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Free testosterone in plasma on Day 1, 10, and 40 after detoxification in subgroups of alcoholics with high and low pre-treatment alcohol use and tobacco use.
Source publication
The present study examined the association between pre-treatment drinking and smoking parameters and plasma testosterone levels before and after alcohol withdrawal.
A total of 51 alcohol-dependent men and 43 age-matched healthy men were investigated. In alcoholics, free testosterone in plasma was measured on the day of admission, after detoxificati...
Contexts in source publication
Context 1
... all four groups (low alcohol-low tobacco, low alcohol- high tobacco, high alcohol-low tobacco, high alcohol-high tobacco), there was a significant increase in testosterone over the 40 days following the withdrawal (F = 19.35, P = 0.0001; Fig. 2). This increase ran more or less parallel for all groups. However, as shown in Fig. 2, the four groups differed signifi- cantly in their testosterone level: the lower the consumption of alcohol and/or cigarettes had been, the lower were the measured free testosterone concentrations during and after the withdrawal period. The severity of the withdrawal symptoms had no effect, neither on the level of testosterone nor on its course over the 40 days after ...
Context 2
... all four groups (low alcohol-low tobacco, low alcohol- high tobacco, high alcohol-low tobacco, high alcohol-high tobacco), there was a significant increase in testosterone over the 40 days following the withdrawal (F = 19.35, P = 0.0001; Fig. 2). This increase ran more or less parallel for all groups. However, as shown in Fig. 2, the four groups differed signifi- cantly in their testosterone level: the lower the consumption of alcohol and/or cigarettes had been, the lower were the measured free testosterone concentrations during and after the withdrawal period. The severity of the withdrawal symptoms had no effect, neither on the level of testosterone nor on its course over the 40 days after ...
Citations
... Previous study found higher proportions of smoking and drinking in patients with early-onset T2DM compared with those in patients with late-onset T2DM [3], and tobacco smoking and alcohol drinking may increase testosterone levels in men [27,28]. However, the proportion of smoking was slightly lower in the early-onset group, and the data of alcohol consumption was lacked in the present study. ...
Objective:
There is a bidirectional interaction between circulating testosterone and blood glucose levels. We aim to investigate the testosterone levels in men with early-onset type 2 diabetes (T2DM).
Methods:
A total of 153 drug naive men with T2DM were enrolled in the study. Early- (n = 63) and late-onset (n = 90) T2DM was classified according to age 40 years old. Clinical characteristics and plasma for biochemical criterions were collected. Gonadal hormones were measured using chemiluminescent immunometric assay. The concentrations of 3β- and 17β-HSD were determined using ELISA.
Results:
Compared with men with late-onset T2DM, those with early-onset T2DM had lower serum total testosterone (TT), sex hormone-binding globulin (SHBG), and FSH, but higher dehydroepiandrosterone sulfate (DHEA-S) level (p < 0.05). The mediating effect analysis showed that the decreased TT levels in patients with early-onset T2DM were associated with the higher HbA1c, BMI, and triglyceride in these patients (both p < 0.05). The early-onset of T2DM directly correlated with increased DHEA-S (both p < 0.01). The 3β-HSD concentration in the early-onset T2DM group was lower than that in the late-onset T2DM group (11.07 ± 3.05 vs. 12.40 ± 2.72 pg/mL, p = 0.048) and was positively correlated with fasting C-peptide, while negatively correlated with HbA1c and fasting glucagon (p all < 0.05).
Conclusions:
Patients with early-onset T2DM showed inhibition of conversion from DHEA to testosterone, which may attribute to the low level of 3β-HSD and high blood glucose in these patients.
... Gonadal dysfunction in alcoholics may be due to the depressant effect of alcohol itself, alcohol-related liver disease, or due to psychological factors [22]. Alcohol affects testosterone levels by multiple mechanisms -it suppresses the HPG axis in men and directly reduces its production at the testicular level [23]. ...
Background and aims:
Liver cirrhosis influences gonadal hormone metabolism by multiple mechanisms and causes gonadal dysfunction. This study aimed to study sex hormones in males with cirrhosis and determine their correlation with prognostic scores.
Methods:
An observational study was conducted between October 2019 and August 2021 in India. Sixty males with liver cirrhosis and 60 healthy age-matched controls were enrolled. Serum-free testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (Prl) were checked. Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD-Na) scores were calculated.
Results:
Mean age of patients was 46.9±8.38 years. Forty-three were alcoholics. A total of 29 (48.33%) patients had low levels of free T. Cirrhotic males had lower testosterone and higher estradiol levels and lower T:E2 ratio compared to controls. Levels of luteinizing hormone, follicle-stimulating hormone, and prolactin were comparable. Lower testosterone was significantly associated with advancing age, alcoholism, duration of cirrhosis, loss of libido, and ascites. The higher the CTP scores, the lower the free testosterone levels and the higher the E2 levels. There was no significant association between low free testosterone levels and MELD-Na score.
