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High and low testosterone levels may be associated with suicidal behavior in young and older men, respectively

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... The vasculature is a target tissue for sex steroid hormones. Estrogen and Testosterone (TT) have become research hotspots in recent years [1][2][3]. The relationship between TT and vascular disease has been the subject of much research. ...
... The relationship between TT and vascular disease has been the subject of much research. However, there is intense debate regarding the role of TT in vascular function and cardiovascular disease (CVD) [3]. Low TT is associated with the progression of atherosclerosis, the production of proinflammatory cytokines, increased arterial thickness, and increased glucose, total cholesterol and low-density lipoprotein, all of which contribute to CVD [4,5]. ...
... Low TT is associated with the progression of atherosclerosis, the production of proinflammatory cytokines, increased arterial thickness, and increased glucose, total cholesterol and low-density lipoprotein, all of which contribute to CVD [4,5]. However, high TT has been associated with sudden cardiac death, liver disease and suicidal behavior [3,6]. Being male is a risk factor for CVD, as males have an earlier occurrence and higher prevalence of many cardiovascular and metabolic-related diseases [7]. ...
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To investigate the relationship between sex hormones and the risk of vascular disease in elderly men and to evaluate the advantages and disadvantages of testosterone replacement. A total of 337 men, aged 60 to 91 years, were enrolled in this single-center, cross-sectional study, and their sex hormone levels were assessed. Linear and logistic regression analyses were utilized to compare the sex hormone levels between patients with and without vascular disease. The nonparametric K-sample test was used for inter-group comparisons. Aging and abnormal metabolism were both significantly associated with an increased risk of vascular diseases and changes in sex hormone levels. Primary linear and logistic regression analyses showed no significant differences in sex hormone concentrations between patients with and without vascular diseases after adjusting for age. Logistic regression with abnormal metabolism as categorical variable showed that free testosterone (FT) and free estradiol (FE2) had significant relationships with CEVD risk (P<0.05). In further regression with all metabolic continuous variables included, the testosterone/estradiol (T/E2) ratio replaced FT and FE2 (P<0.05). Trend line analyses showed that T/E2 actually had a binomial linear correlation with the risk of cerebrovascular disease; its best protective effect occurred at values of 0.13-0.15, with an OR value extremely close to those of FT and FE2 (0.23 vs. 0.24-0.25). T/E2 balance plays a key role in the relationship between sex hormones and the risk of cerebrovascular disease. The balance between T and E2 may be more important than their absolute quantities. Extremely low T/E2 and inappropriately high T/E2 ratio can both harm the brain blood vessels. Careful consideration should be given before beginning testosterone replacement treatment, and supplementing with estrogen seems to be a good way to protect blood vessels of the brain in elderly men.
... A renewed interest within the field of psychiatry in brain-based models of observable behavior supports a more nuanced reflection on biological factors underlying suicide epidemiology. Testosterone, the major male sex hormone, has attracted interest as a putative biological mediator of suicide risk, but observational data have been mixed [2]. However, we believe that age stratification may reveal that high levels of testosterone in adolescents and young adults but low levels in the elderly may mediate suicide risk [2]. ...
... Testosterone, the major male sex hormone, has attracted interest as a putative biological mediator of suicide risk, but observational data have been mixed [2]. However, we believe that age stratification may reveal that high levels of testosterone in adolescents and young adults but low levels in the elderly may mediate suicide risk [2]. ...
Article
This short communication suggests that there may be biological in addition to psychosocial reasons underlying the rise in suicide among older men. Testosterone, the major male sex hormone, has attracted interest as a putative biological mediator of suicide risk, but observational data have been mixed. Age stratification may reveal that high levels of testosterone in adolescents and young adults but low levels in the elderly may mediate suicide risk. A putative age-testosterone-suicide differential may be mediated by divergent central nervous system architecture between adolescents and the elderly. Whereas the prefrontal and prefontal-limbic connectivity underdevelopment observed in adolescents may render vulnerability to testosterone-mediated increases in impulsivity as a risk factor for suicide, declining function of dopaminergic striato-thalamic reward pathways in the aging cohort may render older men vulnerable to the loss of testosterone’s protective effects against anhedonia, thereby increasing suicide risk through a different biological pathway. Further research is needed regarding the role of hypotestosteronemia in elderly suicide.
