group and the mutation-negative group (χ2 = 1.974, p=0.160). The median time of spermatogenesis in the FGFR1 mutation group was longer than that in the mutation-negative group, 16 months vs. 10 months, respectively. The cumulative spermatogenesis success rate at 12 months in the FGFR1 mutation group (35.71%) was lower than that in the mutation-negative group (68.75%) (p=0.047). The sperm concentration in the mutation-negative group was more easily achieved for different thresholds compared with that in the FGFR1 mutation group, but no significant difference was observed (p > 0.05) between the two groups. The last follow-up examination showed that the testicular volume was 7.00 (4.75–12.00) mL and 10.56 ± 4.82 mL (p=0.098), the ejaculate volume of sperm was 2.20 (1.40–2.26) mL and 3.06 ± 1.42 mL (p=0.175), and the sperm concentration was 7.19 (1.00–9.91) million/mL and 18.80 (4.58–53.62) million/mL (p=0.038) in the FGFR1 mutation and mutation-negative groups, respectively, while the sperm motility (A%, A + B%, and A + B + C%) was similar for the two groups (p=0.839, 0.909, and 0.759, respectively). The testosterone level during treatment was 366.02 ± 167.03 ng/dL and 362.27 ± 212.86 ng/dL in the FGFR1 mutation and mutation-negative groups, respectively (p=0.956). Conclusion Patients with FGFR1 mutations have a higher prevalence of cryptorchidism and smaller testicular volume. Although patients with FGFR1 mutations have a similar rate of success for spermatogenesis compared to that of the mutation-negative patients, a longer treatment period was required and a lower sperm concentration was achieved.

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.

Is treatment of hypogonadism safe for men after a solid organ transplant? Results from a retrospective controlled cohort study.

Male solid organ transplant patients are at increased risk of hypogonadism and the safety of treating these patients for hypogonadism is unknown. We sought to evaluate the safety of treating hypogonadism in the solid organ transplant recipient. To accomplish this, we performed a retrospective review between 2009 and 2017 of patients treated at a single academic urology clinic. Men who underwent a solid organ transplant with a diagnosis of hypogonadism (Testosterone <350 ng/dl) were included. In total, 87 hypogonadal transplant recipients were included (29 no treatment; 58 treated). Treatment modalities included non-testosterone therapies (human chorionic gonadotropin, clomiphene), topical, injectable, and subcutaneous T preparations. There was no difference between groups for baseline characteristics including age, length of follow-up since transplant, baseline testosterone, and transplant type. There was no difference in prostate cancer diagnoses, erythrocytosis, rejection, infections, number of unplanned admissions per patient. While there was no difference in the proportion of deaths in untreated (21%; n = 6) and treated transplant recipients (7%; n = 4; p = 0.08), the median survival was longer in men treated with T (p = 0.03). Treatment of hypogonadism in solid organ recipients did not increase the risk for adverse effects related to treatment of hypogonadism or solid organ transplant.

Local adaptation from afar: migratory bird populations diverge in the initiation of reproductive timing while wintering in sympatry.

The initiation of reproduction in many seasonally breeding animals is controlled by photoperiod and tends to be clinal: populations at higher latitudes breed later than those at lower latitudes, often reflecting a higher photoperiodic threshold. Migratory animals presumably time reproduction to match conditions at their breeding grounds, at least in part, by cues perceived on their wintering grounds. We asked how closely related dark-eyed junco (Junco hyemalis) populations that overwinter in sympatry but breed in allopatry respond to their shared winter environment by comparing early spring indices of readiness to migrate (fat and muscle condition) and breed (baseline and elevated testosterone). We measured stable hydrogen isotopes from feathers grown the preceding year and claws grown during winter to estimate breeding and wintering latitudes, respectively. We predicted that if reproductive initiation is adapted to the emergence of resources at their respective breeding destinations, then birds migrating to higher latitudes (slate-coloured junco; J. h. hyemalis) should delay breeding as compared with those migrating to lower latitudes (pink-sided junco; J. h. mearnsi) despite a common overwinter environment. We found higher testosterone in pink-sided juncos, consistent with earlier reproductive initiation, suggesting local adaptation in reproductive phenology is achieved through differential responses to predictive environmental cues.