Conclusions:
Age, alcohol, duration of disease, and low albumin levels are risk factors for hypogonadism in cirrhosis. There was a significant positive correlation between low free testosterone levels and poor CTP scores.
... Svartberg et al. found that smoking is an independent contributor to the variation of total testosterone and SHBG levels [58]. Interestingly, alcohol and tobacco have similar effects on plasma testosterone levels [59]. It has been identified that higher levels of alcohol and tobacco Fig. 2 Scatter diagram of TNR. ...
... It has been identified that higher levels of alcohol and tobacco Fig. 2 Scatter diagram of TNR. *The X-axis represents SNP, and the Y-axis represents −log10 p-values of each variant consumption were associated with higher levels of testosterone before and after alcohol withdrawal [59]. ...
Objective
To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.
Methods
The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.
Results
We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10 –11 ) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10 –8 ) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10 –5 ) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10 –8 ) interacting with total testosterone for fluid intelligence.
Conclusion
Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
... As anticipated, we found higher testosterone levels in those with severe dependence scoring with simultaneous history of smoking than those who were nonsmokers (p ¼ 0.008). 27 The low normal level of serum testosterone obtained can be explained by the concept of free/bioavailable testosterone or dihydrotestosterone and sex hormone-binding globulin effects. 28 The increased LH in the blood may be due to compensatory mechanism. ...
Abstract
Background
Alcohol dependence syndrome (ADS) is a major problem in India. ADS is known to be a systemic disorder involving almost all organ-systems. The evaluation of ADS patients’ needs successive assessment of severity of clinical condition. In this study, we attempted to explore Severity of Alcohol Dependence Questionnaire (SADQ-C) as a severity measure by studying its association with laboratory parameters.
Methods
During the two months study period 155 diagnosed ADS male patients who had been admitted to the Psychiatric Ward of two zonal level hospitals were enrolled for the study. The participants were examined by the Psychiatrist and the severity of alcoholism ascertained by the SADQ-C scoring. Based on SADQ-C scoring they were divided into three groups: severe alcohol dependence, moderate dependence and mild physical dependence. The patients’ blood samples were collected and tested.
Results
In our study, morning and evening level of serum cortisol showed positive correlation with increasing SADQ-C scoring. The differences in morning and evening cortisol level also augmented with increasing severity score (r=0.257; p=0.001). Hemoglobin, mean corpuscular volume (MCV) and serum level of LH, FSH and testosterone levels were not shown any statistically significant alterations amongst the studied groups. Serum LH, total bilirubin, direct bilirubin, AST, ALT and GGT level showed positive correlation with SADQ-C scoring but AST/ALT ratio showed negative correlation.
Conclusion
This study elaborated relationship between SADQ-C scoring and laboratory parameters in Indian male ADS patients. It highlighted the requirement of incorporation of serum cortisol along with presently evaluated laboratory parameters for ADS severity evaluation.
Keywords
ADS
SADQ-C
Indian male alcoholics
Laboratory parameters
Serum cortisol
... These results suggest that males with high testosterone levels tend to show increased risk for alcohol use than males with low testosterone levels. Accordingly, in alcohol-dependent populations, an increase in testosterone concentrations should co-occur with abstaining from alcohol (Hasselblatt et al., 2003;Heinz et al., 1995;King et al., 1995;Lenz et al., 2017) or alcohol withdrawal (Walter et al., 2006a) compared to healthy controls. Such an association of increased testosterone levels and an elevated risk for alcohol consumption in men may be partly accounted for by the extent of prenatal testosterone exposure. ...
... Alcohol withdrawal can reverse these effects (Välimäki et al., 1984) and increased levels of T, E2 and LH have been reported in abstinent patients with alcoholism (Hasselblatt et al., 2003;King et al., 1995). At the onset of alcohol withdrawal, there does not seem to be any difference in peripheral T levels between alcoholics and controls, but increased T levels are seen only after prolonged abstinence (Walter et al., 2007). ...