... 8 In relation to sex hormones, again, the evidence is inconclusive, although lower estrogen levels in women may reduce sleep quality and thus elevate the risk of MDD. 9 By contrast, testosterone is often referenced as a protective factor for the onset on prototypical depression symptoms in men, 10 although some argue that testosterone levels above, or below, normal levels may contribute to depression and suicide risk in men. 11 A recent meta-analysis showed that relationships across baseline, dynamic, and manipulated testosterone levels with men's aggression were weak (e.g., r's ≤ .17). 12 A separate meta-analysis has indicated, however, that testosterone treatment may be a useful approach to managing MDD in men. 13 Overall, sex differences in MDD symptoms (and co-occurring symptoms) therefore occur due to a complex interactive matrix of social and physiological factors. ...
Article
Major depressive disorder (MDD) is a highly heterogeneous diagnosis wherein the nine MDD criterion signs and symptoms reflect 256 unique symptom combinations. Accordingly, MDD comprises a broad set of phenotypes observed across clinical practice, including primary care. With intensifying global efforts to prevent male suicide, attention has rapidly focused on better understanding men's experiences of MDD. Pertinent to these efforts is the operationalization of MDD, which is characterized by the two cardinal symptoms of depressed mood and anhedonia (the loss of interest or pleasure in all, or nearly all, activities for most of the day nearly every day). However, debate remains regarding the adequacy of this conceptualization of depression as applied to men socialized within dominant discourses of masculinity that prohibit men acknowledging or seeking help for depression. The text revision of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) offers a noteworthy change to the sex and gender considerations for MDD. While the nine diagnostic criteria for an MDD diagnosis have remained unchanged relative to the preceding DSM-5 text (because the purpose of DSM's text revision version is to update the text, not change diagnostic criteria), an important new phenomenological statement has been added. Whereas DSM-5 offered no guidance related to associated gendered symptom expression apart from commenting on the epidemiology and gender paradox of suicide attempts (higher among females) and suicide deaths (higher among males), DSM-5-TR offers the following: There is some evidence for sex and gender differences in phenomenology and course of illness. Women tend to experience more disturbances in appetite and sleep, including atypical features such as hyper-phagia and hypersomnia, and are more likely to experience interpersonal sensitivity and gastrointesti-nal symptoms. Men with depression, however, may be more likely than depressed women to report greater frequencies and intensities of maladaptive self-coping and problem-solving strategies, including alcohol or other drug misuse, risk taking, and poor impulse control. In general, women are more likely to internalize (e.g., withdraw , cry), and men are more likely to externalize (e.g., display anger, utilize alcohol to cope). Naturally, this has prompted the consideration of a biological basis for differences. Yet, compelling evidence of biological differences underpinning men's depression symptoms and their maladap-tive self-coping and problem-solving strategies remains scarce. We therefore call for a unified global research effort to address this problem. Consideration should be given to implementing brief screening for male depression symptoms (e.g., the MDRS-7) as part of electronic medical record systems, both in primary care settings and longitudinal studies. At a minimum, incorporation of externalizing symptoms within diagnostic criteria for adult MDD (either via removal of the developmental age caveat for irritability, or through additional symptom criteria) is likely required.
... The etiology of BID remains unknown; however, it has been of bipolar and related disorders, also have evaluated the effect of testosterone level on behavioral brain function. [9][10][11][12] Few studies have assessed the level of testosterone in different phases of bipolar disorder including depression, mania, hypomania, and mix phases of bipolar disorder continuously. [12,13] It should be noted that in some instances, the results of these studies are in concordant with else, especially about the level of testosterone in manic phase of bipolar. ...
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Background Testosterone is considered as a primary sex hormone, also known as an important anabolic steroid, that may involve in various mental disorders such as bipolar I disorder (BID). The goal of this study was to compare the testosterone salivary levels between different phases of BID and its association with the clinical features of BID. Materials and Methods In a case–control study, 15 patients in the mania phase, 10 patients in the depression phase, and 16 in the euthymia phase were selected as patient groups. 18 healthy sex- and age-matched individuals were considered as healthy control group. Salivary samples obtained from all patients and control group and levels of testosterone were determined in saliva using an enzyme-linked immunosorbent assay. All statistical calculations were conducted with the software Statistical Package for Social Science version 20 (IBM Inc., Chicago, IL, USA). Results The mean testosterone level in euthymia phase was 186.34 ± 182.62 pg/mL, mania phase was 239.29 ± 273.22 pg/mL, depression was 153.49 ± 222.50 pg/mL, and healthy participants was 155.73 ± 126.0 pg/mL; no significant difference was found between groups (P = 0.68.(No statistically significant differences were found between psychotic and nonpsychotic as well as between patients who attempted suicide and nonattempter patients in terms of testosterone levels (P > 0.1). Conclusion Our findings do not reveal significant difference between different phases of BID in terms of salivary testosterone levels. However, more comprehensive studies with larger sample size are required to confirm our findings.