An Intramuscular Injection of Mixed Testosterone Esters Does Not Acutely Enhance Strength and Power in Recreationally Active Young Men

Purpose: Limited data are available on the acute performance-enhancing effects of single-dose administration of testosterone in healthy humans. Studies of testosterone administrations to healthy humans are rare due to the difficult nature and necessity of close clinical monitoring. However, our unique physiological experimental facilities combined with close endocrinological collaboration have allowed us to safely complete such a study. We tested the hypothesis that an intramuscular injection of 250 mg mixed testosterone esters (TEs) enhances physical performance in strength and power exercises acutely, measured 24 h after injection. Additionally, we investigated whether the basal serum testosterone concentration influences the performance in countermovement jump (CMJ), 30-s all out cycle sprint, and one-arm isometric elbow flexion.Methods: In a randomized, double-blind, placebo-controlled design, 19 eugonadal men received either a TE (n = 9, 23 ± 1 years, 183 ± 7 cm, 83 ± 10 kg) or a PLA (n = 10, 25 ± 2 years, 186 ± 6 cm, 82 ± 14 kg) injection. Hormonal levels and the performance in CMJ, 30-s all out cycle sprint, and one-arm isometric elbow flexion were measured before and 24 h after injection.Results: Firstly, an intramuscular injection of 250 mg mixed TEs did not enhance the vertical jump height in a CMJ test, peak power, mean power, and fatigue index in a 30-s all-out cycle sprint or rate of force development and maximal voluntary contraction in a one-arm isometric elbow flexion 24 h post-injection. Secondly, baseline testosterone levels appeared not to influence performance in strength and power exercises to a large extent in healthy, recreationally active young men.Conclusion: A single intramuscular injection of 250 mg mixed TEs has no acute ergogenic effects on strength and power performance in recreationally active, young men. This novel information has implication for basic physiological understanding. Whether the same applies to an elite athlete population remains to be determined. If so, this would have implications for anti-doping efforts aiming to determine the most cost-efficient testing programs.

Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer

SummaryBackground Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5–913.7). Median duration of therapy was 6.5 months (2.6–14.0). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by ≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.Trial registration number, date of registration - NCT02796898, June 13, 2016

Testing strategic pluralism: The roles of attractiveness and competitive abilities to understand conditionality in men’s short-term reproductive strategies

The decision to allocate time and energy to find multiple sexual partners or raise children is a fundamental reproductive trade-off. The Strategic Pluralism Hypothesis argues that human reproductive strategies are facultatively calibrated towards either investing in mating or parenting (or a mixture), according to the expression of features dependent on the individual's condition. This study seeks to test predictions derived from this hypothesis in a sample of 242 young men (M ± SD = 22.12 ± 3.08) from Chile's 5th Region (33֯ south latitude). Specifically, two predictions were considered that raise questions about the relationship between traits related to physical and psychological attractiveness (fluctuating facial asymmetry and self-perception of attractiveness) and competitive skills (baseline testosterone and self-perception of fighting ability) with short-term reproductive strategies. Our results indicate that psychological features related to the self-perception of physical attractiveness are related to short-term reproductive strategies. However, no evidence was found that fluctuating facial asymmetry, basal levels of testosterone and self-perception of fighting ability were related to short-term reproductive strategies. These results support the existing evidence of the importance of physical attractiveness in calibrating men's reproductive strategies but cast doubts about the role of fluctuating facial asymmetry. They also suggest that traits related to physical attractiveness, in comparison to competitive capabilities, play a more important role in calibrating men's short-term reproductive strategies.

Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study.

Hypogonadism is associated with poorer glycaemic outcomes/increased all-cause and cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM). Increasing CAG repeat number within exon-1 of the androgen receptor (AR) gene is associated with increased AR resistance/insulin resistance. We determined in a long-term 14-year follow-up cohort of 423 T2DM Caucasian men, the association between baseline androgen status/CAG repeat number (by PCR then Sequenom sequencing) and metabolic/cardiovascular outcomes. Metabolic outcomes: Lower total testosterone was associated with higher BMI (kg/m2) at 14-year-follow-up: regression coefficient -0.30 (95% confidence interval -0.445 to -0.157), P = 0.0001. The range of CAG repeat number was 9-29 repeats. Higher CAG repeat number in exon-1 of the AR gene was associated with higher follow-up HbA1c2016 - each unit increase in CAG repeat-associated with an increment of 0.1% in HbA1C2016 (P = 0.04), independent of baseline testosterone. Cardiovascular outcomes and mortality: At an average of 14-year-follow-up, 55.8% of hypogonadal men had died vs 36.1% of eugonadal men (P = 0.001). There was a 'u' shaped relation between number of CAG repeats and mortality. Twenty-one CAG repeats were associated with an up to nearly 50% lower mortality rate than <21 CAG repeats and >21 CAG repeats - independent of baseline testosterone level. A higher number of CAG repeats at the AR gene associates with higher future HbA1c. There was a 'u' shaped relation between CAG repeat number and mortality rate. Determination of CAG repeat number may become part of assessment of androgen status/its consequences for men with T2DM.

Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function

ObjectivesHere we examine the association between shift work sleep disorder (SWSD) and erectile dysfunction (ED) in shift workers. MethodsMen presenting to a single andrology clinic between January 2014 and July 2017 completed validated questionnaires: International Index of Erectile Function (IIEF), Patient Health Questionnaire-9 (PHQ-9), and the nonvalidated SWSD Questionnaire. Men were also asked about shift work schedule, comorbidities, phosphodiesterase 5 (PDE5) inhibitor use, and testosterone use. Serum total testosterone values were determined for each visit. Linear regression was performed controlling for testosterone use, testosterone levels, PDE5 inhibitor use, age, and comorbidities to determine the effect of SWSD on ED as assessed using the IIEF. ResultsOf the 754 men completing questionnaires, 204 reported nonstandard shift work (begins before 7 am or after 6 pm, regularly extends out of that frame, or rotates frequently) and 48 were found to have SWSD using a screening questionnaire. Nonstandard shift work alone did not result in worse IIEF-EF scores (P = .31), but those who worked nonstandard shifts and had SWSD demonstrated IIEF-EF scores 2.8 points lower than men without SWSD (P < .01). When assessing for the type of shift work performed, men who worked night shifts had IIEF-EF scores 7.6 points lower than men who worked during the day or evening (P < .01). Testosterone use improved IIEF-EF scores for men with SWSD by 2.9 points, ameliorating the effect of SWSD on ED. However, baseline testosterone levels were not associated with worse erectile function in this cohort. ConclusionMen with SWSD have worse erectile function, with men who work night shifts having even poorer erectile function. These findings suggest that circadian rhythm disturbance may significantly impact erectile function. While testosterone therapy may partly reverse the effects of SWSD, shift work is a potential risk factor for ED and should be assessed for as part of the evaluation of men with ED.Rodriguez KM, Kohn TP, Kohn JR, et al. Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function. J Sex Med 2020;17:1687–1693.

The relationship between pre-radiation therapy testosterone levels and prostate cancer aggressiveness.

We investigated whether there is an association between testosterone levels and prostate cancer aggressiveness in patients treated with radiation therapy who underwent a prostatectomy or prostate radiotherapy (EBRT). A total of 380 patients who received primary or post-operative radiotherapy were identified. At the time of radiotherapy, baseline testosterone levels and body mass index (BMI) measurements were available. On multivariate analysis (MVA), higher prostate-specific antigen (PSA) levels were predictive of testosterone ≥10.4 (OR=1.3, p=.04) and testosterone ≥12.0nmol/L (OR=1.3, p=.04). Patients with a Gleason score ≥8 were more likely to have testosterone <8nmol/L than patients with a lower score (31% vs. 20%, p=.043). On univariate analysis, a Gleason score ≥8 was associated with a lower likelihood of having a normal (≥8nmol/L) testosterone level (OR=0.51, 95% CI: 0.3-0.9, p=.02), and on MVA adjusted for post-surgical versus primary EBRT and BMI (≥30kg/m2 ), the Gleason score lost its statistical significance (p=.09). While higher PSA levels are associated with higher testosterone levels, the interaction between Gleason score and testosterone is unclear and merits further study.

Adaptive reshaping of the hormonal phenotype after social niche transition in adulthood

Phenotypic plasticity allows individuals to adjust traits to the environment. Whether long-term adjustments of the phenotype occur during later life stages is largely unknown. To address this question, we examined whether hormonal phenotypes that are shaped by the environment during adolescence can still be reshaped in full adulthood. For this, guinea pig males were either housed in mixed-sex colonies or in heterosexual pairs. In adulthood, males were individually transferred to pair housing with a female. This way, a social niche transition was induced in colony-housed males, but not in pair-housed males. Before transfer, corresponding to findings in adolescence, adult colony-housed males showed significantly higher baseline testosterone levels and lower cortisol responsiveness than pair-housed males. One month after transfer, the hormonal phenotype of colony-housed males was changed towards that of pair-housed males: animals showed comparable baseline testosterone levels and cortisol responsiveness was significantly increased in colony-housed males. This endocrine readjustment builds the basis for an adaptive behavioural tactic in the new social situation. Thus, an adaptive change of the behavioural phenotype may still occur in adulthood via modification of underlying mechanisms. This suggests a greater role for developmental plasticity in later life stages than is commonly presumed.