... Reference(s) Testosterone Acute alcohol consumption increases levels in women Frias et al., 2000;Frias et al., 2002;Sarkola et al., 2000 Acute low dose alcohol consumption increases levels in males Sarkola and Eriksson, 2003 Acute high dose alcohol consumption decreases levels in males Mendelson et al., 1977;Välimäki et al., 1984 Chronic alcohol consumption decreases levels in males e.g. Maneesh et al., 2006;Muthusami and Chinnaswamy, 2005 Alcohol withdrawal and abstinence increase levels Hasselblatt et al., 2003;King et al., 1995;Walter et al., 2007 High levels have been associated with alcoholism Eriksson et al., 2005;La Grange et al., 1995;Martin et al., 1999;Muti et al., 1998;Purohit, 1998;Virkkunen et al., 1994 Dehydroepiandrosterone Acute alcohol consumption increases plasma levels Pierucci-Lagha et al., 2006;Välimäki et al., 1984 High saliva levels associated with drinking to cope with stress in women Wemm et al., 2013 Pregnenolone Acute alcohol consumption increases plasma levels Pierucci-Lagha et al., 2006 ...
Alcohol (ethanol) consumption is one of the leading risk factors for many serious diseases. The pharmacology of ethanol is extremely complex, affecting many of the signaling systems not only in the brain but widely throughout the body. Alcoholics are a heterogeneous group of subjects suffering a wide spectrum of problems. Cloninger’s typology divides the spectrum of alcoholics into two subgroups: anxiety-prone late onset type 1 alcoholics and early onset, impulsive and antisocial type 2 alcoholics. Here the post-mortem brain samples of Cloninger type 1 (N=9) and type 2 (N=8) alcoholics have been studied and compared to non-alcoholic controls (N=10).
The first sub-study evaluated [3H]AMPA binding to AMPA receptors. Increased binding was observed in the anterior cingulate cortex of type 2 alcoholics in comparison with controls. This elevated [3H]AMPA binding could be associated with increased impulsivity in these individuals.
The second study investigated the endocannabinoid levels in the post-mortem samples of hippocampus and amygdala. Increased docosahexaenoylethanolamide levels were observed in late-onset type 1 alcoholics in the amygdala. Furthermore, a negative correlation was observed between anandamide levels and previously published metabotropic glutamate receptor 1/5 levels in the hippocampus in type 1 alcoholics, but not in controls or type 2 alcoholics. These observations could be associated with the transient receptor potential vanilloid type 1 mediated synaptic plasticity which is dependent on metabotropic glutamate receptor 5 and anandamide function.
In the third study, [3H]citalopram binding to serotonin transporters was measured in brain regions associated with social cognition. Decreased [3H]citalopram binding was observed in the posterior cingulate cortex and posterior insula in all alcoholics when compared to non-alcoholic controls. Furthermore, decreased [3H]citalopram binding in the parahippocampal gyrus was seen only in the antisocial type 2 alcoholics. The decreased serotonin transporter binding in alcoholics could be associated with altered social cognitive processes.
The fourth study examined levels of neuroactive steroids in the post-mortem brain samples. Increased dehydroepiandrosterone levels were seen in all alcoholics compared to controls. There were also negative correlations detected between pregnenolone levels and the previously published [3H]naloxone binding to µ-opioid receptors and similarly, increased pregnenolone levels were observed only in a sub-group of alcoholics with decreased [3H]naloxone binding in comparison with the controls.
Overall, the findings of the present thesis improve our understanding of the differences between the brains of alcoholics and controls. Furthermore, they highlight the need to recognize the spectrum of alcoholics in research which hopefully will be translated into improvements in the treatment of alcoholism.
... This contrasts with previous studies showing altered peripheral and cerebrospinal fluid T levels in association with alcoholism and antisocial behavior (Eriksson, Kaprio, Pulkkinen, & Rose, 2005;La Grange, Jones, Erb, & Reyes, 1995;Lenz et al., 2012;Virkkunen et al., 1994;Yildirim & Derksen, 2012). However, peripheral T levels do not differ between alcoholics and controls at the onset of withdrawal, and increased T levels are observed only after a period of abstinence (Walter et al., 2007). Most of the alcoholics in the present study were intoxicated at the time of death (Table 1). ...
Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography–tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [3H]naloxone binding to μ-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between −0.6 and −0.8; p values ≤ 0.002), suggesting an association between the opioid system and brain PREGN levels. Although preliminary, and from relatively small diagnostic groups, these results show significantly increased levels of DHEA and PREGN in the brains of alcoholics, and could be associated with the pathology of alcoholism.
... The present study corroborates these reports as TT levels were significantly reduced in the non-abstinent groups while no significant change was observed in the abstinent group when compared with control. Reports have stated that TT concentrations may be elevated after alcohol withdrawal (7,27,64). Similarly in rodents, plasma TT levels have been reported to decline during withdrawal after moderate ethanol exposure (5,34,53) but rebound after ethanol cessation (46). In their study Emanuele et al. (20) reported a significant increase in TT level during a 3-month recovery period. ...