... So far, gender differences in dopamine and serotonin functions and genetics (6) and associations between cortisol and male suicide have been reported (7,8). Testosterone also plays an important role in the gender effect observable in suicide, and this effect may also interact with age (9). Urocortin and BDNF also appear to play a genderspecific role in male suicidal behavior (10), and interestingly there appears to be a gender difference in the putative antisuicidal effect of lithium as well (11). ...
... Testosterone therapy for transgender men is a proven treatment (Irwig 2016), but it has been related to physical and psychological adverse effects (Wierckx et al. 2014). When suicidal and violent behavior appears with the use of testosterone, major guidelines recommend deferring therapy until associated comorbid psychiatric illnesses with increased suicide and violence risk are controlled (Rice andSher 2013, 2015;Sher 2013Sher , 2014Rice et al. 2015). ...
... How could the higher CSF and plasma testosterone levels in young male suicide attempters be explained? Leo Sher has previously proposed that high and low testosterone levels may be associated with suicidal behaviour in young and older men, respectively, through different pathomechanisms (Sher, 2013). In young men attempting Suicide, one possible explanation could be the role of testosterone in aggression dyscontrol. ...
Article
Very few studies have assessed testosterone levels in the cerebrospinal fluid in suicide attempters. Aggressiveness and impulsivity are common behavioural traits in suicide attempters. Dual-hormone serotonergic theory on human impulsive aggression implies high testosterone/cortisol ratio acting on the amygdala and low serotonin in the prefrontal cortex. Our aim was to examine the CSF and plasma testosterone levels in suicide attempters and in healthy volunteers. We also assessed the relationship between the testosterone/cortisol ratio, aggressiveness and impulsivity in suicide attempters. 28 medication-free suicide attempters and 19 healthy volunteers participated in the study. CSF and plasma testosterone sulfate and cortisol levels were assessed with specific radio-immunoassays. The Karolinska Scales of Personality was used to assess impulsivity and aggressiveness. All patients were followed up for cause of death. The mean follow-up period was 21 years. Male suicide attempters had higher CSF and plasma testosterone levels than age- matched male healthy volunteers. There were no significant differences in CSF testosterone levels in female suicide attempters and healthy female volunteers. Testosterone levels did not differ significantly in suicide victims compared to survivors. In male suicide attempters, the CSF testosterone/cortisol ratio showed a significant positive correlation with both impulsivity and aggressiveness. Higher CSF testosterone levels may be associated with attempted suicide in young men through association with both aggressiveness and impulsivity, a key endophenotype in young male suicide attempters.
... Hence, the current performance of regression analytic methods implying a causal direction needs to be interpreted as preliminary. Future studies are required to replicate our findings, to longitudinally analyze causal processes [particularly with regard to the interaction between HPG and HPA axes due to their great therapeutic and diagnostic potential (33)], and to assess a broader age range in order to more precisely consider the possibility of age-specific features (64)(65)(66). Third, the participants of the laboratory day were selected as a convenience sample. Consequently, a certain selection bias and a restricted external validity cannot be completely excluded. ...
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Article
The main objective of this preliminary study was to further clarify the association between testosterone (T) levels and depression by investigating symptom-based depression subtypes in a sample of 64 men. The data were taken from the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n = 25) and an atypical (n = 14) depression subtype, derived from latent class analysis, were compared with those of healthy controls (n = 18). Serum T was assayed using an enzyme-linked immunosorbent assay procedure. Analysis of variance, analysis of covariance, non-parametrical tests, and generalized linear regression models were performed to examine group differences. The atypical depressive subtype showed significantly lower T levels compared with the melancholic depressives. While accumulative evidence indicates that, beyond psychosocial characteristics, the melancholic and atypical depressive subtypes are also distinguishable by biological correlates, the current study expanded this knowledge to include gonadal hormones. Further longitudinal research is warranted to disclose causality by linking the multiple processes in pathogenesis of depression.
... However, the positive relationship between testosterone level and suicide may not be true for all ages of people. For example, high T levels may be associated with suicidal behavior in young men, and low T levels may be associated with suicidal behavior in older men [12]. ...