Baseline testosterone moderates the effect of money exposure on charitable giving intent

AbstractPrior research has conflicting evidence of the effects of money exposure on prosocial behavior, begging the question of potential moderators of the effect. The current research examines the role of baseline testosterone, a correlate of both status and status‐seeking behaviors, in moderating the effect of money exposure on charitable giving intent. An experiment involving 92 male students (Mage = 20.46, standard deviation = 2.28) found baseline testosterone levels moderating the effect of money exposure (b = −.02, t = 3.46, p &lt; .001, 95% confidence interval [CI] [−0.057, −0.002]), with low‐T males exposed to money showing significantly higher charitable donation intent (vs. control; b = 1.21, t = 2.24, p = .028, 95% CI [0.135, 2.293]) and high‐testosterone males exhibiting significantly lower (b = −1.46, t = 2.68, p = .009, 95% CI [−2.545, −0.378]). These findings show instances where money exposure can enhance, rather than inhibit, prosocial intentions that have broad implications for the study and practice of marketing.

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,...

MP45-06 SHOULD WE TREAT TESTOSTERONE DEFICIENCY IN PATIENTS WHO DO NOT HAVE SYMPTOMS?

INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) is effective for treating the symptoms and ameliorating the metabolic consequences of hypogonadism. TRT improves muscle mass, bone mineral density, mood, and sexual performance. However, a significant number of patients have low serum levels of testosterone without any subjective symptoms or complaints. We evaluated the suitability of TRT for patients with non-symptomatic late-onset hypogonadism. METHODS: Seventy patients whose initial serum levels of testosterone were < 300 ng/dL without any symptoms or complaints were consecutively enrolled and followed for 30 weeks. All patients received 1,000 mg parenteral testosterone undecanoate on day 1, followed by additional injections on weeks 6, 18, and 30. Serological tests (for total testosterone, lipid profile, glucose, and prostate-specific antigen [PSA]) were performed and Body Mass Index (BMI), International Index of Erectile Function (IIEF) score, International Prostate Symptom Score (IPSS), the Aging Males’ Symptoms (AMS) questionnaire, and the Global Assessment Questionnaire (GAQ) were performed at baseline and at the end of the study. RESULTS: Mean patient age was 56.2 ± 10.5 years. The total IIEF score increased from 44.9 ± 12.9 at baseline to 54.8 ± 13.0 on week 30 (p < 0.001). The AMS score improved from 37.9 ± 11.5 at baseline to 24.6 ± 13.2 on week 30 (p < 0.001). Baseline and 30-week total testosterone levels were 272.2 ± 48.2 and 598.2 ± 52.5 ng/dL, respectively (p < 0.0001). No significant changes were detected in the IPSS, lipid profiles, glucose, BMI, or PSA level. The percentage of patients reporting improvement in the GAQ was 58.6%. Improvements in the sexual desire domain of the IIEF, sexual subscale of the AMS, and change in total testosterone (>300 ng/dL) were significantly correlated with a positive GAQ response. The majority of adverse events were mild, reversible, and of short duration. CONCLUSIONS: Although a patient may not complain of any subjective symptoms at the initial visit, TRT can be considered in patients with low testosterone levels and decreased sexual desire and function. It is postulated that patients with low testosterone levels may not recognize their symptoms. Thus, more specific screening is needed for such patients. Source of Funding: None

Across time and space: Hormonal variation across temporal and spatial scales in relation to nesting success.

There is a renewed interest in investigating individual variation in hormone levels in relation to fitness metrics, as hormones act as mediators of life-history trade-offs. Hormone concentrations, however, are labile, responding to both internal and external stimuli, so the relationship between hormones and fitness can be non-consistent. One explanation of this inconsistent relationship is that a single hormone sample may not be representative of individual phenotypes in a free-living species. We addressed this issue by repeatedly sampling a free-living population of mountain white-crowned sparrows, Zonotrichia leucophrys oriantha, for baseline and stress-induced corticosterone (cort) and testosterone (T) across different stages of the breeding season. We measured (co)variation using three different methods, taking into account inter- and intra-individual variances, to determine whether hormone levels and the stress response are repeatable. We documented the temporal (over 3months) and spatial (home-range) variation of individual hormone phenotypes and investigated how these components related to nesting success. At the population level, we found significant repeatability in male stress-induced cort concentrations but no repeatability in male or female baseline cort or male T concentrations. Using a new metric of intra-individual variance focusing on the stress response (profile repeatability), we found a wide range of variance scores, with most individuals showing high variation in their stress response. Similarly, we found a low level of repeatability of the reaction norm intercept and slope for the stress response across different life-history stages. Males with higher concentrations of stress-induced cort had more central home-ranges. Males with higher body condition had larger home-ranges; however, home-range size did not relate to male hormone concentrations or nesting success. We also did not find any significant relationship between variation in hormone levels and nesting success. We recommend that future studies combine both physiological and environmental components to better understand the relationship between hormones and fitness.

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.