Drinking continues to be a major problem in many parts of the world. Significant effects on testicular morphology and function in animals as well as man have been well described. To further explore the impact of chronic ethanol exposure on the testes, we designed this study specifically to define whether or not there was complete recovery after abstinence by examining reproductive hormones, testicular histomorphometry, testicular antioxidants as well as semen parameters after ethanol exposure.
Sexually mature male Sprague–Dawley rats were randomly divided into control, abstinent and non-abstinent groups. Alcohol was administered orally at 7 ml/kg body weight per day thrice in a week for 2, 4 and 8 weeks. Control animals received an equivalent amount of distilled water. Histological analysis of the seminiferous tubules of the animals in the non-abstinent group showed severe reduction of cells of the spermatogenic series, hypocellularity, tubular atrophy and significant reductions in the tubular diameter and cross-sectional areas (p
... Interestingly, the effects of alcohol withdrawal and tobacco on testosterone levels are cumulative. Extensive smoking of alcohol-dependent patients leads to an additional increase in testosterone levels during withdrawal (Walter et al., 2007), indicating a common pathophysiological mechanism. However, the majority of human addiction studies have primarily focused on male patients. ...
... This effect can reverse during and following withdrawal (Castilla-García et al., 1987;Heinz et al., 1995;Vä limä ki et al., 1984). However,Walter et al. (2007)found no significant differences between alcohol-dependent patients and healthy controls in free testosterone levels at the onset of withdrawal. With respect to alcohol-induced changes of LH and FSH, clinical studies report findings which differ between acute and chronic alcohol intake. ...
There are well-known sex differences in the epidemiology and etiopathology of alcohol dependence. Male gender is a crucial risk factor for the onset of alcohol addiction. A directly modifying role of testosterone in alcohol addiction-related behavior is well established. Sex hormones exert both permanent (organizational) and transient (activational) effects on the human brain. The sensitive period for these effects lasts throughout life. In this article, we present a novel early sex hormone activity model of alcohol addiction. We propose that early exposure to sex hormones triggers structural (organizational) neuroadaptations. These neuroadaptations affect cellular and behavioral responses to adult sex hormones, sensitize the brain's reward system to the reinforcing properties of alcohol and modulate alcohol addictive behavior later in life. This review outlines clinical findings related to the early sex hormone activity model of alcohol addiction (handedness, the second-to-fourth-finger length ratio, and the androgen receptor and aromatase) and includes clinical and preclinical literature regarding the activational effects of sex hormones in alcohol drinking behavior. Furthermore, we discuss the role of the hypothalamic-pituitary-adrenal and -gonadal axes and the opioid system in mediating the relationship between sex hormone activity and alcohol dependence. We conclude that a combination of exposure to sex hormones in utero and during early development contributes to the risk of alcohol addiction later in life. The early sex hormone activity model of alcohol addiction may prove to be a valuable tool in the development of preventive and therapeutic strategies.
... The relationship between testosterone levels and ethanol intake appears to be bidirectional, with testosterone not only influencing ethanol consumption, perhaps in a species specific manner, but alcohol use itself inhibiting testosterone secretion in the testes of rats and humans [1,30,27,39]. Indeed, testosterone levels in male alcoholics have often been found to be lower than among healthy controls, but to rise during abstinence, with some studies reporting a return to normal levels within three weeks [16] or more [43] or even to over shoot control levels of the hormone [28]. In the current study, testosterone levels were obtained after a period of voluntary ethanol consumption, and hence the extent to which this consumption may have influenced plasma testosterone concentrations of SH and NM animals cannot be determined. ...
Previous studies have shown that adult female rats consume more ethanol than adult males. Castration of male rats has been found to increase their ethanol intake and preference to levels significantly elevated above their sham-gonadectomized counterparts and similar to levels observed in females. The purpose of the present experiment was to examine whether testosterone replacement in castrated adult male rats would be sufficient to restore the relatively low levels of ethanol drinking characteristic of intact adult male rats. Males were either gonadectomized and implanted with a testosterone propionate pellet (RPL), gonadectomized and implanted with a placebo pellet (GX), sham-gonadectomized and implanted with a placebo pellet (SH), or were left non-manipulated (NM). Voluntary ethanol intake was measured using a 2h limited-access drinking paradigm, with access to two bottles: one containing water, and the other a sweetened ethanol solution. Hormone replacement was sufficient to return ethanol intake and preference of castrates to levels comparable to both SH and NM control males. Ethanol preference of RPL males was also significantly suppressed compared to GX males by the end of the measurement period, whereas these group comparisons did not reach statistical significance for g/kg ethanol intake. These data suggest that testosterone serves to suppress ethanol preference in male rats, and may contribute to the sex differences in ethanol preference and consumption commonly reported in adult rats.