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Suicide is a devastating public health issue that imposes severe psychological, social, and economic burdens not only for the individuals but also for their relatives, friends, clinicians, and the general public. Among the different suicidal behaviors, suicide completion is the worst and the most relevant outcome. The knowledge of biological etiopathological mechanisms involved in suicide completion is limited. Hitherto, no objective markers, either alone or in combination, can reliably predict who will complete a suicide. However, such parameters are strongly needed to establish and optimize prediction and prevention. We introduce here a novel ideation-to-completion framework in suicide research and discuss the problems of studies aiming at identifying and validating clinically useful markers. The male gender is a specific risk factor for suicide, which suggests that androgen effects are implicated in the transition from suicidal ideation to suicide completion. We present multiple lines of direct and indirect evidence showing that both an increased prenatal androgen load (with subsequent permanent neuroadaptations) and increased adult androgen activity are involved in suicide completion. We also review data arguing that modifiable maternal behavioral traits during pregnancy contribute to the offspring's prenatal androgen load and increase the risk for suicide completion later in life. We conclude that in utero androgen exposure and adult androgen levels facilitate suicide completion in an additive manner. The androgen model of suicide completion provides the basis for the development of novel predictive and preventive strategies in the future.
Article
Many studies suggest that testosterone plays a role in the regulation of mood and behavior. Most but not all investigations of the relationship between testosterone and suicidality found relations between testosterone and suicidal behavior. The balance of evidence is in favor of the view that testosterone is involved in the pathophysiology of suicidality. The author has previously proposed that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone levels. However, both high and low testosterone levels can be observed in adolescent, young, middle-aged and older men. In this article, the author proposes that both high and low testosterone levels may play a role in suicidal behavior in men of any age.
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Homicide is overwhelmingly committed by men compared to women. Conservative estimates suggest that more than a third of these individuals have a treatable psychiatric disorder. These data present an opportunity to mental health clinicians to assist in the prevention of homicide by improving men's mental health. We review the current literature on men's mental health with a focus on assessing and reducing homicide risk in men with psychiatric conditions. Bipolar disorder and schizophrenia appear to share a neural endophenotype that is a risk factor for homicide. Dual disorders, or the presence of a substance use disorder with other major mental illness, are a major risk factor for homicide in males. Dual diagnosis disorders, personality disorders and pathological traits and male depression share emotion dysregulation, irritability, and reactive aggression. Promoting physician education, addressing firearm safety, reducing the reluctance of men relative to women to engage in help-seeking behaviour, and using targeted risk interviews which integrate these data are all currently recommended. The main focus in prevention of homicidal behaviour in males with psychiatric disorders should be to identify high risk groups, to provide adequate treatment, and to facilitate compliance with long-term treatment while considering male specific problems and needs.
Article
Objective: This single-centre cross-sectional study aimed to investigate the metabolic and gonadal risk factors of vascular diseases in elderly males. Methods: After screening, 337 subjects aged 60-90 were found to be qualified. Odds ratios (ORs) in cross-table analyses and exp(B) in logistic regression analyses were used to evaluate the vascular risk of dependent factors. R(2) of logistic regression equation was used to estimate the goodness-of-fit of vascular diseases logistic regression models. Results: Hypertension increased the risk of cardiovascular disease (CAVD) in elderly men approximately 3-fold. The number of metabolic diseases also correlated with incremental risks of CAVD; presence of one abnormality approximately increases the risk approximately 62%. Cerebrovascular disease (CEVD) development was closely associated with both metabolic syndrome and sex hormone levels; their explanation effects of single action and combined action were 13.2%, 12.55% and 28.5%. C-peptide might be the underlying mechanism of the metabolic syndrome's effect on CEVD. C-peptide = 2.43 U/L and FE(2) = 0.66 were the tangent points in receiver operating characteristic (ROC) analyses. Conclusions: Metabolic diseases and sex hormones play different roles in the development of CAVD and CEVD, the methods for vascular protection in elderly men should be promoted differently according to the their risks of CAVD and CEVD.
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Abstract Adolescent mass shootings are a special subset of mass killings, which continue despite significant preventative public health efforts. It is often held that these individuals have few salient warning signs that could have been identified. This piece proposes that mass shootings committed by adolescent and post-adolescent young males must be understood from a developmental perspective. The hypothesis proposed in this paper is that such killings occur as the result of the adolescent's frustrated effort to progress along normative development. The goal of normative separation from maternal figures by the boy is presented as a potential risk factor when this goal is thwarted. Childhood case material from the perpetrator of a recent adolescent mass shooting, the Sandy Hook shooting, is discussed as an illustration of this hypothesis. Implications for public health measures and for individualized treatment are presented and developed.
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Abstract Suicide and homicide are much more commonly committed by adolescent males than females. Herein, a proposal in favor of gender-specific understanding and approach to these violent behaviors is presented. Social and healthcare service system factors, including issues of male adolescents' access to care and help-seeking behaviors, are reviewed alongside the epidemiology of adolescent suicide and homicide as a transition into a detailed discussion of the putative biological factors at play. An emphasis upon the male androgen testosterone organizes the discussion. Behavioral manifestations of this brain-based organizational model are presented with a focus on impulsivity, aggression, and externalizing dysregulated emotionality. Treatment considerations and implications are developed.
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The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths).
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The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters. Patients with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters, including lifetime suicidal behavior, were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. The number of major depressive episodes, the maximum lethality of suicide attempts, and the testosterone levels were higher in men compared to women. Current suicidal ideation scores were higher in women compared to men. Controlling for sex, we found that testosterone levels positively correlated with the number of manic episodes and the number of suicide attempts. Our findings are consistent with previous observations of the association between testosterone levels and parameters of mood and behavior. This study suggests that testosterone levels may be related to the course of bipolar disorder and suicidal behavior. Further studies of the role of testosterone in the neurobiology of mood disorders and suicidal behavior are merited.
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There is a paucity of data on the relationship between testosterone and Alzheimer's disease (AD) in older men. The objective of the present study was to investigate the effects of serum total testosterone (TT), bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) levels on the subsequent risk of AD in nondemented Chinese older men. This was a one-year prospective cohort study. 153 ambulatory community-living nondemented Chinese older men, aged 55 years or over, were recruited and followed for one year. Morning serum TT, BT, and SHBG levels were measured at baseline. At one-year of followup, assessment for dementia and AD were performed. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. Overall, the mean age of the subjects was 72.7 (SD 6.9). 6.5% (n = 10) developed dementia (converters), all having AD. 93.5% (n = 143) did not develop dementia (non-converters). Logistic regression analysis for independent predictors of AD showed that the baseline serum BT level, systolic blood pressure (SBP) and ApoE "4 genotype were significant independent predictors, after adjustment for age, education, BMI, fasting plasma glucose, and serum HDLC levels. The baseline serum BT level predicted a reduced risk of AD (adjusted relative risk (RR) 0.22, 95% CI: 0.07-0.69)). Baseline SBP and ApoE "4 genotype but not SHBG were independent risk factors, with RRs of 1.04 and 5.04 respectively. In conclusion, the serum level of bioavailable testosterone in late life predicts a lower risk of future AD development in older men.
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Genital self-multilation is rare, and reports suggest that it is usually associated with psychotic illness. We report a case in which penile self-multilation was an attempt to commit suicide and justified as a rational action. The literature on genital self-mutilation is reviewed. It is argued that the strong association between genital self-mutilation and psychosis may be the result of selective reporting.
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Two psychotic individuals, who performed acts of genital self-amputation, are presented. One of the patients had self-mutilated with the intention of suicide and had also in the past amputated his hand. Psychotic patients with delusions (often religious), sexual conflict associated with guilt, past suicide attempts or other self-destructive behaviour and depression, severe childhood deprivation, and major premorbid personality disorder, are the group at risk for genital self-amputation. It has been proposed that the eponym, the "Klingsor" syndrome, be applied only to acts of genital self-mutation, involving religious delusions. The author suggests that this syndrome should be expanded to include all cases of genital self-mutation resulting from a psychotic illness.
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Subjects for the present study were male cadavers received at a county morgue during a year. The criteria for selection were: the body had to be in the morgue sufficiently soon after death to allow blood samples to be taken; the victim did not die while a patient in a hospital or under a physician's care; and death was by suicide or was "sudden", i.e., primarily due to pulmonary disorder not associated with accident or homicide. Eighty-seven cadavers were identified as subjects (39 suicides, 48 sudden deaths). The ages of the suicide group ranged from 15 tc 76 yr. (M = 39.08 yr., SD = 18.27 and those of the nonsuicide group ranged from 12 to 79 yr. with a mean of 51.54 yr. (SD = 13.79).
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Male genital self-mutilation is a phenomenon which transcends nosological boundaries. This article reviews 98 cases reported in the English language literature. We note that outcome is often better than is assumed. We emphasize the importance of close liaison between the psychiatric and surgical team in managing these patients.